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Sample records for igg4-related tubulointerstitial nephritis

  1. IgG4-Related Tubulointerstitial Nephritis.

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    Zhang, Pingchuan; Cornell, Lynn D

    2017-03-01

    Immunoglobulin G4 (IgG4)-related disease (IgG4-RD) is a fibroinflammatory disorder that can involve nearly any organ. The disorder has increasingly become known as a distinct clinical entity during the last decade. IgG4-related tubulointerstitial nephritis (IgG4-TIN) is the most common manifestation of IgG4-RD in the kidney. Many patients with IgG4-TIN are diagnosed after IgG4-RD has been recognized in other organ systems, but the kidney may also be the first or only site involved. The presenting clinical features of IgG4-TIN are most commonly kidney insufficiency, kidney mass lesion(s), or both. On biopsy, IgG4-TIN shows a dense lymphoplasmacytic infiltrate, increased IgG4+ plasma cells, storiform fibrosis, and often tubular basement membrane immune complex deposits. Elevation of serum IgG4 often accompanies IgG4-RD; however, it is not specific in reaching the diagnosis. Like IgG4-RD in other organs, IgG4-TIN characteristically responds promptly to steroids, although there is a high relapse rate on discontinuation of immunosuppression. The pathogenesis of IgG4-RD is not understood. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  2. Characteristic tubulointerstitial nephritis in IgG4-related disease.

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    Yamaguchi, Yutaka; Kanetsuna, Yukiko; Honda, Kazuho; Yamanaka, Nobuaki; Kawano, Mitsuhiro; Nagata, Michio

    2012-04-01

    Nephropathy associated with IgG4-related disease is characterized by tubulointerstitial nephritis. To better identify its pathology, the present study analyzed clinicopathologic features of IgG4-related tubulointerstitial nephritis cases from across Japan. Sixteen cases were identified as IgG4-related nephropathy using the criterion of high serum IgG4 levels (>135 mg/dL) with abnormal kidney computed tomography or elevated serum creatinine levels. Male predominance (75%) and advanced age (average, 62.0 years) were noted. Eight cases displayed no autoimmune pancreatitis. Renal computed tomography abnormalities were found in 12 of 13 cases examined. Renal dysfunction was found in 15 of 16 cases at biopsy. Distinctive features of tubulointerstitial lesions included (1) well-demarcated borders between involved and uninvolved areas; (2) involvement of the cortex and medulla, often extending beyond the renal capsule and with occasional extension to retroperitoneal fibrosis; (3) interstitial inflammatory cells comprising predominantly plasma cells and lymphocytes, with a high prevalence of IgG4-positive cells often admixed with fibrosis; (4) peculiar features of interstitial fibrosis resembling a "bird's-eye" pattern comprising fibrosis among inter-plasma cell spaces; and (5) deposits visible by light and immunofluorescent microscopy in the tubular basement membrane, Bowman capsule, and interstitium that are restricted to the involved portion, sparing normal parts. Ultrastructural analysis revealed the presence of myofibroblasts with intracellular/pericellular collagen accompanied by plasma cell accumulation from an early stage. Histology could not discriminate between IgG4-related tubulointerstitial nephritis with and without autoimmune pancreatitis. In conclusion, the distinctive histologic features of IgG4-related tubulointerstitial nephritis can facilitate the differential diagnosis of tubulointerstitial nephritis, even without autoimmune pancreatitis or an abnormal

  3. IgG4-related tubulointerstitial nephritis with plasma cell-rich renal arteritis.

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    Sharma, Shree G; Vlase, Horia L; D'Agati, Vivette D

    2013-04-01

    Immunoglobulin G4 (IgG4)-related tubulointerstitial nephritis is a newly recognized clinicopathologic entity that may occur as an isolated renal lesion or as part of a multisystem disorder. It is characterized by plasma cell-rich interstitial nephritis with abundant IgG4-positive plasma cells and IgG-dominant tubulointerstitial immune deposits. We report the first case of IgG4-related tubulointerstitial nephritis with multifocal plasma cell-rich renal arteritis presenting as acute kidney injury in a 72-year-old man. Seven weeks of prednisone therapy led to nearly complete recovery of kidney function. This case enlarges the morphologic spectrum of this disorder and emphasizes the need to distinguish it from other causes of renal vasculitis. Copyright © 2013 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  4. Acute tubulointerstitial nephritis with severe renal impairment associated with multisystem IgG4-related disease

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    Rafael Coimbra Ferreira Beltrame

    Full Text Available Abstract The IgG4-related disease has a wide clinical spectrum where multiple organs can be affected, and the diagnosis depends on typical histopathological findings and an elevated IgG4 expression in plasma cells in the affected tissue. We describe the clinical presentation and evolution of a patient with acute tubulointerstitial nephritis, severe kidney failure and systemic manifestations such as lymphadenomegaly and chronic pancreatitis. The diagnosis was confirmed by the clinical picture and kidney and lymph node histopathology, in which immunohistochemistry of the lymphoid tissue showed policlonality and increased expression of IgG4, with a IgG4/total IgG ratio > 80%. The patient was treated with prednisone at a dose of 60 mg/day, followed by mycophenolate mofetil, and showed clinical and renal function improvement at 6 months of follow-up. The high index of suspicion of IgG4-related disease with multisystem involvement and the early treatment of this condition are essential to improve the prognosis of affected patients.

  5. Overview of IgG4-Related Tubulointerstitial Nephritis and Its Mimickers

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    Hyeon Joo Jeong

    2016-01-01

    Full Text Available Tubulointerstitial nephritis (TIN is the most common form of renal involvement in IgG4-related disease. It is characterized by a dominant infiltrate of IgG4-positive plasma cells in the interstitium and storiform fibrosis. Demonstration of IgG4-positive plasma cells is essential for diagnosis, but the number of IgG4-positive cells and the ratio of IgG4-positive/IgG-positive plasma cells may vary from case to case and depending on the methods of tissue sampling even in the same case. IgG4-positive plasma cells can be seen in TIN associated with systemic lupus erythematosus, Sjögren syndrome, or anti-neutrophil cytoplasmic antibody–associated vasculitis, which further add diagnostic confusion and difficulties. To have a more clear view of IgG4-TIN and to delineate differential points from other TIN with IgG4-positive plasma cell infiltrates, clinical and histological features of IgG4-TIN and its mimickers were reviewed. In the rear part, cases suggesting overlap of IgG4-TIN and its mimickers and glomerulonephritis associated with IgG4-TIN were briefly described.

  6. Acute tubulointerstitial nephritis with severe renal impairment associated with multisystem IgG4-related disease.

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    Beltrame, Rafael Coimbra Ferreira; Friderichs, Maurício; Fior, Bárbara Rayanne; Schaefer, Pedro Guilherme; Thomé, Gustavo Gomes; Silva, Dirceu Reis da; Barros, Elvino José Guardão; Seligman, Renato; Veronese, Francisco Veríssimo

    2016-01-01

    The IgG4-related disease has a wide clinical spectrum where multiple organs can be affected, and the diagnosis depends on typical histopathological findings and an elevated IgG4 expression in plasma cells in the affected tissue. We describe the clinical presentation and evolution of a patient with acute tubulointerstitial nephritis, severe kidney failure and systemic manifestations such as lymphadenomegaly and chronic pancreatitis. The diagnosis was confirmed by the clinical picture and kidney and lymph node histopathology, in which immunohistochemistry of the lymphoid tissue showed policlonality and increased expression of IgG4, with a IgG4/total IgG ratio > 80%. The patient was treated with prednisone at a dose of 60 mg/day, followed by mycophenolate mofetil, and showed clinical and renal function improvement at 6 months of follow-up. The high index of suspicion of IgG4-related disease with multisystem involvement and the early treatment of this condition are essential to improve the prognosis of affected patients. Resumo A doença relacionada à IgG4 tem um espectro clínico amplo em que múltiplos órgãos podem ser afetados, e o diagnóstico depende de achados histopatológicos típicos e elevada expressão de IgG4 em plasmócitos no tecido afetado. Descrevemos o quadro clínico e a evolução de um paciente com nefrite túbulo-intersticial aguda, insuficiência renal grave e manifestações sistêmicas como linfoadenomegalias e pancreatite crônica. O diagnóstico foi confirmado pelas características clínicas e pela histopatologia renal e de linfonodo, na qual a imunohistoquímica mostrou tecido linfoide com policlonalidade e expressão aumentada de IgG4, com uma relação IgG4/IgG total > 80%. O paciente foi tratado com prednisona na dose de 60 mg/dia, seguido de micofenolato mofetil, e apresentou melhora clínica e da função renal depois de 6 meses de tratamento. O alto índice de suspeição da doença relacionada ao IgG4 com comprometimento multissist

  7. Concurrent IgG4-related tubulointerstitial nephritis and IgG4 myeloperoxidase-anti-neutrophil cytoplasmic antibody positive crescentic glomerulonephritis: A case report.

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    Su, Tao; Yang, Li; Cui, Zhao; Wang, Su-Xia; Zhao, Ming-Hui

    2017-05-01

    IgG4-related disease (IgG4-RD) is a newly recognized systemic disease. The typical pathological finding in the kidney is abundant IgG4-positive plasma cell infiltration with characteristic storiform fibrosis in the interstitium. Antibodies of the IgG4 subclass have been linked to certain autoimmune diseases including antiproteinase 3 (PR3) anti-neutrophil cytoplasmic antibody (ANCA) of the IgG4 subclass. Here, we report a rare case of kidney injury with concurrent typical IgG4-related tubulointerstitial nephritis and IgG4 subclass of myeloperoxidase (MPO) ANCA-positive necrotizing crescentic glomerulonephritis. A 42-year-old Chinese man presented with repeated epigastric pain, sausage-shaped pancreas observed morphologically in computed tomography, effectiveness of prednisone therapy and was diagnosed with autoimmune pancreatitis. He subsequently developed acute kidney injury. The patient had an elevated serum IgG4, eosinophilia, and positive MPO-ANCA of IgG4-dominant subclass. Renal biopsy revealed necrotizing crescentic nephritis and typical IgG4-related tubulointerstitial nephritis. The patient was treated with a combination of corticosteroids and cyclophosphamide, and a course of rituximab was later added to deplete peripheral B cells. The patient responded well and his renal function improved. This is the first case report of an IgG4-RD with concurrent IgG4-related tubulointerstitial nephritis and IgG4 MPO-ANCA-associated necrotizing crescentic glomerulonephritis. It raises the difficulty in differentiation diagnosis of the two separate diseases that is worthy of further study.

  8. Tubulointerstitial fibrosis in patients with IgG4-related kidney disease: pathological findings on repeat renal biopsy

    NARCIS (Netherlands)

    Arai, Haruna; Hayashi, Hiroki; Takahashi, Kazuo; Koide, Shigehisa; Sato, Waichi; Hasegawa, Midori; Yamaguchi, Yutaka; Aten, Jan; Ito, Yasuhiko; Yuzawa, Yukio

    2015-01-01

    Renal parenchymal lesions in patients with IgG4-related kidney disease (IgG4-RKD) are characterized by tubulointerstitial nephritis with storiform fibrosis and infiltration by high numbers of IgG4-positive plasma cells. The aim of this study was to evaluate the clinical and pathological effects of

  9. IgG4-related nephropathy.

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    Quattrocchio, Giacomo; Roccatello, Dario

    2016-08-01

    IgG4-related disease (IgG4-RD) is a recently recognized disorder, often with multiple organ involvement, characterized by dense tissue infiltration of IgG4-positive plasma cells, storiform fibrosis, obliterative phlebitis and frequently elevated serum IgG4 concentration. The kidney can be involved either directly or indirectly. The most frequent direct renal manifestations of IgG4-RD are IgG4-related tubulointerstitial nephritis (TIN) and membranous glomerulonephropathy. Retroperitoneal fibrosis (RPF) is another condition that is frequently IgG4-related and that can indirectly affect the kidney causing ureteral obstruction and hydronephrosis. Contrast-enhanced computerized tomography, magnetic resonance imaging and (18)F-fluorodeoxyglucose positron emission tomography/computed tomography show different imaging findings and are useful tools for monitoring therapeutic response. Steroid treatment is the first line of therapy, but relapsing or refractory forms of the disease are frequently observed and require more aggressive therapeutic approaches. At our centre, we treated three cases of aggressive IgG4-related TIN and two cases of IgG4-related RPF with an intensified, immune suppressive protocol, obtaining good results without severe adverse effects.

  10. Immunoglobulin G4-related tubulointerstitial nephritis: A not to be missed diagnosis

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    Smita Mary Matthai

    2017-01-01

    Full Text Available Immunoglobulin G4-related tubulointerstitial nephritis (IgG4-TIN is a newly recognized clinicopathological entity characterized by a dense interstitial infiltrate of IgG4-positive plasma cells accompanied by fibrosis and obliterative phlebitis causing acute or chronic renal dysfunction amenable to corticosteroid therapy. IgG4-TIN is the dominant manifestation of renal involvement in IgG4-related disease (IgG4-RD which is a novel, immune-mediated, fibroinflammatory and multiorgan disorder. We describe a case of IgG4-TIN with isolated renal involvement in an elderly male patient with poor response to corticosteroid therapy. The distinctive serological, histopathological, and ultrastructural features of this condition which can facilitate differential diagnosis of TIN are highlighted to emphasize the need for early diagnosis and preservation of kidney function.

  11. Pathomorphological characteristic of IgG4-related diseases

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    O. O. Dyadyk

    2016-08-01

    Full Text Available IgG4-related diseases are a relatively new group of diseases of unknown etiology which are characterized by the development of fibrosis of organs with the presence of big amounts of IgG4-positive plasma-cells in the area of the lesions and increased levels of IgG4 in serum. The organs that may be affected are pancreas, salivary gland, and others, clinical cases of kidney damage are described as well. Renal involvement in IgG4-related diseases most often occurs on the type of tubulointerstitial nephritis, with the further development of acute or chronic kidney injury. The clinic may be represented by the pseudotumor of kidney, renal tissue heterogeneity on the results of CT-studies; acute or chronic renal disease; combination with other organ damage (autoimmune pancreatitis, sclerosing cholangitis, sclerosing lymphoplasmacytic cholecystitis, colitis, sialadenitis, retroperitoneal fibrosis, etc.. Laboratory findings include an increased level of IgG4 in the blood serum, hypocomplementemia, eosinophilia. Histologically, there is interstitial inflammation with many plasma cells, interstitial fibrosis, tubular atrophy, thickening of the tubular basement membrane, some cases are a type of membranous glomerulonephritis. The aim of the study is to identify the patients with IgG4-related diseases with renal impairment and widening the pathological database of such patients with renal impairment to determine the classification criteria of this pathological condition. Materials and methods will include the deceased kidney screening, screening of patients with autoimmune and allergic diseases, nephrological patients screening with the lifetime biopsy (in some cases – repeat biopsy with chronic or acute kidney impairment. There will be clinical and pathological comparison in kidney damage and other diseases with the development of criteria for the classification of lesions in the presence of IgG4-positive substrates and further development of practical

  12. Acute tubulointerstitial nephritis complicating Legionnaires' disease: a case report

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    Daumas Aurélie

    2012-04-01

    Full Text Available Abstract Introduction Legionnaires' disease is recognized as a multi-systemic illness. Afflicted patients may have pulmonary, renal, gastrointestinal tract and central nervous system complications. However, renal insufficiency is uncommon. The spectrum of renal involvement may range from a mild and transient elevation of serum creatinine levels to anuric renal failure requiring dialysis and may be linked to several causes. In our present case report, we would like to draw attention to the importance of the pathological documentation of acute renal failure by reporting a case of a patient with acute tubulointerstitial nephritis complicating Legionnaires' disease. Case presentation A 55-year-old Caucasian man was admitted to our hospital for community-acquired pneumonia complicated by acute renal failure. Legionella pneumophila serogroup type 1 was diagnosed. Although the patient's respiratory illness responded to intravenous erythromycin and ofloxacin therapy, his renal failure worsened, he became anuric, and hemodialysis was started. A renal biopsy was performed, which revealed severe tubulointerstitial nephritis. After initiation of steroid therapy, his renal function improved dramatically. Conclusions This case highlights the importance of kidney biopsies in cases where acute renal failure is a complicating factor in Legionnaires' disease. If the presence of acute tubulointerstitial nephritis can be confirmed, it will likely respond favorably to steroidal treatment and thus irreversible renal damage and chronic renal failure will be avoided.

  13. IgG4-related kidney disease – an update

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    Kawano, Mitsuhiro; Saeki, Takako

    2015-01-01

    Purpose of review IgG4-related disease (IgG4-RD) is a recently recognized systemic inflammatory disorder that can affect most organs/tissues such as sarcoidosis. The kidney is a frequently affected organ with tubulointerstitial nephritis (TIN), the representative lesion of IgG4-RD. This review focuses on the latest knowledge of IgG4-related kidney disease (IgG4-RKD). Recent findings A wide range of renal manifestations of IgG4-RD, that is TIN, membranous glomerulonephritis (MGN) and other glomerular lesions, and pyelitis, are collectively referred to as IgG4-RKD. Clinically, decreased renal function, or characteristic imaging findings such as multiple low-density lesions on contrast-enhanced computed tomography or diffuse thickening of the renal pelvic wall, are typical presenting features. Although a rapid response to corticosteroid therapy is a very important feature of IgG4-TIN, in cases in which renal function is moderately to severely decreased before therapy, only partial recovery of renal function is obtained. Summary TIN with characteristic imaging findings is a typical manifestation of IgG4-RKD in the interstitium, while MGN is a representative manifestation of the glomerular lesions. Although IgG4 is a central feature of IgG4-RD, the recent discovery of IgG4-negative IgG4-RD raises questions about the causative role of the IgG4 molecule in this context. PMID:25594543

  14. Acute tubulointerstitial nephritis and uveitis syndrome: A report on four adult cases

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    Yosra Ben Ariba

    2017-01-01

    Full Text Available Acute tubulointerstitial nephritis and uveitis (TINU syndrome is a rare disease, generally presenting in children and young women. The interstitial nephritis may precede, follow, or develop concurrent to the uveitis. We report the clinical features and outcomes of four adult patients, aged 41-70 years with the TINU syndrome.

  15. Autoantibodies Targeting a Collecting Duct-Specific Water Channel in Tubulointerstitial Nephritis

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    Landegren, Nils; Pourmousa Lindberg, Mina; Skov, Jakob

    2016-01-01

    Tubulointerstitial nephritis is a common cause of kidney failure and may have diverse etiologies. This form of nephritis is sometimes associated with autoimmune disease, but the role of autoimmune mechanisms in disease development is not well understood. Here, we present the cases of three patien...

  16. Tubulointerstitial nephritis and uveitis syndrome associated with hyperthyroidism.

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    Ebihara, Itaru; Hirayama, Kouichi; Usui, Joichi; Seki, Masanori; Higuchi, Fujiko; Oteki, Takaaki; Kobayashi, Masaki; Yamagata, Kunihiro

    2006-09-01

    We report a 17-year-old male patient with tubulointerstitial nephritis and uveitis (TINU) associated with hyperthyroidism. He presented with a 2-month history of fatigue, loss of appetite, low-grade fever, and a 12-kg weight loss when he was admitted to our hospital. He had iritis, which was complicated by fibrin in the anterior chamber, diagnosed by slit-lamp examination. On laboratory examinations, deteriorated renal function (blood urea nitrogen level was 25.9 mg/dl and creatinine level was 2.82 mg/dl) and elevated urinary levels of N-acetyl-beta-D-glucosaminidase (33.1 U/l) and beta2-microglobulin (78,600 microg/l) were observed. Serum thyroid-stimulating hormone (TSH) was undetectable, at less than 0.01 microIU/ml, and free triiodothyronine and free thyroxine were elevated, up to 5.23 pg/ml and 2.85 ng/dl, respectively. The titers of antithyroglobulin and antithyroid microsomal and TSH-receptor antibodies were not elevated. Abdominal and thyroidal ultrasonography showed evident bilateral enlargement of the kidneys and diffuse enlargement of the thyroid gland. Iodine-123 scintigraphy showed low uptake in the thyroid gland. The biopsied renal specimen showed mild edema and severe diffuse infiltration of mononuclear cells and few eosinophils in the interstitium, without any glomerular or vascular abnormalities. Based on the clinical features and pathological findings, a diagnosis of TINU syndrome with associated hyperthyroidism was made. Treatment was started with 30 mg/day of prednisolone. The iritis disappeared, and the patient's clinical status improved remarkably. This case suggests the possibility of thyroid dysfunction in some patients with TINU syndrome, and we believe thyroid function should be measured in all TINU patients. Moreover, histopathological diagnosis of the thyroid glands before treatment is necessary for TINU patients with thyroid dysfunction.

  17. Acute tubulo-interstitial nephritis leading to acute renal failure following multiple hornet stings

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    Bambery Pradeep

    2006-11-01

    Full Text Available Abstract Background Hornet stings are generally associated with local and occasionally anaphylactic reactions. Rarely systemic complications like acute renal failure can occur following multiple stings. Renal failure is usually due to development of acute tubular necrosis as a result of intravascular haemolysis, rhabdomyolysis or shock. Rarely it can be following development of acute tubulo-interstitial nephritis. Case presentation We describe a young male, who was stung on face, head, shoulders and upper limbs by multiple hornets (Vespa orientalis. He developed acute renal failure as a result of acute tubulo-interstitial nephritis and responded to steroids. Conclusion Rare causes of acute renal failure like tubulo-interstitial nephritis should be considered in a patient with persistent oliguria and azotemia following multiple hornet stings. Renal biopsy should be undertaken early, as institution of steroid therapy may help in recovery of renal function

  18. Presenting A Case with Tubulointerstitial Nephritis and Uveitis (TINU- Syndrome

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    E Fotouhi Ardakani

    2008-10-01

    Full Text Available Concurrence of interstitial nephritis and uveitis named tubulointestitioal nephritis and uveitis syndrome (TINU are unusual and uncommon presentations of interstitial nephritis. This syndrome is considered after ruling out other differential diagnoses. A-38-year old man presented with acute renal failure and uveitis. The histologic findings of renal biopsy showed acute tubulointestitioal nephritis. The patient had no clinical and paraclinical manifestations of other etiologies of interstitial nephritis and uveitis such as Wegener's granulomatosis , Sjogren's syndrome or sarcoidosis. The diagnosis of TINU-Syndrome was therefore considered. The patient was treated by oral and ophthalmic prednisolone and had a good response to treatment.

  19. [Tubulointerstitial nephritis with uveitis (TINU) syndrome. A relatively rare rheumatological differential diagnosis with unexplained uveitis].

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    Häusler, U; Guminski, B; Helmchen, U; Kisters, K; Heinz, C; Braun, J

    2013-05-01

    The tubulo-interstitial nephritis and uveitis (TINU) syndrome, first described in 1975, is a rare disease most probably of autoimmune origin that is characterized by unilateral or bilateral uveitis and tubulointerstitial nephritis. Most patients are adolescents and it is sometimes associated with other autoimmune diseases, such as spondyloarthritis, rheumatoid arthritis and hyperthyroidosis. This article reports the case of a 43-year-old female patient who presented with refractory recurrent bilateral uveitis despite therapy with high doses of corticosteroids in combination with cyclosporin. When the patient was referred to this hospital for rheumatological examination after almost 1 year of therapy, mild renal insufficiency and proteinuria were found. The kidney biopsy revealed interstitial nephritis, partly crescent-shaped and partly chronic. A diagnosis of TINU syndrome was made and treatment with adalimumab in combination with methotrexate was started. The favorable clinical outcome indicated that tumor necrosis factor (TNF) alpha may play an important role in the pathogenesis of TINU syndrome.

  20. Short course of cyclophosphamide therapy may reduce recurrence in patients with tubulointerstitial nephritis and uveitis syndrome

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    Taheri, Shahram; Taheri Diana

    2009-01-01

    We report a 43-year-old woman with tubulointerstitial nephritis and uveitis syndrome (TINU syndrome) presented with a 5-day complaint of chills and fever, anorexia, nausea, and vomiting. She had elevated BUN and creatinine and urinalysis revealed decreased concentration, proteinuria, hematuria, and pyuria. A kidney biopsy showed non-caseating granulomatous tubulointerstitial nephritis. She suffered from anterior uveitis one month before, which was managed with local ophthalmic steroids. She received two months of oral high dose prednisolone, which was tapered over the next two months, and two months of 2 mg/kg cyclophosphamide. Her renal function recovered during the first two months. Her kidney and ocular symptoms did not recur during one year of follow-up. We suggest short course of cyclophosphamide and prednisolone for treatment of TINU syndrome to decrease the recurrence of kidney and ocular involvement. (author)

  1. End-stage Renal Failure as a Complication of Acute Tubulo-Interstitial Nephritis

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    Reda, G.; Ali, R.; Abdelrehman, M.; Sinha, A. K.; Ayman, K.

    2005-01-01

    Acute tubulo-interstitial nephritis (ATIN) is an important cause of acute renal failure, where renal impairement tends to be variable but recovery is the rule. End-stage renal failure (ESRF) has been rarely reported as a complication of ATIN. We report here a case of idiopathic ATIN that resulted in severe acute renal failure. The patient developed ESRF, which required permanent renal replacement therapy. (author)

  2. IgG4-related disease

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    Detlefsen, Sönke; Klöppel, Günter

    2018-01-01

    disease (IgG4-RD). The histologic key findings are lymphoplasmacytic infiltration rich in IgG4-positive plasma cells combined with storiform fibrosis and obliterative phlebitis. Among the organs mainly affected by IgG4-RD are the pancreas and the extrahepatic bile ducts. The pancreatic and biliary...... alterations have been described under the terms autoimmune pancreatitis (AIP) and sclerosing cholangitis, respectively. These diseases are currently more precisely called IgG4-related pancreatitis (or type 1 AIP to distinguish it from type 2 AIP that is unrelated to IgG4-RD) and IgG4-related sclerosing...... cholangitis (IgG4-related SC). Clinically and grossly, both diseases commonly imitate pancreatic and biliary adenocarcinoma, tumors that are well known for their dismal prognosis. As IgG4-RD responds to steroid treatment, making a resection of a suspected tumor unnecessary, a biopsy is often required...

  3. IgG4-related spinal pachymeningitis.

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    Lu, Zhang; Tongxi, Liu; Jie, Luo; Yujuan, Jiao; Wei, Jiang; Xia, Liu; Yumin, Zheng; Xin, Lu

    2016-06-01

    The aim of this study is to study the clinical, laboratory, imaging pathology, and prognosis features of IgG4-related spinal pachymeningitis. We worked with a 55-year-old man suffering from IgG4-related spinal pachymeningitis who had the most widespread lesion in his dura mater. We also review previous related studies and discuss the clinical characteristics of this rare disease. In total, eight IgG4-related spinal pachymeningitis patients have been reported in the literature since 2009. They were mostly male patients, 51.7 ± 11.9 years old on average. Cervical and thoracic vertebrae were the most common sites for lesions. The most prominent symptom was varying numbness and weakness of the limbs and/or body associated with spinal cord compression. There was one patient (1/5) with elevated serum IgG4 levels and three patients (3/3) with increased cerebrospinal fluid (CSF) IgG4 index. Positive histopathologic findings are the strongest basis for a diagnosis. All the patients with IgG4-related spinal pachymeningitis responded well to glucocorticoid therapy. IgG4-related spinal pachymeningitis is an orphan disease that mainly occurs in cervical and thoracic vertebrae. Older males are the most susceptible group. Serum IgG4 levels were consistently normal in these cases, so analysis of CSF for IgG4 production (IgG4 index) could become a useful tool. Pathological findings remain the gold standard for diagnosis. Most patients responded favorably to glucocorticoid treatment.

  4. IgG4-related membranous glomerulonephritis and generalized lymphadenopathy without pancreatitis: a case report.

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    Huart, Justine; Grosch, Stéphanie; Bovy, Christophe; Moutschen, Michel; Krzesinski, Jean-Marie

    2017-04-26

    IgG4-related disease is a recently described pathologic entity. This is the case of a patient with nephrotic syndrome and lymphadenopathy due to IgG4-related disease. Such a kidney involvement is quite peculiar and has only been described a few times recently. Renal biopsy showed a glomerular involvement with membranous glomerulonephritis in association with a tubulo-interstitial nephropathy. Moreover, the patient was not suffering from pancreatitis. The patient is a middle-aged man of Moroccan origin. He has developed recurrent episodes of diffuse lymphadenopathies, renal failure and nephrotic syndrome. Renal biopsies showed membranous glomerulonephritis. The diagnostic approach of this atypical presentation is discussed in this case report as well as diagnostic criteria, therapeutic strategies, biomarkers and pathophysiology of IgG4-related disease. IgG4-related membranous glomerulonephritis is a well-established cause of membranous glomerulonephritis. It must be sought after in every patient with a previous diagnosis of IgG4-related disease and in every patient with this histological finding on renal biopsy. Corticoids are still the first-line treatment of IgG4-related disease. New therapeutic strategies are needed to avoid glucocorticoids long term side-effects. Interestingly, the patient was prescribed cyclophosphamide in addition to glucocorticoids for an immune thrombocytopenia. This treatment had a very good impact on his IgG4-related disease.

  5. A condition closely mimicking IgG4-related disease despite the absence of serum IgG4 elevation and IgG4-positive plasma cell infiltration.

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    Hara, Satoshi; Kawano, Mitsuhiro; Mizushima, Ichiro; Yamada, Kazunori; Fujita, Kentaro; Harada, Kenichi; Matsumura, Masami; Yamagishi, Masakazu; Sato, Yasuharu; Yamaguchi, Yutaka; Nakanuma, Yasuni; Nagata, Michio

    2016-09-01

    We describe a 74-year-old Japanese man with systemic fibroinflammatory conditions closely resembling those of immunoglobulin G4-related disease (IgG4-RD). Radiology and histology showed characteristics of IgG4-related tubulointerstitial nephritis, despite normal serum IgG4 value and scanty IgG4-positive plasma cell infiltration in each organ. This case suggests that a condition closely mimicking IgG4-RD may develop without IgG4-positive plasma cells and those exceptional cases should also be taken into account in the differential diagnosis of IgG4-RD.

  6. IgG4-Related Perineural Disease

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    Dai Inoue

    2012-01-01

    Full Text Available Aims. To elucidate characteristics of IgG4-related disease involving the peripheral nervous system. Methods. Retrospective review of 106 patients with IgG4-related disease identified 21 peripheral nerve lesions in 7 patients. Clinicopathological and radiological features were examined. Results. Peripheral nerve lesions were commonly identified in orbital or paravertebral area, involving orbital (=9, optic (=4, spinal (=7, and great auricular nerves (=1. The predominant radiological feature was a distinct perineural soft tissue mass, ranging 8 to 30 mm in diameter. Histologically, the epineurium was preferentially involved by massive lymphoplasmacytic infiltration rich in IgG4+ plasma cells. All lesions were neurologically asymptomatic and steroid-responsive at the first presentation, but one recurrent lesion around the optic nerve caused failing vision. Conclusion. IgG4-related disease of the peripheral nervous system is characterized by orbital or paravertebral localization, perineural mass formation, and rare neurologic symptoms. The term “IgG4-related perineural disease” seems appropriate to describe this entity.

  7. Tubulointerstitial nephritis accompanying gamma-heavy chain deposition and gamma-heavy chain restricted plasma cells in the kidney.

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    Nayer, Ali; Green, Dollie F; Gonzalez-Suarez, Maria L; Sujoy, Victoria; Ikpatt, Offiong F; Thomas, David B

    2014-09-01

    Monoclonal immunoglobulin heavy chain (HC) diseases are rare proliferative disorders of B lymphocytes or plasma cells characterized by the presence of monoclonal α-, µ-, or γ-HC without associated light chains in the blood, urine, or both. We report a 59-year-old woman with a history of Hodgkin disease who developed hypercalcemia, proteinuria, and impaired kidney function. Protein electrophoresis and immunofixation displayed γ-HC without associated light chains in the serum and urine. Pathologic examination demonstrated severe tubulointerstitial nephritis associated with diffuse and strong linear staining of the glomerular and tubular basement membranes as well as Bowman capsules for γ-HC, but not for κ- or λ-light chains. Immunohistochemical examination of the kidney and bone marrow demonstrated numerous CD138+ plasma cells immunoreactive for γ-HC, but not for κ- or λ-light chains. This is the first report of tubulointerstitial nephritis associated with γ-HC deposition and γ-HC restricted plasma cells in the kidney. This report heightens awareness about tubulointerstitial nephritis as a possible manifestation of γ-HC deposition in the kidney.

  8. IgG4-related prostatitis progressed from localized IgG4-related lymphadenopathy.

    Science.gov (United States)

    Li, Dujuan; Kan, Yunzhen; Fu, Fangfang; Wang, Shuhuan; Shi, Ligang; Liu, Jie; Kong, Lingfei

    2015-01-01

    Immunoglobulin G4-related disease (IgG4-RD) is a recently described inflammatory disease involving multiple organs. Prostate involvement with IgG4-RD is very rare. In this report, we describe a case of IgG4-related prostatitis progressed from localized IgG4-related lymphadenopathy. This patient was present with urine retention symptoms. MRI and CT examination revealed the prostatic enlargement and the multiple lymphadenopathy. Serum IgG4 levels were elevated. Prostatic tissue samples resected both this time and less than 1 year earlier showed the same histological type of prostatitis with histopathologic and immunohistochemical findings characteristic of IgG4-RD. The right submandibular lymph nodes excised 2 years earlier were eventually proven to be follicular hyperplasia-type IgG4-related lymphadenopathy. This is the first case of IgG4-RD that began as localized IgG4-related lymphadenopathy and progressed into a systemic disease involving prostate and multiple lymph nodes. This patient showed a good response to steroid therapy. This leads us to advocate a novel pathogenesis of prostatitis, and a novel therapeutic approach against prostatitis. Pathologists and urologists should consider this disease entity in the patients with elevated serum IgG4 levels and the symptoms of prostatic hyperplasia to avoid ineffective medical or unnecessary surgical treatment.

  9. IgG4-related disease.

    Science.gov (United States)

    Bozzalla Cassione, Emanuele; Stone, John H

    2017-05-01

    Remarkable insights have been gleaned recently with regard to the pathophysiology of IgG4-related disease (IgG4-RD). These findings have direct implications for the development of targeted strategies for the treatment of this condition. Oligoclonal expansions of cells of both the B and T lymphocyte lineages are present in the blood of patients with IgG4-RD. Oligoclonal expansions of plasmablasts are a good biomarker for disease activity. An oligoclonally expanded population of CD4+ cytotoxic T lymphocytes is found not only in the peripheral blood but also at tissue sites of active disease. This cell elaborates cytokines that may drive the fibrosis characteristic of IgG4-RD. T follicular helper cells (Tfhc), particularly the Tfhc2 subset, appear to play a major role in driving the class switch to IgG4 that typifies this disease. The relationship between malignancy and IgG4-RD remains an area of interest. Advances in understanding the pathophysiology of IgG4-RD have proceeded swiftly, leading to the identification of a number of potential targeted treatment strategies. The completion of classification criteria for IgG4-RD, an effort supported jointly by the American College of Rheumatology and the European League Against Rheumatism, will further facilitate studies on this disease.

  10. [IgG4-related kidney disease: what the nephrologist needs to know].

    Science.gov (United States)

    Galeano, Dario; Zanoli, Luca; Scarfia, Viviana Rosalia; L'Imperio, Vincenzo; Malatino, Lorenzo; Fatuzzo, Pasquale; Granata, Antonio

    2016-01-01

    IgG4 related disease is a systemic fibro-inflammatory disorder characterized by multiple organ and multiple tissue lesions. The real pathogenesis is currentlyactually unknown. For these reasons many authors compare IgG4 related disease to sarcoidosis. Lesions are often localized in the pancreas, salivary and lacrimal glands, biliary ducts, retroperitoneum and in many other organs. The diagnosisis difficult because of mild symptoms and the possibility of mimicking other severe diseases. Therefore, histopathology together with clinical and radiological typical findings are mandatory tools for diagnosis. Steroidtherapy usually enables disappearance of tumor like lesions and complete recovery. Kidney has an extensive organ involvement in the contextof IgG4-related disease. Historically, tubule - interstitial nephritis(TIN) is considered the main renal feature of renal lesions, however recent studies extend the spectrum of renal lesions also to glomerular tuft. These findings allow to introduce in the nosography the term of IgG4related kidney disease (IgG4 RKD). This review focuses on renal involvement in IgG4related disease, in order to help nephrologists to improve their clinical, diagnostic and therapeutic approach to this emerging pleiotropic clinical pattern.

  11. Histopathology of IgG4-Related Autoimmune Hepatitis and IgG4-Related Hepatopathy in IgG4-Related Disease.

    Science.gov (United States)

    Nakanuma, Yasuni; Ishizu, Yoji; Zen, Yoh; Harada, Kenichi; Umemura, Takeji

    2016-08-01

    Immunoglobulin G4-related disease (IgG4-RD) is a systemic disease involving many organs; it includes IgG4-related sclerosing cholangitis and inflammatory pseudotumor in the hepatobiliary system. Two types of hepatic parenchymal involvement have been reported in IgG4-RD: IgG4-related autoimmune hepatitis (AIH) and IgG4-hepatopathy. Moreover, only three cases of IgG4-related AIH have been reported. Immunoglobulin G4-related AIH is clinicopathologically similar to AIH, except for an elevated serum IgG4 level and heavy infiltration of IgG4-positive plasma cells in the liver tissue. Interestingly, IgG4-related AIH can be complicated by well-known IgG4-RD(s). Immunoglobulin G4-hepatopathy, which includes various histopathological lesions encountered in the liver of patients with type I autoimmune pancreatitis, is classified into five histological categories: portal inflammation, large bile duct damage, portal sclerosis, lobular hepatitis, and cholestasis. Immunoglobulin G4-hepatopathy is currently a collective term covering hepatic lesions primarily or secondarily related to IgG4-related sclerosing cholangitis and type 1 autoimmune pancreatitis. In conclusion, the liver is not immune to IgG4-RD, and at least two types of hepatic involvement in IgG4-RD have been reported: IgG4-related AIH and IgG4-hepatopathy. Additional studies are required to clarify their precise clinical significance with respect to IgG4-RD and inherent liver diseases. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  12. Extrapancreatic findings of IgG4-related disease

    International Nuclear Information System (INIS)

    Tan, T.J.; Ng, Y.L.; Tan, D.; Fong, W.S.; Low, A.S.C.

    2014-01-01

    IgG4-related disease is a systemic fibro-inflammatory condition, which includes autoimmune pancreatitis as part of the disease spectrum. Imaging has been demonstrated to play a major role in the diagnosis of autoimmune pancreatitis. Recognizing the wide spectrum of extrapancreatic manifestations of IgG4-related disease coupled with a high clinical index of suspicion will allow for an accurate and timely diagnosis to be made, thus avoiding unnecessary invasive procedures and ensuring that early effective corticosteroid therapy is commenced. This review aims to serve as a concise reference tool for both clinicians and radiologists in the diagnosis of extrapancreatic IgG4-related disease

  13. IgG4-related Disease and the Liver.

    Science.gov (United States)

    Chen, Jonathan H; Deshpande, Vikram

    2017-06-01

    Pathologists are likely to encounter IgG4-related disease in several organ systems. This article focuses on helping pathologists diagnose IgG4-related disease in the hepatobiliary system. Missing the diagnosis can result in unnecessary organ damage and/or unnecessary surgical and cancer therapy. In the liver, tumefactive lesion(s) involving the bile ducts with storiform fibrosis and an IgG4-enriched lymphoplasmacytic infiltrate are highly concerning for IgG4-related disease. The recent identification of oligoclonal populations of T cells and B cells in IgG4-related disease may lead to molecular tests, new therapeutics, and a greater mechanistic understanding of the disease. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. IgG4-related disease in autoimmune lymphoproliferative syndrome.

    Science.gov (United States)

    van de Ven, Annick A J M; Seidl, Maximilian; Drendel, Vanessa; Schmitt-Graeff, Annette; Voll, Reinhard E; Rensing-Ehl, Anne; Speckmann, Carsten; Ehl, Stephan; Warnatz, Klaus; Kollert, Florian

    2017-07-01

    A patient with autoimmune lymphoproliferative disorder (ALPS) developed IgG4-related disease. In retrospect, he had high levels of serum IgG4 for several years prior to presenting with IgG4-related pancreatitis. These high IgG4 levels were masked by hypergammaglobulinemia, a common feature of ALPS. We next screened 18 ALPS patients; four of them displayed increased levels of IgG4. Hence, IgG4-related disease should be considered in ALPS patients, especially in those manifesting lymphocytic organ infiltration or excessive hypergammaglobulinaemia. Screening of IgG4-related disease patients for ALPS-associated mutations would provide further information on whether this disease could be a late-onset atypical presentation of ALPS. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Clinical features of IgG4-related rhinosinusitis.

    Science.gov (United States)

    Hanaoka, Machiko; Kammisawa, Terumi; Koizumi, Satomi; Kuruma, Sawako; Chiba, Kazuro; Kikuyama, Masataka; Shirakura, Satoshi; Sugimoto, Taro; Hishima, Tsunekazu

    2017-09-01

    IgG4-related disease is a systemic disease that affects various organs of the body. Aim of this study is to elucidate the clinical characteristics of IgG4-related rhinosinusitis. Clinical features, laboratory findings, radiological and endoscopic findings, associated disease, treatment and prognosis were retrospectively examined in 10 patients with IgG4-related rhinosinusitis. The age was 59.1±11.3 years old and male-to-female ratio was 1:1. The chief nasal complaints were hyposmia (n=4), nasal obstruction (n=3), and nothing (n=3). Serum IgG4 levels were elevated in all patients and the value was 740.4±472.4mg/dl. Other IgG4-related diseases were associated in all 10 patients, including IgG4-related sialadenitis (n=6), IgG4-related dacryoadenitis (n=5), and autoimmune pancreatitis (n=5). Imaging findings on CT/MRI were obstruction of the way of elimination (n=10), thickening of the sinus mucous membrane (n=10), and fluid in the sinus (n=6). All of the cases had bilateral findings. Nasal endoscopic findings were chiefly deviated nasal septum (n=5), polyps (n=4), edema of the mucous membrane (n=3). Histologically, abundant infiltration of IgG4 positive plasma cell and lymphocyte and an elevated IgG4+/IgG+ cell ration was detected in all 8 patients and 5 patients, respectively. Endoscopic sinus surgery was performed in 8 patients. Eight patients were treated with steroid therapy for other associated IgG4-related diseases. Symptoms improved in all 6 patients after an initial treatment (endoscopic surgery (n=5) and steroids (n=1)), but one patient suffered relapse. IgG4-related rhinosinusitis is a distinct entity of IgG4-related disease, and is associated in patients with multiple IgG4-related diseases. Copyright © 2017 Medical University of Bialystok. Published by Elsevier B.V. All rights reserved.

  16. IgG4 related sclerosing mastitis: expanding the morphological spectrum of IgG4 related diseases.

    Science.gov (United States)

    Chougule, Abhijit; Bal, Amanjit; Das, Ashim; Singh, Gurpreet

    2015-01-01

    IgG4 related disease (IgG4RD) is a recently recognised condition characterised by mass forming lesions associated with storiform fibrosis, obliterative phlebitis, lymphoplasmacytic infiltrate rich in IgG4 positive plasma cells and elevated serum IgG4 levels. Although rare, mammary involvement has been reported as IgG4 related sclerosing mastitis, the morphological counterpart of a growing family of IgG4 related diseases. A total of 17 cases belonging to mass forming benign inflammatory breast lesions such as plasma cell mastitis, granulomatous lobular mastitis, non-specific mastitis and inflammatory pseudotumour were investigated as a possible member of IgG4 related sclerosing mastitis. Clinical, radiological, histopathological and immunohistochemistry findings were noted in all cases. Cases diagnosed as inflammatory pseudotumour showed all the histopathological features of IgG4RD along with increased number of IgG4 positive plasma cells and IgG4/IgG ratio >40%. However, only a few IgG4 positive cells were seen in plasma cell mastitis, granulomatous lobular mastitis and non-specific mastitis cases. These cases also did not fulfill the morphological criteria for the diagnosis of IgG4 related diseases. IgG4RD should be excluded in plasma cell rich lesions diagnosed on core biopsies by IgG4 immunostaining. This can avoid unnecessary surgery as IgG4 related diseases respond to simple and effective steroid treatment.

  17. Distribution and components of interstitial inflammation and fibrosis in IgG4-related kidney disease: analysis of autopsy specimens.

    Science.gov (United States)

    Hara, Satoshi; Kawano, Mitsuhiro; Mizushima, Ichiro; Harada, Kenichi; Takata, Takuma; Saeki, Takako; Ubara, Yoshifumi; Sato, Yasuharu; Nagata, Michio

    2016-09-01

    IgG4-related kidney disease (IgG4-RKD) occasionally progresses to chronic renal failure and is pathologically characterized by IgG4-positive lymphoplasmacyte-rich tubulointerstitial nephritis with storiform fibrosis (bird's-eye pattern fibrosis). Although radiology reveals a heterogeneous distribution of affected areas in this disease, their true distribution within the whole kidney is still unknown because of difficulty in estimating this from needle biopsy samples. Using 5 autopsy specimens, the present study histologically characterized the distribution and components of interstitial inflammation and fibrosis in IgG4-RKD. Interstitial lymphoplasmacytic infiltration or fibrosis was observed in a variety of anatomical locations such as intracapsular, subcapsular, cortical, perivascular, and perineural regions heterogeneously in a patchy distribution. They tended to be more markedly accumulated around medium- and small-sized vessels. Storiform fibrosis was limited to the cortex. Immunostaining revealed nonfibrillar collagens (collagen IV and VI) and fibronectin predominance in the cortical lesion, including storiform fibrosis. In contrast, fibril-forming collagens (collagen I and III), collagen VI, and fibronectin were the main components in the perivascular lesion. In addition, α-smooth muscle actin-positive myofibroblasts were prominently accumulated in the early lesion and decreased with progression, suggesting that myofibroblasts produce extracellular matrices forming a peculiar fibrosis. In conclusion, perivascular inflammation or fibrosis of medium- and small-sized vessels is a newly identified pathologic feature of IgG4-RKD. Because storiform fibrosis contains mainly nonfibrillar collagens, "interstitial fibrosclerosis" would be a suitable term to reflect this. The relation between the location and components of fibrosis determined in whole kidney samples provides new clues to the pathophysiology underlying IgG4-RKD. Copyright © 2016 The Authors. Published

  18. Antineutrophil cytoplasmic antibody-associated vasculitides and IgG4-related disease: A new overlap syndrome.

    Science.gov (United States)

    Danlos, François-Xavier; Rossi, Giovanni Maria; Blockmans, Daniel; Emmi, Giacomo; Kronbichler, Andreas; Durupt, Stéphane; Maynard, Claire; Luca, Luminita; Garrouste, Cyril; Lioger, Bertrand; Mourot-Cottet, Rachel; Dhote, Robin; Arlet, Jean-Benoit; Hanslik, Thomas; Rouvier, Philippe; Ebbo, Mikael; Puéchal, Xavier; Nochy, Dominique; Carlotti, Agnès; Mouthon, Luc; Guillevin, Loïc; Vaglio, Augusto; Terrier, Benjamin

    2017-10-01

    Atypical manifestations have been described in patients with ANCA-associated vasculitides (AAV), such as pachymeningitis, orbital mass or chronic periaortitis. Because these manifestations have been associated to the spectrum of IgG4-related disease (IgG4-RD), we hypothesized that both diseases could overlap. We conducted a European retrospective multicenter observational study including patients fulfilling ACR and Chapel Hill criteria for AAV and IgG4-RD Comprehensive Diagnostic Criteria. Eighteen patients were included (median age 55.5years, 13 men). AAV and IgG4-RD were diagnosed concomitantly in 13/18 (72%) patients; AAV preceded IgG4-RD in 3/18 (17%) while IgG4-RD preceded AAV in 2/18 (11%). AAV diagnoses included granulomatosis with polyangiitis in 14 (78%), microscopic polyangiitis in 3 (17%), and eosinophilic granulomatosis with polyangiitis in one case. IgG4-RD diagnosis included definite IgG4-RD in 5 (28%) cases, probable IgG4-RD in 5 (28%) and possible IgG4-RD in 8 (44%). IgG4-RD manifestations were chronic periaortitis in 9/18 (50%) patients, orbital mass and tubulointerstitial nephritis in 4 (22%) cases, prevertebral fibrosis in 3 (17%), pachymeningitis and autoimmune pancreatitis in 2 (11%) cases. Patients required median number of 2 (range 0-4) lines of immunosuppressants in combination with glucocorticoids. During the follow-up (median 49,8months, range 17,25-108months), AAV manifestations relapsed in 10/18 (56%) cases and IgG4-RD lesions in 5/18 (28%). When used, mainly for relapses, rituximab showed response in all cases. AAV and IgG4-RD may overlap. Clinicians should consider that atypical manifestations during AAV could be related to IgG4-RD rather than to refractory granulomatous or vasculitic lesions. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Relapsing tubulointerstitial nephritis in an adolescent with inflammatory bowel disease without aminosalicylate exposure.

    LENUS (Irish Health Repository)

    Shahrani Muhammad, H S

    2012-01-31

    A 14-year-old boy presented with ongoing constipation as a manifestation of newly diagnosed Crohn\\'s disease (CD) and a concomitant decline in renal function with biopsy-proven interstitial nephritis. Initiation of steroid therapy and mesalazine was associated with an improvement in symptoms and renal function. We describe a rare case of a 5-aminosalicylic acid (5-ASA)-naive patient who developed interstitial nephritis in association with CD with no evidence of other primary glomerulopathy. A unique feature of the case being a profound systemic inflammatory response at the time of diagnosis and a relapse in nephritis 2 months after cessation of mesalazine in the absence of any macroscopic colitis.

  20. The Histopathology of IgG4-Related Disease.

    Science.gov (United States)

    Avincsal, Mehmet Ozgur; Zen, Yoh

    2017-01-01

    IgG4-related disease is a multi-organ immune-mediated chronic fibroinflammatory condition characterized by elevated serum IgG4 concentrations, tumefaction, and tissue infiltration by IgG4-positive plasma cells. The exact etiology of IgG4-related disease remains unclear with no known role of the IgG4 molecule itself being identified. Although the pancreas and salivary glands are the main organs affected, the involvement of other organs has also been reported. This multi-organ disease mimics a large number of malignant, infectious, and inflammatory disorders; therefore, a prompt differential diagnosis is important for selecting the right therapeutic strategy. Early steroid therapy assists in preventing tissue fibrosis, parenchymal extinction, and severe functional impairments in the affected organs. The definitive and prompt diagnosis of IgG4-related disease requires both histopathological confirmation and clinicopathological correlations. A histopathological examination is mandatory to exclude neoplastic or inflammatory conditions that mimic IgG4-related disease. The histological changes that occur are basically similar in any organ manifestation, with several site-specific findings being recognized. This chapter summarizes general rules for the pathological examination of IgG4-related disease, as well as the histopathological features and differential diagnoses of major organ manifestations.

  1. The Leptospira outer membrane protein LipL32 induces tubulointerstitial nephritis-mediated gene expression in mouse proximal tubule cells.

    Science.gov (United States)

    Yang, Chih-Wei; Wu, Mai-Szu; Pan, Ming-Jeng; Hsieh, Wang-Ju; Vandewalle, Alain; Huang, Chiu-Ching

    2002-08-01

    Tubulointerstitial nephritis is a main renal manifestation caused by pathogenic leptospira that accumulate mostly in the proximal tubules, thereby inducing tubular injury and tubulointerstitial nephritis. To elucidate the role of leptospira outer membrane proteins in tubulointerstitial nephritis, outer membrane proteins from pathogenic Leptospira shermani and nonpathogenic Leptospira patoc extracted by Triton X-114 were administered to cultured mouse proximal tubule cells. A dose-dependent increase of monocyte chemoattractant protein-1 (MCP-1), RANTES, nitrite, and tumor necrosis factor-alpha (TNF-alpha) in the culture supernatant was observed 48 h after incubating Leptospira shermani outer membrane proteins with mouse proximal tubule cells. RT competitive-PCR experiments showed that Leptospira shermani outer membrane proteins (0.2 microg/ml) increased the expression of MCP-1, nitric oxide synthase (iNOS), RANTES, and TNF-alpha mRNA by 3.0-, 9.4-, 2.5-, and 2.5-fold, respectively, when compared with untreated cells. Outer membrane proteins extract from avirulent Leptospira patoc did not induce significant effects. The pathogenic outer membrane proteins extract contain a major component of a 32-kD lipoprotein (LipL32), which is absent in the nonpathogenic leptospira outer membrane. An antibody raised against LipL32 prevented the stimulatory effect of Leptospira shermani outer membrane proteins extract on MCP-1 and iNOS mRNA expression in cultured proximal tubule cells, whereas recombinant LipL32 significantly stimulated the expression of MCP-1 and iNOS mRNAs and augmented nuclear binding of nuclear factor-kappaB (NF-kappaB) and AP-1 transcription factors in proximal tubule cells. An antibody raised against LipL32 also blunted the effects induced by the recombinant LipL32. This study demonstrates that LipL32 is a major component of pathogenic leptospira outer membrane proteins involved in the pathogenesis of tubulointerstitial nephritis.

  2. Clinicopathologic characteristics, treatment, and outcomes of tubulointerstitial nephritis and uveitis syndrome in adults: A national retrospective strobe-compliant study.

    Science.gov (United States)

    Legendre, Mathieu; Devilliers, Hervé; Perard, Laurent; Groh, Matthieu; Nefti, Habdelamid; Dussol, Bertrand; Trad, Salim; Touré, Fatouma; Abad, Sébastien; Boffa, Jean-Jacques; Frimat, Luc; Torner, Stéphane; Seidowsky, Alexandre; Massy, Ziad André; Saadoun, David; Rieu, Virginie; Schoindre, Yoland; Heron, Emmanuel; Frouget, Thierry; Lionet, Arnaud; Glowacki, François; Arnaud, Laurent; Mousson, Christiane; Besancenot, Jean-François; Rebibou, Jean-Michel; Bielefeld, Philip

    2016-06-01

    Tubulointerstitial nephritis and uveitis (TINU) syndrome is a rare disease, defined by the association of idiopathic acute TINU. The aim of our work was to determine the characteristics of adult TINU syndrome in France, and to assess factors (including treatment) influencing medium-term prognosis.We conducted a nationwide study including 20 French hospitals. Clinical, laboratory, and renal histopathologic data of 41 biopsy-proven TINU syndromes were retrospectively collected. The patients were diagnosed between January 1, 1999 and December 1, 2015.Twenty-five females and 16 males were included (F/M ratio: 1.6:1). The median age at disease onset was 46.8 years (range 16.8-77.4) with a median serum creatinine level at 207 μmol/L (range 100-1687) and a median estimated glomerular filtration rate (eGFR) at 27 mL/min per 1.73 m (range 2-73). Twenty-nine patients (71%) had a bilateral anterior uveitis and 24 (59%) had deterioration in general health at presentation. Moderate proteinuria was found in 32 patients (78%) (median proteinuria 0.52 g/24 h; range 0.10-2.10), aseptic leukocyturia in 25/36 patients (70%). The evaluation of renal biopsies revealed 41 patients (100%) with an acute tubulointerstitial nephritis, 19/39 patients (49%) with light to moderate fibrosis and 5 patients (12%) with an acute tubular necrosis. Thirty-six patients (88%) were treated with oral corticosteroids. After 1 year of follow-up, the median eGFR was 76 mL/min per 1.73 m (range 17-119) and 32% of the patients suffered from moderate to severe chronic kidney disease. Serum creatinine (P uveitis relapses. The use of oral corticosteroids was not associated with a better kidney function but was associated with fewer uveitis relapses (P = 0.44 and 0.02, respectively).In our study, 32% of patients were suffering from moderate to severe chronic kidney disease after 1 year of follow-up, and 40% had uveitis relapses during this follow-up. This work also suggests that oral

  3. IgG4-Related Disease in a Urachal Tumor

    Directory of Open Access Journals (Sweden)

    Travis W. Dum

    2014-01-01

    Full Text Available IgG4-related disease is a newly recognized fibroinflammatory disorder that has the ability to affect nearly every organ system. It is characterized by tumefactive lesions and fibrosis and closely mimics neoplasms. Only one case of IgG4-related bladder mass has been reported in the literature, but there are no reports of IgG4-related disease in a urachal mass. Herein, we report a 26-year-old male who initially presented with symptoms of recurrent UTI. Work-up revealed a 6 cm urachal tumor, a 1.4 cm pulmonary lesion, and mediastinal lymphadenopathy; all metabolically active on PET scan and suspicious for urachal adenocarcinoma. Lung lesion fine needle aspiration and TURBT pathology revealed inflammation but no evidence of malignancy. The patient underwent a partial cystectomy and umbilectomy with pathology demonstrating dense plasmacytic cells, a high rate of immunohistochemistry staining positive for IgG4 plasma cells, a storiform pattern of fibrosis, and an obliterative phlebitis. Furthermore, the patient had an elevated serum IgG4 level of 227 mg/dL (range 2.4–121 mg/dL. IgG4-related disease is a newly recognized fibroinflammatory disorder that can mimic neoplastic processes and a high index of suspicion and accurate tissue pathology is necessary for an accurate diagnosis.

  4. The emerging mysteries of IgG4-related disease

    NARCIS (Netherlands)

    Smit, Wouter; Barnes, Eleanor

    2014-01-01

    IgG4-related disease (IgG4-RD) is increasingly recognised in Western societies as a multi-system, inflammatory, fibrosing disease of unknown aetiology that typically, though not exclusively, presents in older men. The clinical manifestations are diverse and almost any organ may be affected. The

  5. Overview of IgG4 - Related Disease.

    Science.gov (United States)

    Opriţă, R; Opriţă, B; Berceanu, D; Diaconescu, I B

    2017-01-01

    Rationale (hypothesis): IgG4-related disease (IgG4-RD) is a pathological entity recently recognized by the medical world that can affect any organ or system. However, there is insufficient data about this disease in medical literature. Aim (objective): A more extensive clarification of the IgG4 molecule, the diversified aspects of IgG4-related disease, and the response of this disease to treatment, will provide a crucial understanding of the immune system and other diseases now known to be associated with IgG4. The MEDLINE online medical database was used, and, after a comprehensive review of medical articles regarding IgG4-RD, published after 2003, using the search words "IgG4- related disease" and "IgG4 molecule", we have described the clinical, pathological and therapeutic features of IgG4-RD, as well as the presence of the IgG4 molecule in the evolution, diagnosis and management of this syndrome. We characterized the potential disease mechanisms and discussed early observations related to treatment. Given the response to immunosuppressive therapy, it is hypothesized that IgG4-related disease is most likely an autoimmune disease. Therefore, IgG4-related disease is a fibro-inflammatory condition that can affect any organ and can lead to the formation of pseudotumoral lesions requiring differential diagnosis with various malignancies. Positive diagnostic criteria are histopathological and require at least two features out of the following three: dense limphoplasmocitary infiltrate, storiform fibrosis, obliterative phlebitis.

  6. The incidence of IgG4-positive plasma cells staining TIN in patients with biopsy-proven tubulointerstitial nephritis.

    Science.gov (United States)

    Mac, Kathy; Wu, Xiao Juan; Mai, Jun; Howlin, Kenneth; Suranyi, Michael; Yong, Jim; Makris, Angela

    2017-06-01

    IgG4 disease is rare. However, IgG4 tubulointerstitial nephritis (TIN) is the most common renal manifestation. IgG4 disease is usually associated with elevated serum IgG4 levels and other organ involvement, low-density renal lesions on enhanced CT imaging and immune activation. The incidence of IgG4-TIN may be underestimated, as staining for IgG4 is not routine. This study sought to describe the prevalence of previously undiagnosed IgG4-TIN. Due to the complexity of the diagnosis, we only attempt to look at IgG4-positive plasma cell TIN as a potential indication for IgG4 renal disease. A retrospective review of native renal biopsies performed between 2002 and 2012 with a primary diagnosis of TIN was selected. Samples for which interstitial nephritis was secondary to a glomerular disease were excluded. The tissues were stained for IgG4 and scored by two blinded observers. Demographic and follow-up details were collected. This study was approved by the local ethics committee. 82 cases of interstitial nephritis from a total of 1238 renal biopsies (2002-2012) were available after staining for further assessment. 12 samples demonstrated staining consistent with the criteria for IgG4-positive plasma cell TIN, of which 3 had mildly positive staining, 7 moderately positive staining and 2 had markedly positive staining. There were no statistically significant differences in the baseline characteristics between the positive and negative staining groups. A number of cases of IgG4-positive plasma cell TIN were observed histologically that had been previously diagnosed as non-specific chronic TIN. IgG4-positive plasma cell TIN made up 1% of all renal biopsies performed over 10 years and 13% of all biopsies demonstrating TIN not related to glomerular disease. IgG4 staining should be considered routinely in biopsies demonstrating primary TIN. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  7. IgG4-RELATED DISEASE. CLINICAL NOTES

    Directory of Open Access Journals (Sweden)

    Vladimir Ivanovich Vasilyev

    2013-01-01

    Full Text Available IgG4-related diseases are a new nosological entity that encompasses a few previously known diseases. IgG4-related systemic disease is diagnosed if two or more affected organs are detected. This group of diseases has two similar signs: serological (elevated serum IgG4 subclass concentrations and histological (organ and tissue infiltration from plasmo-cytes secreting IgG4, and eosinophils, and the development of fibrosclerosis and phlebitis obliterans. The paper describes two cases. In one case, a multisystemic disease was observed virtually at its onset whereas in the other this lesion was diagnosed several years after the natural course of the disease.

  8. Intrathoracic Manifestations of IgG4-Related Disease

    Directory of Open Access Journals (Sweden)

    Sian Yik Lim

    2016-10-01

    Full Text Available Intrathoracic involvement with IgG4-related disease (IgG4-RD is frequently overlooked in IgG4-related disease patients. In this article we review the intrathoracic findings of IgG4-RD which are variable and protean. IgG4-related disease has been reported to affect the lung parenchyma, pleura, mediastinal/hilar lymph nodes, vasculature, and pericardium within the thorax. Mediastinal and hilar lymphadenopathy is the most common intrathoracic manifestation of IgG4-RD. Four main patterns of pulmonary disease have been described, including the solid nodular type, the bronchovascular type, the alveolar interstitial type, and the round shaped ground glass type. When feasible, a biopsy should be obtained to confirm the diagnosis. Most lesions show characteristic pathologic findings of IgG4-RD: dense lymphoplasmacytic infiltrate, storiform fibrosis, and obliterative phlebitis. While this helps establish the diagnosis, the interpretation of pathology findings in the clinical context is key in making an accurate diagnosis. Mimickers of IgG4-RD should be ruled out, before making a diagnosis. The intrathoracic findings of IgG4-RD can be treated effectively with prednisone, but may require additional immunosuppressive therapies, including rituximab.

  9. A case of severe osteomalacia caused by Tubulointerstitial nephritis with Fanconi syndrome in asymptomotic primary biliary cirrhosis.

    Science.gov (United States)

    Yamaguchi, Shintaro; Maruyama, Tatsuya; Wakino, Shu; Tokuyama, Hirobumi; Hashiguchi, Akinori; Tada, Shinichiro; Homma, Koichiro; Monkawa, Toshiaki; Thomas, James; Miyashita, Kazutoshi; Kurihara, Isao; Yoshida, Tadashi; Konishi, Konosuke; Hayashi, Koichi; Hayashi, Matsuhiko; Itoh, Hiroshi

    2015-11-11

    Primary biliary cirrhosis (PBC) is an immune-mediated chronic cholestatic liver disease, characterized by increased concentrations of serum IgM and the presence of circulating anti-mitochondrial antibodies. Although bone diseases such as osteoporosis or osteodystrophy are commonly associated with PBC, osteomalacia which is caused by abnormal vitamin D metabolism, mineralization defects, and phosphate deficiency has not been recognized as a complication of PBC. We report the case of a 49-year-old Japanese woman who complained of multiple fractures. Hypophosphatemic osteomalacia was diagnosed from a low serum phosphorus level, 1,25-dihydroxyvitamin D3 level, high levels of bone specific alkaline phosphatase and the findings of bone scintigraphy, although a bone biopsy was not performed. Twenty four hour urine demonstrated a low renal fractional tubular reabsorption of phosphate, increased fractional excretion of uric acid and generalized aminoaciduria. An intravenous bicarbonate loading test suggested the presence of proximal renal tubular acidosis (RTA). These biochemical data indicated Fanconi syndrome with proximal RTA. A kidney biopsy demonstrated the features of tubulointerstitial nephritis (TIN). The patient was also suspected as having primary biliary cirrhosis (PBC) because of high levels of alkaline phosphatase, IgM and the presence of anti-mitochondrial M2 antibody, though biochemical liver function was normal. Sequential liver biopsy was compatible with PBC and the diagnosis of PBC was definite. After administration of 1,25 dihydroxyvitamin D3, neutral potassium phosphate, sodium bicarbonate for osteomalacia and subsequent predonizolone for TIN, symptoms of fractures were relieved and renal function including Fanconi syndrome was ameliorated. In this case, asymptomatic PBC was shown to induce TIN with Fanconi syndrome with dysregulation of electrolytes and vitamin D metabolism, which in turn led to osteomalacia with multiple fractures. Osteomalacia has not

  10. Re-recognition of Age-dependent Reference Range for the Serum Creatinine Level in Teenagers - A Case of Slowly Progressive Tubulointerstitial Nephritis which Occurred in an Adolescent.

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    Ono, Hiroyuki; Nagai, Kojiro; Shibata, Eriko; Matsuura, Motokazu; Kishi, Seiji; Inagaki, Taizo; Minato, Masanori; Yoshimoto, Sakiya; Ueda, Sayo; Obata, Fumiaki; Nishimura, Kenji; Tamaki, Masanori; Kishi, Fumi; Murakami, Taichi; Abe, Hideharu; Kinoshita, Yukiko; Urushihara, Maki; Kagami, Shoji; Doi, Toshio

    2017-08-15

    For the first time, a 15-year-old boy was found to have a slight degree of proteinuria and microscopic hematuria during annual school urinalysis screening. His kidney function had already severely deteriorated. A kidney biopsy revealed tubulointerstitial nephritis (TIN) with diffuse inflammatory cell infiltration. His medical records showed his serum creatinine level to be 0.98 mg/dL two years ago, which was abnormally high considering his age. Although the etiology of slowly progressive TIN was unclear, glucocorticoid and immunosuppressant therapy improved his kidney function. This case report suggests that all doctors should recognize the reference range for the serum creatinine level in teenagers.

  11. Large vessel involvement by IgG4-related disease

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    Perugino, Cory A.; Wallace, Zachary S.; Meyersohn, Nandini; Oliveira, George; Stone, James R.; Stone, John H.

    2016-01-01

    Abstract Objectives: IgG4-related disease (IgG4-RD) is an immune-mediated fibroinflammatory condition that can affect multiple organs and lead to tumefactive, tissue-destructive lesions. Reports have described inflammatory aortitis and periaortitis, the latter in the setting of retroperitoneal fibrosis (RPF), but have not distinguished adequately between these 2 manifestations. The frequency, radiologic features, and response of vascular complications to B cell depletion remain poorly defined. We describe the clinical features, radiology findings, and treatment response in a cohort of 36 patients with IgG4-RD affecting large blood vessels. Methods: Clinical records of all patients diagnosed with IgG4-RD in our center were reviewed. All radiologic studies were reviewed. We distinguished between primary large blood vessel inflammation and secondary vascular involvement. Primary involvement was defined as inflammation in the blood vessel wall as a principal focus of disease. Secondary vascular involvement was defined as disease caused by the effects of adjacent inflammation on the blood vessel wall. Results: Of the 160 IgG4-RD patients in this cohort, 36 (22.5%) had large-vessel involvement. The mean age at disease onset of the patients with large-vessel IgG4-RD was 54.6 years. Twenty-eight patients (78%) were male and 8 (22%) were female. Thirteen patients (36%) had primary IgG4-related vasculitis and aortitis with aneurysm formation comprised the most common manifestation. This affected 5.6% of the entire IgG4-RD cohort and was observed in the thoracic aorta in 8 patients, the abdominal aorta in 4, and both the thoracic and abdominal aorta in 3. Three of these aneurysms were complicated by aortic dissection or contained perforation. Periaortitis secondary to RPF accounted for 27 of 29 patients (93%) of secondary vascular involvement by IgG4-RD. Only 5 patients demonstrated evidence of both primary and secondary blood vessel involvement. Of those treated with rituximab, a majority responded positively. Conclusions: IgG4-RD is a distinctive, unique, and treatable cause of large-vessel vasculitis. It can also involve blood vessels secondary to perivascular tumefactive lesions. The most common manifestation of IgG4-related vasculitis is aortitis with aneurysm formation. The most common secondary vascular manifestation is periaortitis with relative sparing of the aortic wall. Both primary vasculitis and secondary vascular involvement respond well to B cell depletion therapy. PMID:27428181

  12. TREATMENT OF IgG4-RELATED DISEASE

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    E. V. Sokol

    2016-01-01

    Full Text Available IgG4-related disease (IgG4-RD is a fibroinflammatory condition characterized by the occurrence of tumor-like foci in different organs with a unique histological pattern (moirо-like fibrosis, obvious lymphoplasmacytic infiltration with large numbers of IgG4+ plasma cells, and obliterating phlebitis and elevated serum IgG4 levels in the majority of patients. Its first-line therapy is glucocorticoids at a starting dose of 0.6 mg/kg/day (equivalent to prednisolone; however, this treatment entails a great number of adverse events and high recurrence rates. The paper provides a review of today's literature on the treatment of IgG4-RD; particular emphasis is laid on the description of therapy with glucocorticoids and rituximab.

  13. IgG4-Related Disease Presenting as Isolated Scleritis

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    Eran Berkowitz

    2017-01-01

    Full Text Available A rare case of IgG4-related disease (IgG4-RD manifesting as nodular scleritis is presented in a 20-year-old female. Patient complained of left eye pain and redness for one week. Ocular examination together with ancillary testing led to the diagnosis of nodular scleritis. Since the patient did not show apparent improvement after one week of systemic steroidal treatment, she underwent a biopsy of the affected area revealing histopathological characteristics of IgG4-RD. Long-term treatment with corticosteroids and a steroid-sparing agent (methotrexate led to significant improvement in signs and symptoms. This case highlights the significance of IgG4-RD in the differential diagnosis of scleritis and raises the question as to whether various organs affected by IgG4-RD may have different underlying pathophysiological mechanisms in which pathogenic T cells play a role.

  14. Diagnosis and Treatment of IgG4-Related Disease.

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    Kamisawa, Terumi; Okazaki, Kazuichi

    2017-01-01

    It is critical to differentiate IgG4-related disease (IgG4-RD) from malignant tumor and similar disease of the affected organ to apply appropriate therapy and avoid unnecessary surgery. IgG4-RD is diagnosed on combination of typical radiological findings; elevation of serum IgG4 levels; histopathological findings of abundant infiltration of IgG4-positive plasma cells and lymphocytes, storiform fibrosis , and obliterative phlebitis ; association with other IgG4-related diseases; and response to steroids. Histopathological approach is particularly recommended. Systemic glucocorticoids are currently the first-line approach for IgG4-RD, and the indications are symptoms. The initial recommended dose of oral prednisolone for induction of remission is 0.6 mg/kg/day, administered for 2-4 weeks. This dose is gradually tapered to a maintenance dose of 2.5-5 mg/day over a period of 2-3 months. As IgG4-RD sometimes relapses after steroids, maintenance therapy is usually performed in Japan. However, as IgG4-RD patients are typically elderly and are at high risk of developing steroid-related complications, cessation of the medication should be attempted at least within 3 years. For relapsed IgG4-RD, re-administration or dose up of steroid is effective, but the addition of immunomodulatory drugs such as azathioprine has been considered to be appropriate. B cell depletion with rituximab (an anti-CD20 antibody) is effective, even in many patients in whom treatment with immunomodulatory drugs was unsuccessful. The short-term clinical, morphological, and functional outcomes of most IgG4-RD patients treated with steroid therapy are good, but the long-term outcomes are less clear due to several unknown factors such as relapse, developed fibrosis, and associated malignancy.

  15. Epstein-Barr virus-infected cells in IgG4-related lymphadenopathy with comparison with extranodal IgG4-related disease.

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    Takeuchi, Mai; Sato, Yasuharu; Yasui, Hiroshi; Ozawa, Hiroaki; Ohno, Kyotaro; Takata, Katsuyoshi; Gion, Yuka; Orita, Yorihisa; Tachibana, Tomoyasu; Itoh, Tomoo; Asano, Naoko; Nakamura, Shigeo; Swerdlow, Steven H; Yoshino, Tadashi

    2014-07-01

    IgG4-related lymphadenopathy with increased numbers of Epstein-Barr virus (EBV)-infected cells has been reported but not fully described. We analyzed 31 cases of IgG4-related lymphadenopathy and 24 cases of extranodal IgG4-related diseases for their possible relationship with EBV. Other types of reactive lymph nodes (22) and angioimmunoblastic T-cell lymphoma (AITL) (10) were also studied for comparison. EBV-encoded RNA (EBER) in situ hybridization revealed EBER(+) cells in 18 of 31 cases (58%) of IgG4-related lymphadenopathy. Increased EBER(+) cells were found in only 4 of 22 (18.1%) non-IgG4-related reactive lymphoid hyperplasia in patients of a similar age (P=0.002) and in only 5 of 24 (21%) extranodal IgG4-related biopsies (P=0.006). Interestingly, all patients with EBER(+) progressively transformed germinal center-type IgG4-related lymphadenopathy had systemic lymphadenopathy and/or extranodal involvement. AITL also is associated with EBV, and IgG4-related lymphadenopathy sometimes mimics the morphology of AITL; however, the number of IgG4(+) cells in AITL was significantly less than that in IgG4-related lymphadenopathy (Pdisease; however, there was not a significant difference between the EBER(+) and EBER(-) cases. In conclusion, the presence of increased numbers of EBV-infected cells in IgG4-related lymphadenopathy, compared with other reactive lymphadenopathy or extranodal IgG4-related disease, suggests that there may be a relationship at least between nodal IgG4-related disease and EBV. It is important to avoid overdiagnosing these cases as malignant lymphomas or EBV-related lymphoproliferative disorders.

  16. IgG4-related Disease of the Genitourinary Tract

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    Mukul K. Divatia

    2014-02-01

    Full Text Available IgG4-related disease (IgG4-RD is a recently established albeit well recognized fibro-inflammatory condition with distinctive features including a characteristic histopathological appearance; a propensity to develop tumefactive lesions in multiple body sites; and oft elevated serum IgG4 levels. The consensus statement on IgG-4 RD equips practicing pathologists with a set of working guidelines for the diagnosis of pathologic lesions identified in a host of different organ system affected with this disease. The diagnosis of IgG4-RD requires the combined presence of the characteristic histopathological appearance and increased numbers of IgG4-positive plasma cells. The essential histopathological features include a dense lymphoplasmacytic infiltrate, a storiform pattern of fibrosis, and obliterative phlebitis. Tissue IgG4-positive plasma cell counts and IgG4: IgG ratios are significant ancillary aids in establishing the diagnosis. The spectrum of IgG4-RD continues to expand and involve multiple body sites. The genitourinary system comprising of the kidneys, ureters, urinary bladder, urethra, prostate gland, testes and penis is one of the multiple organ systems to be affected by IgG4-RD. This review describes the clinical and histopathologic patterns of involvement of the genitourinary system by IgG4-RD, in association with serologic and radiological features. [J Interdiscipl Histopathol 2014; 2(1.000: 3-18

  17. Diagnosis of IgG4-related sclerosing cholangitis

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    Nakazawa, Takahiro; Naitoh, Itaru; Hayashi, Kazuki; Miyabe, Katsuyuki; Simizu, Shuya; Joh, Takashi

    2013-01-01

    IgG4-related sclerosing cholangitis (IgG4-SC) is often associated with autoimmune pancreatitis. However, the diffuse cholangiographic abnormalities observed in IgG4-SC may resemble those observed in primary sclerosing cholangitis (PSC), and the presence of segmental stenosis suggests cholangiocarcinoma (CC). IgG4-SC responds well to steroid therapy, whereas PSC is only effectively treated with liver transplantation and CC requires surgical intervention. Since IgG4-SC was first described, it has become a third distinct clinical entity of sclerosing cholangitis. The aim of this review was to introduce the diagnostic methods for IgG4-SC. IgG4-SC should be carefully diagnosed based on a combination of characteristic clinical, serological, morphological, and histopathological features after cholangiographic classification and targeting of a disease for differential diagnosis. When intrapancreatic stenosis is detected, pancreatic cancer or CC should be ruled out. If multiple intrahepatic stenoses are evident, PSC should be distinguished on the basis of cholangiographic findings and liver biopsy with IgG4 immunostaining. Associated inflammatory bowel disease is suggestive of PSC. If stenosis is demonstrated in the hepatic hilar region, CC should be discriminated by ultrasonography, intraductal ultrasonography, bile duct biopsy, and a higher cutoff serum IgG4 level of 182 mg/dL. PMID:24282356

  18. IgG4-Related Disease of Bilateral Temporal Bones.

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    Li, Lilun; Ward, Bryan; Cocks, Margaret; Kheradmand, Amir; Francis, Howard W

    2017-03-01

    IgG4-related disease (IgG4-RD) is an idiopathic inflammatory condition that causes pseudotumor formation in single or multiple organs, including those of the head and neck. Temporal bone involvement is rare, with only 3 cases of unilateral temporal bone IgG4-RD described in the literature. We report the first known case of IgG4-RD of bilateral temporal bones and describe its clinical presentation, diagnosis, and treatment. The patient was a 52-year-old man with latent tuberculosis (TB) who presented with a 10-year history of bilateral profound hearing loss and vestibular dysfunction. Computed tomography and magnetic resonance imaging demonstrated bilateral labyrinthine destruction with invasion of the posterior fossa. Immunoglobulin level testing showed elevated total serum IgG levels with normal IgG4 levels. Bilateral mastoidectomies were performed, with biopsy samples demonstrating IgG4 staining with IgG4-positive plasma cells up to 40/HPF (high power field) on the right and 20/HPF on the left, consistent with bilateral IgG4-RD. IgG4-RD of bilateral temporal bones presents with chronic and progressive bilateral hearing loss and vestibular dysfunction. Clinical presentation and radiologic findings are nonspecific, and definitive diagnosis must be made with histopathology and immunostaining. Corticosteroids are therapeutic, but surgical resection may be necessary for temporal bone IgG4-RD to improve long-term remission.

  19. Current Concept of IgG4-Related Disease.

    Science.gov (United States)

    Okazaki, Kazuichi; Umehara, Hisanori

    2017-01-01

    IgG4-related disease (IgG4-RD) is a fibroinflammatory disease of unknown etiology, which is characterized by a tendency to form tumefactive lesions, increased serum levels of IgG4, and massive infiltration of IgG4-positive plasma cells with storiform fibrosis and/or obliterative phlebitis. Patients with IgG4-RD have frequently multiorgan involvements such as the pancreas, biliary tree, salivary glands, periorbital tissues, kidneys, lungs, lymph nodes, and retroperitoneum. IgG4-RD mainly affects middle-aged to elderly men except for involvement in lachrymal and salivary glands, so-called Mikulicz's disease. The clinical manifestations of IgG4-RD depend on individually involved organs and respond well to steroid, but the prognosis still remains unclear. Some patients develop serious complications such as obstructive jaundice due to hepatic, gallbladder, or pancreatic lesions; hydronephrosis due to retroperitoneal fibrosis; or respiratory symptoms due to pulmonary lesions. Nomenclatures of individual organ manifestation of IgG4-RD have been internationally consented.

  20. IgG4-Related Disease: A Multispecialty Condition

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    Iuri Usêda Santana

    2014-01-01

    Full Text Available IgG4-related disease (IgG4-RD is a recently recognized group of conditions, characterized by tumor-like swelling of involved organs, lymphoplasmacytic infiltrate rich in IgG4-positive plasma cells, variable degrees of fibrosis, and elevated serum IgG4 concentrations. Currently IgG4-RD is recognized as a systemic condition that can affect several organs and tissues. Herein we report the case of a 34-year-old male patient who was admitted to our hospital with diffuse abdominal pain, weight loss, and painful stiffness in his neck. He had a history of tumoral mass of the left maxillary region, right palpebral ptosis with protrusion of the eyeball, and chronic dry cough for about 6 years. Laboratory tests revealed polyclonal hypergammaglobulinemia and increased serum IgG4 levels. Immunohistochemical staining of the maxillary biopsy was compatible with IgG4-RD. He had an excellent response to corticosteroid therapy. This case highlights that IgG4-RD should be included in the differential diagnosis with multisystem diseases.

  1. Riedel's thyroiditis association with IgG4-related disease.

    Science.gov (United States)

    Stan, Marius N; Sonawane, Vikram; Sebo, Thomas J; Thapa, Prabin; Bahn, Rebecca S

    2017-03-01

    IgG4-positive (+) plasma cells have been reported in both Riedel's thyroiditis (RT) and Hashimoto's thyroiditis (HT). These cells are the hallmark of IgG4-related disease (IgG4-RD). We sought to determine whether RT is part of IgG4-RD spectrum. This was a case-control study performed at a tertiary medical centre. We included RT cases from the period 1958 to 2008 that had sufficient paraffin-embedded tissue for IgG4 immunostaining. Controls were patients with HT, age and gender matched, with similar pathology criteria. The main outcome measures were the intensity of the IgG4 staining and the clinical and histological correlates with IgG4-RD. Six pairs of RT and HT were analysed. The mean age was 44·7 years. In both groups, 5/6 cases had positive IgG4 staining. The mean number of IgG4 + cells/ HPF, normalized to the degree of inflammation, was 3·2 ± 3·0 SD (RT) vs 0·9 ± 0·7 (HT), P = 0·15, for fibrotic areas and 2·1 ± 2·3 SD vs 1·0 ± 0·8 (P = 0·39) for areas with lymphoid aggregates. We found the number of IgG4 +  cells in RT to be inversely correlated with the duration of disease (P = 0·046). Three RT cases had associated comorbidities from the IgG4-RD spectrum while none of the HT cases had such conditions. Riedel's thyroiditis is a component of IgG4-RD with the density of the IgG4 +  lymphocytic infiltrate being time dependent. In this small study, we did not identify differences in IgG4 infiltration between RT and HT, minimizing the utility of this marker in RT diagnosis. © 2016 John Wiley & Sons Ltd.

  2. IgG4 related renal disease: A wolf in sheep′s clothing

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    A Rohan

    2014-01-01

    Full Text Available IgG4 related disease is a fibro-inflammatory condition with involvement of renal and extra renal organs, characterized by lymphoplasmacytic infiltration with organ dysfunction. We describe three cases of IgG4 related renal disease from a tertiary care hospital in south India.

  3. IgG4-related hypophysitis is highly prevalent among cases of histologically confirmed hypophysitis.

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    Bernreuther, Christian; Illies, Christopher; Flitsch, Jörg; Buchfelder, Michael; Buslei, Rolf; Glatzel, Markus; Saeger, Wolfgang

    2017-11-01

    IgG4-related disease is an immune-mediated disease with manifestations in most organ systems among them the pituitary gland. To date, few cases of histologically confirmed cases of IgG-related hypophysitis have been reported. The aim of this study was to retrospectively determine the prevalence of IgG4-related hypophysitis among cases previously diagnosed as primary hypophysitis (lymphocytic hypophysitis, granulomatous hypophysitis and hypophysitis not otherwise specified). Histological and immunohistochemical analysis revealed that 12 of 29 cases (41.4%) previously diagnosed as primary hypophysitis fulfilled the criteria for IgG4-related disease and, thus, IgG4-related hypophysitis should always be considered in the differential diagnosis of primary hypophysitis. All cases of IgG4-related hypophysitis showed a dense lymphoplasmacytic infiltrate with more than 10 IgG4-positive cells per high power field and a ratio of IgG4/IgG-positive cells of more than 40%, whereas storiform fibrosis was an inconsistent histological feature and was also seen in few cases of non-IgG-related hypophysitis, thus lacking sensitivity and specificity. Obliterative phlebitis was not seen in any case. Thus, histological criteria defined for IgG4-related disease in other organs should be modified for IgG4-related hypophysitis, accordingly. © 2016 International Society of Neuropathology.

  4. Retroperitoneal disorders associated with IgG4-related autoimmune pancreatitis

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    Hara, Noboru; Kawaguchi, Makoto; Takeda, Keisuke; Zen, Yoh

    2014-01-01

    IgG4-related autoimmune pancreatitis is frequently accompanied by relevant lesions in the genitourinary tract and retroperitoneal organs, which cause various clinical problems, ranging from non-specific back pain or bladder outlet obstruction to renal failure. The diagnosis of IgG4-related retroperitoneal fibrosis requires a multidisciplinary approach, including serological tests, histological examination, imaging analysis, and susceptibility to steroid therapy. Radiological examinations are helpful to diagnose this condition, but surgical resection is occasionally unavoidable to exclude malignancy, particularly for patients with isolated retroperitoneal involvement. Steroid therapy is the treatment of choice for this condition, the same as for other manifestations of IgG4-related disease. For patients with severe ureteral obstruction, additional ureteral stenting needs to be considered prior to steroid therapy to preserve the renal function. Some papers have suggested that IgG4-related disease can affect male reproductive organs including the prostate and testis. IgG4-related prostatitis usually causes lower urinary tract symptoms, such as dysuria and pollakisuria. Patients sometimes state that corticosteroids given for IgG4-related disease at other sites relieve their lower urinary tract symptoms, which leads us to suspect prostatic involvement in this condition. Because of the limited number of publications available, further studies are warranted to better characterize IgG4-related disease in male reproductive organs. PMID:25469023

  5. Retroperitoneal disorders associated with IgG4-related autoimmune pancreatitis

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    Hara, Noboru; Kawaguchi, Makoto; Takeda, Keisuke; Zen, Yoh

    2014-01-01

    IgG4-related autoimmune pancreatitis is frequently accompanied by relevant lesions in the genitourinary tract and retroperitoneal organs, which cause various clinical problems, ranging from non-specific back pain or bladder outlet obstruction to renal failure. The diagnosis of IgG4-related retroperitoneal fibrosis requires a multidisciplinary approach, including serological tests, histological examination, imaging analysis, and susceptibility to steroid therapy. Radiological examinations are ...

  6. IgG4-related disease with sinonasal involvement: A case series

    International Nuclear Information System (INIS)

    Prabhu, Shailesh M; Yadav, Vikas; Irodi, Aparna; Mani, Sunithi; Varghese, Ajoy Mathew

    2014-01-01

    We present the imaging findings in two cases of IgG4-related disease involving the sinonasal region in the pediatric age group. Imaging findings in IgG4-related disease affecting the nasal cavity and paranasal sinuses have been rarely reported in literature. The diagnosis is made by a combination of clinical, imaging, and histopathologic findings. Radiologists should be aware of the imaging findings of this condition to ensure early diagnosis and treatment

  7. IgG4-related sclerosing cholangitis overlapping with autoimmune hepatitis: Report of a case.

    Science.gov (United States)

    Li, Hongyan; Sun, Li; Brigstock, David R; Qi, Lina; Gao, Runping

    2017-05-01

    IgG4-related sclerosing cholangitis (IgG4-SC) is the biliary manifestation of IgG4-related disease (IgG4-RD) but the presence of IgG4-SC in the porta hepatis is difficult to differentiate from hilar cholangiocarcinoma (HCCA). IgG4-related autoimmune hepatitis (IgG4-related AIH) is extremely rare and it is not fully clear whether IgG4-related AIH is a hepatic manifestation of IgG4-RD or a subtype of AIH. We present a rare case of a 52-year-old male who was admitted with obstructive jaundice and itchy skin. He primarily presented a severe bile duct stricture in the porta hepatis and an elevated serum level of carbohydrate antigen 19-9 (CA19-9) mimicking HCCA. The patient underwent a surgical resection of the left hepatic lobular and cholecyst as well as common bile duct with a right hepatico-jejunostomy. He was finally diagnosed as IgG4-SC accompanied with IgG4-related AIH by immunohistochemistry, but he lacked conventional autoantibodies. The patient responded well to steroid therapy and remains healthy with no signs of recurrence at six-month follow-up. This is the first case report that hepatic portal IgG4-SC overlapping with IgG4-related AIH without the presence of conventional autoantibodies. Additionally, we suggest that IgG4-RD should be always considered in case of a bile duct stricture in the porta hepatis to avoid unnecessary surgical operation. Copyright © 2017 Elsevier GmbH. All rights reserved.

  8. A small subgroup of Hashimoto's thyroiditis is associated with IgG4-related disease.

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    Jokisch, Friedrich; Kleinlein, Irene; Haller, Bernhard; Seehaus, Tanja; Fuerst, Heinrich; Kremer, Marcus

    2016-03-01

    IgG4-related disease is a newly identified syndrome characterized by high serum IgG4 levels and increased IgG4-positive plasma cells in involved organs. The incidence of IgG4-related thyroiditis in the Caucasian population of Europe is unknown. We investigated formalin-fixed thyroid gland samples of 216 patients (191 Hashimoto's thyroiditis, 5 Riedel's thyroiditis, and 20 goiters, as controls), morphologically, and immunohistochemically. Cases were divided into two groups: IgG4-related Hashimoto's thyroiditis (24 cases) together with Riedel thyroiditis (1 case) and 171 non-IgG4-related thyroiditis. Compared to the non-IgG4-related cases, IgG4-related thyroiditis showed a higher IgG4/IgG ratio (0.6 vs. 0.1, p thyroiditis was diagnosed in 23 of the 24 IgG4-related cases (96 %) and in 13 of 167 (18 %, p > 0.001) non-IgG4-related cases. The single case of IgG4-related Riedel's thyroiditis also showed a higher median IgG4 plasma cell count (56.3 vs. 14.3) and a higher IgG4/IgG ratio (0.5 vs. 0.2) than the four cases of non-IgG4-related Riedel's thyroiditis. Our data suggests the incidence of IgG4-related disease (IgG4-RD) of the thyroid gland in Europe is considerably lower than that observed in other studies. A significant elevation of IgG4-positive plasma cells was only found in a small group of Hashimoto's thyroiditis and then accompanied by intense fibrosis, indicating an association with IgG4-RD. Morphologically, IgG4-RD of the thyroid gland differs from that in other organ systems, exhibiting a dense fibrosis without intense eosinophilia or obliterative phlebitis.

  9. Isolated Mass-Forming IgG4-Related Cholangitis as an Initial Clinical Presentation of Systemic IgG4-Related Disease

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    Seokhwi Kim

    2016-07-01

    Full Text Available IgG4-related disease (IgG4-RD may involve multiple organs. Although it usually presents as diffuse organ involvement, localized mass-forming lesions have been occasionally encountered in pancreas. However, the same pattern has been seldom reported in biliary tract. A 61-year-old male showed a hilar bile duct mass with multiple enlarged lymph nodes in imaging studies and he underwent trisectionectomy under impression of cholangiocarcinoma. Gross examination revealed a mass-like lesion around hilar bile duct. Histopathologically, dense lymphoplasmacytic infiltration and storiform fibrosis were identified without evidence of malignancy. Immunohistochemical stain demonstrated rich IgG4-positive plasma cell infiltration. Follow-up imaging studies disclosed multiple enlarged lymph nodes with involvement of pancreas and perisplenic soft tissue. The lesions have been significantly reduced after steroid treatment, which suggests multi-organ involvement of systemic IgG4-RD. Here, we report an unusual localized mass-forming IgG4-related cholangitis as an initial presentation of IgG4-RD, which was biliary manifestation of systemic IgG4-related autoimmune disease.

  10. IgG4-Related Autoimmune Prostatitis: Is It an Unusual or Underdiagnosed Manifestation of IgG4-Related Disease?

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    María T. Bourlon

    2013-01-01

    Full Text Available IgG4-related disease (IgG4-RD encompasses a wide range of extrapancreatic manifestations. Albeit some are relatively well known, others such as autoimmune prostatitis remain poorly described. We present a 61-year-old Latin-American male with autoimmune pancreatitis (AIP who presented with lower urinary tract symptoms (LUTS, normal prostate specific antigen (PSA test, and prostate enlargement attributed to benign prostatic hyperplasia (BPH. He underwent a transurethral resection of the prostate (TURP after which symptoms were resolved. On histopathology, prostatic stroma had a dense inflammatory infiltrate rich in plasma cells and lymphocytes; immunohistochemical morphometric assessment showed >10 IgG4-positive plasma cells/high power field (HPF. The diagnosis of IgG4-related prostatitis was postoperatively. We compared the patient characteristics with those of previous reports on Asian patients. Shared findings included prostate enlargement, LUTS (symptoms that can be confused with BPH, and PSA within normal limits or mild elevations. IgG4-related prostatitis is rarely considered as a preprocedural diagnosis, even in patients with evidence of IgG4-RD. Involved prostate zones include mainly central and transitional zones and less frequently the peripheral. Currently, there is insufficient data about the natural history and outcome. Whether steroids, transurethral resection, or both are the treatment of choice needs to be elucidated.

  11. IgG4-related Pleuritis with Elevated Adenosine Deaminase in Pleural Effusion: A Case Report.

    Science.gov (United States)

    Nagayasu, Atsushi; Kubo, Satoshi; Nakano, Kazuhisa; Nakayamada, Shingo; Iwata, Shigeru; Miyagawa, Ippei; Fukuyo, Shunsuke; Saito, Kazuyoshi; Tanaka, Yoshiya

    2018-03-09

    An 81-year-old man was admitted with bilateral pleural effusion. A clinical examination showed lymphocytic pleura effusion and elevated serum IgG4 levels, so that IgG4-related disease was suggested, whereas tuberculous pleurisy was suspected because of high adenosine deaminase (ADA) levels in the pleural effusion. A surgical pleural biopsy revealed that there were large numbers of IgG4-positive cells and IgG4/IgG positive cell ratio exceeded 40% in several sites. Accordingly, we diagnosed IgG4-related pleuritis and treated with the patient with glucocorticoid therapy. The ADA levels in pleural effusion can increase in IgG4-related pleuritis, and it is therefore important to perform a pleural biopsy.

  12. Clinical and imaging diagnosis of IgG4-related disease in the head and neck

    International Nuclear Information System (INIS)

    Yu Changliang; Liu Bin; Yu Yongqiang

    2013-01-01

    IgG4-related disease in the head and neck is a newly recognized multi-organ system disease characterized by elevated serum IgG4, infiltration of numerous IgG4-positive plasma cells, tissue fibrosis, and dramatic response to corticosteroid treatment. IgG4-related disease of the head and neck has some relative characteristics on CT and MRI, which can provide valuable information for the diagnosis and differential diagnosis, and are helpful for the clinical treatment, evaluation of therapeutic effects and prediction of prognosis. (authors)

  13. Consensus statement on the pathology of IgG4-related disease

    NARCIS (Netherlands)

    Deshpande, Vikram; Zen, Yoh; Chan, John Kc; Yi, Eunhee E.; Sato, Yasuharu; Yoshino, Tadashi; Klöppel, Günter; Heathcote, J. Godfrey; Khosroshahi, Arezou; Ferry, Judith A.; Aalberse, Rob C.; Bloch, Donald B.; Brugge, William R.; Bateman, Adrian C.; Carruthers, Mollie N.; Chari, Suresh T.; Cheuk, Wah; Cornell, Lynn D.; Fernandez-del Castillo, Carlos; Forcione, David G.; Hamilos, Daniel L.; Kamisawa, Terumi; Kasashima, Satomi; Kawa, Shigeyuki; Kawano, Mitsuhiro; Lauwers, Gregory Y.; Masaki, Yasufumi; Nakanuma, Yasuni; Notohara, Kenji; Okazaki, Kazuichi; Ryu, Ji Kon; Saeki, Takako; Sahani, Dushyant V.; Smyrk, Thomas C.; Stone, James R.; Takahira, Masayuki; Webster, George J.; Yamamoto, Motohisa; Zamboni, Giuseppe; Umehara, Hisanori; Stone, John H.

    2012-01-01

    IgG4-related disease is a newly recognized fibro-inflammatory condition characterized by several features: a tendency to form tumefactive lesions in multiple sites; a characteristic histopathological appearance; and-often but not always-elevated serum IgG4 concentrations. An international symposium

  14. Exposure to occupational antigens might predispose to IgG4-related disease

    NARCIS (Netherlands)

    de Buy Wenniger, Lucas J. Maillette; Culver, Emma L.; Beuers, Ulrich

    2014-01-01

    Evidence is mounting that the immune system of patients with IgG4-related disease (IgG4-RD) shows indications of chronic antigenic stimulation. Hypothesizing a possible role for occupational antigenic exposure, we observed in two independent cohorts of patients with IgG4-RD that the majority had had

  15. Case report: A female case of isolated IgG4-related sclerosing cholangitis mimicking cholangiocarcinoma.

    Science.gov (United States)

    Xiao, Jianchun; Li, Guanqiao; Yang, Gang; Jia, Congwei; Li, Binglu

    2017-04-01

    IgG4-related disease is a newly recognized fibroinflammatory disorder, characterized by tumefactive lesions, storiform fibrosis and IgG4-positive plasma cells infiltration. IgG4-related sclerosing cholangitis (IgG4-SC) is the most common extrapancreatic manifestation of IgG4-related disease, but it is frequently associated with autoimmune pancreatitis(AIP). Only few case was reported to be diagnosed with IgG4-SC in the absence of AIP, with a striking male preponderance. Here we report a female case of isolated IgG4 related sclerosing cholangitis mimicking cholangiocarcinoma. A 58-year-old woman complaint of one-month history of jaundice and right upper quadrant discomfort, and the biliary reconstruction showed full-length wall thickening and segmental stenosis. Cholangiocarcinoma was then diagnosed. Choledochoplasty was performed, followed by Roux-en-Y anastomosis. However, pathological examination revealed IgG4-related sclerosing cholangitis (IgG4-SC) and the retrospective measurement of serum IgG4 was 346 mg/dL post-operatively. The patient was followed for another nine monthswithout recurrence. The differential diagnosis between cholangiocarcinoma and IgG4-SC is challenging due to significant overlap of clinical manifestations, lab tests and imaging characteristics. However, as an afterthought of this case, typical cholangiocarcinoma rarely presents full-length wall thickening. What the case taught us was pre-operative IgG4 measurement for patients with long bile duct involvement was highly recommended in order to rule out IgG4-SC.

  16. IgG4-related disease simulating Hodgkin lymphoma in a child

    Directory of Open Access Journals (Sweden)

    D. Eric Ewing, MD

    2016-06-01

    Full Text Available Immunoglobulin (Ig G4-related disease is a recently described syndrome characterized by mass forming lymphoplasmacytic tissue infiltration and elevated serum IgG4 concentrations usually affecting middle-aged or older individuals. Lymphadenopathy is frequently observed and is sometimes the first or only manifestation of the disease. We report a case of IgG4-related disease mimicking Hodgkin lymphoma in a 13-year-old girl. The patient presented with progressive unilateral cervical lymphadenopathy of several months duration. Biopsy showed follicular hyperplasia with progressive transformation of germinal centers. Interfollicular areas were expanded by small lymphocytes, histiocytes, eosinophils and fibrosis with occasional CD30 positive cells initially concerning for interfollicular Hodgkin lymphoma. Immunohistochemical analysis revealed an intrafollicular plasmacytosis with an IgG4-positive/IgG-positive plasma cell ratio of 50% supporting a diagnosis of IgG4-related lymphadenopathy, progressively transformed germinal centers type. Laboratory studies were supportive with elevated serum IgG4 (178 mg/dL and IgE (30.40 kU/L levels along with an elevated serum IgG4/IgG ratio (0.16. Very few cases of IgG4-related disease have been described in children. Within this age group, there is considerable clinical overlap between IgG4-related disease associated lymphadenopathy and Hodgkin lymphoma. In addition, lymphadenopathy secondary to IgG4-related disease demonstrates substantial histologic diversity with the potential to simulate the inflammatory background and fibrosis of Hodgkin lymphoma. The importance of accurate diagnosis is underscored by the prognostic implications considering the marked response of the syndrome to steroid therapy. In addition, appropriate follow up is critical to monitor for relapse and additional organ involvement.

  17. Unusual IgG4-related hypophysitis: one case report and analysis of clinicopathological characteristics

    Directory of Open Access Journals (Sweden)

    Zhen-qi LI

    2014-10-01

    Full Text Available Background Immunoglobulin G4 (IgG4-related disease is a recently characterized autoimmune disease entity marked by elevated serum IgG4 levels and tissue infiltration by IgG4-positive plasma cells in multiple involved organs. Hypophysitis is a rare inflammatory disorder and IgG4-related sclerosing disease involving the ituitary alone is especially rare. Imaging studies may reveal a mass lesion in the sellar area or a thickening of pituitary stalk, mimicking a pituitary tumor. Due to its rarity and non-specific appearance in radiological examination, it is a diagnostic challenge for clinicians and histopathologists to differentiate solitary IgG4-related hypophysitis from other pituitary lesions. The aim of this study is to summarize the clinicopathological features of unusual IgG4-related hypophysitis and discuss the differential diagnosis of histologically similar inflammatory lesions in pituitary. Methods The clinical manifestation of a patient with solitary IgG4-related hypophysitis was presented retrospectively. Resected mass was routinely paraffin-embedded and stained with Hematoxylin and Eosin. Dako EnVision immunohistochemical staining system was used to detect the tumor antigen expressions, including vimentin (Vim, S-100 protein (S-100, pan cytokeratin (PCK, epithelial membrane antigen (EMA, CD3, CD20, CD68, CD1a, κ-light chain, λ-light chain and progestrone receptor (PR.  Results A 47-year-old male patient presented with 1-year history of mild limb weakness and hyposexuality. Laboratory examination revealed hypopituitarism with low levels of serum testosterone, cortisol, luteinizing hormone (LH and follicle stimulating hormone (FSH, although his serum IgG4 level was high. MRI of the pituitary gland revealed a mass lesion in the sellar area with T1WI mild hyperintense and homogeneous enhancement after gadolinium administration. The patient underwent a transsphenoidal mass resection of the pituitary gland. Histological examination showed bland appearing spindle cell proliferation in the sclerotic background with marked infiltration of lymphocytes, plasma cells, as well as multiple foci of meningothelial-like nodules at the periphery of tissues. Immunohistochemical staining showed that the lymphocytes were positive for CD3 and CD20. Plasma cells were distinct and the number of κ and λ-light chains was the same. There were more than 30 IgG4-positive plasma cells per high power field (HPF, which accounted for greater than 40% of the IgG-positive plasma cells. The meningothelial-like nodules were positive for Vim, EMA and PR, but negative for CD68, S-100 and CD1a. A final histological diagnosis of IgG4-related hypophysitis with meningothelial reaction was made. The patient took prednisolone orally at 35 mg/d for 2 weeks, and the symptoms of limb weakness and hyposexuality showed improvement. The mass lesion of pituitary gland demonstrated a reduction in size. The prednisolone therapy was continued at a dose of 30 mg/d to prevent recurrence of IgG4-related disease.  Conclusions IgG4-related hypophysitis is a rare disease of central nervous system with good response to corticosteroid treatment. Due to the relative paucity of reported cases and similarities in histological findings, it may be difficult to differentiate IgG4-related disease from other pituitary lesions with prominent inflammatory cell infiltration and stromal fibrosis. Thorough inspection under the microscopy and more importantly elevated serum IgG4 level are necessary for correct diagnosis. doi: 10.3969/j.issn.1672-6731.2014.10.012

  18. IgG4-related pleural disease presenting as a massive bilateral effusion.

    Science.gov (United States)

    Ishida, Atsuko; Furuya, Naoki; Nishisaka, Takashi; Mineshita, Masamichi; Miyazawa, Teruomi

    2014-07-01

    A 74-year-old woman with massive bilateral pleural effusion, which was exudative in nature, and with mononuclear cell predominance underwent a pleuroscopy. Parietal pleura were thickened and partly reddish in color. Biopsy specimens taken from the parietal pleura revealed lymphoplasmacytic inflammation with fibrosis. As her performance status rapidly worsened with thoracentesis, we performed bilateral pleurodesis using talc. Pathologic evaluation of the pleural biopsy specimen with immunohistochemical staining revealed 91 IgG4-positive plasma cells per high-power field and an IgG4/IgG ratio of 91%. Thus, the diagnosis of pleuritis from IgG4-related disease was established. Our case suggests that IgG4-related disease is one of the causes of pleural effusion, and it should be included in the differential diagnosis of unexplained pleuritis.

  19. Topiramate-induced maculopathy in IgG4-related disease

    OpenAIRE

    DaCosta, Joanna; Younis, Saad

    2016-01-01

    Joanna DaCosta,1,2 Saad Younis1 1Ophthalmology Department, Imperial College Healthcare NHS Trust, Western Eye Hospital, 2Barts Health NHS Trust, Whipps Cross University Hospital, London, UK Abstract: This report describes a case of reversible topiramate-induced maculopathy in a 32-year-old female patient with IgG4-related disease. The patient presented with decreased vision associated with anterior uveitis and cystoid macula edema, which was unresponsive to oral and topical steroids. Followi...

  20. IgG4-related cardiovascular disease. The emerging role of cardiovascular imaging.

    Science.gov (United States)

    Mavrogeni, Sophie; Markousis-Mavrogenis, George; Kolovou, Genovefa

    2017-01-01

    Immunoglobulin 4-related disease (IgG4-related disease) is a systemic inflammatory disease that presents with increases of serum IgG4. It may affect various systems, including the cardiovascular (CV) system. Assessment of serum IgG4 levels and involved organ biopsy are necessary for diagnosis. IgG4-related disease is characterized by fibrosclerosis, lymphocytic infiltration and presence of IgG4-positive plasma cells. The disease usually responds to treatment with corticosteroids and/or immunosuppressive medication. CV involvement may manifest as cardiac pseudotumors, inflammatory periaortitis, coronary arteritis and/or pericarditis. IgG4-related cardiovascular disorders can severely affect patient prognosis. Various imaging techniques, including echocardiography, Computed Tomography (CT), 18FDG-PET, Cardiovascular Magnetic Resonance (CMR) and cardiac catheterisation, have been successfully used for early disease detection and follow-up. Echocardiography and vascular ultrasound are the most commonly used non-invasive, non-radiating imaging techniques for the evaluation of IgG4-related CV disease. Periaortitis/periarteritis can be also assessed by CT, showing a soft tissue thickening around arteries. Coronary artery aneurysms can be easily diagnosed by coronary CT. In case of active periarterial or coronary artery inflammation, 18FDG-PET will show FDG uptake at the area of the lesion. CMR, due to its capability to perform function and tissue characterisation, can offer an integrated imaging of aorta, coronary arteries and the heart, assessment of disease acuity, extent of fibrosis and guide further treatment. However, multimodality imaging may be necessary for assessment of disease activity and fibrosis extent in those cases with multifocal CV involvement. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  1. IgG4-related retroperitoneal fibrosis: a newly characterized disease.

    Science.gov (United States)

    Lian, Linjuan; Wang, Cong; Tian, Jian-Li

    2016-11-01

    Retroperitoneal fibrosis (RPF) is a rare disease characterized by chronic, nonspecific inflammatory and sclerotic or fibrotic tissue in the periaortic or periiliac retroperitoneum that encases adjacent structures. There will be a series of clinical manifestations once the proliferated fibrous tissues encase the abdominal aorta, iliac arteries and urinary duct. RPF is generally divided into two types: idiopathic retroperitoneal fibrosis (IRPF) without identified pathogenesis, making up about two-thirds of cases, and secondary retroperitoneal fibrosis. Recent studies on Immunoglobulin G4-related disease (IgG4-RD) reveal that abundant infiltration of IgG4 positive plasma cells is found in biopsies on the mass of RPF of some IRPF patients, which is identified as one spectrum of IgG4-RD and is named IgG4-related RPF. IgG4-related RPF is often misdiagnosed as retroperitoneal visceral malignancy and is treated with surgery. In addition, because of its good response to glucocorticoid, early detection and treatment is important. We review the definition, epidemiology, clinical features, diagnostic criteria, treatment and prognosis of IgG4-related RPF in this article to raise awareness of this newly characterized disease. © 2016 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.

  2. IgG4-related cardiovascular disease. The emerging role of cardiovascular imaging

    Energy Technology Data Exchange (ETDEWEB)

    Mavrogeni, Sophie, E-mail: soma13@otenet.gr; Markousis-Mavrogenis, George; Kolovou, Genovefa

    2017-01-15

    Highlights: • Assessment of serum IgG4 levels and involved organ biopsy are necessary for diagnosis of IgG4-related disease. • CV involvement may manifest as cardiac pseudotumors, inflammatory periaortitis, coronary arteritis and/or pericarditis. • Echocardiography and vascular ultrasound are the most commonly used non-invasive, non-radiating imaging techniques. • CT can assess periarteritis and coronary artery aneurysms, while 18FDG-PET shows FDG uptake at the area of the lesion. • CMR offers an integrated imaging of CV system, including assessment of disease acuity, extent of fibrosis and can guide further treatment. - Abstract: Immunoglobulin 4-related disease (IgG4-related disease) is a systemic inflammatory disease that presents with increases of serum IgG4. It may affect various systems, including the cardiovascular (CV) system. Assessment of serum IgG4 levels and involved organ biopsy are necessary for diagnosis. IgG4-related disease is characterized by fibrosclerosis, lymphocytic infiltration and presence of IgG4-positive plasma cells. The disease usually responds to treatment with corticosteroids and/or immunosuppressive medication. CV involvement may manifest as cardiac pseudotumors, inflammatory periaortitis, coronary arteritis and/or pericarditis. IgG4-related cardiovascular disorders can severely affect patient prognosis. Various imaging techniques, including echocardiography, Computed Tomography (CT), 18FDG-PET, Cardiovascular Magnetic Resonance (CMR) and cardiac catheterisation, have been successfully used for early disease detection and follow-up. Echocardiography and vascular ultrasound are the most commonly used non-invasive, non-radiating imaging techniques for the evaluation of IgG4-related CV disease. Periaortitis/periarteritis can be also assessed by CT, showing a soft tissue thickening around arteries. Coronary artery aneurysms can be easily diagnosed by coronary CT. In case of active periarterial or coronary artery inflammation, 18FDG-PET will show FDG uptake at the area of the lesion. CMR, due to its capability to perform function and tissue characterisation, can offer an integrated imaging of aorta, coronary arteries and the heart, assessment of disease acuity, extent of fibrosis and guide further treatment. However, multimodality imaging may be necessary for assessment of disease activity and fibrosis extent in those cases with multifocal CV involvement.

  3. IgG4-related cardiovascular disease. The emerging role of cardiovascular imaging

    International Nuclear Information System (INIS)

    Mavrogeni, Sophie; Markousis-Mavrogenis, George; Kolovou, Genovefa

    2017-01-01

    Highlights: • Assessment of serum IgG4 levels and involved organ biopsy are necessary for diagnosis of IgG4-related disease. • CV involvement may manifest as cardiac pseudotumors, inflammatory periaortitis, coronary arteritis and/or pericarditis. • Echocardiography and vascular ultrasound are the most commonly used non-invasive, non-radiating imaging techniques. • CT can assess periarteritis and coronary artery aneurysms, while 18FDG-PET shows FDG uptake at the area of the lesion. • CMR offers an integrated imaging of CV system, including assessment of disease acuity, extent of fibrosis and can guide further treatment. - Abstract: Immunoglobulin 4-related disease (IgG4-related disease) is a systemic inflammatory disease that presents with increases of serum IgG4. It may affect various systems, including the cardiovascular (CV) system. Assessment of serum IgG4 levels and involved organ biopsy are necessary for diagnosis. IgG4-related disease is characterized by fibrosclerosis, lymphocytic infiltration and presence of IgG4-positive plasma cells. The disease usually responds to treatment with corticosteroids and/or immunosuppressive medication. CV involvement may manifest as cardiac pseudotumors, inflammatory periaortitis, coronary arteritis and/or pericarditis. IgG4-related cardiovascular disorders can severely affect patient prognosis. Various imaging techniques, including echocardiography, Computed Tomography (CT), 18FDG-PET, Cardiovascular Magnetic Resonance (CMR) and cardiac catheterisation, have been successfully used for early disease detection and follow-up. Echocardiography and vascular ultrasound are the most commonly used non-invasive, non-radiating imaging techniques for the evaluation of IgG4-related CV disease. Periaortitis/periarteritis can be also assessed by CT, showing a soft tissue thickening around arteries. Coronary artery aneurysms can be easily diagnosed by coronary CT. In case of active periarterial or coronary artery inflammation, 18FDG-PET will show FDG uptake at the area of the lesion. CMR, due to its capability to perform function and tissue characterisation, can offer an integrated imaging of aorta, coronary arteries and the heart, assessment of disease acuity, extent of fibrosis and guide further treatment. However, multimodality imaging may be necessary for assessment of disease activity and fibrosis extent in those cases with multifocal CV involvement.

  4. Current approach to the diagnosis of IgG4-related disease - Combination of comprehensive diagnostic and organ-specific criteria.

    Science.gov (United States)

    Umehara, Hisanori; Okazaki, Kazuichi; Nakamura, Takuji; Satoh-Nakamura, Tomomi; Nakajima, Akio; Kawano, Mitsuhiro; Mimori, Tsuneyo; Chiba, Tsutomu

    2017-05-01

    IgG4-related disease (IgG4-RD) is a fascinating clinical entity proposed by Japanese investigators, and includes a wide variety of diseases, formerly diagnosed as Mikulicz's disease (MD), autoimmune pancreatitis (AIP), interstitial nephritis, prostatitis, retroperitoneal fibrosis, etc. Although all clinicians in every field of medicine may encounter this new disease, a unifying diagnostic criterion has not been established. In 2011, the Japanese IgG4 team, organized by the Ministry of Health, Labor and Welfare (MHLW) of Japan, published comprehensive diagnostic criteria for IgG4-RD. Several problems with these criteria have arisen in clinical practice, however, including the difficulty obtaining biopsy samples from some patients, and the sensitivity and the specificity of techniques used to measure serum IgG4 concentrations. Although serum IgG4 concentration is an important clinical marker for IgG4-RD, its diagnostic utility in differentiating IgG4-RD from other diseases, called IgG4-RD mimickers, remains unclear. This review describes the current optimal approach for the diagnosis of IgG4-RD, based on both comprehensive and organ-specific diagnostic criteria, in patients with diseases such as IgG4-related pancreatitis (AIP), sclerosing cholangitis, and renal, lung and orbital diseases.

  5. Hypermethylation of MST1 in IgG4-related autoimmune pancreatitis and rheumatoid arthritis

    Energy Technology Data Exchange (ETDEWEB)

    Fukuhara, Takataro; Tomiyama, Takashi [Division of Gastroenterology and Hepatology, The Third Department of Internal Medicine, JST CREST, Kansai Medical University, 2-5-1 Shin-machi, Hirakata, Osaka 573-1010 (Japan); Yasuda, Kaneki [Department of Urology and Andrology, Kansai Medical University, 2-5-1 Shin-machi, Hirakata, Osaka 573-1010 (Japan); Ueda, Yoshihiro [Department of Molecular Genetics, Institute of Biomedical Science, and JST CREST, Kansai Medical University, 2-5-1 Shin-machi, Hirakata, Osaka 573-1010 (Japan); Ozaki, Yoshio; Son, Yonsu; Nomura, Shosaku [Department of the First Department of Internal Medicine, Kansai Medical University, 2-5-1 Shin-machi, Hirakata, Osaka 573-1010 (Japan); Uchida, Kazushige; Okazaki, Kazuichi [Division of Gastroenterology and Hepatology, The Third Department of Internal Medicine, JST CREST, Kansai Medical University, 2-5-1 Shin-machi, Hirakata, Osaka 573-1010 (Japan); Kinashi, Tatsuo, E-mail: kinashi@takii.kmu.ac.jp [Department of Molecular Genetics, Institute of Biomedical Science, and JST CREST, Kansai Medical University, 2-5-1 Shin-machi, Hirakata, Osaka 573-1010 (Japan)

    2015-08-07

    The serine/threonine kinase Mst1 plays important roles in the control of immune cell trafficking, proliferation, and differentiation. Previously, we reported that Mst1 was required for thymocyte selection and regulatory T-cell functions, thereby the prevention of autoimmunity in mice. In humans, MST1 null mutations cause T-cell immunodeficiency and hypergammaglobulinemia with autoantibody production. RASSF5C(RAPL) is an activator of MST1 and it is frequently methylated in some tumors. Herein, we investigated methylation of the promoter regions of MST1 and RASSF5C(RAPL) in leukocytes from patients with IgG4-related autoimmune pancreatitis (AIP) and rheumatoid arthritis (RA). Increased number of CpG methylation in the 5′ region of MST1 was detected in AIP patients with extrapancreatic lesions, whereas AIP patients without extrapancreatic lesions were similar to controls. In RA patients, we detected a slight increased CpG methylation in MST1, although the overall number of methylation sites was lower than that of AIP patients with extrapancreatic lesions. There were no significant changes of the methylation levels of the CpG islands in the 5′ region of RASSF5C(RAPL) in leukocytes from AIP and RA patients. Consistently, we found a significantly down-regulated expression of MST1 in regulatory T cells of AIP patients. Our results suggest that the decreased expression of MST1 in regulatory T cells due to hypermethylation of the promoter contributes to the pathogenesis of IgG4-related AIP. - Highlights: • Mst1 controls immune cells trafficking, cell proliferation and differentiation. • Autoimmune pancreatitis (AIP) is an idiopathic pancreatitis affecting multiple organs. • Decreased MST1 expression and increased CpG methylation of promoter of MST1 in AIP. • Slight increased CpG methylation of MST1 in rheumatoid arthritis patients. • MST1 contributes pathogenesis of IgG4-related AIP.

  6. Hypermethylation of MST1 in IgG4-related autoimmune pancreatitis and rheumatoid arthritis

    International Nuclear Information System (INIS)

    Fukuhara, Takataro; Tomiyama, Takashi; Yasuda, Kaneki; Ueda, Yoshihiro; Ozaki, Yoshio; Son, Yonsu; Nomura, Shosaku; Uchida, Kazushige; Okazaki, Kazuichi; Kinashi, Tatsuo

    2015-01-01

    The serine/threonine kinase Mst1 plays important roles in the control of immune cell trafficking, proliferation, and differentiation. Previously, we reported that Mst1 was required for thymocyte selection and regulatory T-cell functions, thereby the prevention of autoimmunity in mice. In humans, MST1 null mutations cause T-cell immunodeficiency and hypergammaglobulinemia with autoantibody production. RASSF5C(RAPL) is an activator of MST1 and it is frequently methylated in some tumors. Herein, we investigated methylation of the promoter regions of MST1 and RASSF5C(RAPL) in leukocytes from patients with IgG4-related autoimmune pancreatitis (AIP) and rheumatoid arthritis (RA). Increased number of CpG methylation in the 5′ region of MST1 was detected in AIP patients with extrapancreatic lesions, whereas AIP patients without extrapancreatic lesions were similar to controls. In RA patients, we detected a slight increased CpG methylation in MST1, although the overall number of methylation sites was lower than that of AIP patients with extrapancreatic lesions. There were no significant changes of the methylation levels of the CpG islands in the 5′ region of RASSF5C(RAPL) in leukocytes from AIP and RA patients. Consistently, we found a significantly down-regulated expression of MST1 in regulatory T cells of AIP patients. Our results suggest that the decreased expression of MST1 in regulatory T cells due to hypermethylation of the promoter contributes to the pathogenesis of IgG4-related AIP. - Highlights: • Mst1 controls immune cells trafficking, cell proliferation and differentiation. • Autoimmune pancreatitis (AIP) is an idiopathic pancreatitis affecting multiple organs. • Decreased MST1 expression and increased CpG methylation of promoter of MST1 in AIP. • Slight increased CpG methylation of MST1 in rheumatoid arthritis patients. • MST1 contributes pathogenesis of IgG4-related AIP

  7. Anti-pituitary antibodies against corticotrophs in IgG4-related hypophysitis.

    Science.gov (United States)

    Iwata, Naoko; Iwama, Shintaro; Sugimura, Yoshihisa; Yasuda, Yoshinori; Nakashima, Kohtaro; Takeuchi, Seiji; Hagiwara, Daisuke; Ito, Yoshihiro; Suga, Hidetaka; Goto, Motomitsu; Banno, Ryoichi; Caturegli, Patrizio; Koike, Teruhiko; Oshida, Yoshiharu; Arima, Hiroshi

    2017-06-01

    IgG4-related disease is a systemic inflammatory disease characterized by infiltration of IgG4-positive plasma cells into multiple organs, including the pituitary gland. Autoimmunity is thought to be involved in the pathogenesis of IgG4-related disease. The diagnosis of IgG4-related hypophysitis (IgG4-RH) is difficult because its clinical features, such as pituitary swelling and hypopituitarism, are similar to those of other pituitary diseases, including lymphocytic hypophysitis and sellar/suprasellar tumors. The presence and significance of anti-pituitary antibodies (APA) in IgG4-RH is unclear. In this case-control study, we used single indirect immunofluorescence on human pituitary substrates to assess the prevalence of serum APA in 17 patients with IgG4-RH, 8 control patients with other pituitary diseases (lymphocytic infundibulo-neurohypophysitis, 3; craniopharyngioma, 2; germinoma, 3), and 9 healthy subjects. We further analyzed the endocrine cells targeted by the antibodies using double indirect immunofluorescence. APA were found in 5 of 17 patients with IgG4-RH (29%), and in none of the pituitary controls or healthy subjects. The endocrine cells targeted by the antibodies in the 5 IgG4-RH cases were exclusively corticotrophs. Antibodies were of the IgG1 subclass, rather than IgG4, in all 5 cases, suggesting that IgG4 is not directly involved in the pathogenesis. Finally, antibodies recognized pro-opiomelanocortin in 2 of the cases. Our study suggests that autoimmunity is involved in the pathogenesis of IgG4-RH and that corticotrophs are the main antigenic target, highlighting a possible new diagnostic marker for this condition.

  8. Mitochondrial-dependent Autoimmunity in Membranous Nephropathy of IgG4-related Disease

    Science.gov (United States)

    Buelli, Simona; Perico, Luca; Galbusera, Miriam; Abbate, Mauro; Morigi, Marina; Novelli, Rubina; Gagliardini, Elena; Tentori, Chiara; Rottoli, Daniela; Sabadini, Ettore; Saito, Takao; Kawano, Mitsuhiro; Saeki, Takako; Zoja, Carlamaria; Remuzzi, Giuseppe; Benigni, Ariela

    2015-01-01

    The pathophysiology of glomerular lesions of membranous nephropathy (MN), including seldom-reported IgG4-related disease, is still elusive. Unlike in idiopathic MN where IgG4 prevails, in this patient IgG3 was predominant in glomerular deposits in the absence of circulating anti-phospholipase A2 receptor antibodies, suggesting a distinct pathologic process. Here we documented that IgG4 retrieved from the serum of our propositus reacted against carbonic anhydrase II (CAII) at the podocyte surface. In patient's biopsy, glomerular CAII staining increased and co-localized with subepithelial IgG4 deposits along the capillary walls. Patient's IgG4 caused a drop in cell pH followed by mitochondrial dysfunction, excessive ROS production and cytoskeletal reorganization in cultured podocytes. These events promoted mitochondrial superoxide-dismutase-2 (SOD2) externalization on the plasma membrane, becoming recognizable by complement-binding IgG3 anti-SOD2. Among patients with IgG4-related disease only sera of those with IgG4 anti-CAII antibodies caused low intracellular pH and mitochondrial alterations underlying SOD2 externalization. Circulating IgG4 anti-CAII can cause podocyte injury through processes of intracellular acidification, mitochondrial oxidative stress and neoantigen induction in patients with IgG4 related disease. The onset of MN in a subset of patients could be due to IgG4 antibodies recognizing CAII with consequent exposure of mitochondrial neoantigen in the context of multifactorial pathogenesis of disease. PMID:26137589

  9. Recurrent Mastoiditis Mimics IgG4 Related Disease: A Potential Diagnostic Pitfall.

    Science.gov (United States)

    Deshpande, Vikram; Zane, Nicolas A; Kraft, Stefan; Stone, John H; Faquin, William C

    2016-09-01

    IgG4-related disease (IgG4-RD) is a recently recognized entity that causes progressive fibrosis and formation of mass lesions. IgG4-RD can be diagnosed histologically by its hallmarks of storiform fibrosis, prominent lymphoplasmacytic infiltrate, and obliterative phlebitis, accompanied by the infiltration of excessive numbers of IgG4-positive plasma cells as well as elevations in serum IgG4 concentrations. A recent publication reported a case of IgG4-RD in the mastoid sinus, representing a new anatomic location for this disease. We report two additional cases of IgG4-RD occurring in the mastoid and causing clinical mastoiditis. The presenting symptoms were varied-tinnitus, hearing loss, and cranial nerve palsies. All three cases showed a dense lymphoplasmacytic infiltrate, storiform type fibrosis as well as elevated numbers of IgG4 positive plasma cells. The three patients responded to immunosuppressive therapy that included steroids and Rituximab. We further investigated 162 consecutive mastoiditis cases at our institution in order to determine the frequency of IgG4-RD as a previously unrecognized cause of mastoiditis. Within this latter cohort we identified nine cases of mastoiditis that had two of the histologic features of IgG4-RD, specifically storiform fibrosis and a dense lymphoplasmacytic infiltrate. Two of these cases showed >50 IgG4-positive plasma cells per high-power field with IgG4-IgG ratio of >40 %, thus fulfilling histological criteria for IgG4-RD. However, both were due to severe acute or chronic infection. In conclusion, we reaffirm IgG4 related mastoiditis as a distinct but uncommon cause of recurrent mastoiditis. The diagnosis of IgG4-related mastoiditis should be rendered with caution, and only after the exclusion of potential mimickers, particularly infection.

  10. IgG4-Related Kidney Disease: Report of a Case Presenting as a Renal Mass

    Directory of Open Access Journals (Sweden)

    Daniele Bianchi

    2017-01-01

    Full Text Available IgG4-related disease (IgG4-RD is a nosological entity defined as a chronic immune-mediated fibro-inflammatory condition characterized by a tendency to form tumefactive, tissue-destructive lesions or by organ failure. Urologic involvement in IgG4-RD has been described in some short series of patients and in isolated case reports, most often involving the kidneys in so-called IgG4-related kidney disease (IgG4-RKD. The disease can occasionally mimic malignancies and is at risk of being misdiagnosed due to its rarity. We report the case of a 56-year-old man presenting with a right renal mass suspected of being malignant. Laboratory tests showed normal creatinine levels, a high erythrocyte sedimentation rate, and high levels of C-reactive protein and microalbuminuria. The patient underwent radical right nephroureterectomy and histopathologic examination revealed features proving IgG4-RKD. He was therefore referred to immunologists. Typical clinical presentation of IgG4-RKD includes altered renal function with inconstant or no radiologic findings. Conversely, in the case we presented, a single nodule was detected upon imaging evaluation, thus mimicking malignancy. This raises the issue of a proper differential diagnosis. A multidisciplinary approach can be useful, although in clinical practice the selection of patients suspected of having IgG4-RKD is critical in the cases presenting with a renal mass that mimics malignancy.

  11. IgG4-related disease in the eye and ocular adnexa.

    Science.gov (United States)

    Derzko-Dzulynsky, Larissa

    2017-11-01

    IgG4-related disease is a multi-organ fibro-inflammatory disease with characteristic histopathology showing lymphoplasmacytic infiltration, increased IgG4+ plasma cells and elevated IgG4/IgG ratios (>40%). The lacrimal gland is the most common ocular site of involvement. Scleritis and intraocular involvement in IgG4-related ophthalmic disease (IgG4-ROD) have recently been reported. The purpose of this review is to describe orbital and intraocular IgG4-ROD with a focus on publications since 2016. Case reports of scleritis and uveitis in IgG4-ROD have been described since 2012. Systemic prednisone is recommended as the first-line treatment, but immunosuppressive therapy may be required for steroid-sparing or in steroid-resistant cases. High rates of systemic IgG4-RD involvement exist in patients with bilateral IgG4-ROD or if the lacrimal gland is involved. Rituximab is the most specific immune targeted therapy available with high rates of remission. IgG4-ROD is an emerging cause of scleritis and uveitis and should be considered in any patient with multisystem inflammatory disease. New targeted immune therapies may improve outcomes and lead to clinical remission.

  12. IgG4-related sialadenitis and Sjögren's syndrome.

    Science.gov (United States)

    Fragoulis, G E; Zampeli, E; Moutsopoulos, H M

    2017-03-01

    IgG4-related disease (IgG4-RD) has emerged as a new entity in the last decade. It comprises numerous conditions previously thought to be unrelated. Macroscopically, these diseases cause diffuse organ swelling and formation of pseudotumorous masses. Histopathologically, they are characterized by a lymphoplasmacytic infiltrate with increased IgG4+ plasma cells and storiform fibrosis. Despite rapid progress within the last years, our knowledge on these conditions is still fragmented. To date, more than forty organs have been reported to be included in IgG4-RD, and salivary gland involvement is amongst the most common organs affected [IgG4-related sialadenitis (IgG4-RS)]. Interestingly, IgG4-RS shares commonalities with Sjögren's syndrome (SS), like glandular enlargement, sicca symptoms, arthralgias, hypergammaglobulinemia, hypocomplementemia, and circulating antinuclear antibodies. Nonetheless, they differ in that the incidence of anti-Ro and anti-La reactivity is not frequently found in patients with IgG4-RS, their salivary glands are infiltrated by a large number of IgG4+ plasma cells and IgG4-RS symptoms respond promptly to steroids. The aim of this review was to describe the clinical, serological, histopathological and pathophysiological aspects of IgG4-RS in the context of IgG4-RD and highlight the differences between IgG4-RS and SS. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. IgG4-Related Disease Presenting as Recurrent Mastoiditis With Central Nervous System Involvement

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    April L. Barnado MD

    2013-09-01

    Full Text Available We report a case of a 43-year-old female who presented with right ear fullness and otorrhea. She was initially diagnosed with mastoiditis that was not responsive to multiple courses of antibiotics and steroids. She was then diagnosed with refractory inflammatory pseudotumor, and subsequent treatments included several mastoidectomies, further steroids, and radiation therapy. The patient went on to develop mastoiditis on the contralateral side as well as central nervous system involvement with headaches and right-sided facial paresthesias. Reexamination of the mastoid tissue revealed a significantly increased number of IgG4-positive cells, suggesting a diagnosis of IgG4-related disease. The patient improved clinically and radiographically with rituximab and was able to taper off azathioprine and prednisone. IgG4-related disease should be considered in patients with otologic symptoms and be on the differential diagnosis in patients with inflammatory pseudotumor. Staining for IgG and IgG4 is essential to ensure a prompt diagnosis and treatment.

  14. Salivary Gland Pathology in IgG4-Related Disease: A Comprehensive Review

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    Ilaria Puxeddu

    2018-01-01

    Full Text Available IgG4-related disease (IgG4-RD is a rare fibroinflammatory condition that can affect almost any organ, characterized by swollen lesions and often by eosinophilia and elevated serum IgG4 concentrations. The diagnosis of IgG4-RD is a challenging task: in fact, single or multiple organs can be affected and clinical, serological, and histological findings can be heterogeneous. In IgG4-RD, the involvement of salivary glands is observed in 27% to 53% of patients. Several organ-specific conditions, now recognized as different manifestations of IgG4-related sialadenitis (IgG4-RS, were viewed in the past as individual disease entities. The study of salivary glands may sometimes be complex, because of the number of pathological conditions that may affect them, often with overlapping clinical pictures. Integration of different imaging techniques is often required in the case of swelling of salivary glands, even though biopsy remains the gold standard for a definite diagnosis of IgG4-RS. Thus, in this review, we discuss new insights in the pathogenesis of IgG4-RD, focusing on its clinical aspects and the tools that are currently available for a correct differential diagnosis when the salivary glands are involved.

  15. [Hashimoto's thyroiditis(chronic thyroiditis), IgG4-related thyroiditis].

    Science.gov (United States)

    Itoh, Mitsuyasu

    2012-11-01

    Hashimoto's thyroiditis emerges in patients who have genetic preponderance such as SNPs of CTLA-4 and risk factors such as excess intake of iodine, pregnancy or postpartum period, and smoking. Such risk factors also affect the entire clinical course. One of the major outcomes in Hashimoto's thyroiditis appears to be increased in cardio-vascular risks through subclinical hypothyroidism and concomitant metabolic syndrome, but in most cases, treatment with L-T4 has little effects on cardio-vascular benefit or quality of life. The pregnant women also have risks for obstetric complications and postpartum thyroid dysfunction. The women who have anti-TPO antibodies, type 1 diabetes, or previous history of post-partum thyroid dysfunction are recommended to be measured their TSH. It is noteworthy that Hashimoto's thyroiditis is sometimes complicated with encephalopathy, papillary carcinoma, or IgG4-related thyroiditis. IgG4-related thyroiditis is partly similar but partly discerned from a variant of Hashimoto's thyroiditis. The pathogenetic roles of this variant on autoimmune-based thyroiditis remain unclear.

  16. IgG4-related disease: with emphasis on the biopsy diagnosis of autoimmune pancreatitis and sclerosing cholangitis.

    Science.gov (United States)

    Detlefsen, Sönke; Klöppel, Günter

    2018-04-01

    In 2011, chronic fibroinflammatory processes occurring simultaneously or metachronously in various organs and associated with elevated IgG4 serum levels and/or tissue infiltration with IgG4-positive plasma cells have been recognized as manifestations of a systemic disorder called IgG4-related disease (IgG4-RD). The histologic key findings are lymphoplasmacytic infiltration rich in IgG4-positive plasma cells combined with storiform fibrosis and obliterative phlebitis. Among the organs mainly affected by IgG4-RD are the pancreas and the extrahepatic bile ducts. The pancreatic and biliary alterations have been described under the terms autoimmune pancreatitis (AIP) and sclerosing cholangitis, respectively. These diseases are currently more precisely called IgG4-related pancreatitis (or type 1 AIP to distinguish it from type 2 AIP that is unrelated to IgG4-RD) and IgG4-related sclerosing cholangitis (IgG4-related SC). Clinically and grossly, both diseases commonly imitate pancreatic and biliary adenocarcinoma, tumors that are well known for their dismal prognosis. As IgG4-RD responds to steroid treatment, making a resection of a suspected tumor unnecessary, a biopsy is often required to establish the preoperative diagnosis. This review discusses the morphologic spectrum of IgG4-related pancreatitis and IgG4-related SC and focuses on the biopsy relevant histologic features for the diagnosis and differential diagnosis of these diseases.

  17. IgG4-related disease: a systemic condition with characteristic microscopic features

    DEFF Research Database (Denmark)

    Detlefsen, Sönke

    2013-01-01

    that a significant proportion of the AIP patients had a variety of extrapancreatic fibroinflammatory lesions, and that AIP therefore was the pancreatic manifestation of a systemic disease. Among these extrapancreatic manifestations, the extrahepatic bile ducts, salivary glands, thyroid, lymph nodes......During the first decade of the 21st century, IgG4-related disease (IgG4-RD), a fibroinflammatory condition occurring at multiple sites of the body, has been newly recognized. As indicated by its name, elevation of IgG4 in the serum and tissue is a common denominator of IgG4-RD. Since...... diseases on their own, others have been included under the umbrella of "multifocal fibrosclerosis". Biopsies or resection specimens from affected organs in IgG4-RD reveal several common microscopic features irrespective of the site of the lesion. Cellular and storiform fibrosis, lymphoplasmacytic...

  18. Perivascular fibrosis and IgG4-related disease: a case report

    Directory of Open Access Journals (Sweden)

    S. Monti

    2014-11-01

    Full Text Available Immunoglobulin G4-related disease (IgG4-RD is a newly recognized fibroinflammatory condition which can potentially involve any organ. Some characteristic histopathologic features with lymphoplasmacytic infiltrate, an increased number of IgG4+ cells, storiform fibrosis and obliterative phlebitis are the mainstay for diagnosis. Serum IgG4 levels often increase. We report the case of a patient with perivascular fibrotic lesions involving the aortic arch and the splenic hilum, with a surgical biopsy-proven diagnosis of IgG4-related disease. The patient is now undergoing a low-dose corticosteroid maintenance therapy without evidence of new localizations of the disease. This case highlights the need for increasing awareness and recognition of this new, emerging clinical condition.

  19. Multi-organ IgG4-related disease: Demystifying the diagnostic enigma

    Directory of Open Access Journals (Sweden)

    S Bhardwaj

    2018-01-01

    Full Text Available IgG4-related disease (IgG4-RD is a multisystemic mass forming immune-mediated disease entity, commonly creating confusion and diagnostic challenges. We present a case of a 25-year-old female who presented with bilateral orbital masses, lymphadenopathy, paraspinal and renal masses, which clinicoradiologically simulated lymphoma. The lymph node biopsy revealed interfollicular sheets of plasma cells creating confusion with Castleman's disease and marginal zone lymphoma. The orbital biopsy revealed ductular destruction, periductular plasma cells, and fibrosis, mimicking Sjogren's syndrome and Castleman's disease. However, the correlation of the clinical features with histopathological findings, IgG4 immunopositivity, and serum studies helped in clinching the diagnosis. This case presents an uncommon combination of clinical features infrequently reported in literature. Furthermore, and more importantly, it highlights the need to keep a differential of IgG4-RD in mind, to aid early and correct treatment of the disease.

  20. Orbital Pseudotumor: Uncommon Initial Presentation of IgG4-Related Disease

    Directory of Open Access Journals (Sweden)

    Teresa Carbone

    2015-01-01

    Full Text Available IgG4-related disease (IgG4-RD encompasses a group of fibroinflammatory conditions recognized in recent times. The main clinical features include variable degrees of tissue fibrosis, tumorlike expansions, perivascular lymphocytic infiltration rich in IgG4-positive plasma cells, and elevated serum IgG4. A case has been reported of an elderly patient with an unexplained unilateral exophthalmia; biopsy was performed and revealed lymphocytic infiltration, suggesting IgG4-RD. High serum levels of IgG4, in association with a good response to steroid therapy and to the exclusion of other diagnoses, confirmed the hypothesis of orbital pseudotumor by IgG4-RD.

  1. Serum Immunoglobulin Free Light Chain Assessment in IgG4-Related Disease

    Directory of Open Access Journals (Sweden)

    Aurélie Grados

    2013-01-01

    Full Text Available Immunoglobulin free light chains are produced in excess during normal antibody synthesis. Their evaluation is commonly used in case of a monoclonal gammopathy. In polyclonal hypergammaglobulinemia related to the Sjögren syndrome or systemic lupus, erythematosus serum free light chain levels are increased and could correlate with disease activity. We show here that the κ ( and λ ( free light chains and the κ : λ ratio ( are increased in sixteen patients with IgG4-related disease when compared to healthy controls. The increase of κ and λ free light chains probably reflects the marked polyclonal B cell activation of the disease. We could not assess in this small cohort of patients a significative correlation of serum free light chain levels and disease activity or extension.

  2. Bilateral IgG4-related ophthalmic disease: a strong indication for systemic imaging.

    Science.gov (United States)

    Wu, Albert; Andrew, Nicholas H; McNab, Alan A; Selva, Dinesh

    2016-10-01

    To investigate whether bilateral or unilateral IgG4-related ophthalmic disease (IgG4-ROD) is associated with extra-ophthalmic IgG4-related disease (IgG4-RD). Twin-centre retrospective observational case series of biopsy-confirmed IgG4-ROD. Clinical and radiology data were reviewed for laterality of IgG4-ROD and presence of extra-ophthalmic disease. The literature was reviewed for case series of IgG4-ROD. 40 IgG4-ROD cases were identified, with median follow-up of 36 months. At diagnosis of IgG4-ROD, all cases were screened for extra-ophthalmic disease with physical examination and blood testing. Systemic imaging was performed in 20 (50%) cases due to clinical suspicion of extra-ophthalmic disease. Of the 21 unilateral IgG4-ROD cases, 3 (14%) had extra-ophthalmic involvement. Of the 19 bilateral cases, 15 (79%) had extra-ophthalmic involvement. Extra-ophthalmic involvement was strongly associated with bilateral IgG4-ROD (pIgG4-ROD is strongly associated with extra-ophthalmic IgG4-RD. We recommend that imaging of the neck, chest, abdomen and pelvis be performed for all bilateral cases. Systemic imaging should also be considered in unilateral cases as a significant proportion of these patients will also have extra-ophthalmic disease. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  3. A case of IgG4-related lung disease complicated by asymptomatic chronic Epstein-Barr virus infection.

    Science.gov (United States)

    Kotetsu, Yasuaki; Ikegame, Satoshi; Takebe-Akazawa, Keiko; Koga, Takaomi; Okabayashi, Kan; Takata, Shohei

    2017-11-01

    IgG4-related disease is characterized by IgG4-positive plasmacyte infiltration into various organs, but its etiology is not unknown. To elucidate the etiology of IgG4-related disease. We experienced an interesting case of IgG4-related lung disease complicated by chronic EB virus infection. A 70-year-old male visited our hospital due to failure of pneumonia treatment. Chest computed tomography (CT) showed consolidation in the right middle field and slight mediastinal lymphadenopathy in the subcarinal region. Lung consolidation improved with antibiotics; subcarinal lymphadenopathy progressed after 4 months. Malignant lymphoma was suspected given elevated sIL2-R levels (1862 U/mL). Patchy ground glass opacities appeared in the bilateral lung field just before surgical biopsy. He was diagnosed with IgG4-related lung disease after inspection of a pathological specimen obtained from the right upper lung and right hilar lymph node. EB virus-infected cells were also detected in the lymph node. Blood examination revealed EB virus viremia, but the patient did not present with symptoms or organ involvement. This led to a diagnosis of asymptomatic chronic EB virus infection. Recent studies have suggested an association between EB virus infection and IgG4-related diseases in the pathological exploration of surgically resected lymph nodes. Our case is the first case of IgG4-related lung disease in which EB virus infection was both pathologically and clinically proved. The present case is of particular interest in view of this newly reported association, and may serve as a fundamental report for future studies connecting EB virus infection with IgG4-related diseases. © 2016 John Wiley & Sons Ltd.

  4. Circulating plasmablasts/plasma cells: a potential biomarker for IgG4-related disease.

    Science.gov (United States)

    Lin, Wei; Zhang, Panpan; Chen, Hua; Chen, Yu; Yang, Hongxian; Zheng, Wenjie; Zhang, Xuan; Zhang, Fengxiao; Zhang, Wen; Lipsky, Peter E

    2017-02-10

    Immunoglobulin G4 (IgG4)-related disease (IgG4-RD) is a multisystem fibroinflammatory disease. We previously reported that a circulating cell population expressing CD19 + CD24 - CD38 hi was increased in patients with IgG4-RD. In this study, we aimed to document that this cell population represented circulating plasmablasts/plasma cells, to identify the detailed phenotype and gene expression profile of these IgG4-secreting plasmablasts/plasma cells, and to determine whether this B-cell lineage subset could be a biomarker in IgG4-related disease (IgG4-RD). A total of 42 untreated patients with IgG4-RD were evaluated. Peripheral B-cell subsets, including CD19 + CD24 - CD38 hi plasmablasts/plasma cells, CD19 + CD24 + CD38 - memory B cells, CD19 + CD24 int CD38 int naïve B cells, and CD19 + CD24 hi CD38 hi regulatory B cells, were assessed and sorted by flow cytometry. Microarray analysis was used to measure gene expression of circulating B-cell lineage subsets. Further characterization of CD19 + CD24 - CD38 hi plasmablasts/plasma cells was carried out by evaluating additional surface markers, including CD27, CD95, and human leukocyte antigen (HLA)-DR, by flow cytometric assay. In addition, various B-cell lineage subsets were cultured in vitro and IgG4 concentrations were measured by cytometric bead array. In untreated patients with IgG4-RD, the peripheral CD19 + CD24 - CD38 hi plasmablast/plasma cell subset was increased and positively correlated with serum IgG4 levels, the number of involved organs, and the IgG4-related Disease Responder Index. It decreased after treatment with glucocorticoids. Characterization of the plasmablast/plasma cell population by gene expression profiling documented a typical plasmablast/plasma cell signature with higher expression of X-box binding protein 1 and IFN regulatory factor 4, but lower expression of paired box gene 5 and B-cell lymphoma 6 protein. In addition, CD27, CD95, and HLA-DR were highly expressed on CD19 + CD24 - CD38 hi plasmablasts/plasma cells from patients with IgG4-RD. Furthermore, CD19 + CD24 - CD38 hi plasmablasts/plasma cells secreted more IgG4 than other B-cell populations. Circulating CD19 + CD24 - CD38 hi plasmablasts/plasma cells are elevated in active IgG4-RD and decreased after glucocorticoid treatment. This IgG4-secreting plasmablast/plasma cell population might be a potentially useful biomarker for diagnosis and assessing response to treatment.

  5. IgG4-related disease with cavernous sinus and intra-orbital lesions diagnosed by nasal mucosa biopsy.

    Science.gov (United States)

    Nakata, Ruka; Yoshimura, Shunsuke; Motomura, Masakatsu; Tsujino, Akira; Hayashi, Tomayoshi; Hara, Minoru

    2016-09-29

    IgG4-related disease is a systemic disease characterized by lesions with IgG4 positive plasma cell infiltration in the involved organs and a raised serum IgG4 level. We report a patient of 70-year-old male presented orbital inflammation of IgG4-related disease. The patient developed right eye pain, double vision, and reduced eye sight. MRI image revealed mild right ocular proptosis and swelling of right carvenous sinus, bilateral intraorbital extraocular muscles and right optic nerve. Right optic nerve showed ring-like enhancement. IgG4-related disease was suspected with increased serum IgG4 level of 355 mg/dl, mediastinal lymphadenopathy and prostate enlargement. Transbronchial lung biopsy and prostate needle biopsy were administered with negative results. The eye related symptoms resolved with time, but serum IgG4 continuously increased. IgG4-related disease was diagnosed by nasal mucosa biopsy, which showed IgG4 positive plasma cells within the inflammatory infiltrate. This report emphasizes the usefulness of nasal mucosa biopsy for the diagnosis of IgG4 related disease with lesions difficult to approach.

  6. Clonal expansion of CD4+ Cytotoxic T Lymphocytes in IgG4-related disease

    Science.gov (United States)

    Mattoo, Hamid; Mahajan, Vinay S.; Maehara, Takashi; Deshpande, Vikram; Della-Torre, Emanuel; Wallace, Zachary S.; Kulikova, Maria; Drijvers, Jefte M.; Daccache, Joe; Carruthers, Mollie N.; Castellino, Flavia; Stone, James R.; Stone, John H.; Pillai, Shiv

    2016-01-01

    Background IgG4-related disease (IgG4-RD) is a systemic condition of unknown etiology, characterized by highly fibrotic lesions with dense lymphoplasmacytic infiltrates. CD4+ T cells constitute the major inflammatory cell population in IgG4-RD lesions. Objective We used an unbiased approach to characterize CD4+ T cell subsets in IgG4-RD subjects based on their clonal expansion and their ability to infiltrate affected tissue sites. Methods We used flow cytometry to identify CD4+ effector/memory T cells (TEM) in a cohort of 101 IgG4-related disease (IgG4-RD) patients. These expanded cells were characterized by gene expression analysis and flow cytometry. Next-generation sequencing of the T cell receptor β chain gene was performed on CD4+SLAMF7+ CTLs and CD4+GATA3+ TH2 cells in a subset of patients to identify their clonality. Tissue infiltration by specific T cells was examined using quantitative multi-color imaging. Results CD4+ effector/memory T cells with a cytolytic phenotype were expanded in IgG4-RD patients. Next-generation sequencing revealed prominent clonal expansions of these CD4+CTLs but not CD4+GATA3+ memory TH2 cells in subjects with IgG4-RD. The dominant T cells infiltrating a range of inflamed IgG4-RD tissue sites were clonally-expanded CD4+CTLs that expressed SLAMF7, granzyme A, IL-1β, and TGF-β1. Clinical remission induced by rituximab-mediated B cell depletion was associated with a reduction in disease-associated CD4+ CTLs Conclusions IgG4-RD is prominently linked to clonally-expanded, IL-1β, and TGF- β1 secreting, CD4+ CTLs in peripheral blood as well as in inflammatory tissue lesions. These active, terminally-differentiated, cytokine-secreting effector CD4+ T cells are now linked to a human disease characterized by chronic inflammation and fibrosis. PMID:26971690

  7. Enterocolic lymphocytic phlebitis as a newly recognized manifestation of IgG4-related disease.

    Science.gov (United States)

    Laco, Jan; Örhalmi, Július; Bártová, Jolana; Zimandlová, Dana

    2015-04-01

    Herein we present a case of a 65-year-old woman with enterocolic lymphocytic phlebitis (ELP) who presented with anemic syndrome and in whom severe stenosis of the right flexure of large bowel was detected. The microscopic examination revealed fibrosis of the submucosa and lymphoplasmacytic phlebitis of small veins and venules, whereas arteries were spared. There were 110 IgG4-positive and 160 IgG-positive plasma cells in 1 high-power field, respectively, with corresponding IgG4/IgG ratio of 0.69. The IgG4 serum level was 2.42 g/L. According to the currently proposed criteria, this ELP case is the first that may be diagnosed as definite IgG4-related disease (IgG4-RD). Although based on the sole case description, taken together with a recent review and a case report, we presume that a subset of ELPs is a manifestation of IgG4-RD. © The Author(s) 2014.

  8. Utility of FDG PET/CT in IgG4-related systemic disease

    Energy Technology Data Exchange (ETDEWEB)

    Nakatani, K., E-mail: koyakn@kuhp.kyoto-u.ac.jp [Department of Diagnostic Imaging and Nuclear Medicine, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto (Japan); Nakamoto, Y.; Togashi, K. [Department of Diagnostic Imaging and Nuclear Medicine, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto (Japan)

    2012-04-15

    IgG4-related systemic disease (IgG4-RSD) is an emerging clinical entity about which much remains to be elucidated, in terms of its aetiology, pathogenesis, diagnosis, treatment and outcome. Autoimmune pancreatitis (AIP) and Mikulicz disease (MD) are the two major, well-studied constituents of IgG4-RSD. AIP and MD have common characteristics of forming tumour-mimicking lesions that consist of lymphoplasmacytic infiltrates and fibrosclerosis with numerous immunoglobulin G4 (IgG4)-positive plasma cells, as well as various multi-organ manifestations of IgG4-RSD. 2-[{sup 18}F]-fluoro-2-deoxy-D-glucose positron-emission tomography/ computed tomography (FDG PET/CT) enables the acquisition of whole-body images and provides functional information about disease activity; as such it has a valuable role in staging extent of disease, guiding biopsy, and monitoring response to treatment. However, FDG PET/CT is likely to be only one component of the management strategy, and clinical, laboratory, imaging and histological findings are crucial in the overall diagnosis of the condition. At present FDG PET/CT does not have a well-established role in the assessment of patients with IgG4-RSD and future prospective studies are required to define the cost-effectiveness and clinical impact in this patient group more accurately.

  9. Invasive cervical cancer accompanied by IgG4-related disease.

    Science.gov (United States)

    Mizuno, Rin; Yamanishi, Yukio; Uda, Satoko; Terashima, Tsuyoshi; Higashi, Tatsuya; Higuchi, Toshihiro

    2016-09-01

    IgG4-related disease (IgG4-RD) is a systemic disease that affects multiple organs and generates nodules or thickening. Discriminating these diseases from malignancy is important because glucocorticoid treatment is effective for patients with IgG4-RD. Coexistence of IgG4-RD with various malignant diseases has been reported, but there are few reports with regard to gynecologic malignant diseases. We encountered a case of invasive cervical cancer stage IIB accompanied by IgG4-RD. The patient was a 46-year-old woman. On pelvic magnetic resonance imaging, fluorodeoxyglucose-positron emission tomography and computed tomography, systemic multiple lymph node swelling was seen, including in the neck and the mediastinum in addition to uterine cervix. Diagnosis (and hence, appropriate treatment choice) was achieved on pathology of the submandibular gland and uterus, and analysis of serum IgG4. IgG4-RD should be suspected in patients presenting with malignancy and unusual multiple lymph node swelling. © 2016 Japan Society of Obstetrics and Gynecology.

  10. Fine needle aspiration cytology of IgG4-related disease: A potential diagnostic pitfall?

    Science.gov (United States)

    Kaur, Rajwant; Mitra, Suvradeep; Rajwanshi, Arvind; Das, Ashim; Nahar Saikia, Uma; Dey, Pranab

    2017-01-01

    IgG4-related disease (IgG4-RD) is a tumefactive fibro-inflammatory lesion that can affect any organ system in the body. Till date, no cytological data on IgG4-RD are available and this is the first study depicting the cytopathology features of IgG4-RD. To describe the cytopathological features and potential diagnostic errors of IgG4-RD. The cytological features of 10 histopathology proven IgG4-RD cases (11 samples) were retrospectively reviewed along with corresponding histopathology. The cellularity of the cytology smears was low (36.4%) to moderate (45.4%) to high (18.1%). The low cellularity correlated well with the pattern C in histopathology (predominant fibrosis pattern). The non-epithelial background showed a preponderance of lymphocytes along with polymorphs and spindle-shaped fibroblasts. Most of these cases showed the presence of plasma cells and eosinophils. Epithelial atypia was seen in 18.2% cases. The causes of misdiagnosis were low cellularity, epithelial atypia, and non-representative background. The important diagnostic clues to suspect a diagnosis of IgG4-RD include low cellularity despite adequate effort, inflammatory background rich in lymphocytes and spindle cells admixed with a few plasma cells and eosinophils along with radiological features and raised serum IgG4 Diagn. Cytopathol. 2017;45:14-21. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  11. Multifocal fibrosclerosis and IgG4-related disease involving the cardiovascular system

    International Nuclear Information System (INIS)

    Ishizaka, Nobukazu; Terasaki, Fumio; Sakamoto, Aiko; Imai, Yasushi; Nagai, Ryozo

    2012-01-01

    The cardiovascular system may be involved as a target organ of multifocal fibrosclerosis, which may manifest as idiopathic retroperitoneal fibrosis, inflammatory aortic aneurysm, inflammatory periarteritis, and inflammatory pericarditis. These pathological conditions can sometimes occur concomitantly. Idiopathic retroperitoneal fibrosis and inflammatory abdominal aortic aneurysm are both characterized by the presence of fibro-inflammatory tissue around the abdominal aorta expanding into the surrounding retroperitoneal structures, and together they may be termed 'chronic periaortitis'. Cardiovascular fibrosclerosis has become non-uncommonly encountered condition since imaging modalities have made its diagnosis more feasible. In addition, recent studies have demonstrated that a certain fraction, but not all, of cardiovascular fibrosclerosis may have a link with immunoglobulin-G4 (IgG4)-related sclerosing disease (IgG4-SD). IgG4-SD is histologically characterized by dense fibrosclerosis and infiltration of lymphocytes and IgG4-positive plasma cells, and these histopathologic findings seem to be essentially similar regardless of the organs involved. In this mini review, we summarize what is known so far about multifocal fibrosclerosis of the cardiovascular system and its association with IgG4-SD, and what remains to be clarified in future investigations. (author)

  12. Utility of FDG PET/CT in IgG4-related systemic disease

    International Nuclear Information System (INIS)

    Nakatani, K.; Nakamoto, Y.; Togashi, K.

    2012-01-01

    IgG4-related systemic disease (IgG4-RSD) is an emerging clinical entity about which much remains to be elucidated, in terms of its aetiology, pathogenesis, diagnosis, treatment and outcome. Autoimmune pancreatitis (AIP) and Mikulicz disease (MD) are the two major, well-studied constituents of IgG4-RSD. AIP and MD have common characteristics of forming tumour-mimicking lesions that consist of lymphoplasmacytic infiltrates and fibrosclerosis with numerous immunoglobulin G4 (IgG4)-positive plasma cells, as well as various multi-organ manifestations of IgG4-RSD. 2-[ 18 F]-fluoro-2-deoxy-D-glucose positron-emission tomography/ computed tomography (FDG PET/CT) enables the acquisition of whole-body images and provides functional information about disease activity; as such it has a valuable role in staging extent of disease, guiding biopsy, and monitoring response to treatment. However, FDG PET/CT is likely to be only one component of the management strategy, and clinical, laboratory, imaging and histological findings are crucial in the overall diagnosis of the condition. At present FDG PET/CT does not have a well-established role in the assessment of patients with IgG4-RSD and future prospective studies are required to define the cost-effectiveness and clinical impact in this patient group more accurately.

  13. IgG4-related multiorgan disease: report of the first autopsy case.

    Science.gov (United States)

    Ochoa, Minerva Lazos; López, Belem Gabiño; Cabello, Raúl Romero; Feregrino, Raúl Romero

    2013-05-02

    IgG4-related disease (IgG4RD) is a chronic recurring fibro-inflammatory pathology that is considered to be of autoimmune origin. Histopathology is considered to be the gold standard method for diagnosis. IgG4RD affects multiple organs. IgG4RD was first identified in the pancreas and was called autoimmune pancreatitis (AIP). During the following years, the disease spectrum was expanded and it was realised that the extrapancreatic lesions can precede, coexist or appear after the diagnosis of AIP. At present, several illnesses such as Mikulicz disease, Küttner tumour, multifocal fibrosclerosis, etc, are considered to be part of the IgG4RD spectrum. The symptoms of the disease tend to appear over months and years and diagnosis is achieved on average 13.5 months (4-60 months) after the onset. The purpose of this report was to provide information about a case that was sadly fatal but that permitted a complete histopathological study of the damaged tissues.

  14. IgG4-related Mikulicz's disease associated with thyroiditis: a case report and review of the literature.

    Science.gov (United States)

    Zhang, Yujiao; Du, Yi; Li, Kaijun; He, Jianfeng

    2014-03-01

    To report an unusual case of IgG4-related Mikulicz's disease associated with thyroiditis. We describe a 25-year-old Chinese man who presented with bilateral, painless swellings of the lachrymal glands, parotid glands, and thyroid nodules. The patient underwent left-sided dacryoadenectomy and the diagnosis of IgG4-related Mikulicz's disease was pathologically confirmed. The size of the right-sided lachrymal gland and parotid glands recovered fundamentally after one month of glucocorticoid therapy. IgG4-related Mikulicz's disease associated with thyroiditis should be considered in the differential diagnosis of bilateral swellings of lachrymal glands, salivary glands, and thyroid nodules. Surgical excision is recommended in order to treat the tumor and to ensure the pathological diagnosis. Glucocorticoid therapy should be considered in association with surgery after removal.

  15. Riedel's thyroiditis and multifocal fibrosclerosis are part of the IgG4-related systemic disease spectrum.

    Science.gov (United States)

    Dahlgren, Mollie; Khosroshahi, Arezou; Nielsen, G Petur; Deshpande, Vikram; Stone, John H

    2010-09-01

    Riedel's thyroiditis is a chronic fibrosing disorder of unknown etiology often associated with "multifocal fibrosclerosis." IgG4-related systemic disease is characterized by IgG4+ plasma cell infiltration and fibrosis throughout many organs. We hypothesized that Riedel's thyroiditis is part of the IgG4-related systemic disease spectrum. We searched our institution's pathology database using the terms "Riedel's," "struma," "thyroid," and "fibrosis," and identified 3 cases of Riedel's thyroiditis. Riedel's thyroiditis was diagnosed if there was a fibroinflammatory process involving all or a portion of the thyroid gland, with evidence of extension of the process into surrounding tissues. Immunohistochemical stains for IgG4 and IgG were performed. The histopathologic and immunohistochemical features of each involved organ were evaluated. The clinical features of one patient with multiple organ system disease were described. All 3 thyroidectomy samples stained positively for IgG4-bearing plasma cells. One patient had extensive extrathyroidal involvement diagnostic of IgG4-related systemic disease, including cholangitis, pseudotumors of both the lung and lacrimal gland, and a lymph node contiguous to the thyroid that stained intensely for IgG4+ plasma cells. The histologic features of all organs involved were consistent with IgG4-related systemic disease. Patient 3 had 10 IgG4+ plasma cells per high-power field initially, but rebiopsy 2 years later demonstrated no IgG4+ plasma cells. That patient's second biopsy, characterized by fibrosis and minimal residual inflammation, further solidifies the link between IgG4-bearing plasma cells in tissue and the histologic evolution to Riedel's thyroiditis. Riedel's thyroiditis is part of the IgG4-related systemic disease spectrum. In many cases, multifocal fibrosclerosis and IgG4-related systemic disease are probably the same entity.

  16. Steroid-responsive IgG4-related disease with isolated prostatic involvement: An unusual presentation with elevated serum PSA

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    Vikas Jain

    2016-01-01

    Full Text Available Autoimmune prostatitis is known to occur as a part of multisystem fibro-inflammatory disorder known as IgG4 related disease (IgG4 RD. The usual presentation is with symptoms of gastro-intestinal disease with prostatic involvement presenting as lower urinary tract symptoms. The disease responds to corticosteroids. We report an asymptomatic young man who was diagnosed to have IgG4 related prostatitis on TRUS-guided prostate biopsy done for elevated serum PSA, in the absence of any other systemic involvement. The treatment with steroid resulted in normalization of S PSA levels.

  17. IgG4-related Hashimoto’s thyroiditis – A new variant of a well known disease

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    Luiz, Henrique Vara; Gonçalves, Diogo; Silva, Tiago Nunes da; Nascimento, Isabel; Ribeiro, Ana; Mafra, Manuela; Manita, Isabel; Portugal, Jorge

    2014-01-01

    Hashimoto’s thyroiditis (HT) has been characterized for many years as a well-defined clinicopathologic entity, but is now considered a heterogeneous disease. IgG4-related HT is a new subtype characterized by thyroid inflammation rich in IgG4-positive plasma cells and marked fibrosis. It may be part of the systemic IgG4-related disease. We report a case of a 56-year-old Portuguese man who presented with a one-month history of progressive neck swelling and dysphagia. Laboratory testing revealed...

  18. Histopathologic Overlap between Fibrosing Mediastinitis and IgG4-Related Disease

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    Tobias Peikert

    2012-01-01

    Full Text Available Fibrosing mediastinitis (FM and IgG4-related disease (IgG4-RD are two fibroinflammatory disorders with potentially overlapping clinical and radiological features. In this paper, we looked for histopathologic features of IgG4-RD and enumerated infiltrating IgG4-positive plasma cells within mediastinal tissue biopsies from FM patients. We identified 15 consecutive FM surgical mediastinal tissue biopsies between 1985 and 2006. All patients satisfied the clinical and radiological diagnostic criteria for FM. All patients had either serological or radiological evidence of prior histoplasmosis or granulomatous disease, respectively. Formalin-fixed paraffin-embedded tissue sections of all patients were stained for H&E, IgG, and IgG4. Three samples met the predefined diagnostic criteria for IgG4-RD. In addition, characteristic histopathologic changes of IgG4-RD in the absence of diagnostic numbers of tissue infiltrating IgG4-positive plasma cells were seen in a number of additional cases (storiform cell-rich fibrosis in 11 cases, lymphoplasmacytic infiltrate in 7 cases, and obliterative phlebitis/arteritis in 2 cases. We conclude that up to one-third of histoplasmosis or granulomatous-disease-associated FM cases demonstrate histopathological features of IgG4-RD spectrum. Whether these changes occur as the host immune response against Histoplasma or represent a manifestation of IgG4-RD remains to be determined. Studies to prospectively identify these cases and evaluate their therapeutic responses to glucocorticoids and/or other immunosuppressive agents such as rituximab are warranted.

  19. IgG4-related disease-experience of 100 consecutive cases from a specialist centre.

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    Bateman, Adrian C; Culver, Emma L

    2017-04-01

    To describe the features of 100 consecutive cases referred to a single UK institution in which a diagnosis of IgG4-related disease (IgG4-RD) was under consideration. The histological features were reviewed by a single histopathologist, and cases were categorized according to the 2012 Boston criteria: Category 1-histologically highly suggestive of IgG4-RD; Category 2-probable histopathological features of IgG4-RD; and Category 3-insufficient histopathological evidence of IgG4-RD. A 'global assessment' was performed with the available clinical information: Assessment group 1-'definite/very likely IgG4-RD'; Assessment group 2-'possible IgG4-RD'; Assessment group 3-'not IgG4-RD'; and Assessment group 4-insufficient information. The mean IgG4+ plasma cell count and IgG4+/IgG+ ratio were highest in Category 1 [134/high-power field (HPF); 57%] and Assessment group 1 (113/HPF; 52%), and lowest in Category 3 (11/HPF; 18%) and Assessment group 3 (43/HPF; 31%) (Category comparison of IgG4+ count and ratio, both P IgG4+ count, P IgG4-RD diagnosis was rare in Category 1 (7%) but common in Category 2 (60%) and Category 3 (47%). Stromal reactions to neoplasia and chronic oral ulceration were simulants of IgG4-RD. The Boston criteria are linked to the likelihood of IgG4-RD. Other conditions may show some histological features of IgG4-RD. The likelihood of IgG4-RD is much greater when the histological features reach the threshold for Category 1 than when they reach the thresholds for Categories 2 and 3. Despite the utility of the Boston criteria, this study highlights the crucial importance of careful clinicopathological correlation when a diagnosis of IgG4-RD is under consideration. © 2016 John Wiley & Sons Ltd.

  20. Prohibitin Is Involved in Patients with IgG4 Related Disease.

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    Hongwu Du

    Full Text Available IgG4-related disease (IgG4-RD is a chronic systemic disease involved in many organs and tissues. As only limited autoantigens have been found since the beginning of this century, the aim of this study was to reveal new candidate autoantigens of IgG4-RD.Multiple cell lines including HT-29, EA.hy926, HEK 293 and HepG2 were used to test the binding ability of circulating autoantibodies from IgG4-RD sera. The amino-acid sequence was then analyzed by matrix-assisted laser desorption/ionization time-of-flight tandem (MALDI-TOF/TOF mass spectrometry. After the cloning and expression of recombinant putative autoantigen in a bacterial expression system, the corresponding immuno assay was set up and utilized to observe the prevalence of serum autoantibodies in a large set of confirmed clinical samples.One positive autoantigen was identified as prohibitin. ELISA analysis showed that a majority of patients with IgG4-RD have antibodies against prohibitin. Anti-prohibitin antibodies were present in the sera of patients with definite autoimmune pancreatitis (25/34; 73.5%, Mikulicz's disease (8/15; 53.3%, retroperitoneal fibrosis (6/11; 54.5%, other probable IgG4-RD (26/29; 89.7% and Sjögren's syndrome (4/30; 13.3% but not in apparently healthy donors (1/70; 1.4%.An association between prohibitin and patients with some IgG4-RD was observed, although the results were quite heterogeneous among different individuals within autoimmune pancreatitis, Mikulicz's disease and retroperitoneal fibrosis.

  1. IgG4-related disease of the biliary tract and pancreas: clinical and experimental advances.

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    Hubers, Lowiek M; Beuers, Ulrich

    2017-07-01

    IgG4-related disease (IgG4-RD) is an immune-mediated disease of unknown cause. It predominantly affects the biliary tract [IgG4-associated cholangitis (IAC)] and pancreas [autoimmune pancreatitis (AIP)] of mostly elderly men. Accurate diagnostic tests are lacking. Patients benefit from predniso(lo)ne treatment. However, disease relapse is often seen. This review will address pathophysiological aspects and advances in diagnostic and therapeutic strategies. The role of IgG1 and IgG4 in the pathophysiology of IgG4-RD was studied in mice which showed more intense organ damage of pancreas and salivary glands when IgG1 rather than IgG4 of patients with IgG4-RD was injected. Coadministration of IgG1+IgG4 led to dampening of IgG1-mediated injury supporting the view that IgG4 exerts immune-dampening effects. IgG4+ B-cell receptor clones identified by next-generation sequencing and the IgG4/IgG RNA ratio in human blood assessed by quantitative PCR were able to accurately distinguish IAC/AIP from primary sclerosing cholangitis or pancreatobiliary malignancies. Long-term treatment with low-dose prednisolone was safe and reduced the number of flare-ups in patients with AIP. Early diagnosis by a novel accurate and easy-to-use qPCR test may prevent life-threatening complications, unnecessary interventions and fatal course because of misdiagnosis. Prednisolone treatment remains the standard of care in patients with IgG4-RD.

  2. IgG4-related disease and lymphocyte-variant hypereosinophilic syndrome: A comparative case series.

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    Carruthers, Mollie N; Park, Sujin; Slack, Graham W; Dalal, Bakul I; Skinnider, Brian F; Schaeffer, David F; Dutz, Jan P; Law, Joanna K; Donnellan, Fergal; Marquez, Vladimir; Seidman, Michael; Wong, Patrick C; Mattman, Andre; Chen, Luke Y C

    2017-04-01

    To compare the clinical and laboratory features of IgG4-related disease (IgG4-RD) and lymphocyte-variant hypereosinophilic syndrome (L-HES), two rare diseases that often present with lymphadenopathy, gastrointestinal symptoms, eosinophilia, and elevated immunoglobulins/IgE. Comparative case series of 31 patients with IgG4-RD and 13 patients with L-HES. Peripheral blood eosinophilia was present in eight of 31 patients with IgG4-RD compared to 13 of 13 patients with L-HES (median eosinophils 0.4 vs 7.0 giga/L, P=.001) and 12 of 20 patients with IgG4-RD had increased serum IgE compared to eight of 13 patients with L-HES, P=.930. Twenty-seven of 30 patients with IgG4-RD had elevated serum IgG4 compared to five of 12 patients with L-HES (median IgG4 9.6 g/L vs 0.80 g/L, P=.002). Flow cytometry demonstrated an aberrant T-cell phenotype in 7 of 23 patients with IgG4-RD and 13 of 13 patients with L-HES (PIgG4-RD vs 10 of 13 patients with L-HES (P=.143). Patients in both groups received corticosteroids as first-line therapy. For refractory disease in IgG4-RD, rituximab was the most common steroid-sparing agent, whereas in L-HES, it was pegylated interferon-α-2a. The overlapping features of these two diseases with divergent treatment options demonstrate the importance of familiarity with both entities to optimize diagnosis and treatment. © 2016 The Authors. European Journal of Haematology Published by John Wiley & Sons Ltd.

  3. Deconstructing IgG4-related disease involvement of midline structures: Comparison to common mimickers.

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    Lanzillotta, Marco; Campochiaro, Corrado; Trimarchi, Matteo; Arrigoni, Gianluigi; Gerevini, Simonetta; Milani, Raffaella; Bozzolo, Enrica; Biafora, Matteo; Venturini, Elena; Cicalese, Maria Pia; Stone, John H; Sabbadini, Maria Grazia; Della-Torre, Emanuel

    2017-07-01

    A series of destructive and tumefactive lesions of the midline structures have been recently added to the spectrum of IgG4-related disease (IgG4-RD). We examined the clinical, serological, endoscopic, radiological, and histological features that might be of utility in distinguishing IgG4-RD from other forms of inflammatory conditions with the potential to involve the sinonasal area and the oral cavity. We studied 11 consecutive patients with erosive and/or tumefactive lesions of the midline structures referred to our tertiary care center. All patients underwent serum IgG4 measurement, flow cytometry for circulating plasmablast counts, nasal endoscopy, radiological studies, and histological evaluation of tissue specimens. The histological studies included immunostaining studies to assess the number of IgG4 + plasma cells/HPF for calculation of the IgG4+/IgG + plasma cell ratio. Five patients with granulomatosis with polyangiitis (GPA), three with cocaine-induced midline destructive lesions (CIMDL), and three with IgG4-RD were studied. We found no clinical, endoscopic, or radiological findings specific for IgG4-RD. Increased serum IgG4 and plasmablasts levels were not specific for IgG4-RD. Rather, all 11 patients had elevated blood plasmablast concentrations, and several patients with GPA and CIMDL had elevated serum IgG4 levels. Storiform fibrosis and an IgG4+/IgG + plasma cell ratio >20% on histological examination, however, were observed only in patients with IgG4-RD. Histological examination of bioptic samples from the sinonasal area and oral cavity represents the mainstay for the diagnosis of IgG4-RD involvement of the midline structures.

  4. Pathogenicity of IgG in patients with IgG4-related disease.

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    Shiokawa, Masahiro; Kodama, Yuzo; Kuriyama, Katsutoshi; Yoshimura, Kenichi; Tomono, Teruko; Morita, Toshihiro; Kakiuchi, Nobuyuki; Matsumori, Tomoaki; Mima, Atsushi; Nishikawa, Yoshihiro; Ueda, Tatsuki; Tsuda, Motoyuki; Yamauchi, Yuki; Minami, Ryuki; Sakuma, Yojiro; Ota, Yuji; Maruno, Takahisa; Kurita, Akira; Sawai, Yugo; Tsuji, Yoshihisa; Uza, Norimitsu; Matsumura, Kazuyoshi; Watanabe, Tomohiro; Notohara, Kenji; Tsuruyama, Tatsuaki; Seno, Hiroshi; Chiba, Tsutomu

    2016-08-01

    IgG4-related disease (IgG4-RD) is a systemic disease characterised by elevated serum IgG4 and IgG4-positive lymphoplasmacytic infiltration in the affected tissues. The pathogenic role of IgGs, including IgG4, in patients with IgG4-RD, however, is unknown. We examined the pathogenic activity of circulating IgGs in patients with IgG4-RD by injecting their IgGs into neonatal male Balb/c mice. Binding of patient IgGs to pancreatic tissue was also analysed in an ex vivo mouse organ culture model and in tissue samples from patients with autoimmune pancreatitis (AIP). Subcutaneous injection of patient IgG, but not control IgG, resulted in pancreatic and salivary gland injuries. Pancreatic injury was also induced by injecting patient IgG1 or IgG4, with more destructive changes induced by IgG1 than by IgG4. The potent pathogenic activity of patient IgG1 was significantly inhibited by simultaneous injection of patient IgG4. Binding of patient IgG, especially IgG1 and IgG4, to pancreatic tissue was confirmed in both the mouse model and AIP tissue samples. IgG1 and IgG4 from patients with IgG4-RD have pathogenic activities through binding affected tissues in neonatal mice. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  5. Clinical pathology observation on orbit IgG4 related disease

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    Ji-Hua Guo

    2015-09-01

    Full Text Available AIM:To discuss clinical pathological features of orbit IgG4 related disease(IgG4-RD. METHODS: The clinical pathological materials of 23 patients(35 eyeswith orbit IgG4-RD were collected. They were observed in terms of histology and immunohistochemistry, and its clinical and pathologic characteristics were summarized. RESULTS: There were 23 patients(35 eyeswith orbit IgG4-RD(8 male patients, 9 eyes; 15 female patients, 26 eyes, with an average age of 52.1 year-old(from age 28 to 72. 19 patients(30 eyesoccured in lacrimal gland and 4 cases(5 eyesin other places, and they went to hospital for lacrimal gland cyst or exophthalmos. There were 11 cases in one side and 12 cases in both sides. The disease lasted from 1mo to 10a, averaging 27mo. It recureded in one patient(1 eyeafter 1mo. In general inspection: Gray nodular goiter, thin fibrous coat wrapping around the lacrimal gland could be observed. Histologic characteristics: lacrimal gland bubble and catheter group shrinked or even disappeared, substituted by lymphocyte, plasma cells and lymphoid follicle and accompanied with fibrosis. Immunohistochemical staining: IgG4 positive plasma cells of 23 cases(35 eyeswas >50/HPF, and IgG4/IgG ratio of positive plasma cells was >40%. CONCLUSION: Orbit IgG4-RD mainly occures in lacrimal gland tissue, and expression of IgG4 can be detected through histologic characteristics and immunohistochemical staining. IgG4-RD should be screened, prevented and treated in the early phase.

  6. IgG4-producing lymphoma arising in a patient with IgG4-related disease.

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    Igawa, Takuro; Hayashi, Toshiaki; Ishiguro, Kazuya; Maruyama, Yumiko; Takeuchi, Mai; Takata, Katsuyoshi; Yoshino, Tadashi; Sato, Yasuharu

    2016-12-01

    We herein report a case in which an IgG4-producing lymphoma arose in a patient with a previous diagnosis consistent with an IgG4-related disease. A 43-year-old man presented with enlarged cervical lymph nodes and was treated with steroids and radiation for what was initially assumed to be Kimura's disease, although the lesions were later histologically re-diagnosed as IgG4-related lymphadenopathy. Fourteen years later, when the patient was 58-years-old, he presented with retroperitoneal fibrosis and swollen lymph nodes. The suspicious lesions were not histologically examined as the patient did not give consent. However, the serum IgG4 concentration was high (1400 mg/dL) and he was clinically diagnosed with systemic IgG4-related disease. Although steroid administration reduced the size of the lesions, tapering the dose finally resulted in systemic, prominently enlarged lymph nodes. Analysis of the biopsy specimen revealed that these multiple lymph node lesions were marginal zone B cell lymphomas that themselves expressed IgG4. Complete remission was achieved after a total of six courses of chemotherapy including rituximab. This case suggests that the infiltrating IgG4-expressing cells observed in IgG4-related disease can clonally expand to malignant lymphomas.

  7. [IgG4-related lung disease: analysis of 8 cases and literature review].

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    Han, G J; Hu, H; Mao, D; Bai, X; She, D Y; Zhao, S F; Wen, Z L; Gao, J

    2017-03-12

    Objective: To improve the understanding and treatment of IgG4-related lung disease (IgG4-RLD). Methods: The clinical characteristics, serum IgG4 levels, pathological features, chest CT, therapy and prognosis of 8 patients with IgG4-RLD were retrospectively analyzed. These patients were admitted to the People's Liberation Army General Hospital and the pathological diagnosis was made between December 2005 and March 2016. Relevant literatures were reviewed. Results: The 8 patients with IgG4-RLD included 4 men and 4 women, with an average age of (59±4) years (range, 37-74). The respiratory symptoms included shortness of breath, cough, and expectoration. Extra-pulmonary symptoms included abdominal pain, facial edema, and fever. Extrapulmonary organs were involved in 7 cases. Serum IgG4 levels were elevated in 8 cases, with an average concentration of(17±6)g/L. Chest CT showed solid lung nodules in 6, alveolar-interstitial infiltration in 5, bronchovascular lesions in 3 and ground glass shadows in 2 cases. PET/CT was performed in 2 cases and it showed multiple organ involvement with higher radioactivity uptake(SUVmax2.9-4.2). The pathological examination found lymphocyte and plasma cell infiltration in 7, fibrous tissue hyperplasia in 5, and occlusive vasculitis in 2 cases. On immunohistochemical staining, the ratio of IgG4-positive plasma cells to IgG-positive plasma cells was higher than 40%in 3 cases. The number of IgG4-positive plasma cells was 10-50/HP in 8 cases. The misdiagnosis rate was 100% before the final diagnosis was made. Three cases received glucocorticoids with immunosuppressant therapy, 2 received surgery combined with glucocorticoid therapy, 2 received glucocorticoid therapy alone, and 1 only received surgery. The follow-up time was 4-132 months, with remission in 7 cases, and disease progression in 1 case, but no death. A total of 195 cases of IgG4-RLD were reviewed from the literature, among whom 111 cases were admitted with respiratory symptoms, 144 with extra-pulmonary involvement. Serum IgG4 levels were detected in 179 cases, with an average concentration of 5.408 g/L. The nodular type was predominant, accounting for 36.9%. Of these cases, 178 received glucocorticoid treatment with disease remission. Conclusions: The major clinical manifestations of IgG4-RLD were shortness of breath, cough and expectoration. Multiple organ lesions were common. The misdiagnosis rate was extremely high. The diagnosis could be made based on pathological features and IgG4 serum levels . Glucocorticoid treatment was effective.

  8. IgG4-related Hypophysitis with Subtle Hypopituitarism in an Elderly Diabetic Patient: Is Treatment or Observation Preferable?

    Science.gov (United States)

    Kawasaki, Motoki; Tsujino, Motoyoshi; Sato, Fuminori; Sakurada, Maya; Nishida, Kenji; Kise, Takayasu; Hijioka, Yuko; Ishizawa, Mitsugu; Enatsu, Kazuaki; Ogawa, Yoshihiro

    2017-10-15

    A 70-year-old man with diabetes mellitus presented with an enlarged pituitary stalk in 2014. IgG4-related parotitis and submandibular sialoadenitis were diagnosed in 2012. He denied any symptoms related to a pituitary mass. His visual field was intact, and his hypopituitarism was subtle. The serum IgG4 level was elevated. A lip biopsy revealed strong fibrosis and hyper-infiltration of IgG4-positive plasma cells. Based on these findings, IgG4-related hypophysitis was diagnosed. The patient was carefully followed without specific intervention. His clinical condition showed no change until December 2016, suggesting a stable, natural course. Care should be taken when considering glucocorticoid therapy, especially for elderly diabetic patients, given possible side effects.

  9. Sjögren’s syndrome versus IgG4-related diseases – classification difficulties and treatment progress

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    Anna Nowakowska-Płaza

    2014-09-01

    Full Text Available Sjögren’s syndrome (SS is a chronic autoimmune disorder characterized by lymphocytic infiltration in exocrine glands mainly salivary and lacrimal which affects impairment of their functions. Some patients develop extraglandular symptoms such as chronic fatigue, arthralgia, or lung, renal, central or peripheral nervous system involvement. Recent decades have brought understanding of some pathogenetic mechanisms and offered new therapeutic options by depleting B cells. Furthermore, the American College of Rheumatology proposed a new set of classification criteria based on objective symptoms. IgG4-related diseases are new nosological entities. The clinical course similarities of SS to Mikulicz’s disease (a subtype of IgG4-related disease result in diagnostic difficulties. Typical conditions of them are: an increased IgG4 level and infiltrations of parenchymal organs by plasmatic cells. This review summarizes classification difficulties, pathogenesis and treatment strategies of SS and IgG4-related diseases.

  10. IgG4 plasma cell myeloma: new insights into the pathogenesis of IgG4-related disease.

    Science.gov (United States)

    Geyer, Julia T; Niesvizky, Ruben; Jayabalan, David S; Mathew, Susan; Subramaniyam, Shivakumar; Geyer, Alexander I; Orazi, Attilio; Ely, Scott A

    2014-03-01

    IgG4-related disease is a newly described systemic fibroinflammatory process, characterized by increase in IgG4-positive plasma cells. Its pathogenesis, including the role of IgG4, remains poorly understood. Plasma cell myeloma is typically associated with a large monoclonal serum spike, which is frequently of IgG isotype. We sought to identify and characterize a subset of IgG4-secreting myeloma, as it may provide a biological model of disease with high serum levels of IgG4. Six out of 158 bone marrow biopsies (4%) from patients with IgG myeloma expressed IgG4. Four patients were men and two were women, with a mean age of 64 (range 53-87) years. Imaging showed fullness of pancreatic head (1), small non-metabolic lymphadenopathy (1), and bone lytic lesions (6). Two patients developed necrotizing fasciitis. All had elevated serum M-protein (mean 2.4, range 0.5-4.2 g/dl), and none had definite signs or symptoms of IgG4-related disease. Four myelomas had plasmablastic morphology. Four had kappa and two had lambda light chain expression. Three cases expressed CD56. Two patients had a complex karyotype. In conclusion, the frequency of IgG4 myeloma correlates with the normal distribution of IgG4 isoform. The patients with IgG4 myeloma appear to have a high rate of plasmablastic morphology and could be predisposed to necrotizing fasciitis. Despite high serum levels of IgG4, none had evidence of IgG4-related disease. These findings suggest that the increased number of IgG4-positive plasma cells is not the primary etiologic agent in IgG4-related disease. Elevated serum levels of IgG4 is not sufficient to produce the typical disease presentation and should not be considered diagnostic of IgG4-related disease.

  11. IgG4-related disease in thymus. A very rare case of chronic fibrosis mimicking sarcoidosis.

    Science.gov (United States)

    Simonetti, Sara; Pérez Muñoz, Noelia; López Vivancos, Josefa; Sanchez Sitjes, Lluís; Herranz Pérez, Javier Cesar; Leal Bohorquez, Nelson; Maestre Alcacer, José Antonio; de García, Inessa Koptseva; Carrasco García, Miguel Ángel

    2017-11-15

    IgG4-related disease (IgG4-RD) is a multi-organ immune-mediated chronic fibroinflammatory condition, with unclear certain etiology. It is morphologically characterized by storiform fibrosis, dense IgG4-positive lymphoplasmacytic infiltrate, and obliterative phlebitis. It was recognized as a systemic condition as recently as 2003. IgG4-RD has been described in virtually every organ, forming sclerosing masses, and often mimicking tumors. Clinically, patients present unspecific symptoms and this condition is often recognized incidentally. The epidemiology remains poorly studied, but it has been noted that in the majority of recorded instances, patients are middle-aged men. IgG4-RD could mimic conditions other than tumors, such as infection, inflammation, or other systemic disorders. To ensure accuracy of diagnosis, an exhaustive histopathological analysis is required, together with clinical, radiological, and serological data. Thymic fibrosis in the absence of other primary thymic lesions is a very rare occurrence; in English literature only 1 case has been reported with scattered IgG4 plasma cells infiltrate and focal obliterative phlebitis. We will describe, for the first time, the case of a 49-year-old man displaying an anterior mediastinic, hilar, and intramyocardial mass simulating a sarcoidosis, with a definitive diagnosis of IgG4-related thymic fibrosis extending to the mediastinum and the heart. At the histological examination, we found many features of IgG4-RD in the thymic tissue, such as diffused storiform fibrosis, dense lymphoplasmacytic infiltrate with abundant plasma cells IgG4 positive (ratio IgG/IgG4: 40%), obliterative phlebitis, eosinophilic infiltrate, and Castleman-like lymphoid follicles. We discussed the differential diagnosis and reviewed the literature and the other cases of IgG4-related diseases that had been diagnosed in our department.

  12. High Expression of Galectin-3 in Patients with IgG4-Related Disease: A Proteomic Approach

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    Adeeb Salah

    2017-01-01

    Full Text Available Objectives. Immunoglobulin G4-related disease (IgG4-RD is a multiorgan condition manifesting itself in different forms. This study aimed to investigate protein expression profiles and to find the possible biomarker for IgG4-RD by liquid chromatography mass spectrometry (LC-MS using tissue sections in IgG4-RD patients. Methods. Protein expression profiles in five IgG4-related pancreatitis and three normal pancreatic samples were compared using LC-MS and were validated by quantitative real-time PCR (qRT-PCR, immunoblotting, and immunohistochemistry. ELISA was employed in the serum of 20 patients with systemic IgG4-RD before and during steroid treatment. Results. LC-MS indicated that the levels of 17 proteins were significantly higher and 12 others were significantly lower in IgG4-related pancreatitis patients compared to controls. Among these proteins, galectin-3 levels were 13-fold higher in IgG4-related pancreatitis (P<0.01. These results were confirmed by immunoblotting and qRT-PCR. The average number of galectin-3 + cells in various organs of IgG4-RD patients, including salivary glands, lungs, and lymph nodes, was higher than in controls. Galectin-3 was detectable in macrophages, dendritic cells, and stromal myofibroblast-like cells, but not in lymphocytes by immunofluorescence staining. Serum galectin-3 levels were higher in patients with IgG4-RD compared with healthy donors and remained high during steroid therapy. Conclusion. Galectin-3 was overexpressed in IgG4-RD and the levels were indirectly related to clinical activity.

  13. An IgG4-Related Salivary Gland Disorder: A Case Series Presenting with a Different Clinical Setting

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    Masayuki Ishida

    2011-01-01

    Full Text Available Küttner tumor is a chronic inflammatory disease that presents with a firm swelling of the submandibular gland and often mimics a neoplasm. Recently evidence suggests that Küttner tumor may be a type of disorder characterized by IgG4-related inflammations. Herein, we report 3 cases of submandibular gland swellings with severe fibrosis, inflammation with marked lymphoplasmacytic infiltration; this pathology mimics clinical manifestation of a malignant tumor in 18-fluorodeoxyglucose positron emission tomography (FDG-PET findings.

  14. IgG4-related lung disease presenting as interstitial lung disease with bronchiolitis: A case report.

    Science.gov (United States)

    Chen, Chiu-Fan; Chu, Kuo-An; Tseng, Yen-Chiang; Wu, Chang-Che; Lai, Ruay-Sheng

    2017-12-01

    IgG4-related disease is a rare and novel disease entity that tends to involve multiple organs. The pulmonary manifestation of this disease is highly variable and may mimic lung cancer, pneumonia, interstitial lung disease (ILD), sarcoidosis, and so forth. Small airway disease is rarely reported in IgG4-related lung disease (IgG4-RLD). In the current study, we describe a rare case of IgG4-RLD with patterns of ILD and bronchiolitis. A 43-year-old man had chronic cough and dyspnea on exertion for 4 years. Initial chest radiography showed diffuse interstitial infiltration. Follow-up chest computed tomography 4 years later revealed bilateral diffuse centrilobular nodules with tree-in-bud pattern, bronchial wall thickening, and mediastinal lymph nodes. Bilateral diffuse multifocal ground-glass opacities and mosaic attenuation were also observed. Pulmonary function test revealed mixed restrictive and obstructive ventilatory impairment. Video-assisted thoracoscopic surgery (VATS) lung biopsy showed interstitial fibrosis with lymphoplasmacytic infiltration rich in IgG4-positive plasma cells. Serum IgG4 level also showed remarkable elevation. Therefore, IgG4-RLD is confirmed. VATS wedge resection of right upper lobe and mediastinal lymph node. The patient responded well to steroid and immunosuppression therapy, and was regular followed-up in outpatient clinic. IgG4-RLD should be considered not only in ILD, but also in small airway disease. Serum IgG4 level may be a useful tool for screening.

  15. Early Prediction of Lupus Nephritis Using Advanced Proteomics

    Science.gov (United States)

    2012-06-01

    Gupta IR . Evaluation of activity, chronicity and tubulointerstitial indices for childhood lupus nephritis. Pediatr Nephrol 2008;23:83–91. 34. Isenberg DA...University of Okla- homa Health Sciences Center, Oklahoma City: Drs. Michael Hen- drickson and James N. Jarvis (data collection); Tracy Fuelling...Duffy CM, Bernard C, Gupta IR : Evaluation of activity, chronicity and tubulointerstitial indices for childhood lupus nephritis. Pediatr Nephrol 2008

  16. Solely lung-involved IgG4-related disease : a case report and review of the literature.

    Science.gov (United States)

    Zhang, Xiao-Qin; Chen, Guo-Ping; Wu, Sheng-Chang; Yu, Sa; Wang, Hong; Chen, Xuan-Yi; Ren, Zhuo-Chao

    2016-12-23

    By analyzing the clinical data of 1 case of IgG4-related lung disease(IgG4-RLD) and the review of literature, the author investigated the clinical characteristics of IgG4-RLD. IgG4-RLD is a rare disease characterized by significant elevation of serum IgG4 and infiltration of a large number of IgG4+ plasma cells. The clinical manifestations of the disease were nonspecific, and the imaging features were mixed with several types. The disease can only be involved in the lung, but also multiple organ involvement. Solely lung-involved IgG4-RD is not only extremely rare but also easily misdiagnosed as tuberculosis, lung cancer, lymphoma and other common pulmonary diseases. Histopathological examination is the key to the diagnosis of the disease. Corticosteroids are the first choice of treatment, and the overall prognosis is good.

  17. IgG4-related disease and its pathogenesis—cross-talk between innate and acquired immunity

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    Nakajima, Akio; Nakamura, Takuji; Kawanami, Takafumi; Tanaka, Masao; Dong, Lingli; Kawano, Mitsuhiro

    2014-01-01

    IgG4-related disease (IgG4-RD) is a novel clinical entity proposed in Japan in the 21th century and is attracting strong attention over the world. The characteristic manifestations of IgG4-RD are increased serum IgG4 concentration and tumefaction by IgG4+ plasma cells. Although the clinical manifestations in various organs have been established, the pathogenesis of IgG4-RD is still unknown. Recently, many reports of aberrant acquired immunity such as Th2-diminated immune responses have been published. However, many questions still remain, including questions about the pathogenesis of IgG4-RD and the roles of IgG4. In this review, we discuss the pathogenesis of IgG4-RD by focusing on the cross-talk between innate and acquired immunity. PMID:25024397

  18. IgG4-Related Disease Combined with Autoimmune Hemolytic Anemia and Steroid-Responsive Transient Hypercalcemia

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    Sho Hasegawa

    2015-01-01

    Full Text Available A 67-year-old man with elevated serum immunoglobulin G4 (IgG4 levels, systemic lymphadenopathy infiltrated by IgG4-positive plasma cells, and Coombs-positive autoimmune hemolytic anemia (AIHA showed marked hypercalcemia. Although the intact parathyroid hormone (PTH level was elevated, 99mTc-MIBI scintigraphy and thyroid ultrasonography revealed no evidence of primary hyperparathyroidism. Liver biopsy showed marked infiltration of IgG4-positive plasma cells, which confirmed the diagnosis of IgG4-related disease (IgG4-RD. Corticosteroid therapy was initiated, and subsequently, intact PTH and serum calcium levels gradually normalized. Transient hypercalcemia in a patient with AIHA may therefore be associated with IgG4-RD.

  19. The prevalence of IgG4-related hypophysitis in 170 consecutive patients with hypopituitarism and/or central diabetes insipidus and review of the literature.

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    Bando, Hironori; Iguchi, Genzo; Fukuoka, Hidenori; Taniguchi, Masaaki; Yamamoto, Masaaki; Matsumoto, Ryusaku; Suda, Kentaro; Nishizawa, Hitoshi; Takahashi, Michiko; Kohmura, Eiji; Takahashi, Yutaka

    2014-02-01

    The prevalence and clinical characteristics of IgG4-related hypophysitis remain unclear due to the limited number of case reports. Therefore, in this study, we screened consecutive outpatients with hypopituitarism and/or diabetes insipidus (DI) to estimate its prevalence. A total of 170 consecutive outpatients with hypopituitarism and/or central DI were screened at Kobe University Hospital for detecting IgG4-related hypophysitis by pituitary magnetic resonance imaging, measuring serum IgG4 concentrations, assessing the involvement of other organs, and carrying out an immunohistochemical analysis to detect IgG4-positive cell infiltration. Among the screened cases, 116 cases were excluded due to diagnosis of other causes such as tumors and congenital abnormalities. Additionally, 22 cases with isolated ACTH deficiency were analyzed and were found not to meet the criteria of IgG4-related hypophysitis. The remaining 32 cases were screened and seven were diagnosed with IgG4-related hypophysitis, of which three cases were diagnosed by analyzing pituitary specimens. IgG4-related hypophysitis was detected in 30% (seven of 23 patients) of hypophysitis cases and 4% of all hypopituitarism/DI cases. The mean age at the onset of IgG4-related hypophysitis was 61.8±8.8 years, and the serum IgG4 concentration was 191.1±78.3 mg/dl (normal values 5-105 mg/dl and values in IgG4-related disease (RD) ≥135 mg/dl). Pituitary gland and/or stalk swelling was observed in six patients, and an empty sella was observed in one patient. Multiple co-existing organ involvement was observed in four of the seven patients prior to the onset of IgG4-related hypophysitis. These data suggest that the prevalence of IgG4-related hypophysitis has been underestimated. We should also consider the possibility of the development of hypopituitarism/DI caused by IgG4-related hypophysitis during the clinical course of other IgG4-RDs.

  20. Cutoff Values of Serum IgG4 and Histopathological IgG4+ Plasma Cells for Diagnosis of Patients with IgG4-Related Disease

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    Yasufumi Masaki

    2012-01-01

    Full Text Available IgG4-related disease is a new disease classification established in Japan in the 21st century. Patients with IgG4-related disease display hyper-IgG4-gammaglobulinemia, massive infiltration of IgG4+ plasma cells into tissue, and good response to glucocorticoids. Since IgG4 overexpression is also observed in other disorders, it is necessary to diagnose IgG4-related disease carefully and correctly. We therefore sought to determine cutoff values for serum IgG4 and IgG4/IgG and for IgG4+/IgG+ plasma cells in tissue diagnostic of IgG4-related disease. Patients and Methods. We retrospectively analyzed serum IgG4 concentrations and IgG4/IgG ratio and IgG4+/IgG+ plasma cell ratio in tissues of 132 patients with IgG4-related disease and 48 patients with other disorders. Result. Serum IgG4 >135  mg/dl demonstrated a sensitivity of 97.0% and a specificity of 79.6% in diagnosing IgG4-related disease, and serum IgG4/IgG ratios >8% had a sensitivity and specificity of 95.5% and 87.5%, respectively. IgG4+cell/IgG+ cell ratio in tissues >40% had a sensitivity and specificity of 94.4% and 85.7%, respectively. However, the number of IgG4+ cells was reduced in severely fibrotic parts of tissues. Conclusion. Although a recent unanimous consensus of all relevant researchers in Japan recently established the diagnostic criteria for IgG4-related disease, findings such as ours indicate that further discussion is needed.

  1. Lesional CD4+ IFN-γ+ cytotoxic T lymphocytes in IgG4-related dacryoadenitis and sialoadenitis

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    Maehara, Takashi; Mattoo, Hamid; Ohta, Miho; Mahajan, Vinay S; Moriyama, Masafumi; Yamauchi, Masaki; Drijvers, Jefte; Nakamura, Seiji; Stone, John H; Pillai, Shiv S

    2017-01-01

    Objectives IgG4-related disease (IgG4-RD) is a chronic, systemic, inflammatory condition of unknown aetiology. We have recently described clonally expanded circulating CD4+ cytotoxic T lymphocytes (CTLs) in IgG4-RD that infiltrate affected tissues where they secrete interleukin (IL)-1β and transforming growth factor -β1 (TGF-β1). In this study, we sought to examine the role of CD4+ CTLs in the pathogenesis of IgG4-related dacryoadenitis and sialoadenitis (IgG4-DS) and to determine whether these cells secrete interferon-gamma (IFN-γ) at lesional sites. Methods Salivary glands of 25 patients with IgG4-DS, 22 patients with Sjögren’s syndrome (SS), 12 patients with chronic sialoadenitis (CS) and 12 healthy controls were analysed in this study. Gene expression analysis was performed on submandibular glands (SMGs) from five patients with IgG4-DS, three with CS and three healthy controls. Infiltrating CD4+ CTLs were examined by quantitative multicolour imaging in tissue samples from 20 patients with IgG4-DS, 22 patients with SS, 9 patients with CS and 9 healthy controls. Results In IgG4-DS tissues, nine genes associated with CD4+ CTLs were overexpressed. The expression of granzyme A (GZMA) mRNA was significantly higher in samples from patients with IgG4-RD compared with corresponding tissues from SS and healthy controls. Quantitative imaging showed that infiltrating CD4+ GZMA+ CTLs were more abundant in patients with IgG4-DS than in the other groups. The ratio of CD4+GZMA+ CTLs in SMGs from patients with IgG4-DS correlated with serum IgG4 concentrations and the number of affected organs. A large fraction of CD4+GZMA+ CTLs in SMGs from patients with IgG4-DS secreted IFN-γ. Conclusions The pathogenesis of IgG4-DS is associated with tissue infiltration by CD4+GZMA+ CTLs that secrete IFN-γ. PMID:27358392

  2. A Challenging Diagnosis of IgG4-Related Disease When Understanding Limitations of Laboratory Testing Was Pivotal

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    Victoria Y. Y. Xu

    2017-01-01

    Full Text Available A 76-year-old man was incidentally found on a CT scan to have lymphadenopathy and bilateral kidney enlargement suggestive of infiltrative renal disease. He was largely asymptomatic but had bilateral salivary and lacrimal gland enlargement. A grossly elevated serum IgG (>70 g/L with concomitant suppression of other immunoglobulins, a small IgG restriction, and a parotid biopsy revealing lymphoplasmacytic infiltrate with slight kappa light chain excess all suggested a lymphoproliferative disorder (LPD. The diagnostic workup was further confounded by a normal serum IgG4 concentration. Moreover, bone marrow and renal biopsies did not reveal evidence of LPD. Discussion with the laboratory not only clarified that the markedly increased total IgG could not be accounted for by the small IgG restriction, but also identified a discrepancy in the IgG4 measurement. Repeat analysis of a follow-up sample revealed an elevated IgG4 of 5.94 (reference interval: 0.039–0.864 g/L, which prompted a repeat parotid biopsy that showed predominant IgG4+ lymphocytic infiltrates. Despite the deluding presentations, a final diagnosis of IgG4-related disease (IgG4-RD was made based on elevated serum IgG4 concentrations and histopathological findings. This case highlights the importance of recognizing limitations of laboratory testing and the benefit of close communications among clinical subspecialties and the laboratory.

  3. Jugular Foramen Collision Tumor (Schwannoma and Plasma Cell Pseudotumor), a Probable IgG4-Related Disease.

    Science.gov (United States)

    Bakhit, Mudathir S; Fujii, Masazumi; Jinguji, Shinya; Sato, Taku; Sakuma, Jun; Saito, Kiyoshi

    2017-06-01

    Lower cranial nerve sheath tumors are relatively rare. Cases of schwannoma collision tumors have rarely been reported, with most of the reported cases describing schwannoma and meningioma collision tumors. We report a very rare case of a cerebellopontine angle collision tumor of the ninth cranial nerve schwannoma with an IgG4 plasma cell pseudotumor. IgG4 plasma cell pseudotumors comprise a group of diseases called IgG4-related diseases (IgG4-RDs). These diseases usually affect organs such as the pancreas and salivary gland. Few cases of nervous system IgG4-RDs have been reported. Under intraoperative microscopy, the tumor in our case did not appear different from usual cases of schwannoma, but histopathology showed significant infiltration of IgG4 plasma cells. IgG4-RDs have a distinctive histopathologic pattern; however, their pathophysiology remains unclear. Special attention must be paid to the diagnosis of such diseases because they mimic other diseases and can be missed. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. A subset of ocular adnexal marginal zone lymphomas may arise in association with IgG4-related disease

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    Ohno, Kyotaro; Sato, Yasuharu; Ohshima, Koh-ichi; Takata, Katsuyoshi; Miyata-Takata, Tomoko; Takeuchi, Mai; Gion, Yuka; Tachibana, Tomoyasu; Orita, Yorihisa; Ito, Toshihiro; Swerdlow, Steven H.; Yoshino, Tadashi

    2015-01-01

    We previously suggested a relationship between ocular immunoglobulin (Ig)G4-related disease (IgG4-RD) and marginal zone lymphomas (MZLs). However, the cytokine background associated with these disorders and whether it differs between ocular adnexal MZLs with (IgG4-associated MZL) and without (IgG4-negative MZL) numerous IgG4+ plasma cells are unknown. In this study, we identified the mRNA expression pattern of Th2 and regulatory T-cell (Treg) cytokines in IgG4-RD and in IgG4-associated MZL and IgG4-negative MZL using real-time polymerase chain reaction analysis. Ocular IgG4-RD and IgG4-associated MZL exhibited significantly higher expression ratios of interleukin (IL)-4/β-actin, IL-10/β-actin, IL-13/β-actin, transforming growth factor (TGF) β1/β-actin, and FOXP3/β-actin than did IgG4-negative MZL (p IgG4-RD. Furthermore, the presence of a different inflammatory background in IgG4-negative MZLs suggests that IgG4-associated MZLs may have a different pathogenesis. PMID:26311608

  5. Recent advances in knowledge regarding the head and neck manifestations of IgG4-related disease.

    Science.gov (United States)

    Takano, Kenichi; Yamamoto, Motohisa; Takahashi, Hiroki; Himi, Tetsuo

    2017-02-01

    IgG4-related disease (IgG4-RD) is a chronic inflammatory disorder, characterized by elevated serum IgG4 levels as well as abundant infiltration of IgG4-positive plasmacytes and fibrosis in various organs, including the head and neck region. In particular, the salivary glands, orbit, and thyroid are common sites of disease involvement. IgG4-RD is diagnosed based on various clinical, serological, and histopathological findings, none of which are pathognomonic. Hence, various differential diagnoses, which exhibit elevated serum IgG4 levels and infiltration of IgG4-postive cells into tissues, need to be excluded, especially malignant diseases and mimicking disorders. Systemic corticosteroids are generally effective in inducing IgG4-RD remission; however, recurrent or refractory cases are common. In addition, although the pathogenic mechanisms of IgG4-RD remain unclear, an antigen-driven inflammatory condition is believed to be involved. Recent studies have indicated the important pathogenic role of B cell/T cell collaboration and innate immunity in this disease. Nevertheless, additional research and discussions are needed to resolve many remaining questions. In this review, we provide an overview of the recent insights on the history, clinical features, diagnosis, and treatment of IgG4-RD in the head and neck region. Furthermore, we have also addressed the pathogenesis of this disease. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  6. IgG4-related disease -Mechanistic insights from both clinical and immunologic understanding of this condition.

    Science.gov (United States)

    Maehara, Takashi

    2017-01-01

    IgG4-related disease (IgG4-RD) is a chronic inflammatory disease characterized by tumescent lesions with characteristic storiform fibrosis, obliterative phlebitis and a marked lymphoplasmacytic infiltrate that includes a large number of IgG4 positive plasma cells. It's widely accepted that rituximab-mediated B cell depletion therapy is effective for this disease. Important mechanistic insights correlated with the pathogenesis of IgG4-RD have been gradually disclosed from studies of patients treated by B cell depletion. 1) IgG4-RD patients have the large clonal expansion of activated plasmablasts and CD4 + CTLs, so this disease might be antigen-driven. 2) CD4 + CTLs are the dominant population in affected tissues, on the other hands direct examination of T H1 and T H2 cells in tissues reveal that these subsets are sparse. 3) CD4 + CTLs into affected lesions secret cytotoxic, inflammatory, and pro-fibrotic cytokines, indicating reactivation by antigen in tissue sites. 4) The decline in CD4 + CTLs number by B cell depletion is associated with clinical remission of IgG4-RD patients. 5) CD4 + CXCR5 + T FH cells that express IL-4 are located outside germinal centers and specialized T FH cells that expanded dramatically in conditions with polarized class switching to IgG4. These results suggested that the disease pathogenesis might be based on orchestrating of activated plasmablasts, CD4 + CTLs, and T FH cells.

  7. Development of a scoring system for differentiating IgG4-related sclerosing cholangitis from primary sclerosing cholangitis.

    Science.gov (United States)

    Moon, Sung-Hoon; Kim, Myung-Hwan; Lee, Jong Kyun; Baek, Seunghee; Woo, Young Sik; Cho, Dong Hui; Oh, Dongwook; Song, Tae Jun; Park, Do Hyun; Lee, Sang Soo; Seo, Dong Wan; Lee, Sung Koo

    2017-04-01

    Recent research has shown that a substantial number of patients with primary sclerosing cholangitis (PSC) can also have elevated serum/tissue IgG4. The aim of our study was to develop a simple scoring system for the discrimination of IgG4-related sclerosing cholangits (IgG4-SC) from PSC. Patients with IgG4-SC (n = 39) and PSC (n = 76) who had intrahepatic/hilar strictures were included. Candidate-differentiating variables included patient age, other organ involvement (OOI), inflammatory bowel disease, serum IgG4, and cholangiographic features. A scoring system was developed on the basis of these variables, and its performance was internally validated using a bootstrapping-based method. The scoring system in the final model included age (IgG4-SC. The discrimination between IgG4-SC and PSC using the scoring system was excellent (area under the receiver operating characteristic curve, 0.986). A reliable differentiation of IgG4-SC from PSC can be made using the scoring system presented here. We suggest the diagnosis of IgG4-SC at a cutoff of 7 points or higher and the indication of diagnostic steroid trial at 5 or 6 points. External validation of our scoring system is warranted.

  8. Surgical management of isolated mesenteric autoimmune disease: addressing the spectrum of IgG4-related disease and sclerosing mesenteritis.

    Science.gov (United States)

    Greenbaum, Alissa; Yadak, Nour; Perez, Steven; Rajput, Ashwani

    2017-06-08

    IgG 4 -related disease (IgG 4 -RD) is a rare form of autoimmune sclerosing disease, characterised by elevated serum IgG 4 and tissue IgG 4 levels, specific histopathological findings, multiorgan involvement and adequate response to glucocorticoid treatment. The low incidence and the heterogeneous nature of the disease has made consensus on diagnostic criteria for IgG 4 -RD difficult. Whether sclerosing mesenteritis (SM) is considered a manifestation of IgG 4 -RD is strongly debated. We present the case of a patient with a history of rheumatoid arthritis who presented with a calcified abdominal mass. She was found to have an isolated, pedunculated mesenteric mass positive for IgG 4 and concurrently elevated serum IgG 4 levels. Clinical features did not classify her disease as either SM or IgG 4 -RD as currently described in consensus statements. Concurrent diagnoses of IgG 4 -RD, SM and other autoimmune disorders, as well as postoperative recommendations for resected isolated IgG 4 -positive masses, are discussed. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  9. An International, Multi-Specialty Validation Study of the IgG4-Related Disease Responder Index.

    Science.gov (United States)

    Wallace, Zachary S; Khosroshahi, Arezou; Carruthers, Mollie D; Perugino, Cory A; Choi, Hyon; Campochiaro, Corrado; Culver, Emma L; Cortazar, Frank; Della-Torre, Emanuel; Ebbo, Mikael; Fernandes, Ana; Frulloni, Luca; Hart, Philip; Karadag, Omer; Kawa, Shigeyuki; Kawano, Mitsuhiro; Kim, Myung-Hwan; Lanzillotta, Marco; Matsui, Shoko; Okazaki, Kazuichi; Ryu, Jay H; Saeki, Takako; Schleinitz, Nicolas; Tanasa, Paula; Umehara, Hisanori; Webster, George; Zhang, Wen; Stone, John H

    2018-02-18

    IgG4-related disease (IgG4-RD) can cause fibro-inflammatory lesions in nearly any organ, leading to organ dysfunction and failure. The IgG4-RD Responder Index (RI) was developed to help investigators assess the efficacy of treatment in a structured manner. We sought to validate the RI in a multi-national investigation. The RI guides investigators through assessments of disease activity and damage in 25 domains, incorporating higher weights for disease manifestations that require treatment urgently or that worsen despite treatment. After a training exercise, investigators reviewed 12 written IgG4-RD vignettes (mean length: 279 words, range: 76-511 words) based upon real patients. Investigators calculated both an RI score as well as a physician global assessment (PGA) for each vignette. Three investigators used the RI on fifteen patients followed over serial visits after treatment. We assessed inter- and intra-rater reliability, precision, validity, and responsiveness. Twenty-six physician-investigators included representatives from 6 specialties and 9 countries. The inter-rater and intra-rater reliabilities of the RI were strong (0.88 and 0.69, respectively) and superior to those of the PGA. Correlations (construct validity) between the RI and PGA were high (Spearman's r=0.9, Preliable disease activity assessment tool that can be used to measure response to therapy. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  10. Successful treatment of pediatric IgG4 related systemic disease with mycophenolate mofetil: case report and a review of the pediatric autoimmune pancreatitis literature

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    Cron Randy Q

    2011-01-01

    Full Text Available Abstract Autoimmune pancreatitis is frequently associated with elevated serum and tissue IgG4 levels in the adult population, but there are few reports of pediatric autoimmune pancreatitis, and even fewer reports of IgG4 related systemic disease in a pediatric population. The standard of care treatment in adults is systemic corticosteroids with resolution of symptoms in most cases; however, multiple courses of corticosteroids are occasionally required and some patients require long term corticosteroids. In these instances, steroid sparing disease modify treatments are in demand. We describe a 13-year-old girl with IgG4 related systemic disease who presented with chronic recurrent autoimmune pancreatitis resulting in surgical intervention for obstructive hyperbilirubinemia and chronic corticosteroid treatment. In addition, she developed fibrosing medianstinitis as part of her IgG4 related systemic disease. She was eventually successfully treated with mycophenolate mofetil allowing for discontinuation of corticosteroids. This is the first reported use of mycophenolate mofetil for IgG4 related pancreatitis. Although autoimmune pancreatitis as part of IgG4 related systemic disease is rarely reported in pediatrics, autoimmune pancreatitis is also characterized as idiopathic fibrosing pancreatitis. All pediatric autoimmune pancreatitis cases reported in the world medical literature were identified via a PUBMED search and are reviewed herein. Twelve reports of pediatric autoimmune pancreatitis were identified, most of which were treated with corticosteroids or surgical approaches. Most case reports failed to report IgG4 levels, so it remains unclear how commonly IgG4 related autoimmune pancreatitis occurs during childhood. Increased evaluation of IgG4 levels in patients with autoimmune pancreatitis may shed further light on the association of IgG4 with pancreatitis and the underlying pathophysiology.

  11. IgG4-related kidney disease: MRI findings with emphasis on the usefulness of diffusion-weighted imaging

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    Kim, Bohyun; Kim, Jin Hee, E-mail: kimjhrad@amc.seoul.kr; Byun, Jae Ho; Kim, Hyoung Jung; Lee, Seung Soo; Kim, So Yeon; Lee, Moon-Gyu

    2014-07-15

    Objectives: To investigate the imaging findings of immunoglobulin G4 (IgG4)-related kidney disease (IgG4-KD) on magnetic resonance imaging (MRI) including diffusion-weighted imaging (DWI) and to evaluate the usefulness of DWI in lesion detection. Methods: This retrospective cohort study included 31 patients with IgG4-KD who underwent MRI covering both kidneys. Two radiologists reviewed in consensus the MR images to determine the distribution pattern (location, laterality, and multiplicity) and the visually assessed signal intensity (hypointense, isointense or hyperintense) of the renal lesions compared to the normal renal parenchyma on each sequence. Per-patient sensitivity for detecting IgG4-KD and the number of detectable lesions were compared in T2-weighted images, DWI, and dynamic contrast-enhanced images. Results: IgG4-KD typically manifested as bilateral (83.9%), multiple (93.5%), and renal parenchymal (87.1%) nodules appearing isointense (93.5%) on T1-weighted images, hypointense (77.4%) on T2-weighted images, hyperintense (100%) on DWI (b = 1000), and hypointense (83.3%) in the arterial phase and with a progressive enhancement pattern on dynamic contrast-enhanced images. The sensitivity of DWI for detecting IgG4-KD was significantly higher than that of T2-weighted images (100% vs. 77.4%, P = 0.034). The median number of detectable lesions was significantly greater in DWI (n = 9) than in T2-weighted images (n = 2) and dynamic contrast-enhanced images (n = 5) (P ≤ 0.008). Conclusions: The characteristic MRI findings of IgG4-KD were bilateral, multiple, renal parenchymal nodules with T2 hypointensity, diffusion restriction, and a progressive enhancement pattern. As DWI was useful in the detection of IgG4-KD, adding DWI to conventional MRI for patients suspected of having IgG4-KD may enhance the diagnosis.

  12. IgG4-Related Disease: Baseline clinical and laboratory features in 125 patients with biopsy-proven disease

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    Wallace, Zachary S.; Deshpande, Vikram; Mattoo, Hamid; Mahajan, Vinay S.; Kulikova, Maria; Pillai, Shiv; Stone, John H.

    2015-01-01

    Purpose IgG4-related disease (IgG4-RD) is an immune-mediated fibroinflammatory condition that can affect nearly any organ. No detailed clinical and laboratory assessments have been reported in large numbers of patients with IgG4-RD diagnoses established by strict clinicopathological correlation. Methods We reviewed the baseline features of 125 patients with biopsy-proven disease. The diagnosis was confirmed by pathology review according to consensus diagnostic criteria. Disease activity and damage were assessed by the IgG4-RD Responder Index (RI). Flow cytometry was used to assess levels of circulating plasmablasts. Results Of the 125 patients, 103 had active disease and 86 were on no treatment. Only 51% of the patients with active disease had elevated serum IgG4 concentrations. However, patients with active disease and elevated serum IgG4 concentrations were older, had a higher RI, a greater number of organs involved, lower complement levels, higher absolute eosinophil counts, and higher IgE levels compared to those with active disease but normal serum IgG4 (PIgG4+ plasmablast level and RI (R=0.45, P=0.003) was stronger than that of total plasmablasts and RI. Seventy-six (61%) of the patients were male, but no significant differences according to gender were observed with regard to disease severity, organ involvement, or serum IgG4 concentrations. Glucocorticoids failed to produce sustained remission in the majority of patients. Conclusion Nearly 50% of this patient cohort with biopsy-proven, clinically-active IgG4-RD had normal serum IgG4 concentrations. Serum IgG4 elevation identify a subset with more inflammatory features. IgG4+ plasmablasts correlate well with disease activity. PMID:25988916

  13. IgG4-Related Sclerosing Disease, an Emerging Entity: A Review of a Multi-System Disease

    Science.gov (United States)

    Divatia, Mukul; Kim, Sun A

    2012-01-01

    Immunoglobulin G4-related systemic disease (IgG4-RSD) is a recently defined emerging entity characterized by a diffuse or mass forming inflammatory reaction rich in IgG4-positive plasma cells associated with fibrosclerosis and obliterative phlebitis. IgG4-RSD usually affects middle aged and elderly patients, with a male predominance. It is associated with an elevated serum titer of IgG4, which acts as a marker for this recently characterized entity. The prototype is IgG4-related sclerosing pancreatitis or autoimmune pancreatitis (AIP). Other common sites of involvement are the hepatobiliary tract, salivary gland, orbit, and lymph node, however practically any organ can be involved, including upper aerodigestive tract, lung, aorta, mediastinum, retroperitoneum, soft tissue, skin, central nervous system, breast, kidney, and prostate. Fever or constitutional symptoms usually do not comprise part of the clinical picture. Laboratory findings detected include raised serum globulin, IgG and IgG4. An association with autoantibody detection (such as antinuclear antibodies and rheumatoid factor) is seen in some cases. Steroid therapy comprises the mainstay of treatment. Disease progression with involvement of multiple organ-sites may be encountered in a subset of cases and may follow a relapsing-remitting course. The principal histopathologic findings in several extranodal sites include lymphoplasmacytic infiltration, lymphoid follicle formation, sclerosis and obliterative phlebitis, along with atrophy and destruction of tissues. Immunohistochemical staining shows increased IgG4+ cells in the involved tissues (>50 per high-power field, with IgG4/IgG ratio >40%). IgG4-RSD may potentially be rarely associated with the development of lymphoma and carcinoma. However, the nature and pathogenesis of IgG4-RSD are yet to be fully elucidated and provide immense scope for further studies. PMID:22187229

  14. Clonally expanded cytotoxic CD4+ T cells and the pathogenesis of IgG4-related disease.

    Science.gov (United States)

    Mattoo, Hamid; Stone, John H; Pillai, Shiv

    2017-02-01

    IgG4-related disease (IgG4-RD) is a systemic condition of unknown cause characterized by highly fibrotic lesions, with dense lymphoplasmacytic infiltrates containing a preponderance of IgG4-expressing plasma cells. CD4 + T cells and B cells constitute the major inflammatory cell populations in IgG4-RD lesions. IgG4-RD patients with active, untreated disease show a marked expansion of plasmablasts in the circulation. Although the therapeutic depletion of B cells suggests a role for these cells in the disease, a direct role for B cells or IgG4 in the pathogenesis of IgG4-RD is yet to be demonstrated. Among the CD4 + T-cell subsets, Th2 cells were initially thought to contribute to IgG4-RD pathogenesis, but many previous studies were confounded by the concomitant history of allergic diseases in the patients studied and the failure to use multi-color staining to definitively identify T-cell subsets in tissue samples. More recently, using an unbiased approach to characterize CD4 + T-cell subsets in patients with IgG4-RD - based on their clonal expansion and ability to infiltrate affected tissue sites - CD4 + CTLs have been identified as the major CD4 + T-cell subset in disease lesions as well as in the circulation. CD4 + CTLs in affected tissues secrete pro-fibrotic cytokines including IL-1β, TGF-β1, and IFN-γ as well as cytolytic molecules such as perforin and granzymes A and B. In this review, we examine possible mechanisms by which activated B cells and plasmablasts may collaborate with the expanded CD4 + CTLs in driving the fibrotic pathology of the disease and describe the lacunae in the field and in our understanding of IgG4-RD pathogenesis.

  15. IgG4-related kidney disease: MRI findings with emphasis on the usefulness of diffusion-weighted imaging

    International Nuclear Information System (INIS)

    Kim, Bohyun; Kim, Jin Hee; Byun, Jae Ho; Kim, Hyoung Jung; Lee, Seung Soo; Kim, So Yeon; Lee, Moon-Gyu

    2014-01-01

    Objectives: To investigate the imaging findings of immunoglobulin G4 (IgG4)-related kidney disease (IgG4-KD) on magnetic resonance imaging (MRI) including diffusion-weighted imaging (DWI) and to evaluate the usefulness of DWI in lesion detection. Methods: This retrospective cohort study included 31 patients with IgG4-KD who underwent MRI covering both kidneys. Two radiologists reviewed in consensus the MR images to determine the distribution pattern (location, laterality, and multiplicity) and the visually assessed signal intensity (hypointense, isointense or hyperintense) of the renal lesions compared to the normal renal parenchyma on each sequence. Per-patient sensitivity for detecting IgG4-KD and the number of detectable lesions were compared in T2-weighted images, DWI, and dynamic contrast-enhanced images. Results: IgG4-KD typically manifested as bilateral (83.9%), multiple (93.5%), and renal parenchymal (87.1%) nodules appearing isointense (93.5%) on T1-weighted images, hypointense (77.4%) on T2-weighted images, hyperintense (100%) on DWI (b = 1000), and hypointense (83.3%) in the arterial phase and with a progressive enhancement pattern on dynamic contrast-enhanced images. The sensitivity of DWI for detecting IgG4-KD was significantly higher than that of T2-weighted images (100% vs. 77.4%, P = 0.034). The median number of detectable lesions was significantly greater in DWI (n = 9) than in T2-weighted images (n = 2) and dynamic contrast-enhanced images (n = 5) (P ≤ 0.008). Conclusions: The characteristic MRI findings of IgG4-KD were bilateral, multiple, renal parenchymal nodules with T2 hypointensity, diffusion restriction, and a progressive enhancement pattern. As DWI was useful in the detection of IgG4-KD, adding DWI to conventional MRI for patients suspected of having IgG4-KD may enhance the diagnosis

  16. A Patient with Autoimmune Pancreatitis Type 1 with Previously Known Lymphadenopathy, Both in the Context of IgG4-related Disease

    OpenAIRE

    Alidjan, Fazil M.; Karim, Faiz; Verdijk, Rob M.; van Esser, Joost W.; van Heerde, Marianne J.

    2015-01-01

    Patient: Male, 62 Final Diagnosis: Auto-immune pancreatitis Symptoms: Jaundice ? lymfadenopathy Medication: ? Clinical Procedure: Laboratory ? imaging Specialty: Gastroenterology and Hepatology Objective: Unusual clinical course Background: Autoimmune pancreatitis (AIP) is an important clinical pathologic concept of IgG-4-related disease. AIP is a rare cause of chronic pancreatitis, characterized by a fibroinflammatory process by lymphoplasmacytic infiltrates, storiform fibrosis, obliterative...

  17. Clonal expansion of CD4(+) cytotoxic T lymphocytes in patients with IgG4-related disease.

    Science.gov (United States)

    Mattoo, Hamid; Mahajan, Vinay S; Maehara, Takashi; Deshpande, Vikram; Della-Torre, Emanuel; Wallace, Zachary S; Kulikova, Maria; Drijvers, Jefte M; Daccache, Joe; Carruthers, Mollie N; Castelino, Flavia V; Stone, James R; Stone, John H; Pillai, Shiv

    2016-09-01

    IgG4-related disease (IgG4-RD) is a systemic condition of unknown cause characterized by highly fibrotic lesions with dense lymphoplasmacytic infiltrates. CD4(+) T cells constitute the major inflammatory cell population in IgG4-RD lesions. We used an unbiased approach to characterize CD4(+) T-cell subsets in patients with IgG4-RD based on their clonal expansion and ability to infiltrate affected tissue sites. We used flow cytometry to identify CD4(+) effector/memory T cells in a cohort of 101 patients with IgG4-RD. These expanded cells were characterized by means of gene expression analysis and flow cytometry. Next-generation sequencing of the T-cell receptor β chain gene was performed on CD4(+)SLAMF7(+) cytotoxic T lymphocytes (CTLs) and CD4(+)GATA3(+) TH2 cells in a subset of patients to identify their clonality. Tissue infiltration by specific T cells was examined by using quantitative multicolor imaging. CD4(+) effector/memory T cells with a cytolytic phenotype were expanded in patients with IgG4-RD. Next-generation sequencing revealed prominent clonal expansions of these CD4(+) CTLs but not CD4(+)GATA3(+) memory TH2 cells in patients with IgG4-RD. The dominant T cells infiltrating a range of inflamed IgG4-RD tissue sites were clonally expanded CD4(+) CTLs that expressed SLAMF7, granzyme A, IL-1β, and TGF-β1. Clinical remission induced by rituximab-mediated B-cell depletion was associated with a reduction in numbers of disease-associated CD4(+) CTLs. IgG4-RD is prominently linked to clonally expanded IL-1β- and TGF-β1-secreting CD4(+) CTLs in both peripheral blood and inflammatory tissue lesions. These active, terminally differentiated, cytokine-secreting effector CD4(+) T cells are now linked to a human disease characterized by chronic inflammation and fibrosis. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  18. Comparison of the multidetector-row computed tomography findings of IgG4-related sclerosing cholangitis and extrahepatic cholangiocarcinoma

    International Nuclear Information System (INIS)

    Yata, M.; Suzuki, K.; Furuhashi, N.; Kawakami, K.; Kawai, Y.; Naganawa, S.

    2016-01-01

    Aim: To compare the multidetector-row computed tomography (MDCT) findings of IgG4-related sclerosing cholangitis (IgG4-SC) and extrahepatic cholangiocarcinoma (EH-CCA). Materials and methods: Two radiologists who had no knowledge of the patients' clinical information retrospectively evaluated the CT findings of patients with IgG4-SC (n=33) and EH-CCA (n=39) on a consensus basis. Another radiologist measured the biliary lesions. IgG4-SC was diagnosed using the Japan Biliary Association criteria (2012) or the Mayo Clinic's HISORt criteria. EH-CCA was diagnosed based on surgical findings. Results: Compared with EH-CCA, IgG4-SC exhibited the following findings significantly more frequently: (a) wall thickening alone, (b) concentric wall thickening, (c) smooth inner margins, (d) homogeneous attenuation in the arterial phase, (e) a lesion involving the intrapancreatic bile duct, (f) smooth outer margins, (g) fully visible lumen, (h) a funnel-shaped proximal bile duct, (i) skip lesions, and (j) abnormal pancreatic findings. Conversely, (k) dual-layered attenuation in all phases was significantly more common in EH-CCA. The specificity values of parameters (e–k) were >80%. Regarding dimensions, (l) the biliary lesions were longer in IgG4-SC than in EH-CCA. (m) The diameters of the dilated proximal common bile duct and (n) the dilated proximal intrahepatic bile duct were smaller in IgG4-SC than in EH-CCA. Conclusion: A number of CT findings are useful for differentiating between IgG4-SC and EH-CCA. CT findings (e–k) are particularly useful for this purpose. - Highlights: • Some CT findings are useful for differentiating between IgG4-SC and EH-CCA. • Homogeneous attenuation in all phases was more common in IgG4-SC than in EH-CCA. • Abnormal pancreatic findings showed high sensitivity and specificity values. • Dual-layered attenuation in all phases was more common in EH-CCA than in IgG4-SC.

  19. Detection of Serum IgG4 Levels in Patients with IgG4-Related Disease and Other Disorders

    Science.gov (United States)

    Wang, Chenqiong; Wu, Xuefen; Miao, Ye; Xiong, Hui; Bai, Lin; Dong, Lingli

    2015-01-01

    Objective Elevated serum IgG4 levels are an important hallmark for diagnosing IgG4-related disease (IgG4-RD), but can also be observed in other diseases. This study aimed to compare two different testing methods for IgG4: ELISA and nephelometric assay. Both assays were used to measure serum IgG4 concentrations, and to assess the prevalence of high serum IgG4 levels in both IgG4-RD and non-IgG4-RD diseases. Methods A total of 80 serum samples were tested using the nephelometric assay and ELISA method that we established. Serum IgG4 concentrations were determined by ELISA for 957 patients with distinct diseases, including 12 cases of IgG4-RD and 945 cases of non-IgG4-RD. Results IgG4 levels from 80 selected serum samples examined by ELISA were in agreement with those detected using the nephelometry assay. Meanwhile, the serum IgG4 concentrations measured by ELISA were also consistent with the clinical diagnoses of patients with IgG4-RD during the course of disease. The Elevated levels of serum IgG4 (>1.35 g/L) were detected in all IgG4-RD (12/12) patients, and the prevalence of high IgG4 serum levels was 3.39% in non-IgG4-RD cases. Among them, the positive rates of serum IgG4 were 2.06% in patients with carcinoma and 6.3% in patients with other non-IgG4 autoimmune diseases. Conclusion Our established ELISA method is a reliable and convenient technique, which could be extensively used in the clinic to measure serum IgG4 levels. High levels of IgG4 were observed in IgG4-RD. However, this phenomenon could also be observed in other diseases, such as carcinomas and other autoimmune diseases. Thus, a diagnosis of IgG4 disease cannot only be dependent on the detection of elevated serum IgG4 levels. PMID:25885536

  20. Characterizing IgG4-related disease with 18F-FDG PET/CT: a prospective cohort study

    International Nuclear Information System (INIS)

    Zhang, Jingjing; Ma, Yanru; Niu, Na; Wang, Xinwei; Li, Fang; Zhu, Zhaohui; Chen, Hua; Lin, Wei; Zhang, Fengchun; Zhang, Wen; Xiao, Yu; Liang, Zhiyong

    2014-01-01

    IgG4-related disease (IgG4-RD) is an increasingly recognized clinicopathological disorder with immune-mediated inflammatory lesions mimicking malignancies. A cohort study was prospectively designed to investigate the value of 18 F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in characterizing IgG4-RD. Thirty-five patients diagnosed with IgG4-RD according to the consensus criteria were enrolled with informed consent. All patients underwent baseline 18 F-FDG PET/CT evaluation. Among them, 29 patients underwent a second 18 F-FDG PET/CT scan after 2 to 4 weeks of steroid-based therapy. All 35 patients were found with 18 F-FDG-avid hypermetabolic lesion(s); 97.1 % (34/35) of these patients showed multi-organ involvement. Among the 35 patients, 71.4 % (25/35) patients were found with more organ involvement on 18 F-FDG PET/CT than conventional evaluations including physical examination, ultrasonography, and computed tomography (CT). 18 F-FDG PET/CT demonstrated specific image characteristics and pattern of IgG4-RD, including diffusely elevated 18 F-FDG uptake in the pancreas and salivary glands, patchy lesions in the retroperitoneal region and vascular wall, and multi-organ involvement that cannot be interpreted as metastasis. Comprehensive understanding of all involvement aided the biopsy-site selection in seven patients and the recanalization of ureteral obstruction in five patients. After 2 to 4 weeks of steroid-based therapy at 40 mg to 50 mg prednisone per day, 72.4 % (21/29) of the patients showed complete remission, whereas the others exhibited > 81.8 % decrease in 18 F-FDG uptake. F-FDG PET/CT is a useful tool for assessing organ involvement, monitoring therapeutic response, and guiding interventional treatment of IgG4-RD. The image pattern is suggested to be updated into the consensus diagnostic criteria for IgG4-RD. (orig.)

  1. Diagnostic Performance of Serum IgG4 Levels in Patients With IgG4-Related Disease

    Science.gov (United States)

    Yu, Kuang-Hui; Chan, Tien-Ming; Tsai, Ping-Han; Chen, Ching-Hui; Chang, Pi-Yueh

    2015-01-01

    Abstract The aim of this study is to study the clinical features and diagnostic performance of IgG4 in Chinese populations with IgG4-related diseases (IgG4-RDs). The medical records of 2901 adult subjects who underwent serum IgG4 level tests conducted between December 2007 and May 2014 were reviewed. Serum concentrations of IgG4 were measured in 2901 cases, including 161 (5.6%) patients with IgG4-RD and 2740 (94.4%) patients without IgG4-RD (non-IgG4-RD group). The mean age of the IgG4-RD patients was 58.4 ± 16.1 years (range: 21–87), and 48 (29.8%) were women. The mean serum IgG4 level was significantly much higher in IgG4-RD patients than in non-IgG4-RD (1062.6 vs 104.3 mg/dL, P IgG4 >135 mg/dL, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), likelihood ratio (LR)+, and LR− were 86%, 77%, 18%, 99%, 3.70, and 0.19, respectively. When the upper limit of normal was doubled for an IgG4 >270 mg/dL, the corresponding data were 75%, 94%, 43%, 98%, 12.79, and 0.26, respectively. For IgG4 >405 mg/dL (tripling the upper limit of normal), the corresponding data were 62%, 98%, 68%, 98%, 37.00, and 0.39, respectively. When calculated according to the manufacturer's package insert cutoff (>201 mg/dL) for the diagnosis of IgG4-RD, the corresponding sensitivity, specificity, PPV, NPV, LR+, and LR− were 80%, 89%, 29%, 99%, 7.00, and 0.23, respectively. For IgG4 >402 mg/dL (>2× the upper limit of the normal range), the corresponding data were 62%, 98%, 68%, 98%, 36.21, and 0.39, respectively. For IgG4 >603 mg/dL (>3× the upper limit of the normal range), the corresponding data were 50%, 99%, 84%, 97%, 90.77 and 0.51, respectively. The optimal cutoff value of serum IgG4 (measured by nephelometry using a Siemens BN ProSpec instrument and Siemens reagent) for the diagnosis of IgG4-RD was 248 mg/dL, the sensitivity and specificity were 77.6% and 92.8%, respectively. The present study demonstrated that 2 or 3 times the upper limit of the manufacturer's reference range of the IgG4 level was a useful marker for the diagnosis of various types of IgG4-RD and the optimal cutoff level was 248 mg/dL. PMID:26469909

  2. Early treatment for IgG4-related disease may prevent cognitive impairment caused by cerebral vasculitis: A case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Toshihiko Usami

    2018-03-01

    Full Text Available IgG4-related disease (IgG4-RD is a recently recognized disease entity. A 74-year-old male presented with transient headache. He was diagnosed IgG4-RD by pancreatic biopsy at the age of 72. Magnetic Resonance Imaging (MRI showed disseminated cerebral microbleeds and microinfarctions in time and space. It suggested cerebral vasculitis, however any causative factor were not confirmed. IgG4-RD rarely causes cerebral vasculitis. This might be a first case of an asymptomatic cerebral vasculitis due to IgG4-RD. Patient was started on oral prednisolone, and no neurological or neuropsychological symptom was clinically observed. The MRI findings improved after treatment, and revealed no indication of newly lesions at 6-months follow-up. Early treatment for IgG4-RD may be recommended to prevent irreversible cognitive dysfunction. Keywords: IgG4-related disease, Treatment, Cerebral vasculitis

  3. Are Classification Criteria for IgG4-RD Now Possible? The Concept of IgG4-Related Disease and Proposal of Comprehensive Diagnostic Criteria in Japan

    Directory of Open Access Journals (Sweden)

    Kazuichi Okazaki

    2012-01-01

    Full Text Available Recent studies suggest simultaneous or metachronous lesions in multiorgans characterized by elevated serum levels of IgG4 and abundant infiltration of IgG4-positive plasma cells with various degrees of fibrosis. Two Japanese research committees for IgG4-RD, one from fibrosclerosis (Okazaki team and the other from lymph proliferation (Umehara team supported by the “Research Program for Intractable Disease” of the Ministry of Health, Labor, and Welfare of Japan, have agreed with the unified nomenclature as “IgG4-RD” and proposed the comprehensive diagnostic criteria (CDC for IgG4-RD. Validation of the CDC demonstrated satisfactory sensitivity for the practical use of general physicians and nonspecialists but low sensitivity in the organs to be difficult in taking biopsy specimens such as type1 autoimmune pancreatitis (IgG4-related AIP, compared with IgG4-related sialadenitis/dacryoadenitis (Mikulicz's disease and IgG4-related kidney disease. Although the diagnostic criteria covering all IgG4-RD are hard to be established, combination with the CDC and organ-specific diagnostic criteria should improve sensitivity.

  4. IgG4-related retroperitoneal fibrosis and sclerosing cholangitis independent of autoimmune pancreatitis. A recurrent case after a 5-year history of spontaneous remission.

    Science.gov (United States)

    Miura, Hideaki; Miyachi, Yasutaka

    2009-07-06

    A new clinicopathological concept of IgG4-related sclerosing disease affecting various organs has recently been proposed in relation to autoimmune pancreatitis. This report describes the case of IgG4-related retroperitoneal fibrosis and sclerosing cholangitis independent of autoimmune pancreatitis, which recurred after a long period of spontaneous remission. An 80-year-old Japanese man presented with obstructive jaundice owing to a hepatic hilum bile duct stricture. Coincidentally, a soft tissue mass surrounding the abdominal aorta, suggesting retroperitoneal fibrosis, was identified. Unexpectedly, spontaneous regression of obstructive jaundice together with retroperitoneal fibrosis occurred. The presence of high serum IgG4 concentrations measured later led us to consider a possible association with autoimmune pancreatitis; however, there were no clinical features confirming autoimmune pancreatitis. After a 5-year history of spontaneous clinical remission, there was an elevation of serum IgG4 levels and renal dysfunction owing to bilateral hydronephrosis caused by a reemergence of the retroperitoneal mass. Evaluation by endoscopic retrograde cholangiopancreatography revealed a biliary stricture, suggesting sclerosing cholangitis which was observed without the presence of any pancreatic duct abnormality. The subsequent excellent results obtained using steroid therapy, namely the decrease in serum IgG4 levels and the regression of the retroperitoneal mass, strongly suggested that the present case was an IgG4-related sclerosing disease. Aside from high serum IgG4 concentrations, markedly elevated levels of serum IgE was found retrospectively, although the clinical significance remains unknown. When we encounter fibrotic diseases of unknown etiology, we should measure serum IgG4 concentrations and monitor the disease activity over long periods even after achieving clinical remission.

  5. Graves' Disease Patients with Persistent Hyperthyroidism and Diffuse Lymphoplasmacytic Infiltration in the Thyroid Show No Histopathological Compatibility with IgG4-Related Disease.

    Directory of Open Access Journals (Sweden)

    Eijun Nishihara

    Full Text Available IgG4-related disease is a novel disease entity characterized by diffuse lymphoplasmacytic infiltration rich in IgG4-positive plasma cells and fibrosis into multiple organs. There is still controversy over whether some thyroid diseases are actually IgG4-related disease. The objective of this study was to elucidate the clinicopathological features of Graves' disease with diffuse lymphoplasmacytic infiltration in the thyroid.Among 1,484 Graves' disease patients who underwent thyroidectomy, we examined their histopathological findings including the degree of lymphoplasmacytic and fibrotic infiltration and levels of IgG4-positive plasma cells in the thyroid. Their clinical pictures were defined by laboratory and ultrasonographic evaluation.A total of 11 patients (0.74% showed diffuse lymphoplasmacytic infiltration in the stroma of the thyroid gland. Meanwhile, other patients showed variable lymphoid infiltration ranging from absent to focally dense but no aggregation of plasma cells in the thyroid gland. Based on the diagnostic criteria of IgG4-related disease, 5 of the 11 subjects had specifically increased levels of IgG4-positive plasma cells in the thyroid. Fibrotic infiltration was present in only 1 patient developing hypothyroidism after anti-thyroid drug treatment for 4 years, but not in the other 10 patients with persistent hyperthyroidism. Obliterative phlebitis was not identified in any of the 11 subjects. Thyroid ultrasound examination showed 1 patient developing hypothyroidism who had diffuse hypoechogenicity, but the other hyperthyroid patients had a coarse echo texture.In our study, Graves' disease patients with persistent hyperthyroidism who had diffuse lymphoplasmacytic infiltration rich in IgG4-positive plasma cells in the thyroid showed no concomitant fibrosis or obliterative phlebitis.

  6. Type 1 Autoimmune Pancreatitis and IgG4-Related Sclerosing Cholangitis Is Associated With Extrapancreatic Organ Failure, Malignancy, and Mortality in a Prospective UK Cohort

    Science.gov (United States)

    Kumar, M.; Hurst, J.M.; Rodriguez-Justo, M.; Chapman, M.H.; Johnson, G.J.; Pereira, S.P.; Chapman, R.W.

    2015-01-01

    OBJECTIVES Type I autoimmune pancreatitis (AIP) and IgG4-related sclerosing cholangitis (IgG4-related SC) are now recognized as components of a multisystem IgG4-related disease (IgG4-RD). We aimed to define the clinical course and long-term outcomes in patients with AIP/IgG4-SC recruited from two large UK tertiary referral centers. METHODS Data were collected from 115 patients identified between 2004 and 2013, and all were followed up prospectively from diagnosis for a median of 33 months (range 1–107), and evaluated for response to therapy, the development of multiorgan involvement, and malignancy. Comparisons were made with national UK statistics. RESULTS Although there was an initial response to steroids in 97%, relapse occurred in 50% of patients. IgG4-SC was an important predictor of relapse (P IgG4-RD, including three hepatopancreaticobiliary cancers. The risk of any cancer at diagnosis or during follow-up when compared with matched national statistics was increased (odds ratio = 2.25, CI = 1.12–3.94, P = 0.02). Organ dysfunction occurred within the pancreas, liver, kidney, lung, and brain. Mortality occurred in 10% of patients during follow-up. The risk of death was increased compared with matched national statistics (odds ratio = 2.07, CI = 1.07–3.55, P = 0.02). CONCLUSIONS Our findings suggest that AIP and IgG4-SC are associated with significant morbidity and mortality owing to extrapancreatic organ failure and malignancy. Detailed clinical evaluation for evidence of organ dysfunction and associated malignancy is required both at first presentation and during long-term follow-up. PMID:25155229

  7. IgG4-related systemic disease of the pancreas with involvement of the lung: a case report and literature review

    Directory of Open Access Journals (Sweden)

    Hurley JR

    2013-08-01

    Full Text Available IgG-related systemic disease (ISD remains exceedingly rare and unfamiliar, particularly extrapancreatic disease. We report a patient with separate presentations of IgG4 pulmonary disease and recurring IgG4 related biliary sclerosis and pancreatitis. Because of the intricate and perplexing pathogenesis, overlapping organ systems and wide variation in disease presentation, ISD in its entirety remains undefined. Accurate identification of ISD is critical to avoid permanent organ damage especially since treatment is nearly always successful with corticosteroids. As recognition and awareness of this disease grows, development of standard diagnostic criteria and treatment plans are needed.

  8. Lupus nephritis

    African Journals Online (AJOL)

    1991-03-02

    Mar 2, 1991 ... A recent large Australian series! on lupus nephritis emphasises .... patent capillary lumina and thickened capillary walls. ... (Australia). 135. 27. 58. 15. This study (RSA). 51. 33. 63. 4 have been documented.2-5 All included patients with lupus nephritis, but while the series from Natal' gave a detailed list.

  9. Interstitial nephritis.

    Science.gov (United States)

    Papper, S

    1980-01-01

    There are many causes of interstitial nephritis other than pyelonephritis. The term interstitial nephritis does not connote a single etiologic or pathogenetic mechanism; it rather arbitrarily places together a wider variety of renal diseases that have a predilection for early and major involvement of the renal interstitium. The prototype of acute interstitial nephritis is acute pyelonephritis. In addition, there is a drug-related acute interstitial disease that is probably of immunological nature and usually reverses with discontinuance of the offending drug. Chronic interstitial nephritis includes many diverse illnesses. Nonobstructive pyelonephritis occurs but its prevalence is debated. Analgesic abuse nephropathy is not rare and is potentially reversible. Papillary necrosis has many causes and a wide spectrum of clinical presentations. Heavy metals, such as lead, cause interstitial nephritis. Balkan nephropathy occurs in an endemic area and although not bacterial in origin is of unknown cause.

  10. A Patient with Autoimmune Pancreatitis Type 1 with Previously Known Lymphadenopathy, Both in the Context of IgG4-related Disease.

    Science.gov (United States)

    Alidjan, Fazil M; Karim, Faiz; Verdijk, Rob M; van Esser, Joost W; van Heerde, Marianne J

    2015-11-05

    Autoimmune pancreatitis (AIP) is an important clinical pathologic concept of IgG-4-related disease. AIP is a rare cause of chronic pancreatitis, characterized by a fibroinflammatory process by lymphoplasmacytic infiltrates, storiform fibrosis, obliterative phlebitis, and increased IgG4+ plasma cells, leading to dysfunction of the pancreas. Affected patients with AIP frequently have disease affecting other organs or sites with similar histologic changes, elevated IgG4+ plasma cell infiltrate, and good response to corticosteroid therapy. These diseases often are not limited to the pancreas and the pancreas may not be involved at all. We report a 62-year-old man with obstructive jaundice with pre-existent submandibular lymphadenopathy. Diagnosis of AIP was based on diagnostic criteria by the HISORT-criteria in combination with elevated IgG-4 serum levels. CT revealed a focal enlargement of the head of the pancreas, as well as mesenteric peripancreatic and mediastinal lymphadenopathy. He was treated with high-dose steroid in combination with azathioprine and showed good clinical response. We report a case with pre-existent submandibular lymphadenopathy and obstructive jaundice based on AIP type 1, both in the context of IgG4-related disease.

  11. Cutting Edge: A Critical Role of Lesional T Follicular Helper Cells in the Pathogenesis of IgG4-Related Disease.

    Science.gov (United States)

    Kamekura, Ryuta; Takano, Kenichi; Yamamoto, Motohisa; Kawata, Koji; Shigehara, Katsunori; Jitsukawa, Sumito; Nagaya, Tomonori; Ito, Fumie; Sato, Akinori; Ogasawara, Noriko; Tsubomatsu, Chieko; Takahashi, Hiroki; Nakase, Hiroshi; Himi, Tetsuo; Ichimiya, Shingo

    2017-10-15

    IgG4-related disease (IgG4-RD) is a newly recognized systemic chronic fibroinflammatory disease. However, the pathogenesis of IgG4-RD remains unknown. To determine the pathophysiologic features of IgG4-RD, we examined T follicular helper (Tfh) cells in lesions and blood from patients with IgG4-RD. Patients with IgG4-related dacryoadenitis and sialadenitis (IgG4-DS) showed increased infiltration of Tfh cells highly expressing programmed death 1 and ICOS in submandibular glands. Tfh cells from IgG4-DS submandibular glands had higher expression of B cell lymphoma 6 and a greater capacity to help B cells produce IgG4 than did tonsillar Tfh cells. We also found that the percentage of programmed death 1 hi circulating Tfh cells in IgG4-DS patients was higher than that in healthy volunteers and was well correlated with clinical parameters. Our findings indicate that anomalous Tfh cells in tissue lesions of IgG4-RD have features distinct from those in lymphoid counterparts or blood and potentially regulate local IgG4 production in IgG4-RD. Copyright © 2017 by The American Association of Immunologists, Inc.

  12. An initial exploration for comprehensive assessment of IgG4-related lung disease: analyses on the cases enrolled from a systematic review.

    Science.gov (United States)

    Wang, An; Fan, Jie; Chen, Xiaofeng; Wang, Shaohua

    2018-03-01

    The existence of two diagnostic systems, the Boston and Japan criteria, for immunoglobulin G4-related disease (IgG4-RD) confuse the medical practice. We aimed to develop a comprehensive assessment based on the weight of each diagnostic item in the existing criteria to improve the diagnostic efficiency of Boston criteria. We assessed the patients enrolled by a systematic review of the literatures using the Boston criteria, Japan criteria and a tentative comprehensive assessment respectively, and evaluated the efficiency of each system and their consistency. Our analysis showed that the distinction in pathological diagnostic items was similar for the Boston criteria (IgG4+/IgG+ ratio, Pcomprehensive assessment (IgG4+/IgG+ ratio and the number of pathological features, Pcomprehensive assessment. The current two diagnostic systems have poor consistency. Comprehensive assessment has good agreement with the Boston criteria, but can identify those cases in Boston Category 3 who could still be diagnosed as IgG4-related lung disease. Considering the weight of diagnostic items, the scoring system is a tentative exploration that should be improved with further experience in diagnosing IgG4-related lung disease.

  13. IgG4-related tumour-forming mastitis with histological appearances of granulomatous lobular mastitis: comparison with other types of tumour-forming mastitis.

    Science.gov (United States)

    Ogura, Kanako; Matsumoto, Toshiharu; Aoki, Yuji; Kitabatake, Toshiaki; Fujisawa, Minoru; Kojima, Kuniaki

    2010-07-01

    Sometimes, mastitis needs to be differentiated from carcinoma because of its association with induration and with ultrasound findings (such as low-echo lesions) that resemble those in carcinoma. The aim was to define this type of mastitis and to examine 18 cases to clarify its clinicopathological features. All cases were categorized into three types: non-specific mastitis with neutrophilic infiltration (n = 7); non-specific mastitis with lymphoplasmacytic infiltration (n = 9); and granulomatous lobular mastitis (n = 2). The three types of mastitis presented similar ultrasound findings and shared certain histological features including fibrosis and diffuse or lobulocentric inflammation. Granulomatous lobular mastitis showed specific clinicopathological features including lobulocentric inflammation with giant cells, diffuse IgG4+ plasma cells, and also a high level of serum IgG4. Granulomatous lobular mastitis could be categorized into IgG4-related and non-IgG4-related granulomatous lobular mastitis. IgG4 immunohistochemistry serum IgG4 might be useful for diagnosis of IgG4-related granulomatous lobular mastitis and could help to avoid overtreatment such as wide excision.

  14. IgG4-Related Disease Simulating Carcinoma Colon With Diffuse Peritoneal Carcinomatosis on 18F-FDG PET/CT.

    Science.gov (United States)

    Vadi, Shelvin Kumar; Parihar, Ashwin Singh; Kumar, Rajender; Singh, Harmandeep; Mittal, Bhagwant Rai; Bal, Amanjit; Sinha, Saroj Kumar

    2018-05-14

    IgG4-related disease (IgG4-RD) continues to be a diagnostic challenge and a great mimicker of malignancies. We report here a case of young man who presented with subacute intestinal obstruction with initial imaging and clinical features suggestive of carcinoma colon. 18F-FDG PET/CT showed diffuse peritoneal carcinomatosis pattern typically seen with abdominal malignancies. However, the histopathology and the raised IgG4 levels diagnosed it to be IgG4-RD. Although 18F-FDG PET/CT has typical patterns corresponding to the multisystemic involvement of IgG4-RD, the index case did not show any such findings.

  15. Infraorbital nerve involvement on magnetic resonance imaging in European patients with IgG4-related ophthalmic disease: a specific sign

    Energy Technology Data Exchange (ETDEWEB)

    Soussan, J. Ben; Sadik, J.C.; Savatovsky, J.; Heran, F.; Lecler, A. [Fondation Ophtalmologique Adolphe de Rothschild, Department of Radiology, Paris (France); Deschamps, R. [Fondation Ophtalmologique Adolphe de Rothschild, Department of Neurology, Paris (France); Deschamps, L. [Bichat Hospital, APHP, Department of Pathology, Paris (France); Puttermann, M. [Necker-Enfants Malades Hospital, APHP, Department of Pathology, Paris (France); Zmuda, M.; Galatoire, O. [Fondation Ophtalmologique Adolphe de Rothschild, Department of Orbitopalpebral Surgery, Paris (France); Picard, H. [Fondation Ophtalmologique Adolphe de Rothschild, Clinical Research Unit, Paris (France)

    2017-04-15

    To measure the frequency of infraorbital nerve enlargement (IONE) on magnetic resonance imaging (MRI) in European patients suffering from an IgG4-related ophthalmic disease (IgG4-ROD) as compared to patients suffering from non-IgG4-related ophthalmic disease (non-IgG4-ROD). From January 2006 through April 2015, 132 patients were admitted for non-lymphoma, non-thyroid-related orbital inflammation. Thirty-eight had both pre-therapeutic orbital MRI and histopathological IgG4 immunostaining. Fifteen patients were classified as cases of IgG4-ROD and 23 patients as cases of non-IgG4-ROD. Two readers performed blinded analyses of MRI images. The main criterion was the presence of an IONE, defined as the infraorbital nerve diameter being greater than the optic nerve diameter in the coronal section. IONE was present in 53% (8/15) of IgG4-ROD cases whereas it was never present (0/23) in cases of non-IgG4-ROD (P < 0.0001). IONE was only present in cases where, on MRI, the inflammation of the inferior quadrant was present and in direct contact with the ION canal. In European patients suffering from orbital inflammation, the presence of IONE on an MRI is a specific sign of IgG4-ROD. Recognition of this pattern may facilitate the accurate diagnosis for clinicians and allow for the adequate management and appropriate care of their patients. (orig.)

  16. Increased IgG4-Positive Plasma Cells in Granulomatosis with Polyangiitis: A Diagnostic Pitfall of IgG4-Related Disease

    Directory of Open Access Journals (Sweden)

    Sing Yun Chang

    2012-01-01

    Full Text Available Granulomatosis with polyangiitis (Wegener’s (GPA may mimic IgG4-related disease (IgG4-RD on histologic examination of some biopsies, especially those from head and neck sites. IgG4 immunostain is often performed in this context for differential diagnosis with IgG4-RD. However, the prevalence of IgG4+ cells in GPA has not been explored. We examined the IgG4+ cells in 26 cases confirmed as GPA by a thorough clinical and pathologic assessment. Twenty-six biopsies consisted of 14 sinonasal/oral cavity/nasopharynx, 7 orbit/periorbital, 3 lung/pleura, 1 iliac fossa/kidney, and 1 dura specimens. Eight of 26 (31% biopsies revealed increased IgG4+ cells (>30/HPF and >40% in IgG4+/IgG+ ratio. The IgG4+ cells and IgG4+/IgG+ ratio ranged 37–137/hpf and 44–83%, respectively. Eight biopsies with increased IgG4+ cells were from sinonasal (n=4 or orbital/periorbital (n=4 sites. In conclusion, increased IgG4+ cells are not uncommonly seen in sinonasal or orbital/periorbital biopsies of GPA, which could pose as a diagnostic pitfall.

  17. Histopathological Diagnostic Value of the IgG4+/IgG+ Ratio of Plasmacytic Infiltration for IgG4-Related Diseases

    Science.gov (United States)

    Deng, Chuiwen; Li, Wenli; Chen, Si; Zhang, Wen; Li, Jing; Hu, Chaojun; Wen, Xiaoting; Zhang, Fengchun; Li, Yongzhe

    2015-01-01

    Abstract This article aims to perform a meta-analysis to evaluate the diagnostic value of the immunoglobulin G (IgG)4+/IgG+ ratio of plasmacytic infiltration for IgG4-related diseases. Four databases—EMBASE, ISI Web of Knowledge, PubMed, and the Cochrane Library—were systematically searched. Approximately 200 participants from several studies were included in this research. STATA 11.2 software (Stata Corporation, College Station, TX) and Meta-DiSc 1.4 (Unit of Clinical Biostatistics, Ramon y Cajal Hospital, Madrid, Spain) were used to perform the meta-analysis. Nine studies were included in the meta-analysis. The pooled diagnostic odds ratio was 18.94 [95% confidence interval (CI), 2.89–124.30]. The sensitivity was 58.80% (95% CI, 50.90–66.30) and the specificity was 90.20% (95% CI, 81.20–95.80). The positive and negative likelihood ratios were 3.12 (95% CI, 1.07–9.16) and 0.26 (95% CI, 0.09–0.70), respectively. The area under the curve of the summary receiver-operating characteristic was 0.88. To conclude, the IgG4+/IgG+ ratio of plasmacytic infiltration is modestly effective in diagnosing IgG-related disease. PMID:25738476

  18. Infraorbital nerve involvement on magnetic resonance imaging in European patients with IgG4-related ophthalmic disease: a specific sign.

    Science.gov (United States)

    Soussan, J Ben; Deschamps, R; Sadik, J C; Savatovsky, J; Deschamps, L; Puttermann, M; Zmuda, M; Heran, F; Galatoire, O; Picard, H; Lecler, A

    2017-04-01

    To measure the frequency of infraorbital nerve enlargement (IONE) on magnetic resonance imaging (MRI) in European patients suffering from an IgG4-related ophthalmic disease (IgG4-ROD) as compared to patients suffering from non-IgG4-related ophthalmic disease (non-IgG4-ROD). From January 2006 through April 2015, 132 patients were admitted for non-lymphoma, non-thyroid-related orbital inflammation. Thirty-eight had both pre-therapeutic orbital MRI and histopathological IgG4 immunostaining. Fifteen patients were classified as cases of IgG4-ROD and 23 patients as cases of non-IgG4-ROD. Two readers performed blinded analyses of MRI images. The main criterion was the presence of an IONE, defined as the infraorbital nerve diameter being greater than the optic nerve diameter in the coronal section. IONE was present in 53% (8/15) of IgG4-ROD cases whereas it was never present (0/23) in cases of non-IgG4-ROD (P IgG4-ROD. Recognition of this pattern may facilitate the accurate diagnosis for clinicians and allow for the adequate management and appropriate care of their patients. • IONE on an MRI is a specific sign of IgG4-ROD. • IONE recognition allows for a quicker diagnosis and appropriate management. • IONE appears when inflammation is in direct contact with the ION canal.

  19. Change of Serum IgG4 in Patients with Ocular Adnexal Marginal Zone B Cell Lymphoma Associated with IgG4-Related Ophthalmic Disease After Treatment.

    Science.gov (United States)

    Wu, Yuan-Hung; Wang, Lei-Chi; Yen, Sang-Hue; Yu, Wei-Kuang; Kao, Shu-Ching; Kau, Hui-Chuan; Tsai, Chieh-Chih; Liu, Catherine Jui-Ling

    2017-09-01

    To investigate the change of serum IgG4 concentrations correlated with clinical evolution in patients with ocular adnexal marginal zone B cell lymphoma associated with IgG4-related ophthalmic disease (IgG4-ROD). Three consecutive patients with histopathologically confirmed ocular adnexal marginal zone B cell lymphoma associated with IgG4-ROD were evaluated. Two patients received radiotherapy and 1 patient received steroid therapy. Treatment outcome was evaluated by clinical symptoms, radiologic examination, and change of serum IgG4 level in these patients. All patients had elevated serum IgG4 before treatment (462, 338, and 780 mg/dL respectively.) The 2 patients who received radiotherapy achieved complete remission and the serum IgG4 decreased to 345 and 92 mg/dL, respectively. The patient who underwent systemic steroid achieved partial remission and the serum IgG4 decrease to 161 mg/dL. Our study showed elevated serum IgG4 in all patients with ocular adnexal marginal zone B cell lymphoma associated with IgG4-ROD. In addition, the elevated serum IgG4 may decrease or keep stable after treatment, accompanied by improvement in clinical symptoms and reduction of lesions.

  20. Infraorbital nerve involvement on magnetic resonance imaging in European patients with IgG4-related ophthalmic disease: a specific sign

    International Nuclear Information System (INIS)

    Soussan, J. Ben; Sadik, J.C.; Savatovsky, J.; Heran, F.; Lecler, A.; Deschamps, R.; Deschamps, L.; Puttermann, M.; Zmuda, M.; Galatoire, O.; Picard, H.

    2017-01-01

    To measure the frequency of infraorbital nerve enlargement (IONE) on magnetic resonance imaging (MRI) in European patients suffering from an IgG4-related ophthalmic disease (IgG4-ROD) as compared to patients suffering from non-IgG4-related ophthalmic disease (non-IgG4-ROD). From January 2006 through April 2015, 132 patients were admitted for non-lymphoma, non-thyroid-related orbital inflammation. Thirty-eight had both pre-therapeutic orbital MRI and histopathological IgG4 immunostaining. Fifteen patients were classified as cases of IgG4-ROD and 23 patients as cases of non-IgG4-ROD. Two readers performed blinded analyses of MRI images. The main criterion was the presence of an IONE, defined as the infraorbital nerve diameter being greater than the optic nerve diameter in the coronal section. IONE was present in 53% (8/15) of IgG4-ROD cases whereas it was never present (0/23) in cases of non-IgG4-ROD (P < 0.0001). IONE was only present in cases where, on MRI, the inflammation of the inferior quadrant was present and in direct contact with the ION canal. In European patients suffering from orbital inflammation, the presence of IONE on an MRI is a specific sign of IgG4-ROD. Recognition of this pattern may facilitate the accurate diagnosis for clinicians and allow for the adequate management and appropriate care of their patients. (orig.)

  1. Lupus nephritis

    African Journals Online (AJOL)

    1991-03-02

    Mar 2, 1991 ... will benefit from immunosuppressive therapy. Our study found hypertension, which persisted at the most recent follow-up, to be associated with a poor outcome, as was poor renal function both at biopsy and follow-up. Leaker er al. I found that survival in lupus nephritis is unaffected by age, sex, nephrotic ...

  2. Long-term efficacy and safety of rituximab in IgG4-related disease: Data from a French nationwide study of thirty-three patients.

    Directory of Open Access Journals (Sweden)

    Mikael Ebbo

    Full Text Available To assess efficacy and safety of rituximab (RTX as induction therapy, maintenance of remission and treatment of relapses in a cohort of IgG4-related disease (IgG4-RD patients.Nationwide retrospective multicenter study of IgG4-RD patients treated with at least one course of RTX. Clinical, biological and radiological response, relapse rate and drug tolerance were analyzed. Kaplan-Meier curves were plotted and risk factors for relapse studied with a Cox regression model.Among 156 IgG4-RD patients included in the French database, 33 received rituximab. Clinical response was noted in 29/31 (93.5% symptomatic patients. Glucocorticoids withdrawal was achieved in 17 (51.5% patients. During a mean follow-up of 24.8 ±21 months, 13/31 (41.9% responder patients relapsed after a mean delay of 19 ±11 months after RTX. Active disease, as defined by an IgG4-RD Responder Index >9 before RTX, was significantly associated with relapse (HR = 3.68, 95% CI: 1.1, 12.6 (P = 0.04, whereas maintenance therapy with systematic (i.e. before occurrence of a relapse RTX retreatment was associated with longer relapse-free survival (41 versus 21 months; P = 0.02. Eight severe infections occurred in 4 patients during follow-up (severe infections rate of 12.1/100 patient-years and hypogammaglobulinemia ≤5 g/l in 3 patients.RTX is effective for both induction therapy and treatment of relapses in IgG4-RD, but relapses are frequent after B-cell reconstitution. Maintenance therapy with systematic RTX infusions is associated with longer relapse-free survival and might represent a novel treatment strategy. Yet, the high rate of infections and the temporary effect of RTX might be hindrances to such strategy.

  3. Comparison of clinical and pathological features of lung lesions of systemic IgG4-related disease and idiopathic multicentric Castleman's disease.

    Science.gov (United States)

    Terasaki, Yasuhiro; Ikushima, Soichiro; Matsui, Shoko; Hebisawa, Akira; Ichimura, Yasunori; Izumi, Shinyu; Ujita, Masuo; Arita, Machiko; Tomii, Keisuke; Komase, Yuko; Owan, Isoko; Kawamura, Tetsuji; Matsuzawa, Yasuo; Murakami, Miho; Ishimoto, Hiroshi; Kimura, Hiroshi; Bando, Masashi; Nishimoto, Norihiro; Kawabata, Yoshinori; Fukuda, Yuh; Ogura, Takashi

    2017-06-01

    The lung lesion [immunoglobulin (Ig)G4-L] of IgG4-related disease (IgG4-RD) is a condition that occurs together with IgG4-RD and often mimics the lung lesion [idiopathic multicentric Castleman's disease (iMCD-L)] of idiopathic multicentric Castleman's disease (iMCD). Because no clinical and pathological studies had previously compared features of these diseases, we undertook this comparison with clinical and histological data. Nine patients had IgG4-L (high levels of serum IgG4 and of IgG4 + cells in lung specimens; typical extrapulmonary manifestations). Fifteen patients had iMCD-L (polyclonal hyperimmunoglobulinaemia, elevated serum interleukin-6 levels and polylymphadenopathy with typical lymphadenopathic lesions). Mean values for age, serum haemoglobin levels and IgG4/IgG ratios were higher in the IgG4-L group and C-reactive protein levels were higher in the iMCD-L group. All IgG4-RD lung lesions showed myxomatous granulation-like fibrosis (active fibrosis), with infiltration of lymphoplasmacytes and scattered eosinophils within the perilymphatic stromal area, such as interlobular septa and pleura with obstructive vasculitis. All 15 lung lesions of iMCD, however, had marked accumulation of polyclonal lymphoplasmacytes in lesions with lymphoid follicles and dense fibrosis, mainly in the alveolar area adjacent to interlobular septa and pleura without obstructive vasculitis. Although both lesions had lymphoplasmacytic infiltration, lung lesions of IgG4-RD were characterized by active fibrosis with eosinophilic infiltration within the perilymphatic stromal area with obstructive vasculitis, whereas lung lesions of iMCD had lymphoplasmacyte proliferating lesions mainly in the alveolar area adjacent to the perilymphatic stromal area. These clinicopathological features may help to differentiate the two diseases. © 2017 John Wiley & Sons Ltd.

  4. A Comparative Analysis of Serum IgG4 Levels in Patients With IgG4-Related Disease and Other Disorders.

    Science.gov (United States)

    Wang, Li; Chu, Xinmin; Ma, Yan; Zhang, Min; Wang, Xue; Jin, Li; Tan, Zhen; Li, Xiangpei; Li, Xiaomei

    2017-09-01

    Elevated serum IgG4 levels are an important hallmark for diagnosing IgG4-related disease (IgG4-RD) but can also be found and reported in other diseases. The present study intended to compare the serum IgG4 levels in both IgG4-RD and non-IgG4-RD and determine the serum IgG4 levels in patients with IgG4-RD before and after glucocorticoid therapy. The study included 323 patients from Anhui Medical University Affiliated Provincial Hospital (China) and was conducted from July 2014-January 2016. A total of 25 patients were eventually diagnosed as having IgG4-RD, according to the IgG4-RD diagnostic criteria. Our study also included 108 patients with connective tissue disease, 94 patients with pancreatic lesions, 66 patients with bile duct lesions, 13 patients with carcinoma of the duodenal papilla and 20 control participants. The assay for serum IgG4 detection was peformed using the nephelometric method. Elevated levels of serum IgG4 (>1.35g/L) were detected in all patients with IgG4-RD, and reduced levels of serum IgG4 (IgG4-RD. The serum IgG4 level in patients with IgG4-RD after glucocorticoid therapy was significantly lower than that before glucocorticoid therapy (t = 2.426, P = 0.04). High levels of IgG4 were observed in IgG4-RD. However, a diagnosis of IgG4 disease can not only be dependent on the detection of elevated serum IgG4 levels but also may need clinical manifestations, serology, histopathology and other comprehensive information for verification. Copyright © 2017 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

  5. Long-term efficacy and safety of rituximab in IgG4-related disease: Data from a French nationwide study of thirty-three patients

    Science.gov (United States)

    Grados, Aurélie; Samson, Maxime; Groh, Matthieu; Loundou, Anderson; Rigolet, Aude; Terrier, Benjamin; Guillaud, Constance; Carra-Dallière, Clarisse; Renou, Frédéric; Pozdzik, Agnieszka; Labauge, Pierre; Palat, Sylvain; Berthelot, Jean-Marie; Pennaforte, Jean-Loup; Wynckel, Alain; Lebas, Céline; Le Gouellec, Noémie; Quémeneur, Thomas; Dahan, Karine; Carbonnel, Franck; Leroux, Gaëlle; Perlat, Antoinette; Mathian, Alexis; Cacoub, Patrice; Hachulla, Eric; Costedoat-Chalumeau, Nathalie; Harlé, Jean-Robert; Schleinitz, Nicolas

    2017-01-01

    Objectives To assess efficacy and safety of rituximab (RTX) as induction therapy, maintenance of remission and treatment of relapses in a cohort of IgG4-related disease (IgG4-RD) patients. Methods Nationwide retrospective multicenter study of IgG4-RD patients treated with at least one course of RTX. Clinical, biological and radiological response, relapse rate and drug tolerance were analyzed. Kaplan-Meier curves were plotted and risk factors for relapse studied with a Cox regression model. Results Among 156 IgG4-RD patients included in the French database, 33 received rituximab. Clinical response was noted in 29/31 (93.5%) symptomatic patients. Glucocorticoids withdrawal was achieved in 17 (51.5%) patients. During a mean follow-up of 24.8 ±21 months, 13/31 (41.9%) responder patients relapsed after a mean delay of 19 ±11 months after RTX. Active disease, as defined by an IgG4-RD Responder Index >9 before RTX, was significantly associated with relapse (HR = 3.68, 95% CI: 1.1, 12.6) (P = 0.04), whereas maintenance therapy with systematic (i.e. before occurrence of a relapse) RTX retreatment was associated with longer relapse-free survival (41 versus 21 months; P = 0.02). Eight severe infections occurred in 4 patients during follow-up (severe infections rate of 12.1/100 patient-years) and hypogammaglobulinemia ≤5 g/l in 3 patients. Conclusion RTX is effective for both induction therapy and treatment of relapses in IgG4-RD, but relapses are frequent after B-cell reconstitution. Maintenance therapy with systematic RTX infusions is associated with longer relapse-free survival and might represent a novel treatment strategy. Yet, the high rate of infections and the temporary effect of RTX might be hindrances to such strategy. PMID:28915275

  6. Usefulness of Flow Cytometry in Diagnosis of IgG4-Related Ophthalmic Disease and Extranodal Marginal Zone B-Cell Lymphoma of the Ocular Adnexa.

    Science.gov (United States)

    Kase, Satoru; Ishijima, Kan; Uraki, Takehiko; Suimon, Yuka; Suzuki, Yasuo; Kase, Manabu; Ishida, Susumu

    2017-09-01

    Although flow cytometry (FCM) is used to evaluate cell surface markers of various leucocyte populations quantitatively, little is known about the usefulness of FCM in lymphoproliferative disorders of the ocular adnexa. The aim of this study was to disclose results of FCM, which were compared among IgG4-related ophthalmic disease (IgG4-ROD), idiopathic orbital inflammation (IOI), and extranodal marginal zone B-cell lymphoma (EMZL). This is a retrospective observational study. Sixty-nine tumors comprising of 16 IgG4-ROD, 24 IOI, and 29 EMZL were enrolled in the study. All tumors, surgically excised, were diagnosed based on histopathology, immunoglobulin (Ig) heavy chain gene rearrangement, and FCM. In FCM, the percentage of T-cell markers (CD2, CD3, CD4, CD5, CD7, CD8), B-cell markers (CD10, CD19, CD20, CD23), NK cell marker (CD56) and cell surface kappa/lambda was searched based on medical records. Ig light chain restriction was evaluated from results in kappa/lambda deviation by FCM. The percentage of CD2, CD3, CD4, CD7, and CD10 was significantly higher in IgG4-ROD/IOI than EMZL (pIgG4-ROD/IOI (pIgG4-ROD and IOI. Kappa-positive cells were significantly greater in EMZL than IgG4-ROD/IOI (pIgG4-ROD/IOI and false-negative was observed in 10 (34.5%) EMZL cases. Sensitivity and specificity of Ig light chain restriction were 65.5 and 92.5%, respectively. Analyses of cell surface markers using FCM were useful in differentiating EMZL from IgG4-ROD/IOI. Sensitivity of Ig light chain restriction was relatively low in diagnosis of EMZL using FCM. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  7. Immunohistochemical analysis of IgA expression differentiates IgG4-related disease from plasma cell-type Castleman disease.

    Science.gov (United States)

    Manabe, Akihiro; Igawa, Takuro; Takeuchi, Mai; Gion, Yuka; Yoshino, Tadashi; Sato, Yasuharu

    2017-03-01

    Plasma cell-type Castleman disease (PCD) is often encountered when differentiating IgG4-related disease (IgG4-RD). Given that serum IgA is often elevated in Castleman disease, we investigated whether IgA expression levels in histological specimens can be used to differentiate between the two diseases. Lymph node lesions obtained from 12 IgG4-RD and 11 PCD patients were analysed by immunohistochemistry with anti-IgG, -IgG4, and -IgA antibodies. In addition to all 12 cases of IgG4-RD, 8/11 cases (72.7 %) of PCD also met the diagnostic criteria of IgG4-RD (serum IgG4 ≥135 mg/dl and IgG4/IgG-positive cells ≥40 %). IgA-positive cells were sparsely and densely distributed in IgG4-RD and PCD cases, respectively. The median number of IgA-positive cells ± SD in all 12 cases of IgG4-RD was 31 ± 37 cells per three high-powered fields (3HPFs) (range 4-118 cells/3HPFs). In contrast, the median number of IgA-positive cells, which was significantly higher in all 11 cases of PCD, was 303 ± 238 cells/3HPFs (range 74-737 cells/3HPFs) (P IgG4-RD.

  8. Establishment of a serum IgG4 cut-off value for the differential diagnosis of IgG4-related disease in Chinese population.

    Science.gov (United States)

    Li, Ping; Chen, Hua; Deng, Chuiwen; Wu, Ziyan; Lin, Wei; Zeng, Xiaofeng; Zhang, Wen; Zhang, Fengchun; Li, Yongzhe

    2016-07-01

    This study was performed to better know diagnosis associated with serum IgG4 concentration, and to explore the possibility for development of a serum IgG4 for IgG4-related disease (IgG4-RD) in Chinese populations. We studied retrospectively 497 IgG4 serum subclass measurements from Peking Union Medical College Hospital during the four-year period, including 242 IgG4-RD, 130 other diseases and 125 healthy individuals. Serum IgG4 concentrations were significantly higher in IgG4-RD than in other pathologies (1662.9 ± 3760.9 mg/L, p IgG4 level between other pathologies group and healthy individuals (p = 0.075). Among the 242 IgG4-RD patients analyzed, serum IgG4 concentrations were normal in 46 patients (19.0%). We found 32 patients (24.6%) with elevated serum IgG4 levels among the 130 patients who suffered from other pathologies. There were seven (5.6%) with serum IgG4 over 1350 mg/L in healthy individuals. The ROC curve analysis revealed that the optimal sensitivity and specificity were 80.0% and 88.2%, respectively, at the concentration of 1575 mg/L for Chinese patients. Our study demonstrated that serum IgG4 elevation was not specific of IgG4-RD. Further studies are needed to define the sensibility and specificity of IgG4 values for the diagnosis of IgG4-RD.

  9. Increased IgG4 responses to multiple food and animal antigens indicate a polyclonal expansion and differentiation of pre-existing B cells in IgG4-related disease

    NARCIS (Netherlands)

    Culver, Emma L.; Vermeulen, Ellen; Makuch, Mateusz; van Leeuwen, Astrid; Sadler, Ross; Cargill, Tamsin; Klenerman, Paul; Aalberse, Rob C.; van Ham, S. Marieke; Barnes, Eleanor; Rispens, Theo

    2015-01-01

    IgG4-related disease (IgG4-RD) is a systemic fibroinflammatory condition, characterised by an elevated serum IgG4 concentration and abundant IgG4-positive plasma cells in the involved organs. An important question is whether the elevated IgG4 response is causal or a reflection of immune-regulatory

  10. Value of serum IgG4 in the diagnosis of IgG4-related disease and in differentiation from rheumatic diseases and other diseases.

    Science.gov (United States)

    Yamamoto, Motohisa; Tabeya, Tetsuya; Naishiro, Yasuyoshi; Yajima, Hidetaka; Ishigami, Keisuke; Shimizu, Yui; Obara, Mikiko; Suzuki, Chisako; Yamashita, Kentaro; Yamamoto, Hiroyuki; Hayashi, Toshiaki; Sasaki, Shigeru; Sugaya, Toshiaki; Ishida, Tadao; Takano, Ken-Ichi; Himi, Tetsuo; Suzuki, Yasuo; Nishimoto, Norihiro; Honda, Saho; Takahashi, Hiroki; Imai, Kohzoh; Shinomura, Yasuhisa

    2012-06-01

    IgG4-related disease (IgG4-RD) is a novel disease entity that includes Mikulicz's disease, autoimmune pancreatitis (AIP), and many other conditions. It is characterized by elevated serum IgG4 levels and abundant IgG4-bearing plasmacyte infiltration of involved organs. We postulated that high levels of serum IgG4 would comprise a useful diagnostic tool, but little information is available about IgG4 in conditions other than IgG4-RD, including rheumatic diseases. Several reports have described cutoff values for serum IgG4 when diagnosing IgG4-RD, but these studies mostly used 135 mg/dL in AIP to differentiate from pancreatic cancer instead of rheumatic and other common diseases. There is no evidence for a cutoff serum IgG4 level of 135 mg/dL for rheumatic diseases and common diseases that are often complicated with rheumatic diseases. The aim of this work was to re-evaluate the usual cutoff serum IgG4 value in AIP (135 mg/dL) that is used to diagnose whole IgG4-RD in the setting of a rheumatic clinic by measuring serum IgG4 levels in IgG4-RD and various disorders. We therefore constructed ROC curves of serum IgG4 levels in 418 patients who attended Sapporo Medical University Hospital due to IgG4-RD and various rheumatic and common disorders. The optimal cut-off value of serum IgG4 for a diagnosis of IgG4-RD was 144 mg/dL, and the sensitivity and specificity were 95.10 and 90.76%, respectively. Levels of serum IgG4 were elevated in IgG4-RD, Churg-Strauss syndrome, multicentric Castleman's disease, eosinophilic disorders, and in some patients with rheumatoid arthritis, systemic sclerosis, chronic hepatitis, and liver cirrhosis. The usual cut-off value of 135 mg/dL in AIP is useful for diagnosing whole IgG4-RD, but high levels of serum IgG4 are sometimes observed in not only IgG4-RD but also other rheumatic and common diseases.

  11. Combination therapy of leflunomide and glucocorticoids for the maintenance of remission in patients with IgG4-related disease: a retrospective study and literature review.

    Science.gov (United States)

    Wang, Yiwen; Li, Kunpeng; Gao, Dai; Luo, Gui; Zhao, Yurong; Wang, Xiuru; Zhang, Jie; Jin, Jingyu; Zhao, Zheng; Yang, Chunhua; Zhu, Jian; Zhang, Jianglin; Huang, Feng

    2017-06-01

    Although glucocorticoids are effective in IgG4-related disease (IgG4-RD), patients may relapse during or after glucocorticoid tapering. Immunosuppressive agents, including leflunomide (LEF), are regarded as steroid-sparing agents in other autoimmune disorders and need to be discussed in the management of IgG4-RD. To identify the efficacy and safety of combination therapy of LEF and glucocorticoids in IgG4-RD. We retrospectively summarised data of patients diagnosed with IgG4-RD between November 2012 and November 2015. Only patients treated with LEF plus glucocorticoids and had been followed up for more than three visits and 6 months were analysed with clinical symptoms, laboratory and imaging findings, treatment protocol, LEF-related adverse events and disease activity reflected by IgG4-RD Responder Index (IgG4-RD RI). A total of 18 patients, including 14 untreated patients and 4 relapsing patients, was included. The mean (SD) onset age was 54.0 (9.6) years. The mean (SD) follow-up period was 12.1 (7.4) months. All patients had active disease with mean (SD) IgG4-RD RI of 15.0 (5.6) at baseline and experienced improvements at 1 month. At the last follow up, the mean (SD) IgG4-RD Responder Index declined to 3.1 (1.7) in all patients and to 2.5 (1.2) in patients without relapse. The mean (SD) dose of GC declined to 6.9 (2.7) mg/day. A total of 12 (66.7%) and 11 (61.1%) patients were in remission at 6 months and the last follow up respectively. Three (16.7%) patients relapsed in clinical course. Two reversible adverse events were observed. The combination therapy of LEF and glucocoticoids is effective and safe in IgG4-RD. © 2017 Royal Australasian College of Physicians.

  12. B cell subsets and dysfunction of regulatory B cells in IgG4-related diseases and primary Sjögren’s syndrome: the similarities and differences

    Science.gov (United States)

    2014-01-01

    Introduction IgG4-related disease (IgG4-RD) is a multisystem-involved autoimmune disease. Abnormally activated and differentiated B cells may play important roles. Regulatory B cells (Breg) are newly defined B cell subgroups with immunosuppressive functions. In this study, we investigated the differences of B cell subsets, the expressions of co-stimulatory molecules on B cells, and the function of Breg cells in patients with IgG4-RD, primary Sjögren’s syndrome (pSS) as well as in healthy controls (HC). Methods Newly diagnosed IgG4-RD patients (n = 48) were enrolled, 38 untreated pSS patients and 30 healthy volunteers were recruited as disease and healthy controls. To analyze B cell subsets and B cell activity, PBMCs were surface stained and detected by flow cytometry. The function of Breg cells was tested by coculturing isolated CD19 + CD24hiCD38hi Breg cells with purified CD4 + CD25- T cells. Serum cytokines were measured by ELISA and cytometric bead array. Relationship between clinical data and laboratory findings were analyzed as well. Results Compared with pSS patients and HC, IgG4-RD patients had a lower frequency of peripheral Breg cells. Interestingly, CD19 + CD24-CD38hi B cell subsets were significantly higher in peripheral B cells from IgG4-RD patients than in pSS patients and HC, which correlated with serum IgG4 levels. The expression of BAFF-R and CD40 on B cells was significantly lower in IgG4-RD patients compared with those in pSS patients and HC. Unlike HC, Breg cells from pSS patients lacked suppressive functions. Conclusions B cells in patients with IgG4-RD and pSS display a variety of abnormalities, including disturbed B cell subpopulations, abnormal expression of key signaling molecules, co-stimulatory molecules, and inflammatory cytokines. In addition, a significantly increased B cell subset, CD19 + CD24-CD38hi B cells, may play an important role in the pathogenesis of IgG4-RD. PMID:24887143

  13. Quantitative measurement of 18F-FDG PET/CT uptake reflects the expansion of circulating plasmablasts in IgG4-related disease.

    Science.gov (United States)

    Berti, Alvise; Della-Torre, Emanuel; Gallivanone, Francesca; Canevari, Carla; Milani, Raffaella; Lanzillotta, Marco; Campochiaro, Corrado; Ramirez, Giuseppe Alvise; Bozzalla Cassione, Emanuele; Bozzolo, Enrica; Pedica, Federica; Castiglioni, Isabella; Arcidiacono, Paolo Giorgio; Balzano, Gianpaolo; Falconi, Massimo; Gianolli, Luigi; Dagna, Lorenzo

    2017-12-01

    [18F]Fluorodeoxyglucose (18F-FDG) PET/CT is increasingly used to assess organ involvement and response to treatment in IgG4-related disease (IgG4-RD), but clear correlations between 18F-FDG uptake and disease activity have not been established yet. We aimed to correlate the intensity and distribution of 18F-FDG uptake with validated clinical, serological and immunological parameters of IgG4-RD activity. Twenty patients with active IgG4-RD underwent a baseline 18F-FDG PET/CT. Ten patients repeated 18F-FDG PET/CT after immunosuppressive treatments. 18F-FDG tissue uptake was measured using the standardized uptake value corrected for the partial volume effect (PVC-SUV) and the total lesion glycolysis (TLG) with (TLGtot+ln) and without (TLGtot-ln) lymph nodes. Disease activity was assessed by means of clinical parameters [IgG4-RD Responder Index (RI)], serological (ESR and CRP) and immunological (serum IgG4 and circulating plasmablasts) biomarkers. The enhanced liver fibrosis score was exploited as a biomarker for fibroblast activation. Thirteen (65%) patients had two or more organs affected by IgG4-RD. All patients had active IgG4-RD as defined by a median IgG4-RD RI value of 9 (range 6-15; normal IgG4 and plasmablasts were elevated in 85% of patients. Circulating plasmablasts positively correlated with PVC-SUV (P = 0.027), inversely correlated with TLGtot-ln (P = 0.023) and did not correlate with TLGtot+ln (P > 0.05). No statistically significant correlation was found between PVC-SUV or TLG and IgG4-RD RI, ESR, CRP, serum IgG4 or enhanced liver fibrosis score (P > 0.05). Clinical response to immunosuppressive therapies was associated with a consensual reduction of circulating plasmablasts, PVC-SUV, TLGtot+ln and TLGtot-ln values (P IgG4-RD lesions reflects immunological perturbations of the B cell compartment rather than fibroblast activation and extracellular matrix deposition. Conventional biomarkers of disease activity, namely IgG4-RD RI, ESR, CRP and serum IgG4 levels, do not appear to correlate with the radiometabolic activity of IgG4-RD lesions. In light of our results PET/CT represents a reliable instrument for assessing IgG4-RD activity, although lymph-node uptake deserves careful interpretation. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  14. Overlap of Post-obstructive Diuresis and Unmasked Diabetes Insipidus in a Case of IgG4-related Retroperitoneal Fibrosis and Tuberoinfundibular Hypophysitis: A Case Report and Review of the Literature.

    Science.gov (United States)

    Sasaki Yatabe, Midori; Watanabe, Kimio; Hayashi, Yoshimitsu; Yatabe, Junichi; Morimoto, Satoshi; Ichihara, Atsuhiro; Nakayama, Masaaki; Watanabe, Tsuyoshi

    The clinical picture of IgG4-related disease (IgG4-RD) is diverse because various organs can be affected. We describe the case of a 56-year-old man with acute renal failure and tuberoinfundibular hypophysitis due to IgG4-RD. Steroid therapy lowered the serum IgG4 level and ameliorated renal dysfunction, bilateral hydronephrosis and retroperitoneal fibrosis. However, polyuria from post-obstructive diuresis and unmasked central diabetes insipidus ensued. The patient's polyuria continued despite the administration of a therapeutic dose of glucocorticoid; the patient's pituitary swelling and anterior pituitary dysfunction were partially ameliorated. The pituitary swelling recurred seven months later. In patients with IgG4-RD, the manifestation of polyuria after steroid therapy should prompt suspicion of post-obstructive diuresis and the unmasking of central diabetes insipidus.

  15. IgG4-Related Sclerosing Cholangitis.

    Science.gov (United States)

    Nakazawa, Takahiro; Shimizu, Shuya; Naitoh, Itaru

    2016-08-01

    More men than women develop immunoglobulin G4-related sclerosing cholangitis (IgG4-SC). Age at clinical onset is significantly older in patients with IgG4-SC. Patients with IgG4-SC appear similar to those with cholangiocarcinoma and primary sclerosing cholangitis (PSC). The association between IgG4-SC and autoimmune pancreatitis (AIP) is useful for the diagnosis of IgG4-SC. However, some IgG4-SC cases are isolated from AIP and are difficult to diagnose. The authors focus on three distinct features of IgG4-SC. First, diffuse inflammation induces a longer stenosis on cholangiography in contrast to the short stenosis of patients with PSC. Second, fibroinflammatory involvement is observed mainly in the stroma of the bile duct wall, whereas the bile duct epithelium is intact. Third, steroid therapy results in remarkable improvement. Although the prognosis of patients with IgG4-SC is good, some cases have developed portal hypertension and liver cirrhosis during their clinical course. Further study is needed to elucidate the long-term outcomes and mechanism of IgG4-SC. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  16. Radiation nephritis causing nephrotic syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Jennette, J.C.; Ordonez, N.G.

    1983-12-01

    Clinical symptoms of acute radiation nephritis with nephrotic syndrome developed in a fifty-six-year-old woman after abdominal radiation therapy for an astrocytoma of the spinal cord. The diagnosis of radiation nephritis was confirmed by renal biopsy. To our knowledge, this is the first documented case of radiation nephritis associated with nephrotic syndrome.

  17. Estimation of the number of histological diagnosis for IgG4-related kidney disease referred to the data obtained from the Japan Renal Biopsy Registry (J-RBR) questionnaire and cases reported in the Japanese Society of Nephrology Meetings.

    Science.gov (United States)

    Nakashima, Hitoshi; Kawano, Mitsuhiro; Saeki, Takako; Ubara, Yoshifumi; Hisano, Satoshi; Nagata, Michio; Zen, Yoh; Yanagita, Motoko; Yamaguchi, Yutaka; Nishi, Shinichi; Saito, Takao

    2017-02-01

    More than 2 years have passed since the proposal of the diagnostic criteria for IgG4-related kidney disease (IgG4-RKD). The aim of this study was to estimate the number of histological diagnosis for IgG4-RKD throughout Japan and to clarify the regional distribution of the development of this disease. A questionnaire was supplied to 140 research facilities registered in the Japan Renal Biopsy Registry (J-RBR). The items of the questionnaire were the total number of renal biopsies performed and the number of cases diagnosed as IgG4-RKD in 2012 and 2013 at each facility. Age, sex, and diagnosis category were also included for the IgG4-RKD cases. The geographic distribution of the disease development was evaluated using clinical case reports presented at the Eastern/Western regional meeting of the Japanese Society of Nephrology during the 15 years following 2001. Forty-seven facilities completed the questionnaire, resulting in a collection rate of 34 %. The total numbers of renal biopsies in 2012 and 2013 were 3387 and 3591, respectively. Forty-seven of these cases (24 in 2012 and 23 in 2013) were diagnosed as IgG4-RKD. The frequency of development of IgG4-RKD per one million over 40-year-old individuals during these 15 years varied between 0.9 and 3.1, depending on Japanese geographic region of Japan. The results of the present survey indicate that the number of diagnosis for IgG4-RKD is approximately 130 cases per year throughout Japan, and no regional differences in disease frequency appear to exist.

  18. Serum IgG2 and tissue IgG2 plasma cell elevation in orbital IgG4-related disease (IgG4-RD): Potential use in IgG4-RD assessment.

    Science.gov (United States)

    Chan, Anita S Y; Mudhar, Hardeep; Shen, Sunny Yu; Lang, Stephanie S; Fernando, Malee; Hilmy, Maryam Hazly; Guppy, Naomi Jayne; Rennie, Ian; Dunkley, Lisa; Al Jajeh, Issam

    2017-11-01

    To determine the role of serum and tissue IgG2 in orbital biopsies with the histological features of IgG4-related disease (IgG4-RD) in comparison with non-IgG4-related orbital inflammatory disorders (OID), including autoimmune disorders. This is an international (Sheffield, UK, and Singapore) collaborative, retrospective case review of 69 patients (38 from Singapore National Eye Centre and 31 from Royal Hallamshire Hospital, Sheffield) with orbital inflammatory biopsies between 2002 and 2016. Clinical information and histology were reviewed and cases were classified into three groups: Group 1: IgG4-RD orbital inflammation (n=43); Group 2: idiopathic OID (n=12) and Group 3: autoimmune OID (n=14). Serum IgG1, IgG2, IgG3 and IgG4 levels were collated where available and immunohistochemistry (IHC) for tissue IgG2 plasma cells was performed. Dual IHC showed IgG2 plasma cells as a distinct population from IgG4 plasma cells. Significant (twofold) serum IgG2 elevation was noted among IgG4-RD (group 1), idiopathic (group 2) and autoimmune OID (group 3). Similarly, significant elevation of tissue IgG2 plasma cells was also seen among IgG4-RD (group 1), idiopathic and autoimmune OID (groups 2 and 3). Significant elevations of serum IgG2 and tissue IgG2 plasma cells are present in orbital IgG4-RD in comparison with non-IgG4 orbital inflammation (idiopathic and autoimmune OID), suggesting that IgG2 may play a role in IgG4-RD. A serum IgG2 cut-off >5.3 g/L was found to be 80% sensitive and 91.7% specific for orbital IgG4-RD, with an accuracy of 0.90. Tissue IgG2 and IgG4 subclass reporting may provide additional insight regarding the 'IgG4-RD' pathogenesis. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  19. Enhanced IgG4 production by follicular helper 2 T cells and the involvement of follicular helper 1 T cells in the pathogenesis of IgG4-related disease.

    Science.gov (United States)

    Akiyama, Mitsuhiro; Yasuoka, Hidekata; Yamaoka, Kunihiro; Suzuki, Katsuya; Kaneko, Yuko; Kondo, Harumi; Kassai, Yoshiaki; Koga, Keiko; Miyazaki, Takahiro; Morita, Rimpei; Yoshimura, Akihiko; Takeuchi, Tsutomu

    2016-07-13

    The aim of this study was to elucidate the function of circulating follicular helper T (Tfh) cell subsets in helping B cells in patients with active, untreated IgG4-related disease (IgG4-RD) and determine their relationship with disease activity. Seventeen consecutive patients with active, untreated IgG4-RD, 20 with primary Sjögren syndrome (pSS), 5 with multicentric Castleman's disease (MCD), and 12 healthy controls (HC) were enrolled. Tfh cell subset function was evaluated by co-culture with naïve B cells in vitro. Activated Tfh cell subsets were defined as a CCR7(low)PD-1(high) subset among Tfh cell subsets. Disease activity was evaluated by IgG4-RD responder index (IgG4-RD RI) score. The number of Tfh2 cells was significantly higher in IgG4-RD compared to pSS, MCD, or HC, and correlated with serum IgG4 level or the number of plasmablasts. In vitro, Tfh2 cells more efficiently induced the differentiation of naïve B cells into plasmablasts compared to Tfh1 or Tfh17 cells. Of note, while IgG production in culture supernatants of Tfh2 cells was comparable between IgG4-RD and HC, IgG4 production was significantly higher with Tfh2 cells from patients with IgG4-RD than in those from HC. Accordingly, the IgG4:IgG ratio in culture supernatants was also significantly higher with Tfh2 cells from IgG4-RD compared to HC. Moreover, the number of activated Tfh2 cells was higher in IgG4-RD compared to pSS, MCD, or HC, and strongly correlated with IgG4-RD RI score in the baseline active phase. Particularly, the number of activated Tfh2 cells was associated with the number of affected organs and serum IgG4 level. Importantly, the number of activated Tfh2 cells was decreased after glucocorticoid treatment and paralleled disease improvement. Moreover, the number of activated Tfh1 cells was also increased in IgG4-RD compared to pSS, MCD, or HC, correlating with IgG4-RD RI score, but not with serum IgG4 level. Tfh2 cells, but not Tfh1 or Tfh17 cells, induce the differentiation of naïve B cells into plasmablasts and enhanced production of IgG4 in patients with active, untreated IgG4-RD. Furthermore, activated Tfh2 cells reflect disease activity, suggesting the involvement of this T cell subset in the pathogenesis of IgG4-RD. Interestingly, the number of activated Tfh1 cells was also increased in IgG4-RD, correlating with disease activity but not with serum IgG4 level, suggesting the involvement of Tfh1 cells but not in the process of IgG4 production in patients with IgG4-RD.

  20. Vitamin C-induced hyperoxaluria causing reversible tubulointerstitial nephritis and chronic renal failure: a case report

    Directory of Open Access Journals (Sweden)

    Rathi Shradha

    2007-11-01

    Full Text Available Abstract Vitamin C is a precursor of oxalate and promoter of its absorption, potentially causing hyperoxaluria. Malabsorption causes Calcium (Ca chelation with fatty acids, producing enteric hyperoxaluria. Case A 73-year-old man with both risk factors was hospitalized with serum creatinine of 8.4 mg/dL (versus 1.2 mg/dL four months earlier (normal 0.6–1.3 mg/dL. Given his oxalate-rich diet, chronic diarrhea, and daily 680 mg vitamin C and furosemide, we postulated Ca oxalate-induced nephropathy, a diagnosis confirmed by documenting hyperoxaluria, and finding of diffuse intraluminal crystals and extensive interstitial fibrosis on biopsy. He was hemodialysed 6 times to remove excess oxalate. Two weeks off vitamin C, his creatinine spontaneously fell to 3.1 mg/dL. Three months later, on low oxalate diet and 100 mg vitamin B6, urine oxalate to creatinine ratio decreased from 0.084 to 0.02 (normal Conclusion 1 High-dose vitamin C can induce hyperoxaluric nephropathy and progressive renal failure, especially if aggravated by diarrhea, oxalate-rich diet, metabolic acidosis, and dehydration. 2 The diagnosis should be suspected in unexplained renal insufficiency when associated with these risk factors. 3 Since prompt treatment could avert end-stage renal disease, we recommend monitoring urinary oxalate in patients on high-dose vitamin C and renal biopsy if necessary.

  1. Pro: Cyclophosphamide in lupus nephritis

    NARCIS (Netherlands)

    Kallenberg, Cees G. M.

    Based on efficacy and toxicity considerations, both low-dose pulse cyclophosphamide as part of the Euro-Lupus Nephritis protocol and mycophenolate mofetil (MMF) with corticosteroids may be considered for induction of remission in patients with proliferative lupus nephritis. The long-term follow-up

  2. Prognostic factors in lupus nephritis

    DEFF Research Database (Denmark)

    Faurschou, Mikkel; Starklint, Henrik; Halberg, Poul

    2006-01-01

    To evaluate the prognostic significance of clinical and renal biopsy findings in an unselected cohort of patients with systemic lupus erythematosus (SLE) and nephritis.......To evaluate the prognostic significance of clinical and renal biopsy findings in an unselected cohort of patients with systemic lupus erythematosus (SLE) and nephritis....

  3. Renal sarcoidosis presenting as acute kidney injury with granulomatous interstitial nephritis and vasculitis.

    Science.gov (United States)

    Agrawal, Varun; Crisi, Giovanna M; D'Agati, Vivette D; Freda, Benjamin J

    2012-02-01

    Among the various renal manifestations of sarcoidosis, granulomatous inflammation confined to the tubulointerstitial compartment is the most commonly reported finding. We present the case of a 66-year-old man with acute kidney injury, hypercalcemia, mild restrictive pulmonary disease, and neurologic signs of parietal lobe dysfunction. Kidney biopsy showed diffuse interstitial inflammation with noncaseating granulomas that exhibited the unusual feature of infiltrating the walls of small arteries with destruction of the elastic lamina, consistent with granulomatous vasculitis. The findings of granulomatous interstitial nephritis on kidney biopsy, hypercalcemia, and possible cerebral and pulmonary involvement in the absence of other infectious, drug-induced, or autoimmune causes of granulomatous disease established the diagnosis of sarcoidosis. Pulse methylprednisolone followed by maintenance prednisone therapy led to improvement in kidney function, hypercalcemia, and neurologic symptoms. Vasculocentric granulomatous interstitial nephritis with granulomatous vasculitis is a rare and under-recognized manifestation of renal sarcoidosis. Copyright © 2012 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  4. Lupus nephritis in Lebanon.

    Science.gov (United States)

    Uthman, I W; Muffarij, A A; Mudawar, W A; Nasr, F W; Masri, A F

    2001-01-01

    This is a retrospective study of the clinicopathological characteristics of 50 systemic lupus erythematosus patients with nephritis who underwent a kidney biopsy and were admitted to the American University of Beirut Medical Center, in Lebanon, between 1979 and 1999. There were 43 females and seven males, with a median age of 24 y. Renal histology slides from these patients were assessed according to the World Health Organization classification, and were distributed as follows: class I (n = 3, 6%); class II (n = 14, 28%); class III (n = 11, 22%); class IV (n = 19, 38%); class V (n = 1, 2%); class VI (n = 2, 4%). All the patients received oral prednisone, in addition the following treatments were used: pulse intravenous (i.v.) cyclophosphamide (n = 23, 46%); azathioprine (n = 22, 44%); pulse i.v. steroids (n = 19, 38%); chloroquine sulfate (n = 17, 34%); methotrexate (n = 5, 10%); and plasmapheresis (n = 2, 4%). The median duration of follow-up was 5 y (range 1-33 y). On their last evaluation, out of 37 patients who were followed, 20 patients (54%) had controlled disease, eight patients (22%) were still on active medical treatment, four patients (11%) were on chronic hemodialysis, and five patients (13%) had died. Unlike three other Arab populations studies from Kuwait, United Arab Emirates and Saudi Arabia, where the most frequent histopathologic abnormality was class III, diffuse proliferative LN (class IV) was the most common type of lupus nephritis in Lebanon, similarly to reports from USA, France, Netherlands, South Africa, Thailand and Taiwan.

  5. Toward a Comprehensive Hypothesis of Chronic Interstitial Nephritis in Agricultural Communities.

    Science.gov (United States)

    Orantes-Navarro, Carlos Manuel; Herrera-Valdés, Raúl; Almaguer-López, Miguel; López-Marín, Laura; Vela-Parada, Xavier Fernando; Hernandez-Cuchillas, Marcelo; Barba, Lilly M

    2017-03-01

    Over the past 20 years, there has been an increase in chronic interstitial nephritis in agricultural communities (CINAC) not associated with traditional risk factors. This disease has become an important public health problem and is observed in several countries in Central America and Asia. CINAC predominantly affects young male farmers between the third and fifth decades of life with women, children, and adolescents less often affected. Clinically, CINAC behaves like a chronic tubulointerstitial nephropathy but with systemic manifestations not attributable to kidney disease. Kidney biopsy reveals chronic tubulointerstitial nephritis with variable glomerulosclerosis and mild chronic vascular damage, with the severity depending on sex, occupation, and CKD stage. The presence of toxicological, occupational, and environmental risk factors within these communities suggests a multifactorial etiology for CINAC. This may include exposure to agrochemicals, a contaminated environment, repeated episodes of dehydration with heat stress, and an underlying genetic predisposition. An understanding of these interacting factors using a multidisciplinary approach with international cooperation and the formulation of a comprehensive hypothesis are essential for the development of public health programs to prevent this devastating epidemic. Copyright © 2016 National Kidney Foundation, Inc. All rights reserved.

  6. Lupus nephritis management guidelines compared.

    Science.gov (United States)

    Wilhelmus, Suzanne; Bajema, Ingeborg M; Bertsias, George K; Boumpas, Dimitrios T; Gordon, Caroline; Lightstone, Liz; Tesar, Vladimir; Jayne, David R

    2016-06-01

    In the past years, many (randomized) trials have been performed comparing the treatment strategies for lupus nephritis. In 2012, these data were incorporated in six different guidelines for treating lupus nephritis. These guidelines are European, American and internationally based, with one separate guideline for children. They offer information on different aspects of the management of lupus nephritis including induction and maintenance treatment of the different histological classes, adjunctive treatment, monitoring of the patient, definitions of response and relapse, indications for (repeat) renal biopsy, and additional challenges such as the presence of vascular complications, the pregnant SLE patient, treatment in children and adolescents and considerations about end-stage renal disease and transplantation. In this review, we summarize the guidelines, determine the common ground between them, highlight the differences and discuss recent literature. © The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

  7. The Pathogenesis of Lupus Nephritis

    Science.gov (United States)

    Lech, Maciej

    2013-01-01

    Lupus nephritis is an immune complex GN that develops as a frequent complication of SLE. The pathogenesis of lupus nephritis involves a variety of pathogenic mechanisms. The extrarenal etiology of systemic lupus is based on multiple combinations of genetic variants that compromise those mechanisms normally assuring immune tolerance to nuclear autoantigens. This loss of tolerance becomes clinically detectable by the presence of antinuclear antibodies. In addition, nucleic acids released from netting or apoptotic neutrophils activate innate and adaptive immunity via viral nucleic acid-specific Toll-like receptors. Therefore, many clinical manifestations of systemic lupus resemble those of viral infection. In lupus, endogenous nuclear particles trigger IFN-α signaling just like viral particles during viral infection. As such, dendritic cells, T helper cells, B cells, and plasma cells all contribute to the aberrant polyclonal autoimmunity. The intrarenal etiology of lupus nephritis involves antibody binding to multiple intrarenal autoantigens rather than the deposition of circulating immune complexes. Tertiary lymphoid tissue formation and local antibody production add to intrarenal complement activation as renal immunopathology progresses. Here we provide an update on the pathogenic mechanisms that lead to lupus nephritis and provide the rationale for the latest and novel treatment strategies. PMID:23929771

  8. Intrachiasmatic abscess caused by IgG4-related hypophysitis

    DEFF Research Database (Denmark)

    Hadjigeorgiou, Georgios F; Lund, Eva Løbner; Poulsgaard, Lars

    2017-01-01

    INTRODUCTION: Autoimmune hypophysitis is a rare disease of the pituitary, which may affect vision by inflammation and compression of the optic chiasm. However, intrachiasmatic abscess formation has not been previously reported. METHODS: In this study, we report a case of a 29-year-old female with...

  9. Immunology of IgG4-related disease

    Science.gov (United States)

    Della-Torre, E; Lanzillotta, M; Doglioni, C

    2015-01-01

    Immunoglobulin G4-related disease (IgG4-RD) is a fibroinflammatory condition that derives its name from the characteristic finding of abundant IgG4+ plasma cells in affected tissues, as well as the presence of elevated serum IgG4 concentrations in many patients. In contrast to fibrotic disorders, such as systemic sclerosis or idiopathic pulmonary fibrosis in which the tissues fibrosis has remained largely intractable to treatment, many IgG4-RD patients appear to have a condition in which the collagen deposition is reversible. The mechanisms underlying this peculiar feature remain unknown, but the remarkable efficacy of B cell depletion in these patients supports an important pathogenic role of B cell/T cell collaboration. In particular, aberrant T helper type 2 (Th2)/regulatory T cells sustained by putative autoreactive B cells have been proposed to drive collagen deposition through the production of profibrotic cytokines, but definitive demonstrations of this hypothesis are lacking. Indeed, a number of unsolved questions need to be addressed in order to fully understand the pathogenesis of IgG4-RD. These include the identification of an antigenic trigger(s), the implications (if any) of IgG4 antibodies for pathophysiology and the precise immunological mechanisms leading to fibrosis. Recent investigations have also raised the possibility that innate immunity might precede adaptive immunity, thus further complicating the pathological scenario. Here, we aim to review the most recent insights on the immunology of IgG4-RD, focusing on the relative contribution of innate and adaptive immune responses to the full pathological phenotype of this fibrotic condition. Clinical, histological and therapeutic features are also addressed. PMID:25865251

  10. [IgG4-related disease - a case report].

    Science.gov (United States)

    Milczarek-Banach, Justyna; Brodzińska, Kinga; Jankowska, Anna; Ambroziak, Urszula; Szczepankiewicz, Benedykt; Nałęcz-Janik, Jolanta; Miśkiewicz, Piotr

    2017-09-29

    Immunoglobulin G4-related disease (IgG4-RD) is a comparatively new condition that may involve more than one organ. The lack of characteristic, pathognomonic clinical symptoms may delay the diagnosis of this disease. The diagnosis is based upon clinical manifestation, elevated serum levels of IgG4 and histopathologic examination with immunohistochemical staining to reveal infiltration of IgG4-positive plasma cells. The first line treatment is oral glucocorticoids. 38-year-old woman with Hashimoto disease, chronic sinusitis and chronic hepatitis of unknown etiology was admitted to the Department of Endocrinology because of moderate eyelids swelling accompanied by redness for 3 years. Graves' orbitopathy and systemic vasculitis were suspected, however both were excluded (negative antibodies results: anty-TSHR, ANCA, ANA). Serologic investigation of Sjögren's syndrome was also negative. In Magnetic Resonance Imaging (MRI) of orbits there were described bilateral mild extension of lateral rectus muscles, normal signal of adipose tissue and bilateral lacrimal glands enlargement. Moreover, increased IgG4 serum levels were detected. The material derived from perinasal sinuses surgery was analyzed in histopathology examination with immunohistochemical staining, which revealed characteristic features of chronic inflammatory process and increased numbers of IgG4 - positive plasma cells (>50 in a large field of view). The diagnosis of IgG4-RD was established. Because of non-effective oral methylprednisolone therapy in the past, the patient was referred to Clinic of Rheumatology for further treatment. After the therapy with methylprednisolone and azathioprine there were observed the significant reduction of symptoms. Because of lack of characteristic symptoms of IgG4- RD, it should be always considered in differential diagnosis of chronic inflammatory diseases of various organs.

  11. Persistent Lymphadenopathy due to IgG4-Related Disease

    Science.gov (United States)

    2012-10-01

    capsid IgM negative), CMV (IgM negative, IgG negative), parvovirus B19 (IgM negative, IgG negative), Hepatitis (HBs Ag negative, HBc Ab negative, HBs...lymphadenopathy). Figure 2: Hematoxylin and eosin stain of a resected lymph node, 2x magnification. This preparation shows nonspecific reactive follicular

  12. Mechanisms underlying the ameliorative property of lisinopril in progressive mesangioproliferative nephritis.

    Science.gov (United States)

    Shinosaki, Toshihiro; Miyai, Ikuko; Nomura, Yasuharu; Kobayashi, Tatsuo; Sunagawa, Norio; Kurihara, Hidetake

    2002-08-01

    The present study was performed to clarify the mechanism underlying the beneficial effects of lisinopril on chronic glomerulonephritis. Chronic glomerulonephritis was induced by a single injection of E30 monoclonal antibody (E30) recognizing Thy-1.1 antigen to unilaterally nephrectomized rats. E30 injection resulted in persistent massive proteinuria with a decrease in anionic charge sites on the glomerular basement membrane (GBM) at 8 weeks. Also, renal tissue from rats treated with E30 showed typical glomerulosclerosis and tubulointerstitial fibrosis. Lisinopril exerted a potent antiproteinuric effect and suppressed the progression of both glomerulosclerosis and tubulointerstitial fibrosis. Lisinopril recovered the reduced number of anionic charge sites on GBM, accounting for the positive action against massive proteinuria. Immunostaining for desmin revealed that lisinopril treatment prevented the injury of glomerular epithelial cells (GECs) occurring in the chronic nephritic stage. Also, the level of gene expression of transforming growth factor-beta (TGF-beta) and plasminogen activator inhibitor-1 (PAI-1) in the renal cortex were reduced, suggesting that lisinopril improved extracellular matrix (ECM) metabolism. These results indicated that proteinuria in Thy-1.1 antibody-induced chronic nephritis is associated with a decrease in anionic charge sites on GBM, and that the antiproteinuric effect of lisinopril is attributable to protection against GEC damage. Suppression of TGF-beta and PAI-1 expression contributed to the preventive effect of lisinopril on ECM deposition in renal tissue. Copyright 2002 S. Karger AG, Basel

  13. Biomarkers for Lupus Nephritis: A Critical Appraisal

    Directory of Open Access Journals (Sweden)

    Chi Chiu Mok

    2010-01-01

    Full Text Available Kidney disease is one of the most serious manifestations of systemic lupus erythematosus (SLE. Despite the improvement in the medical care of SLE in the past two decades, the prognosis of lupus nephritis remains unsatisfactory. Besides exploring more effective but less toxic treatment modalities that will further improve the remission rate, early detection and treatment of renal activity may spare patients from intensive immunosuppressive therapies and reduce renal damage. Conventional clinical parameters such as creatinine clearance, proteinuria, urine sediments, anti-dsDNA, and complement levels are not sensitive or specific enough for detecting ongoing disease activity in the lupus kidneys and early relapse of nephritis. Thus, novel biomarkers are necessary to enhance the diagnostic accuracy and sensitivity of lupus renal disease, prognostic stratification, monitoring of treatment response, and detection of early renal flares. This paper reviews promising biomarkers that have recently been evaluated in longitudinal studies of lupus nephritis.

  14. The frequency and outcome of lupus nephritis

    DEFF Research Database (Denmark)

    Hanly, John G; O'Keeffe, Aidan G; Su, Li

    2016-01-01

    OBJECTIVE: To determine nephritis outcomes in a prospective multi-ethnic/racial SLE inception cohort. METHODS: Patients in the Systemic Lupus International Collaborating Clinics inception cohort (≤15 months of SLE diagnosis) were assessed annually for estimated glomerular filtration rate (e...

  15. Lupus nephritis, pregnancy and rituximab

    Directory of Open Access Journals (Sweden)

    Enrique Dorado

    2017-04-01

    Full Text Available La nefritis lúpica (NL proliferativa es una de las complicaciones más graves del LES. La respuesta terapéutica con los esquemas clásicos no existe en el 20 al 70% de los casos, siendo la amplitud de dicho rango explicada por variaciones étnicas, falta de consenso en la definición de remisión, diferencias en los tiempos de tratamiento, seguimiento y en la clase de NL. En presencia de NL recidivante o refractaria los tratamientos y el nivel de evidencia sobre su eficacia son más limitados. Rituximab es un anticuerpo monoclonal quimérico (ratón-humano dirigido contra el antígeno CD 20 localizado en la superficie celular de los linfocitos B. Estos participan en la patogénesis del LES a partir de su maduración en células plasmáticas, producción de anticuerpos, secreción de citoquinas proinflamatorias, presentación de autoantígenos a las células T y en la activación de células T. La administración de rituximab genera un rápido y sostenido descenso de los linfocitos B CD 20+ circulantes y una reducción de los títulos de auto-anticuerpos. Se reportó una disminución significativa en los niveles de antiDNA a partir de la semana 14 y de los niveles de IgM, sin compromiso de IgG ni de IgA. Se detectó droga activa en sangre periférica luego de la semana 24 de la última infusión. La depleción de linfocitos B se puede mantener por 6 meses, su reconstitución es heterogénea y puede tardar más de un año. Esta linfopenia selectiva tendría un valor predictivo de respuesta terapéutica, la remisión clínica prolongada tendría asociación con repoblación incompleta de células B de memoria varios años luego del tratamiento. En estudios observacionales realizados en pacientes con NL refractaria se reportó respuesta terapéutica con rituximab entre 67-77 % luego de 6 a 12 meses de seguimiento. Sin embargo los resultados del estudio Lupus Nephritis Assesment with Rituximab (LUNAR, randomizado controlado, a doble ciego

  16. An unusual presentation of juvenile lupus nephritis

    Directory of Open Access Journals (Sweden)

    Malleshwar Bottu

    2016-01-01

    Full Text Available The incidence of juvenile lupus varies widely ranging between 4 and 250 per 100,000 population. Most common organ involvement in juvenile lupus is kidney. Neurological, cutaneous and hematological involvements are also involved. Skeletal muscle involvement in the form of myositis is rare. Myositis as presenting manifestation in juvenile lupus is also unusual. Herein, we report one such case wherein myositis preceded the onset of lupus nephritis

  17. Dutch guidelines for diagnosis and therapy of proliferative lupus nephritis

    NARCIS (Netherlands)

    van Tellingen, A.; Voskuyl, A. E.; Vervloet, M. G.; Bijl, M.; de Sevaux, R. G. L.; Berger, S. P.; Derksen, R. H. W. M.; Berden, J. H. M.

    Proliferative lupus nephritis is a strong predictor of morbidity and mortality in patients with systemic lupus erythematosus. Despite improvements in the management of lupus nephritis, a significant number of the patients do not respond to immunosuppressive therapy and progress to end-stage renal

  18. The medical response to trench nephritis in World War One.

    Science.gov (United States)

    Atenstaedt, R L

    2006-08-01

    Around the 90-year anniversary of the Battle of the Somme, it is important to remember the international effort that went into responding to the new diseases, which appeared during the First World War, such as trench nephritis. This condition arose among soldiers in spring 1915, characterized by breathlessness, swelling of the face or legs, headache, sore throat, and the presence of albumin and renal casts in urine. It was speedily investigated by the military-medical authorities. There was debate over whether it was new condition or streptococcal nephritis, and the experts agreed that it was a new condition. The major etiologies proposed were infection, exposure, and diet (including poisons). Research pointed to the origin of the disease as being infective rather than toxic, but no definite cause was discovered. A number of labels were given to the disease, including war nephritis. However, trench nephritis was the one used most widely. Trench nephritis was a serious problem for the Allies, leading to 35 000 casualties in the British and 2000 in the American forces. There were also hundreds of deaths. The condition was treated in line with pre-war regimens designed for acute nephritis. No significant preventative methods were implemented for trench nephritis, as there was no consensus regarding causation. The medical response to trench nephritis was largely ineffective, with medical commentators recognizing that there had been a lack of medical progress.

  19. Prognosis and predictors of convulsion among pediatric lupus nephritis patients

    International Nuclear Information System (INIS)

    Beiraghdar, Fatemeh; Einollahi, Behzad; Taheri, Saeed; Panahi, Yunes; Maddani, Abbas; Esfahani, Taher; Sharifi-Bonab, Mir Mohsen

    2009-01-01

    In this study, we aimed to analyze features and outcome of convulsion in pediatric lupus nephritis patients. We retrospectively reviewed data of 14 Iranian children with lupus nephritis who developed seizures and compared them with a group of the same number of well matched pediatric lupus nephritis patients. Higher serum creatinine levels and higher frequencies of anemia and lymphopenia were observed in the convulsion group. Multivariable logistic regression analysis revealed that the only risk factor for development of convulsion in pediatric lupus patients with nephritis was lymphopenia. Survival analysis showed that convulsion had no impact on patient and renal function outcomes in our pediatric lupus nephritis subjects. In conclusion, we found that lymphopenia is a predictive factor for convulsion occurrence in our patients and special attention to neurological status assessment may be needed in this situation. (author)

  20. Chronic interstitial nephritis in agricultural communities: a worldwide epidemic with social, occupational and environmental determinants.

    Science.gov (United States)

    Jayasumana, Channa; Orantes, Carlos; Herrera, Raul; Almaguer, Miguel; Lopez, Laura; Silva, Luis Carlos; Ordunez, Pedro; Siribaddana, Sisira; Gunatilake, Sarath; De Broe, Marc E

    2017-02-01

    Increase in the prevalence of chronic kidney disease (CKD) is observed in Central America, Sri Lanka and other tropical countries. It is named chronic interstitial nephritis in agricultural communities (CINAC). CINAC is defined as a form of CKD that affects mainly young men, occasionally women. Its aetiology is not linked to diabetes, hypertension, glomerulopathies or other known causes. CINAC patients live and work in poor agricultural communities located in CINAC endemic areas with a hot tropical climate, and are exposed to toxic agrochemicals through work, by ingestion of contaminated food and water, or by inhalation. The disease is characterized by low or absent proteinuria, small kidneys with irregular contours in CKD stages 3–4 presenting tubulo-interstitial lesions and glomerulosclerosis at renal biopsy. Although the aetiology of CINAC is unclear, it appears to be multifactorial. Two hypotheses emphasizing different primary triggers have been proposed: one related to toxic exposures in the agricultural communities, the other related to heat stress with repeated episodes of dehydration heath stress and dehydration. Existing evidence supports occupational and environmental toxins as the primary trigger. The heat stress and dehydration hypothesis, however, cannot explain: why the incidence of CINAC went up along with increasing mechanization of paddy farming in the 1990s; the non-existence of CINAC in hotter northern Sri Lanka, Cuba and Myanmar where agrochemicals are sparsely used; the mosaic geographical pattern in CINAC endemic areas; the presence of CINAC among women, children and adolescents who are not exposed to the harsh working conditions; and the observed extra renal manifestations of CINAC. This indicates that heat stress and dehydration may be a contributory or even a necessary risk factor, but which is not able to cause CINAC by itself.

  1. Renal cell apoptosis in human lupus nephritis: a histological study

    DEFF Research Database (Denmark)

    Faurschou, M; Penkowa, Milena; Andersen, C B

    2009-01-01

    Nuclear autoantigens from apoptotic cells are believed to drive the immunological response in systemic lupus erythematosus (SLE). Conflicting data exist as to the possible renal origin of apoptotic cells in SLE patients with nephritis. We assessed the level of renal cell apoptosis in kidney...... biopsies from 35 patients with lupus nephritis by means of terminal deoxynucleotidyl-transferase (TdT)-mediated deoxyuridine triphosphate (dUTP)-digoxigenin nick end labeling (TUNEL). Five samples of normal kidney tissue served as control specimens. We did not observe apoptotic glomerular cells in any...... cells constitute a quantitatively important source of auto-antibody-inducing nuclear auto-antigens in human lupus nephritis....

  2. Experimental anti-GBM nephritis as an analytical tool for studying spontaneous lupus nephritis.

    Science.gov (United States)

    Du, Yong; Fu, Yuyang; Mohan, Chandra

    2008-01-01

    Systemic lupus erythematosus (SLE) is an autoimmune disease that results in immune-mediated damage to multiple organs. Among these, kidney involvement is the most common and fatal. Spontaneous lupus nephritis (SLN) in mouse models has provided valuable insights into the underlying mechanisms of human lupus nephritis. However, SLN in mouse models takes 6-12 months to manifest; hence there is clearly the need for a mouse model that can be used to unveil the pathogenic processes that lead to immune nephritis over a shorter time frame. In this article more than 25 different molecules are reviewed that have been studied both in the anti-glomerular basement membrane (anti-GBM) model and in SLN and it was found that these molecules influence both diseases in a parallel fashion, suggesting that the two disease settings share common molecular mechanisms. Based on these observations, the authors believe the experimental anti-GBM disease model might be one of the best tools currently available for uncovering the downstream molecular mechanisms leading to SLN.

  3. Detection of avian nephritis virus and chicken astrovirus in Nigerian ...

    African Journals Online (AJOL)

    2012-02-28

    Feb 28, 2012 ... Avian nephritis virus (ANV) and chicken astrovirus (CAstV) are widely distributed in poultry flocks ... sheep, cats, dogs, deer, mice, turkeys, guinea fowl and ..... complex: turkey astrovirus, turkey coronavirus, and turkey reovirus.

  4. Severe IgG4-Related Disease in a Young Child: A Diagnosis Challenge

    Directory of Open Access Journals (Sweden)

    Susana Corujeira

    2015-01-01

    Full Text Available Immunoglobulin G4-related disease (IgG4-RD is an increasingly recognized syndrome that can appear with multiple organ involvement, typically with tumor-like swelling, lymphoplasmacytic infiltrate rich in IgG4-positive plasma cells, and elevated serum IgG4 concentrations. We report the case of a 22-month-old female child with failure to thrive and recurrent respiratory tract infections since 8 months of age. Physical examination was normal except for pulmonary auscultation with bilateral crackles and wheezes. Laboratory tests revealed elevated erythrocyte sedimentation rate, and elevated serum IgG and IgG4 with polyclonal hypergammaglobulinemia. Thoracic CT and MRI showed multiple mediastinal lymphadenopathies and a nodular posterior mediastinal mass in right paratracheal location with bronchial compression. Initial fine needle aspiration biopsy was compatible with reactive lymphadenopathy but after clinical worsening a thoracoscopic partial resection of the mass was performed and tissue biopsy revealed lymphoplasmacytic infiltrate and increased number of IgG4-positive plasma cells and a ratio of IgG4/IgG positive cells above 40%. Glucocorticoids therapy was started with symptomatic improvement, reduction in the size of the mass, and decrease of serum IgG4 levels after 6 weeks. There are very few reports of IgG4-RD in children. Long-term follow-up is necessary to monitor relapses and additional organ involvement.

  5. The Geoepidemiology and Clinical Aspects of IgG4-Related Disease.

    Science.gov (United States)

    Uchida, Kazushige; Tanaka, Toshihiro; Gershwin, M Eric; Okazaki, Kazuichi

    2016-08-01

    Immunoglobulin G4-related disease (IgG4-RD) is a recently described systemic inflammatory disease characterized by increased serum IgG4 concentrations, lymphoplasmacytic infiltrations, storiform fibrosis, and obliterative phlebitis. However, although IgG4-RD has become increasingly recognized, the number of patients with IgG4-RD remains unclear. Data from several studies indicate that patients who have a T-helper type 2 (Th2-) dominant immune response, which leads to the hyperproduction of Th2 cytokines, then progress to IgG4-RD. Glucocorticoids are the most common treatment for IgG4-RD and generally, patients have a good response-a characteristic of IgG4-RD. However, relapses during the tapering of glucocorticoid therapy are common. Second-line therapy after glucocorticoids includes immunosuppressant agents. Although the long-term outcome still remains unclear, there is increased interest in the relationships between IgG-RD and malignancies. In this review, the authors provide a detailed overview of the geoepidemiology, pathogenesis, diagnostic features, treatment, and prognosis of IgG4-RD. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  6. IgG4- related disease: an orphan disease with many faces

    Science.gov (United States)

    2014-01-01

    Immunoglobulin G4- related disease (IgG4-RD) is a rare systemic fibro-inflammatory disorder (ORPHA284264). Although patients have been described more than 100 years ago, the systemic nature of this disease has been recognized in the 21st century only. Type 1 autoimmune pancreatitis is the most frequent manifestation of IgG4-RD. However, IgG4-RD can affect any organ such as salivary glands, orbits, retroperitoneum and many others. Recent research enabled a clear clinical and histopathological description of IgG4-RD. Typically, lymphoplasmacellular inflammation, storiform fibrosis and obliterative phlebitis are found in IgG4-RD biopsies and the tissue invading plasma cells largely produce IgG4. Elevated serum IgG4 levels are found in many but not all patients. Consequently, diagnostic criteria for IgG4-RD have been proposed recently. Treatment is largely based on clinical experience and retrospective case series. Glucocorticoids are the mainstay of therapy, although adjunctive immunosuppressive agents are used in relapsing patients. This review summarizes current knowledge on clinical manifestations, pathophysiology and treatment of IgG4-RD. PMID:25026959

  7. A case developing minimal change disease during the course of IgG4-related disease.

    Science.gov (United States)

    Yamada, Kazunori; Zoshima, Takeshi; Ito, Kiyoaki; Mizushima, Ichiro; Hara, Satoshi; Horita, Shigeto; Nuka, Hiromi; Hamano, Ryoko; Fujii, Hiroshi; Yamagishi, Masakazu; Kawano, Mitsuhiro

    2017-07-01

    We describe a 66-year-old male with immunoglobulin G4-related disease (IgG4-RD) presenting with minimal change disease (MCD). Three years prior to this admission, the patient had been diagnosed with IgG4-RD. The development of sudden massive proteinuria (4+; 16.7 g/gCr) with a weight gain of 8 kg within a two-week period was noted, and nephrotic syndrome was suspected. The patient's serum IgG4 level did not increase and hypocomplementemia was not found. A renal biopsy showed no cellular infiltration in the renal interstitium, and no spiking or bubbling was found on periodic acid methenamine silver staining. On electron microscopy, foot process effacement was seen, but no subepithelial electron-dense deposits were found. The patient was diagnosed with MCD. Ten days after starting prednisolone (60 mg/day), proteinuria was negative. Since IgG4-RD and MCD share a T-helper 2-dominant immunoreaction, the development of MCD in IgG4-RD patients may reflect more than a mere coincidence.

  8. Thoracic Paravertebral Mass as an Infrequent Manifestation of IgG4-Related Disease

    Directory of Open Access Journals (Sweden)

    Melissa Matzumura Kuan

    2017-01-01

    Full Text Available Case. A 50-year-old African American male presented with abdominal pain and significant weight loss. On physical examination, he had parotid and submandibular gland enlargement associated with right eye proptosis. Computed tomography showed a thoracic paravertebral soft tissue mass, enlarged lymph nodes, and ascending aortic aneurysm. Laboratory results were remarkable for elevated total IgG and IgG4 subclass. The submandibular gland pathology revealed chronic sclerosing sialadenitis, with a large subset of inflammatory cells positively staining for IgG4. The histology of the paravertebral mass demonstrated fibrosclerosis with increased lymphocytic infiltrate, associated with increased IgG4 plasma cells. He was diagnosed with immunoglobulin G4-related disease (IgG4-RD. Steroid therapy initially yielded improvement; however, after steroids were stopped, there was disease recurrence. Prednisone was restarted, and the plan was to start him on rituximab. Interestingly, the patient’s brother also had IgG4-RD. Conclusion. IgG4-RD can present as a paravertebral mass which is usually responsive to steroids; however, recurrent and resistant disease can be seen for which steroid-sparing agents such as rituximab should be considered. In addition, to the best of our knowledge, this is the first reported case of IgG4-RD in two family members presenting as a paravertebral mass, highlighting an exciting area for more research in the future.

  9. Clinicopathological features of Riedel's thyroiditis associated with IgG4-related disease in Japan.

    Science.gov (United States)

    Takeshima, Ken; Inaba, Hidefumi; Ariyasu, Hiroyuki; Furukawa, Yasushi; Doi, Asako; Nishi, Masahiro; Hirokawa, Mitsuyoshi; Yoshida, Akira; Imai, Ryoukichi; Akamizu, Takashi

    2015-01-01

    Riedel's thyroiditis (RT) is a rare chronic fibrosing disorder characterized by a hard, infiltrative lesion in the thyroid gland, which is often associated with multifocal fibrosclerosis. Immunoglobulin G4-related disease (IgG4-RD) is typified by infiltration of IgG4-positive plasma cells into multiple organs, resulting in tissue fibrosis and organ dysfunction. In order to evaluate the clinicopathological features of RT and its relationship with IgG4-RD, we performed a Japanese literature search using the keywords "Riedel" and "Riedel's thyroiditis." We used the electronic databases Medline and Igaku Chuo Zasshi, the latter of which is the largest medical literature database in Japan. The diagnosis of RT was based on the presence of a fibroinflammatory process with extension into surrounding tissues. Only 10 patients in Japan fulfilled RT diagnostic criteria during the 25-year period between 1988 and 2012. Two patients with confirmed IgG4/IgG immunohistochemical findings demonstrated 43 and 13 IgG4-positive plasma cells per high-power field, respectively, and the IgG4-positive/IgG-positive plasma cell ratios of 20% and less than 5%. Of the 10 patients with RT, two received glucocorticoids, one of whom experienced marked shrinkage of the thyroid lesion. One patient had extra-thyroid involvement in the form of retroperitoneal fibrosis. Although the clinicopathological features of RT suggest that IgG4-RD may be the underlying condition in some cases, further investigation is needed to clarify the etiology of RT in relation to IgG4-RD.

  10. Fibrosing variant of Hashimoto thyroiditis is an IgG4 related disease.

    Science.gov (United States)

    Deshpande, Vikram; Huck, Amelia; Ooi, Esther; Stone, John H; Faquin, William C; Nielsen, G Petur

    2012-08-01

    Hashimoto thyroiditis (HT) and the fibrosing variant of Hashimoto thyroiditis (FVHT) are immune-mediated tumefactive lesions of the thyroid. Immunoglobulin G4-related disease (IgG4-RD) is now a widely recognised multi-organ system disease characterised by elevated serum and tissue concentrations of IgG4. In this study, the authors address several unresolved questions pertaining to the relationship between HT and FVHT, and the association of each of these diseases with IgG4-RD. The authors evaluated 28 consecutive cases of HT and nine cases of FVHT. The clinical, demographic and serological data were recorded. The slides were stained immunohistochemically using antibodies to IgG4 and IgG and the quantitative analysis was recorded. Data on thyroid function tests were available on seven cases of FVHT and 14 cases of HT. Based on the availability of data, hypothyroidism was noted in 62% (9/14) of HT and 86% of FVHT (6/7). FVHT demonstrated an exaggerated lobular pattern with lobules separated by cellular storiform-type fibrosis, resembling fibrosis seen in other forms of IgG-RD. The median IgG4 counts per high power field (×40) in HT and FVHT were 2.3 and 22, respectively. The median IgG4:IgG ratios in HT and FVHT were 0.11 and 0.58, respectively. The authors propose that FVHT belongs to the spectrum of IgG4-RD. Although a proportion of cases of HT show elevated numbers of IgG4 positive plasma cells, these cases lack the histological features typically associated with IgG4-RD, and thus the relationship between HT and IgG4-RD remains unproven.

  11. Overlapping Morphologic and Immunohistochemical Features of Hashimoto Thyroiditis and IgG4-Related Thyroid Disease.

    Science.gov (United States)

    Raess, Philipp W; Habashi, Arlette; El Rassi, Edward; Milas, Mira; Sauer, David A; Troxell, Megan L

    2015-05-01

    Immunoglobulin G4-related disease (IgG4-RD) is an emerging clinicopathologic entity characterized by both IgG4+ plasma cell infiltration and fibrosis in one or more organs, prototypically pancreas or salivary/lacrimal glands. IgG4-RD in the thyroid (IgG4-RTD) is an area of active study, and the relationship between IgG4-RTD and Hashimoto thyroiditis is not fully delineated due to their overlapping histologic features. Retrospective review was performed of all thyroidectomy cases demonstrating lymphocytic inflammation at a single institution over a 4-year period. Approximately half (23/38) of patients had a clinical diagnosis of Hashimoto thyroiditis (HT). Nine of the 38 patients had increased absolute and relative numbers of IgG4+ plasma cells. Patients with a clinical diagnosis of HT had increased lymphoplasmacytic inflammation, but the relative proportion of IgG4+ plasma cells was not increased compared to patients without HT. There was no correlation between IgG4 levels and the amount of fibrosis in patients with or without HT. Patients identified as having the fibrosing variant of HT were not more likely to have increased levels of IgG4+ plasma cells than those without. There is significant morphologic and immunohistochemical overlap between HT and IgG4-RTD. Future studies to identify specific characteristics of IgG4-RTD involving the thyroid are necessary to accurately define this entity.

  12. Renal expression of polyomavirus large T antigen is associated with nephritis in human systemic lupus erythematosus

    DEFF Research Database (Denmark)

    Fenton, Kristin Andreassen; Mjelle, Janne Erikke; Jacobsen, Søren

    2008-01-01

    ) that these complexes bound induced anti-nucleosome antibodies and finally (iv) that they associated with glomerular membranes as immune complexes. This process may be relevant for human lupus nephritis, since productive polyomavirus infection is associated with this organ manifestation. Here, we compare nephritis...... to the evolution of lupus nephritis in human SLE....

  13. 77 FR 38305 - Guidance for Industry on Lupus Nephritis Caused by Systemic Lupus Erythematosus-Developing...

    Science.gov (United States)

    2012-06-27

    ...] Guidance for Industry on Lupus Nephritis Caused by Systemic Lupus Erythematosus--Developing Medical... ``Lupus Nephritis Caused By Systemic Lupus Erythematosus--Developing Medical Products for Treatment... of medical products for the treatment of lupus nephritis. Dated: June 22, 2012. Leslie Kux, Assistant...

  14. Bmi-1 plays a critical role in protection from renal tubulointerstitial injury by maintaining redox balance

    Science.gov (United States)

    Jin, Jianliang; Lv, Xianhui; Chen, Lulu; Zhang, Wei; Li, Jinbo; Wang, Qian; Wang, Rong; Lu, Xiang; Miao, Dengshun

    2014-01-01

    To determine whether Bmi-1 deficiency could lead to renal tubulointerstitial injury by mitochondrial dysfunction and increased oxidative stress in the kidney, 3-week-old Bmi-1-/- mice were treated with the antioxidant N-acetylcysteine (NAC, 1 mg mL−1) in their drinking water, or pyrro-quinoline quinone (PQQ, 4 mg kg−1 diet) in their diet for 2 weeks, and their renal phenotypes were compared with vehicle-treated Bmi1-/- and wild-type mice. Bmi-1 was knocked down in human renal proximal tubular epithelial (HK2) cells which were treated with 1 mm NAC for 72 or 96 h, and their phenotypes were compared with control cells. Five-week-old vehicle-treated Bmi-1-/- mice displayed renal interstitial fibrosis, tubular atrophy, and severe renal function impairment with decreased renal cell proliferation, increased renal cell apoptosis and senescence, and inflammatory cell infiltration. Impaired mitochondrial structure, decreased mitochondrial numbers, and increased oxidative stress occurred in Bmi-1-/- mice; subsequently, this caused DNA damage, the activation of TGF-β1/Smad signaling, and the imbalance between extracellular matrix synthesis and degradation. Oxidative stress-induced epithelial-to-mesenchymal transition of renal tubular epithelial cells was enhanced in Bmi-1 knocked down HK2 cells. All phenotypic alterations caused by Bmi-1 deficiency were ameliorated by antioxidant treatment. These findings indicate that Bmi-1 plays a critical role in protection from renal tubulointerstitial injury by maintaining redox balance and will be a novel therapeutic target for preventing renal tubulointerstitial injury. PMID:24915841

  15. Excess 25-hydroxyvitamin D3 exacerbates tubulointerstitial injury in mice by modulating macrophage phenotype.

    Science.gov (United States)

    Kusunoki, Yasuo; Matsui, Isao; Hamano, Takayuki; Shimomura, Akihiro; Mori, Daisuke; Yonemoto, Sayoko; Takabatake, Yoshitsugu; Tsubakihara, Yoshiharu; St-Arnaud, René; Isaka, Yoshitaka; Rakugi, Hiromi

    2015-11-01

    Vitamin D hydroxylated at carbon 25 (25(OH)D) is generally recognized as a precursor of active vitamin D. Despite its low affinity for the vitamin D receptor (VDR), both deficient and excessive 25(OH)D levels are associated with poor clinical outcomes. Here we studied direct effects of 25(OH)D3 on the kidney using 25(OH)D-1α-hydroxylase (CYP27B1) knockout mice. The effects of 25(OH)D3 on unilateral ureteral obstruction were analyzed as proximal tubular cells and macrophages are two major cell types that take up 25(OH)D and contribute to the pathogenesis of kidney injury. Excess 25(OH)D3 in obstructed mice worsened oxidative stress and tubulointerstitial fibrosis, whereas moderate levels of 25(OH)D3 had no effects. The exacerbating effects of excess 25(OH)D3 were abolished in CYP27B1/VDR double-knockout mice and in macrophage-depleted CYP27B1 knockout mice. Excess 25(OH)D3 upregulated both M1 marker (TNF-α) and M2 marker (TGF-β1) levels of kidney-infiltrating macrophages. In vitro analyses verified that excess 25(OH)D3 directly upregulated TNF-α and TGF-β1 in cultured macrophages but not in tubular cells. TNF-α and 25(OH)D3 cooperatively induced oxidative stress by upregulating iNOS in tubular cells. Aggravated tubulointerstitial fibrosis in mice with excess 25(OH)D3 indicated that macrophage-derived TGF-β1 also had a key role in the pathogenesis of surplus 25(OH)D3. Thus, excess 25(OH)D3 worsens tubulointerstitial injury by modulating macrophage phenotype.

  16. Lysyl oxidase‑like 2 is expressed in kidney tissue and is associated with the progression of tubulointerstitial fibrosis.

    Science.gov (United States)

    Choi, Sung-Eun; Jeon, Nara; Choi, Hoon Young; Shin, Jae Il; Jeong, Hyeon Joo; Lim, Beom Jin

    2017-09-01

    Tubulointerstitial fibrosis is a common end point of chronic kidney diseases, and preventing its progression is key to avoiding renal failure. Transforming growth factor‑β (TGF‑β) and associated molecules promote tubulointerstitial fibrosis; however, effective therapies targeting these molecules have yet to be developed. Lysyl oxidase‑like 2 (LOXL2), which is involved in invasive growth and metastasis of malignant neoplasms, has recently been reported to serve a key role in hepatic and pulmonary fibrosis. However, little is currently known regarding LOXL2 expression in the kidney and its involvement in tubulointerstitial fibrosis. The present study evaluated LOXL2 expression in human and mouse kidney tissues, as well as in cultured renal cells. LOXL2 protein expression was detected in glomerular capillary loops and tubular epithelial cells in human and mouse kidneys. Glomerular LOXL2 was localized to the cytoplasm of podocytes, as determined by double immunofluorescence microscopy using a podocyte marker (synaptopodin). This result was supported by western blot analysis, which demonstrated that LOXL2 protein expression is present in cultured human podocytes and HK‑2 human proximal tubular cells. In addition, the mRNA and protein expression levels of LOXL2 were higher in a mouse model of tubulointerstitial fibrosis compared with in control mice. In addition, immunohistochemistry results demonstrated that LOXL2 is present in the fibrous interstitium and infiltrating mononuclear cells in a mouse model of tubulointerstitial fibrosis. The present study demonstrated that LOXL2 is expressed in compartments of renal tissue, where it appears to contribute to the progression of tubulointerstitial fibrosis.

  17. Monomeric neutrophil gelatinase associated lipocalin is associated with tubulointerstitial damage in chronic kidney disease

    Science.gov (United States)

    Nickolas, Thomas L.; Forster, Catherine; Sise, Meghan E.; Barasch, Nicholas; Valle, David Solá-Del; Viltard, Melanie; Buchen, Charles; Kupferman, Shlomo; Carnevali, Maria Luisa; Bennett, Michael; Mattei, Silvia; Bovino, Achiropita; Argentiero, Lucia; Magnano, Andrea; Devarajan, Prasad; Mori, Kiyoshi; Erdjument-Bromage, Hediye; Tempst, Paul; Allegri, Landino; Barasch, Jonathan

    2012-01-01

    The rate of progression of chronic kidney disease (CKD) is difficult to predict using single measurements of serum creatinine or proteinuria. On the other hand, documented tubulointerstitial disease presages worsening CKD, but kidney biopsy is not practical for routine use and generally does not sample the tubulointerstitial compartment of the medulla. Perhaps a urine test that correlates with specific histological findings may serve as a surrogate for the kidney biopsy. Here we compared both immunoblot analysis (under non-reducing conditions) and a commercially available monomer immunoassays of Neutrophil Gelatinase Associated Lipocalin (NGAL) with pathological changes found in kidney biopsies, to determine whether specific histological characteristics associated with a specific NGAL species. We found that the urine of patients with advanced CKD contained NGAL monomers as well as higher molecular weight complexes containing NGAL, identified by MALDI-TOF/TOF mass spectroscopy. The NGAL monomer significantly correlated with glomerular filtration rate, interstitial fibrosis and tubular atrophy. Hence, specific assays of the NGAL monomer implicate histology associated with progressive, severe CKD. PMID:22695331

  18. Autosomal dominant tubulointerstitial kidney disease caused by uromodulin mutations: seek and you will find.

    Science.gov (United States)

    Raffler, Gabriele; Zitt, Emanuel; Sprenger-Mähr, Hannelore; Nagel, Mato; Lhotta, Karl

    2016-04-01

    Uromodulin (UMOD)-associated kidney disease belongs to the group of autosomal dominant interstitial kidney diseases and is caused by mutations in the UMOD gene. Affected patients present with hyperuricemia, gout, and progressive renal failure. The disease is thought to be very rare but is probably underdiagnosed. Two index patients from two families with tubulointerstitial nephropathy and hyperuricemia were examined, including blood and urine chemistry, ultrasound, and mutation analysis of the UMOD gene. In addition, other available family members were studied. In a 46-year-old female patient with a fractional excretion of uric acid of 3 %, analysis of the UMOD gene revealed a p.W202S missense mutation. The same mutation was found in her 72-year-old father, who suffers from gout and end-stage renal disease. The second index patient was a 47-year-old female with chronic kidney disease and gout for more than 10 years. Her fractional uric acid excretion was 3.5 %. Genetic analysis identified a novel p.H250Q UMOD mutation that was also present in her 12-year-old son, who had normal renal function and uric acid levels. In patients suffering from chronic tubulointerstitial nephropathy, hyperuricemia, and a low fractional excretion of uric acid mutation, analysis of the UMOD gene should be performed to diagnose UMOD-associated kidney disease.

  19. Understanding lupus nephritis: diagnosis, management, and treatment options

    Directory of Open Access Journals (Sweden)

    Mok CC

    2012-05-01

    Full Text Available Chi Chiu MokDepartment of Medicine, Tuen Mun Hospital and Center for Assessment and Treatment of Rheumatic Diseases, Pok Oi Hospital, Hong Kong, ChinaAbstract: Systemic lupus erythematosus (SLE predominantly affects women in their reproductive years. Renal disease (glomerulonephritis is one of the most frequent and serious manifestations of SLE. Of the various histological types of lupus glomerulonephritis, diffuse proliferative nephritis carries the worst prognosis. Combined with high-dose prednisone, mycophenolate mofetil (MMF has emerged as a first-line immunosuppressive treatment, although data regarding the efficacy of MMF on the long-term preservation of renal function are forthcoming. Cyclophosphamide is reserved for more severe forms of lupus nephritis, such as crescentic glomerulonephritis with rapidly deteriorating renal function, patients with significant renal function impairment at presentation, and refractory renal disease. Evidence for the calcineurin inhibitors in the treatment of lupus nephritis is weaker, and it concerns patients who are intolerant or recalcitrant to other agents. While further controlled trials are mandatory, B cell modulation therapies, such as rituximab, belimumab and epratuzumab are confined to refractory disease. Non-immunosuppressive measures, such as angiotensin-converting enzyme inhibitors, vigorous blood pressure control, prevention and treatment of hyperlipidemia and osteoporosis, are equally important.Keywords: lupus, nephritis, nephropathy, glomerulonephritis, treatment, therapy, women

  20. Kidney disease in lupus is not always 'lupus nephritis'

    NARCIS (Netherlands)

    H.J. Anders (Hans-Joachim); J.J. Weening (Jan)

    2013-01-01

    textabstractIn lupus erythematosus, elevated serum creatinine levels and urinary abnormalities implicate a kidney disorder, which may not always be lupus nephritis as defined by the current classification of the International Society of Nephrology/Renal Pathology Society. The signs of renal

  1. Incidence of systemic lupus erythematosus and lupus nephritis in Denmark

    DEFF Research Database (Denmark)

    Hermansen, Marie-Louise From; Lindhardsen, Jesper; Torp-Pedersen, Christian

    2016-01-01

    Objective. To determine the incidence of systemic lupus erythematosus (SLE) and SLE with concomitant or subsequent lupus nephritis (LN) in Denmark during 1995.2011, using data from the Danish National Patient Registry (NPR).  Methods. To assess the incidence of SLE, we identified all persons aged...

  2. Renal cell apoptosis in human lupus nephritis: a histological study

    DEFF Research Database (Denmark)

    Faurschou, M; Penkowa, Milena; Andersen, C B

    2009-01-01

    Nuclear autoantigens from apoptotic cells are believed to drive the immunological response in systemic lupus erythematosus (SLE). Conflicting data exist as to the possible renal origin of apoptotic cells in SLE patients with nephritis. We assessed the level of renal cell apoptosis in kidney...

  3. An Experimental Study for Radiation Nephritis in Rabbits

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Myung Jae [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    1972-09-15

    Experimental radiation nephritis was produced in 15 rabbits by X-irradiation. About 2, 000gamma(tissue doses) were given to both kidneys of a rabbit in 5 days. Other tissues and organs except both kidneys were protected with 2 mm thickened lead plates. 5 weeks after the last irradiation, blood pictures, blood pressures, B.U.N., serum creatinine, Ca, Mg, Fe levels and serum erythropoietin activity of the irradiated rabbits were studied. After finishing above studies, rabbits were sacrificed and both kidneys were removed and examined histopathologically. Same laboratory and pathological studies were performed in 6 control rabbits. In this study, the author obtained following results. 1) Both kidneys of rabbits with experimental radiation nephritis showed marked histopathological changes, i.e.: renal tubules showed diffuse cloudy swelling, impacted intraluminal hyaline casts and focal precipitations of lime salts on the tubular epithelium. Diffuse interstitial fatty necrosis and various degrees of fibrotic infiltrations on the interstitium were also seen in association with focal lymphocytic infiltrations. Hyaline degenerations were observed on the glomeruli and small vessels. 2) Experimental radiation nephritis rabbits showed marked lowering in R.B.C. counts, decreased hemoglobin levels, low hematocrit values and leucopenia in comparison with those of control rabbits. (P<0.01). (Table 1 and 2). 3) Mild proteinuria were observed in experimental radiation nephritis in rabbits. 4) The levels of B.U.N. and serum creatinine increased in experimental radiation nephritis. (P<0.01). (Table 1, 3 and 4). 5) The levels of serum Ca and Mg Showed no statistical difference in comparison with those of control rabbits. (P>0.05). (Table 3 and 4). 6) No statistical correlations were observable between the levels of B.U.N. and Hb. values. (gamma=-0. 223). No close correlations (gamma=-0.338) were noticed between the levels of B.U.N. and serum iron levels. 7) Erythropoietin activity (R

  4. Acute ciprofloxacin-induced crystal nephropathy with granulomatous interstitial nephritis

    Directory of Open Access Journals (Sweden)

    R Goli

    2017-01-01

    Full Text Available Crystal-induced acute kidney injury (AKI is caused by the intratubular precipitation of crystals, which results in obstruction and kidney injury. Ciprofloxacin, a commonly used antibiotic, causes AKI secondary to immune-mediated interstitial injury. Rare mechanisms of ciprofloxacin-induced renal injury include crystalluria, rhabdomyolysis, and granulomatous interstitial nephritis. Clinical and experimental studies have suggested that crystalluria and crystal nephropathy due to ciprofloxacin occur in alkaline urine. Preexisting kidney function impairment, high dose of the medication, and advanced age predispose to this complication. We report a case of ciprofloxacin-induced crystal nephropathy and granulomatous interstitial nephritis in a young patient with no other predisposing factors. The patient responded to conservative treatment without the need for glucocorticoids.

  5. Levetiracetam-induced interstitial nephritis in a patient with glioma.

    Science.gov (United States)

    Mahta, Ali; Kim, Ryan Y; Kesari, Santosh

    2012-01-01

    A 45-year-old man with a new diagnosis of low grade glioma was started on an escalating dose of levetiracetam (Lev) for seizure management. He gradually developed intractable nausea/vomiting and a high creatinine concentration due to acute renal failure which was attributed to Lev-induced interstitial nephritis. The medication was changed and his renal function rapidly improved to his baseline. Copyright © 2011 Elsevier Ltd. All rights reserved.

  6. Pediatric lupus nephritis presenting with terminal renal failure.

    Science.gov (United States)

    Besouw, Martine T P; Vande Walle, Johan G; Ilias, Mohamad I; Raes, Ann M; Prytula, Agnieszka A; Claeys, Lieve; Dehoorne, Jo L

    2016-12-01

    A 12-year-old Congolese girl presented with acute renal failure, edema, hypertension, hemoptysis, hematuria, and proteinuria after a history of throat infection. Renal ultrasound showed kidneys of normal size, with increased echogenicity of the cortical parenchyma and decreased corticomedullary differentiation. Other additional investigations showed pancytopenia with decreased complement (low C3 and C4). Antinuclear antibodies were strongly positive, including anti-double stranded DNA. Renal biopsy confirmed severe grade IV lupus nephritis. She was treated with high-dose steroids, mycophenolate mofetil and hydroxychloroquine, in addition to hemodialysis. After one week of intensive treatment, diuresis recovered and dialysis could be stopped after six sessions. We describe an uncommon case of severe lupus nephritis, presenting with terminal renal failure. Since the rarity of this disease presentation, other more common diagnoses have to be considered. Once the diagnosis of lupus nephritis is established, a choice has to be made between the different induction treatment protocols. The patient's ethnic background and other supportive therapies, such as the need for dialysis, can help to make this choice.

  7. Integrative medicine for managing the symptoms of lupus nephritis

    Science.gov (United States)

    Choi, Tae-Young; Jun, Ji Hee; Lee, Myeong Soo

    2018-01-01

    Abstract Background: Integrative medicine is claimed to improve symptoms of lupus nephritis. No systematic reviews have been performed for the application of integrative medicine for lupus nephritis on patients with systemic lupus erythematosus (SLE). Thus, this review will aim to evaluate the current evidence on the efficacy of integrative medicine for the management of lupus nephritis in patients with SLE. Methods and analyses: The following electronic databases will be searched for studies published from their dates of inception February 2018: Medline, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL), as well as 6 Korean medical databases (Korea Med, the Oriental Medicine Advanced Search Integrated System [OASIS], DBpia, the Korean Medical Database [KM base], the Research Information Service System [RISS], and the Korean Studies Information Services System [KISS]), and 1 Chinese medical database (the China National Knowledge Infrastructure [CNKI]). Study selection, data extraction, and assessment will be performed independently by 2 researchers. The risk of bias (ROB) will be assessed using the Cochrane ROB tool. Dissemination: This systematic review will be published in a peer-reviewed journal and disseminated both electronically and in print. The review will be updated to inform and guide healthcare practice and policy. Trial registration number: PROSPERO 2018 CRD42018085205 PMID:29595669

  8. Experimental anti-GBM disease as a tool for studying spontaneous lupus nephritis.

    Science.gov (United States)

    Fu, Yuyang; Du, Yong; Mohan, Chandra

    2007-08-01

    Lupus nephritis is an immune-mediated disease, where antibodies and T cells both play pathogenic roles. Since spontaneous lupus nephritis in mouse models takes 6-12 months to manifest, there is an urgent need for a mouse model that can be used to delineate the pathogenic processes that lead to immune nephritis, over a quicker time frame. We propose that the experimental anti-glomerular basement membrane (GBM) disease model might be a suitable tool for uncovering some of the molecular steps underlying lupus nephritis. This article reviews the current evidence that supports the use of the experimental anti-GBM nephritis model for studying spontaneous lupus nephritis. Importantly, out of about 25 different molecules that have been specifically examined in the experimental anti-GBM model and also spontaneous lupus nephritis, all influence both diseases concordantly, suggesting that the experimental model might be a useful tool for unraveling the molecular basis of spontaneous lupus nephritis. This has important clinical implications, both from the perspective of genetic susceptibility as well as clinical therapeutics.

  9. High risk of ischemic heart disease in patients with lupus nephritis

    DEFF Research Database (Denmark)

    Faurschou, Mikkel; Mellemkjaer, Lene; Starklint, Henrik

    2011-01-01

    To investigate the occurrence of ischemic heart disease (IHD) in a cohort of 104 Danish patients with biopsy-proven lupus nephritis (LN).......To investigate the occurrence of ischemic heart disease (IHD) in a cohort of 104 Danish patients with biopsy-proven lupus nephritis (LN)....

  10. Crescentic glomerular nephritis associated with rheumatoid arthritis: a case report.

    Science.gov (United States)

    Balendran, K; Senarathne, L D S U; Lanerolle, R D

    2017-07-21

    Rheumatoid arthritis is a systemic disorder where clinically significant renal involvement is relatively common. However, crescentic glomerular nephritis is a rarely described entity among the rheumatoid nephropathies. We report a case of a patient with rheumatoid arthritis presenting with antineutrophil cytoplasmic antibody-negative crescentic glomerular nephritis. A 54-year-old Sri Lankan woman who had recently been diagnosed with rheumatoid arthritis was being treated with methotrexate 10 mg weekly and infrequent nonsteroidal anti-inflammatory drugs. She presented to our hospital with worsening generalized body swelling and oliguria of 1 month's duration. Her physical examination revealed that she had bilateral pitting leg edema and periorbital edema. She was not pale or icteric. She had evidence of mild synovitis of the small joints of the hand bilaterally with no deformities. No evidence of systemic vasculitis was seen. Her blood pressure was 170/100 mmHg, and her jugular venous pressure was elevated to 7 cm with an undisplaced cardiac apex. Her urine full report revealed 2+ proteinuria with active sediment (dysmorphic red blood cells [17%] and granular casts). Her 24-hour urinary protein excretion was 2 g. Her serum creatinine level was 388 μmol/L. Abdominal ultrasound revealed normal-sized kidneys with acute parenchymal changes and mild ascites. Her renal biopsy showed renal parenchyma containing 20 glomeruli showing diffuse proliferative glomerular nephritis, with 14 of 20 glomeruli showing cellular crescents, and the result of Congo red staining was negative. Her rheumatoid factor was positive with a high titer (120 IU/ml), but results for antinuclear antibody, double-stranded deoxyribonucleic acid, and antineutrophil cytoplasmic antibody (perinuclear and cytoplasmic) were negative. Antistreptolysin O titer rheumatoid arthritis, awareness of which would facilitate early appropriate investigations and treatment.

  11. Pulse cyclophospamide in severe lupus nephritis: Southern Indian experience

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    Das Uttara

    2010-01-01

    Full Text Available To evaluate the efficacy and safety of the monthly pulse IV cyclophosphamide (IVC therapy in patients with severe lupus nephritis, we studied 39 patients of lupus nephritis on IVC therapy between 1998 to 2002. Single monthly cyclophosphamide (0.75-1 g/m² was infused intravenously with oral prednisolone (0.5 mg/kg per day and appropriate hydration. Of the 39 pa-tients 25 (86.2% patients were females and 4 (13.8% were males. Six (2% cases had irregular follow-up and 3 patients had expired during the initial cycles and were excluded from the study. The mean age was 25.6 + 6.72 years (range 10-40 years. The mean duration of the disease from the onset to renal biopsy was 24.2 + 18.5 months. The clinical presentations included nephrotic syndrome (34.5%, acute glomerulonephritis (31.0%, Pyrexia of unknown origin (PUO (10.3%, and rapidly progressive renal failure (6.7%. Renal insufficiency was present in 47.2% cases. Twenty-two (75.9% patients had diffuse proliferative glomerulonephritis (class IV, 6 (20.7% focal proliferative glomerulonephritis (class III, and one (3.4% class Vd. After a mean follow-up of 15.8 months, out of 29 patients, 13 (44.8% had achieved complete remission, 7 (24.1% partial remission and 9 (31.0% cases did not respond to the therapy. Side effects of the therapy included vomiting and nausea (100% and hair loss during the first few doses of IVC. In addition, one case had dysfunctional uterine bleeding and two patients had avascular necrosis of femoral head. We conclude that our data indicate that IVC in severe lupus nephritis is effective in Indian patients though longer follow-up is required.

  12. Acute radiation nephritis. Light and electron microscopic observations

    International Nuclear Information System (INIS)

    Kapur, S.; Chandra, R.; Antonovych, T.

    1977-01-01

    Light and electron microscopy were used to observe acute radiation nephritis. By light microscopy the changes were of fibrinoid necrosis of the arteries and arterioles with segmental necrosis of the glomerular tufts. By electron microscopy the endocapillary cells reacted by hypertrophy and hyperplasia with increase in cytoplasmic organelles. In addition, disruption of endothelial and epithelial cells from the basement membranes were seen. It is concluded that the electron microscopic changes were unique and may be helpful in differentiating the necrotizing glomerulitis seen in other conditions, especially malignant hypertension

  13. Murine nephrotoxic nephritis as a model of chronic kidney disease

    DEFF Research Database (Denmark)

    Ougaard, M. K.E.; Kvist, P. H.; Jensen, H. E.

    2018-01-01

    Using the nonaccelerated murine nephrotoxic nephritis (NTN) as a model of chronic kidney disease (CKD) could provide an easily inducible model that enables a rapid test of treatments. Originally, the NTN model was developed as an acute model of glomerulonephritis, but in this study we evaluate...... progressive mesangial expansion and significant renal fibrosis within three weeks suggesting CKD development. CD1 and C57BL/6 females showed a similar disease progression, but female mice seemed more susceptible to NTS compared to male mice. The presence of albuminuria, GFR decline, mesangial expansion...

  14. Allergic Interstitial Nephritis Manifesting as a Striated Nephrogram

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    Irfan Moinuddin

    2015-01-01

    Full Text Available Allergic interstitial nephritis (AIN is an underdiagnosed cause of acute kidney injury (AKI. Guidelines suggest that AIN should be suspected in a patient who presents with an elevated serum creatinine and a urinalysis that shows white cells, white cell casts, or eosinophiluria. Drug-induced AIN is suspected if AKI is temporally related to the initiation of a new drug. However, patients with bland sediment and normal urinalysis can also have AIN. Currently, a definitive diagnosis of AIN is made by renal biopsy which is invasive and fraught with risks such as bleeding, infection, and hematoma. Additionally, it is frequently unclear when a kidney biopsy should be undertaken. We describe a biopsy proven case of allergic interstitial nephritis which manifested on contrast enhanced Magnetic Resonance Imaging (MRI as a striated nephrogram. Newer and more stable macrocyclic gadolinium contrast agents have a well-demonstrated safety profile. Additionally, in the presentation of AKI, gadolinium contrast agents are safe to administer in patients who demonstrate good urine output and a downtrending creatinine. We propose that the differential for a striated nephrogram may include AIN. In cases in which the suspicion for AIN is high, this diagnostic consideration may be further characterized by contrast enhanced MRI.

  15. Treatment of intractable lupus nephritis with total lymphoid irradiation

    International Nuclear Information System (INIS)

    Strober, S.; Field, E.; Hoppe, R.T.; Kotzin, B.L.; Shemesh, O.; Engleman, E.; Ross, J.C.; Myers, B.D.

    1985-01-01

    Ten patients with lupus nephritis and marked proteinuria (3.9 g or more/d) that did not respond adequately to treatment with prednisone alone or prednisone in combination with azathioprine were treated with total lymphoid irradiation in an uncontrolled feasibility study. Within 6 weeks after the start of total lymphoid irradiation, the serum albumin level rose in all patients in association with a reduction in the serum level of anti-DNA antibodies, an increase in the serum complement level, or both. Improvement in these variables persisted in eight patients followed for more than 1 year, with the stabilization or reduction of the serum creatinine level. Urinary leakage of albumin was substantially reduced in all patients. Side effects associated with radiotherapy included transient constitutional complaints in ten patients, transient blood element depressions in three, localized viral and bacterial infections in four, and ovarian failure in one. The results suggest that total lymphoid irradiation may provide an alternative to cytotoxic drugs in the treatment of lupus nephritis

  16. Association of STAT4 polymorphism with severe renal insufficiency in lupus nephritis.

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    Karin Bolin

    Full Text Available Lupus nephritis is a cause of significant morbidity in systemic lupus erythematosus (SLE and its genetic background has not been completely clarified. The aim of this investigation was to analyze single nucleotide polymorphisms (SNPs for association with lupus nephritis, its severe form proliferative nephritis and renal outcome, in two Swedish cohorts. Cohort I (n = 567 SLE cases, n = 512 controls was previously genotyped for 5676 SNPs and cohort II (n = 145 SLE cases, n = 619 controls was genotyped for SNPs in STAT4, IRF5, TNIP1 and BLK. Case-control and case-only association analyses for patients with lupus nephritis, proliferative nephritis and severe renal insufficiency were performed. In the case-control analysis of cohort I, four highly linked SNPs in STAT4 were associated with lupus nephritis with genome wide significance with p = 3.7 × 10(-9, OR 2.20 for the best SNP rs11889341. Strong signals of association between IRF5 and an HLA-DR3 SNP marker were also detected in the lupus nephritis case versus healthy control analysis (p <0.0001. An additional six genes showed an association with lupus nephritis with p <0.001 (PMS2, TNIP1, CARD11, ITGAM, BLK and IRAK1. In the case-only meta-analysis of the two cohorts, the STAT4 SNP rs7582694 was associated with severe renal insufficiency with p = 1.6 × 10(-3 and OR 2.22. We conclude that genetic variations in STAT4 predispose to lupus nephritis and a worse outcome with severe renal insufficiency.

  17. Outcome of childhood lupus nephritis in Saudi children

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    Sulaiman Mohammed Al-Mayouf

    2017-01-01

    Full Text Available Our aim in this study is to report the long-term renal outcome of a cohort of Saudi children with systemic lupus erythematosus (SLE. All patients with childhood lupus nephritis (cLN proved by renal biopsy seen between January 2000 and June 2015 were reviewed. The renal outcome was assessed according to serum creatinine level, protein/creatinine ratio at the last follow-up visit, and/or evidence of renal impairment during follow-up period and end-stage renal disease (ESRD. Additional outcome measures include accrual damage measured by pediatric adaptation of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (pSDI, and death related to SLE was determined. A total of 84 (72 females cLN patients with follow-up duration of 9.3 years (±5.2 were included in this study. The mean current age was 19.4 years (±5.5 and mean age at onset was 9.2 years (±2.4. The most frequent histopathological class was proliferative glomerulonephritis (64.3% followed by membranous nephritis (27.4%. The mean activity and chronicity indices were 5.9 (±3.9 and 2.9 (±2.2, respectively. Renal microthrombosis was found in 9 (10.7% patients. All patients treated with immunosuppressive medications; cyclophosphamide used in 64 followed by mycophenolate mofetil in 42, then azathioprine in 19 patients, while rituximab used in 24 patients. At the last follow-up visit, the mean serum creatinine was 147 umol/L (±197 and the mean protein/ creatinine ratio was 0.8 (± 1.1 while the mean total pSDI was 1.9 (±1.9 and mean renal SDI was 0.7 (±1.1. Sixteen (19% patients had ESRD and eight of them had class IV nephritis. However, there was no significant difference in ESRD by histological class. The overall survival rates were five years: 94% and 10 years: 87%. Infection was the leading cause of mortality. Our patients had severe cLN and required intensive treatment. Despite the survival rate is comparable to other studies, ESRD is more

  18. Factors promoting development of renal tubulointerstitial lesions in patients with diabetes mellitus

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    Minara Shamkhalovna Shamkhalova

    2010-09-01

    patients without CKD and healthy subjects. These changes were unrelated to the type of diabetes or the cause ofnephropathy, which suggests their contribution to renal pathology through the universal mechanism of tubulointerstitial fibrosis. Activation of profibrogeniccytokines in DM patients with CKD was closely associated with endothelial dysfunction manifest as enhanced production of blood adhesive angiogenic, thrombogenic factors (FW, PAI, VICAM, sICAM, VEGF, and endothelium-affecting factors (ADMA, homocysteine. Mediators of inflammationand fibrogenesis in these patients negatively correlated with GFR and positively with AU, the main markers of renal dysfunction. Hyperuricemia,TGF-1b, ADMA, and MCP-1 are considered to be the risk factors of impaired renal filtration function. Conclusion. The level of profibrogenic cytokines and ndothelial dysfunction factors in DM patients with different renal lesions reflects severity of tubulointerstitialfibrosis. It may be used for the purpose of prognostication and substantiation of intensification of secondary prophylaxis of renal insufficiency.

  19. Parvovirus B19 induced lupus-like syndrome with nephritis.

    Science.gov (United States)

    Georges, Elodie; Rihova, Zuzana; Cmejla, Radek; Decleire, Pierre-Yves; Langen, Corinne

    2016-12-01

    We report a case of a 65-year-old man who developed an acute illness with fever, arthralgia and nephritic syndrome. Antinuclear antibodies were slightly positive and complement levels were low. Renal biopsy showed exudative diffuse proliferative endocapillary glomerulonephritis with diffuse immunoglobulin (IgG, IgA, IgM) and complement deposition (C3d, C4d, C1q) on immunofluorescence. The patient was first treated with corticosteroids and mycophenolate mofetil for suspected lupus with WHO class IV glomerulonephritis. The diagnosis was questioned and a diagnosis of parvovirus B19-associated nephritis was made based on elevation of serum IgM antibodies for parvovirus B19 and detection of parvovirus B19 DNA on renal biopsy. The immunosuppressive treatment was stopped and progressive spontaneous regression of clinical and laboratory abnormalities was observed. We conclude that human parvovirus B19 infection should be considered as a cause of lupus-like symptomatology and acute glomerulonephritis.

  20. Renal Localization of {sup 67}Ga Citrate in Noninfectious Nephritis

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Kang Wook; Jeong, Min Soo; Rhee, Sunn Kgoo; Kim, Sam Yong; Shin, Young Tai; Ro, Heung Kyu [Chungnam University College of Medicine, Deajeon (Korea, Republic of)

    1992-07-15

    {sup 67}Ga citrate scan has been requested for detection or follow-up of inflammatory or neoplastic disease. Visualization of {sup 67}Ga citrate in the kidneys at 48 and 72 hr post injection is usually interpreted as evidence of renal pathology. But precise mechanisms of abnormal {sup 67}Ga uptake in kidneys were unknown. We undertook a study to determine the clinical value of {sup 67}Ga citrate imaging of the kidneys in 68 patients with primary or secondary nephropathy confirmed by renal biopsy and 66 control patients without renal disease. Renal uptake in 48 to 72 hr images was graded as follows: Grade 0=background activity;1=faint uptake greater than background; 2=definite uptake, but less than lumbar vertebrae;3 same uptake as lumbar vertebrae, but less than liver; 4=same or higher uptake than liver. The results were as follows. 1) 42 of 68(62%) patients with noninfectious nephritis showed grade 2 or higher {sup 67}Ga renal uptake but only 10 percent of control patients showed similar uptake. 2) In 14 patients with systemic lupus erythematosus, 8 of 9 (89%) patients with lupus nephritis exhibited marked renal uptake. 3) 36 of 41 patients (88%) with combined nephrotic syndrome showed Grade 2 or higher renal uptake. 4) Renal {sup 67}Ga uptake was correlated with clinical severity of nephrotic syndrome determined by serum albumin level, 24 hr urine protein excretion and serum lipid levels. 5) After complete remission of nephrotic syndrome, renal uptake in all 8 patients who were initially Grade 3 or 4, decreased to Grade 1 or 0. In conclusion, we think that the mechanism of renal {sup 67}Ga uptake in nephrotic syndrome might be related to the pathogenesis of nephrotic syndrome. In systemic lupus erythematosus, {sup 67}Ga citrate scan is useful in predicting renal involvement.

  1. Renal Localization of 67Ga Citrate in Noninfectious Nephritis

    International Nuclear Information System (INIS)

    Lee, Kang Wook; Jeong, Min Soo; Rhee, Sunn Kgoo; Kim, Sam Yong; Shin, Young Tai; Ro, Heung Kyu

    1992-01-01

    67 Ga citrate scan has been requested for detection or follow-up of inflammatory or neoplastic disease. Visualization of 67 Ga citrate in the kidneys at 48 and 72 hr post injection is usually interpreted as evidence of renal pathology. But precise mechanisms of abnormal 67 Ga uptake in kidneys were unknown. We undertook a study to determine the clinical value of 67 Ga citrate imaging of the kidneys in 68 patients with primary or secondary nephropathy confirmed by renal biopsy and 66 control patients without renal disease. Renal uptake in 48 to 72 hr images was graded as follows: Grade 0=background activity;1=faint uptake greater than background; 2=definite uptake, but less than lumbar vertebrae;3 same uptake as lumbar vertebrae, but less than liver; 4=same or higher uptake than liver. The results were as follows. 1) 42 of 68(62%) patients with noninfectious nephritis showed grade 2 or higher 67 Ga renal uptake but only 10 percent of control patients showed similar uptake. 2) In 14 patients with systemic lupus erythematosus, 8 of 9 (89%) patients with lupus nephritis exhibited marked renal uptake. 3) 36 of 41 patients (88%) with combined nephrotic syndrome showed Grade 2 or higher renal uptake. 4) Renal 67 Ga uptake was correlated with clinical severity of nephrotic syndrome determined by serum albumin level, 24 hr urine protein excretion and serum lipid levels. 5) After complete remission of nephrotic syndrome, renal uptake in all 8 patients who were initially Grade 3 or 4, decreased to Grade 1 or 0. In conclusion, we think that the mechanism of renal 67 Ga uptake in nephrotic syndrome might be related to the pathogenesis of nephrotic syndrome. In systemic lupus erythematosus, 67 Ga citrate scan is useful in predicting renal involvement.

  2. Control of lupus nephritis by changes of gut microbiota.

    Science.gov (United States)

    Mu, Qinghui; Zhang, Husen; Liao, Xiaofeng; Lin, Kaisen; Liu, Hualan; Edwards, Michael R; Ahmed, S Ansar; Yuan, Ruoxi; Li, Liwu; Cecere, Thomas E; Branson, David B; Kirby, Jay L; Goswami, Poorna; Leeth, Caroline M; Read, Kaitlin A; Oestreich, Kenneth J; Vieson, Miranda D; Reilly, Christopher M; Luo, Xin M

    2017-07-11

    Systemic lupus erythematosus, characterized by persistent inflammation, is a complex autoimmune disorder with no known cure. Immunosuppressants used in treatment put patients at a higher risk of infections. New knowledge of disease modulators, such as symbiotic bacteria, can enable fine-tuning of parts of the immune system, rather than suppressing it altogether. Dysbiosis of gut microbiota promotes autoimmune disorders that damage extraintestinal organs. Here we report a role of gut microbiota in the pathogenesis of renal dysfunction in lupus. Using a classical model of lupus nephritis, MRL/lpr, we found a marked depletion of Lactobacillales in the gut microbiota. Increasing Lactobacillales in the gut improved renal function of these mice and prolonged their survival. We used a mixture of 5 Lactobacillus strains (Lactobacillus oris, Lactobacillus rhamnosus, Lactobacillus reuteri, Lactobacillus johnsonii, and Lactobacillus gasseri), but L. reuteri and an uncultured Lactobacillus sp. accounted for most of the observed effects. Further studies revealed that MRL/lpr mice possessed a "leaky" gut, which was reversed by increased Lactobacillus colonization. Lactobacillus treatment contributed to an anti-inflammatory environment by decreasing IL-6 and increasing IL-10 production in the gut. In the circulation, Lactobacillus treatment increased IL-10 and decreased IgG2a that is considered to be a major immune deposit in the kidney of MRL/lpr mice. Inside the kidney, Lactobacillus treatment also skewed the Treg-Th17 balance towards a Treg phenotype. These beneficial effects were present in female and castrated male mice, but not in intact males, suggesting that the gut microbiota controls lupus nephritis in a sex hormone-dependent manner. This work demonstrates essential mechanisms on how changes of the gut microbiota regulate lupus-associated immune responses in mice. Future studies are warranted to determine if these results can be replicated in human subjects.

  3. Anti-Myeloperoxidase Antibodies Associate with Future Proliferative Lupus Nephritis

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    S. W. Olson

    2017-01-01

    Full Text Available Background. The subclinical pathophysiology of proliferative lupus nephritis (PLN has not been fully elucidated. Myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA is associated with PLN, but prediagnostic levels have not been reported. Methods. We performed a retrospective case-control Department of Defense Serum Repository (DoDSR study comparing MPO-ANCA levels in longitudinal prediagnostic serum samples for 23 biopsy confirmed proliferative lupus nephritis (PLN patients to DoDSR identified age, sex, race, and age of serum matched healthy and SLE without LN disease controls. We also compared the temporal relationship of MPO-ANCA to anti-double stranded DNA antibodies (dsDNAab. Results. A greater proportion of PLN patients had prediagnostic MPO-ANCA levels above ≥3 U/mL and ≥6 U/mL compared to SLE without LN (91% versus 43%, p<0.001; 57% versus 5%, p<0.001, resp.. In subgroup analysis, the MPO-ANCA threshold of ≥3 U/mL was significant at <1 year (88% versus 39%, p=0.007 and 1–4 years (87% versus 38%, p=0.009 prior to diagnosis. Statistically significant subclinical MPO-ANCA levels (≥3 U/mL occurred prior to statistically significant dsDNAab ≥ 3 IU/ml (89% versus 11%, p=0.003. Conclusions. Subclinical MPO-ANCA levels could distinguish future PLN from SLE without LN. MPO-ANCA manifests prior to clinical disease and subclinical dsDNAab to suggest that it may contribute directly to PLN pathogenicity.

  4. Long-term mortality and renal outcome in a cohort of 100 patients with lupus nephritis

    DEFF Research Database (Denmark)

    Faurschou, Mikkel; Dreyer, Lene; Kamper, Anne-Lise

    2010-01-01

    To evaluate the long-term mortality and renal outcome in a cohort of Danish patients with lupus nephritis (LN) and to identify outcome predictors among findings registered at the time of the first renal biopsy.......To evaluate the long-term mortality and renal outcome in a cohort of Danish patients with lupus nephritis (LN) and to identify outcome predictors among findings registered at the time of the first renal biopsy....

  5. Childhood lupus nephritis: 12 years of experience from a developing country's perspective.

    Science.gov (United States)

    Samanta, Moumita; Nandi, Madhumita; Mondal, Rakesh; Hazra, Avijit; Sarkar, Sumatra; Sabui, Tapas; Kundu, Chanchal Kumar; Biswas, Arnab

    2017-09-01

    To assess the long-term outcome of lupus nephritis in children with systemic lupus erythematosus followed up over 12 years at a tertiary care teaching hospital in Eastern India. This is a retrospective observational study of the clinicopathological presentation, management, and outcome in 46 children with lupus nephritis over a period of 12 years at a tertiary teaching hospital in Eastern India. Mortality was compared between different lupus classes and therapy groups with Kaplan-Meier analysis and log-rank test. The incidence of lupus nephritis was 58.97% [95% confidence interval (CI) 48.06%-59.89%] with the mean age at presentation being 10.2±2.43 years (range 5.5-14.5) years. Majority belonged to class IV (30.43%), followed by class II (26.91%), class III (23.91), and class V (8.70%). Outcome analysis of children with lupus nephritis over 12 years revealed that 24 (52.17%) achieved complete remission of disease activity, 5 attained partial remission, 4 continued to have active disease, 5 developed end-stage renal disease (ESRD), and 8 died. Overall mortality thus observed was 17.39% with septicemia in the background of ESRD being the commonest cause. No significant difference in mortality was observed between different lupus nephritis classes or therapy arm groups. The study throws light on various aspects of lupus nephritis and their long-term outcome patterns in children from developing countries such as India.

  6. Epstein-Barr virus in the enlarged salivary tissues of patients with IgG4-related disease.

    Science.gov (United States)

    Furukawa, Takatoshi; Shimotai, Yoshitaka; Ohta, Nobuo; Ishida, Akihiro; Kurakami, Kazuya; Suzuki, Hitoshi; Yamakawa, Mitsunori; Hongo, Seiji; Kakehata, Seiji

    2015-09-01

    Immunoglobulin G4-related disease (IgG4-RD) is a recently recognized disease entity characterized by high-serum IgG4 concentration and IgG4-producing plasma cell production with fibrotic or sclerotic changes in affected organs. We aimed to clarify the roles of Epstein-Barr virus (EBV) in patients with IgG4-RDs. A retrospective clinical study at the Yamagata University School of Medicine, Yamagata, Japan. The patient group consisted of four males and four females with an average age of 62 years (range: 48-73). Expression of IgG4, latent member protein 1, EBV nuclear antigens-2, and EBV-encoded RNA in affected salivary glands from patients with IgG4-RD was examined by using immunohistochemistry and in situ hybridization. The copy number of EBV DNA in the salivary glands was also investigated by real-time polymerase chain reaction. All patients had hard masses in the salivary or lacrimal glands, or both, bilaterally. Serum concentrations of IgG4 were elevated in all cases (mean 589.1, range 129-1750), and IgG4-positive plasmacytes were observed in the involved salivary glands. Four patients developed potentially life-threatening systemic involvement after initial salivary gland swelling. EBV-associated molecules (EBNA and EBER) were overexpressed in the affected salivary glands. The copy number of EBV DNA was significantly higher in patients with potentially life-threatening systemic involvement than in patients without systemic involvement (P < 0.05). These results suggest that the copy number of EBV DNA could be useful as diagnostic findings in IgG4-RD to predict potentially life-threatening systemic involvement. 4. © 2015 The American Laryngological, Rhinological and Otological Society, Inc.

  7. IgG4-related disease: description of a case with pulmonary lesions, mediastinal lymphadenopathies and rapidly progressive renal failure.

    Science.gov (United States)

    Fernández Lorente, Loreto; Álvarez, Dolores López; López, Virginia García; Kollros, Vesna Abujder; Ariza, Aurelio; Gálvez, Alejandro; Bonet, Josep

    2015-01-01

    This is a case report of a 73-year-old man with new-onset acute renal failure while being investigated for pulmonary infiltrates and mediastinal lymphadenopathies. Urine tests showed tubular range proteinuria with no microhaematuria. Immunology tests showed elevated serum IgG and hypocomplementaemia (classical pathway activation). Renal biopsy and clinical-pathological correlation were crucial in this case, reinforcing their important role in the final diagnosis of acute kidney injury. Copyright © 2015. Published by Elsevier España, S.L.U.

  8. On the role of IgG4 in inflammatory conditions: lessons for IgG4-related disease

    NARCIS (Netherlands)

    Trampert, David C.; Hubers, Lowiek M.; van de Graaf, Stan F. J.; Beuers, Ulrich

    2017-01-01

    The pathophysiology of immunoglobulin G4-related disease (IgG4-RD) and its most common manifestations, IgG4-associated (sclerosing) cholangitis and autoimmune pancreatitis, remains largely unknown, but IgG4 is presumably involved. IgG4 is a promiscuous antibody, which could be directly pathogenic,

  9. IgG4-related disease: description of a case with pulmonary lesions, mediastinal lymphadenopathies and rapidly progressive renal failure

    Directory of Open Access Journals (Sweden)

    Loreto Fernández Lorente

    2015-03-01

    Full Text Available This is a case report of a 73-year-old man with new-onset acute renal failure while being investigated for pulmonary infiltrates and mediastinal lymphadenopathies. Urine tests showed tubular range proteinuria with no microhaematuria. Immunology tests showed elevated serum IgG and hypocomplementaemia (classical pathway activation. Renal biopsy and clinical-pathological correlation were crucial in this case, reinforcing their important role in the final diagnosis of acute kidney injury.

  10. Analysis of IgG4-positive clones in affected organs of IgG4-related disease.

    Science.gov (United States)

    Kakuchi, Yasushi; Yamada, Kazunori; Ito, Kiyoaki; Hara, Satoshi; Fujii, Hiroshi; Yamagishi, Masakazu; Kawano, Mitsuhiro

    2016-11-01

    We investigated class switch reaction (CSR) in affected organs and evaluated whether the same or genetically related clones exist in IgG4-RD. We studied three patients with IgG4-RD. Total cellular RNA was extracted from salivary glands and peripheral blood and lung tissue. Activation-induced cytidine deaminase (AID) and immunoglobulin heavy chain third complementarity determining region (IgVH-CDR3) of IgM and IgG4 were detected by reverse transcription polymerase chain reaction (RT-PCR). We analyzed the clonal relationship of infiltrating IgG4-positive cells, as compared with IgM. We determined the existence of common clones among organs and patients. AID was expressed in salivary glands of all patients and lung tissue in one. Closely related IgVH-CDR3 sequences in infiltrating IgG4-positive cells were detected in salivary glands and lung tissue. Identical IgVH-CDR3 sequence between IgM and IgG4 in salivary glands was detected in one patient, indicating CSR in salivary glands. Identical IgVH-CDR3 sequences of IgG4-positive cells were detected between salivary glands and peripheral blood in two patients. Four identical sequences of IgVH-CDR3 existed between patients. Interestingly, one of the four sequences was detected in all patients. Our results demonstrate the existence of common antigen(s) shared by patients with IgG4-RD.

  11. LatY136F knock-in mouse model for human IgG4-related disease.

    Science.gov (United States)

    Yamada, Kazunori; Zuka, Masahiko; Ito, Kiyoaki; Mizuguchi, Keishi; Kakuchi, Yasushi; Onoe, Tamehito; Suzuki, Yasunori; Yamagishi, Masakazu; Izui, Shozo; Malissen, Marie; Malissen, Bernard; Kawano, Mitsuhiro

    2018-01-01

    The adaptor protein Linker for activation of T cell (LAT) is a key signaling hub used by the T cell antigen receptor. Mutant mice expressing loss-of-function mutations affecting LAT and including a mutation in which tyrosine 136 is replaced by a phenylalanine (LatY136F) develop lymphoproliferative disorder involving T helper type 2 effector cells capable of triggering a massive polyclonal B cell activation that leads to hypergammaglobulinemia G1 and E and to non-resolving inflammation and autoimmunity. The purpose of this study was to evaluate whether the phenotypes of LatY136F knock-in mice resemble the immunohistopathological features of immunoglobulin G4-related disease (IgG4-RD). LatY136F knock-in mice were sacrificed at 4-20 weeks of age, and pancreas, kidney, salivary gland and lung were obtained. All organs were stained with hematoxylin-eosin and with Azan for estimation of collagen in fibrosis, and the severity scores of inflammation and fibrosis were evaluated. Immunostainings were performed to analyze the types of infiltrating cells. In addition, the effects of corticosteroid treatment on the development of tissue lesions and serum levels of IgG1 were assessed. Tissue lesions characterized by inflammatory mononuclear cell infiltration and fibrosis were detected in pancreas, kidney, and salivary gland starting from 6 weeks of age. Immunostainings showed pronounced infiltration of plasma cells, CD4-positive T cells, and macrophages. Infiltrating plasma cells predominantly expressed IgG1. The extent of inflammation in pancreas and salivary glands was markedly reduced by corticosteroid treatment. LatY136F knock-in mice displayed increased production of Th2-type IgG1 (a homologue of human IgG4) and developed multiple organ tissue lesions reminiscent of those seen in patients with IgG4-RD. Moreover, the development of these tissue lesions was highly sensitive to corticosteroid treatment like in IgG4-RD. For these reasons we consider the LatY136F knock-in mouse strain to represent a promising model for human IgG4-RD.

  12. Heterozygous Loss-of-Function SEC61A1 Mutations Cause Autosomal-Dominant Tubulo-Interstitial and Glomerulocystic Kidney Disease with Anemia

    Czech Academy of Sciences Publication Activity Database

    Bolar, N. A.; Golzio, C.; Živná, M.; Hayot, G.; Van Hemelrijk, C.; Schepers, D.; Vandeweyer, G.; Hoischen, A.; Huyghe, J. R.; Raes, A.; Matthys, E.; Sys, E.; Azou, M.; Gubler, M. C.; Praet, M.; Van Camp, G.; McFadden, K.; Pediaditakis, I.; Přistoupilová, A.; Hodaňová, K.; Vyleťal, P.; Hartmannová, H.; Stránecký, V.; Hůlková, H.; Barešová, V.; Jedličková, I.; Sovová, J.; Hnízda, Aleš; Kidd, K.; Bleyer, A. J.; Spong, R. S.; Vande Walle, J.; Mortier, G.; Brunner, H.; Van Laer, L.; Kmoch, S.; Katsanis, N.; Loeys, B. L.

    2016-01-01

    Roč. 99, č. 1 (2016), s. 174-187 ISSN 0002-9297 R&D Projects: GA MŠk(CZ) LO1304 Institutional support: RVO:61388963 Keywords : Sec61 * tubulo-interstitial kidney disease * rare disease Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 9.025, year: 2016 http://www.sciencedirect.com/science/article/pii/S0002929716301999

  13. Identification of Tisp40 as an Essential Regulator of Renal Tubulointerstitial Fibrosis via TGF-β/Smads Pathway

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    Cheng-cheng Xiao

    2017-06-01

    Full Text Available Background: Tisp40, a transcription factor of the CREB/CREM family, is involved in cell proliferation, differentiation and other biological functions, but its role in renal tubulointerstitial fibrosis is unknown. Methods: In our study, we investigated the effects of Tisp40 on extracellular matrix (ECM accumulation, epithelial-mesenchymal transition (EMT and the underlying molecular mechanisms in transforming growth factor-β (TGF-β-stimulated TCMK-1 cells by quantitative real-time polymerase chain reaction (qPCR, Western blot analysis and immunofluorescence in vitro, and further explored the role of Tisp40 on renal fibrosis induced by ischemia-reperfusion (I/R by qPCR, Western blot analysis, hydroxyproline analysis, Masson trichrome staining and immunohistochemistry staining in vivo. Results: The data showed that Tisp40 was upregulated in a model of renal fibrosis induced by I/R injury (IRI. Upon IRI, Tisp40-deficient mice showed attenuated renal fibrosis compared with wild-type mice. Furthermore, the expression of α-smooth muscle actin, E-cadherin, fibronectin, and collagen I was suppressed. Tisp40 overexpression aggravated ECM accumulation and EMT in the TGF-β-stimulated TCMK-1 cell line, whereas the opposite occurred in cells treated with small interfering RNA (siRNA targeting Tisp40. Importantly, it is changes in the Smad pathway that attenuate renal fibrosis. Conclusion: These findings suggest that Tisp40 plays a critical role in the TGF-β/ Smads pathway involved in this process. Hence, Tisp40 could be a useful therapeutic target in the fight against renal tubulointerstitial fibrosis.

  14. Acute interstitial nephritis with acetaminophen and alcohol intoxication

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    Alexopoulou Iakovina

    2011-04-01

    Full Text Available Abstract Drug-induced acute interstitial nephritis (AIN represents a growing cause of renal failure in current medical practice. While antimicrobials and non-steroidal anti-inflammatory drugs are typically associated with drug-induced AIN, few reports have been made on the involvement of other analgesics. We report our experience in managing a 17-year-old female with AIN and subsequent renal injury following an acetaminophen overdose in conjunction with acute alcohol intoxication. It is well established that acetaminophen metabolism, particularly at high doses, produces reactive metabolites that may induce renal and hepatic toxicity. It is also plausible however, that such reactive species could instead alter renal peptide immunogenicity, thereby inducing AIN. In the following report, we review a possible mechanism for the acetaminophen-induced AIN observed in our patient and also discuss the potential involvement of acute alcohol ingestion in disease onset. The objective of our report is to increase awareness of healthcare professionals to the potential involvement of these commonly used agents in AIN pathogenesis.

  15. Intracranial hypertension: A rare presentation of lupus nephritis.

    Science.gov (United States)

    Yadav, Praveen; Nair, Anishkumar; Cherian, Ajith; Sibi, N S; Kumar, Ashwini

    2010-07-01

    A 14-year-old male presented with bilateral papilledema, growth retardation and absent secondary sexual characters. He had a past history of fever, headache and fatigue of 6 months duration. The diagnosis of intracranial hypertension (IH) was confirmed by an increased intracranial pressure and normal neuroimaging studies of the brain, except for partial empty sella, prominent perioptic cerebrospinal fluid (CSF) spaces and buckling of optic nerves. Evaluation showed erythrocyte sedimentation rate (ESR) of 150 mm/hr, positive antinuclear antibody (ANA), anti dsDNA and anti ribosomal P protein. Renal biopsy revealed diffuse segmental proliferative lupus nephritis (LN) class IV S (A) confirming the diagnosis of systemic lupus erythematosus (SLE). Treatment of LN with intravenous pulse methyl prednisolone and cyclophosphamide was effective in normalizing the CSF pressure, resulting in express and dramatic resolution of symptomatology. In a case of IH, SLE must be considered. IH, growth retardation and absence of sexual characters may be presenting manifestations of a chronic systemic inflammatory disease like SLE. These manifestations may act as a pointer to associated advanced grades of LN, which can be totally asymptomatic and missed without a renal biopsy.

  16. Pregnancy and renal outcomes in lupus nephritis: an update and guide to management.

    Science.gov (United States)

    Bramham, K; Soh, M C; Nelson-Piercy, C

    2012-10-01

    Systemic lupus erythematosis (SLE) commonly affects women of child bearing-age, and advances in treatment have resulted in an increasing number of women with renal involvement becoming pregnant. Knowledge of the relationship of the condition with respect to fertility and pregnancy is important for all clinicians involved in the care of women with lupus nephritis because they have complicated pregnancies. Presentation of lupus nephritis can range from mild asymptomatic proteinuria to rapidly progressive renal failure and may occur before, during, or after pregnancy. The timing of diagnosis may influence pregnancy outcome. Pregnancy may also affect the course of lupus nephritis. All pregnancies in women with lupus nephritis should be planned, preferably after more than six-months of quiescent disease. Predictors of poor obstetric outcome include active disease at conception or early pregnancy, baseline poor renal function with Creatinine >100 μmol/L, proteinuria >0.5 g/24 hours, presence of concurrent antiphospholipid syndrome and hypertension. In this review the most recent studies of pregnancies in women with lupus nephritis are discussed and a practical approach to managing women prepregnancy, during pregnancy and post-partum is described.

  17. Subacute bacterial endocarditis and subsequent shunt nephritis from ventriculoatrial shunting 14 years after shunt implantation

    DEFF Research Database (Denmark)

    Burström, Gustav; Andresen, Morten; Bartek, Jiri Jr.

    2014-01-01

    of causing subacute bacterial endocarditis and subsequent shunt nephritis. The patient was successfully treated with antibiotics combined with ventriculoatrial shunt removal and endoscopic third ventriculocisternostomy (VCS). This case illustrates the nowadays rare, but potentially severe complication...... of subacute bacterial endocarditis and shunt nephritis. It also exemplifies the VCS as an alternative to implanting foreign shunt systems for CSF diversion....

  18. The renal metallothionein expression profile is altered in human lupus nephritis

    DEFF Research Database (Denmark)

    Faurschou, Mikkel; Penkowa, Milena; Andersen, Claus Bøgelund

    2008-01-01

    of standard statistical methods. RESULTS: Proximal tubules displaying epithelial cell MT-I+II depletion in combination with luminal MT-I+II expression were observed in 31 out of 37 of the lupus nephritis specimens, but not in any of the control sections (P = 0.006). The tubular MT score, defined as the median......INTRODUCTION: Metallothionein (MT) isoforms I + II are polypeptides with potent antioxidative and anti-inflammatory properties. In healthy kidneys, MT-I+II have been described as intracellular proteins of proximal tubular cells. The aim of the present study was to investigate whether the renal MT......-I+II expression profile is altered during lupus nephritis. METHODS: Immunohistochemistry was performed on renal biopsies from 37 patients with lupus nephritis. Four specimens of healthy renal tissue served as controls. Clinicopathological correlation studies and renal survival analyses were performed by means...

  19. Identification of unique microRNA signature associated with lupus nephritis.

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    Jeannie L Te

    2010-05-01

    Full Text Available MicroRNAs (miRNA have emerged as an important new class of modulators of gene expression. In this study we investigated miRNA that are differentially expressed in lupus nephritis. Microarray technology was used to investigate differentially expressed miRNA in peripheral blood mononuclear cells (PBMCs and Epstein-Barr Virus (EBV-transformed cell lines obtained from lupus nephritis affected patients and unaffected controls. TaqMan-based stem-loop real-time polymerase chain reaction was used for validation. Microarray analysis of miRNA expressed in both African American (AA and European American (EA derived lupus nephritis samples revealed 29 and 50 differentially expressed miRNA, respectively, of 850 tested. There were 18 miRNA that were differentially expressed in both racial groups. When samples from both racial groups and different specimen types were considered, there were 5 primary miRNA that were differentially expressed. We have identified 5 miRNA; hsa-miR-371-5P, hsa-miR-423-5P, hsa-miR-638, hsa-miR-1224-3P and hsa-miR-663 that were differentially expressed in lupus nephritis across different racial groups and all specimen types tested. Hsa-miR-371-5P, hsa-miR-1224-3P and hsa-miR-423-5P, are reported here for the first time to be associated with lupus nephritis. Our work establishes EBV-transformed B cell lines as a useful model for the discovery of miRNA as biomarkers for SLE. Based on these findings, we postulate that these differentially expressed miRNA may be potential novel biomarkers for SLE as well as help elucidate pathogenic mechanisms of lupus nephritis. The investigation of miRNA profiles in SLE may lead to the discovery and development of novel methods to diagnosis, treat and prevent SLE.

  20. Serum Renalase Levels Correlate with Disease Activity in Lupus Nephritis.

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    Chaojun Qi

    Full Text Available Lupus nephritis (LN is among the most serious complications of systemic lupus erythematosus (SLE, which causes significant morbidity and mortality. Renalase is a novel, kidney-secreted cytokine-like protein that promotes cell survival. Here, we aimed to investigate the relationship of serum renalase levels with LN and its role in the disease progression of LN.For this cross-sectional study, 67 LN patients and 35 healthy controls were enrolled. Seventeen active LN patients who received standard therapies were followed up for six months. Disease activity was determined by the SLE Disease Activity-2000 (SLEDAI-2K scoring system and serum renalase amounts were determined by ELISA. Predictive value of renalase for disease activity was assessed. Furthermore, the expression of renalase in the kidneys of patients and macrophage infiltration was assessed by immunohistochemistry.Serum renalase amounts were significantly higher in LN patients than in healthy controls. Moreover, patients with proliferative LN had more elevated serum renalase levels than Class V LN patients. In proliferative LN patients, serum renalase levels were significantly higher in patients with active LN than those with inactive LN. Serum renalase levels were positively correlated with SLEDAI-2K, 24-h urine protein excretion, ds-DNA and ESR but inversely correlated with serum albumin and C3. Renalase amounts decreased significantly after six-months of standard therapy. The performance of renalase as a marker for diagnosis of active LN was 0.906 with a cutoff value of 66.67 μg/ml. We also observed that the amount of renalase was significantly higher in glomerular of proliferative LN along with the co-expression of macrophages.Serum renalase levels were correlated with disease activity in LN. Serum renalase might serve as a potential indicator for disease activity in LN. The marked increase of glomerular renalase and its association with macrophages suggest that it might play an

  1. Local CD34-positive capillaries decrease in mouse models of kidney disease associating with the severity of glomerular and tubulointerstitial lesions.

    Science.gov (United States)

    Masum, Md Abdul; Ichii, Osamu; Elewa, Yaser Hosny Ali; Nakamura, Teppei; Kon, Yasuhiro

    2017-09-04

    The renal vasculature plays important roles in both homeostasis and pathology. In this study, we examined pathological changes in the renal microvascular in mouse models of kidney diseases. Glomerular lesions (GLs) in autoimmune disease-prone male BXSB/MpJ-Yaa (Yaa) mice and tubulointerstitial lesions (TILs) in male C57BL/6 mice subjected to unilateral ureteral obstruction (UUO) for 7 days were studied. Collected kidneys were examined using histopathological techniques. A nonparametric Mann-Whitney U test (P < 0.05) was performed to compare healthy controls and the experimental mice. The Kruskal-Wallis test was used to compare three or more groups, and multiple comparisons were performed using Scheffe's method when significant differences were observed (P < 0.05). Yaa mice developed severe autoimmune glomerulonephritis, and the number of CD34 + glomerular capillaries decreased significantly in GLs compared to that in control mice. However, UUO-treated mice showed severe TILs only, and CD34 + tubulointerstitial capillaries were decreased significantly in TILs with the progression of tubulointerstitial fibrosis compared to those in untreated control kidneys. Infiltrations of B-cells, T-cells, and macrophages increased significantly in the respective lesions of both disease models (P < 0.05). In observations of vascular corrosion casts by scanning electron microscopy and of microfil rubber-perfused thick kidney sections by fluorescence microscopy, segmental absences of capillaries were observed in the GLs and TILs of Yaa and UUO-treated mice, respectively. Further, transmission electron microscopy revealed capillary endothelial injury in the respective lesions of both models. The numbers of CD34 + glomerular and tubulointerstitial capillaries were negatively correlated with all examined parameters in GLs (P < 0.05) and TILs (P < 0.01), respectively. From the analysis of mouse models, we identified inverse pathological correlations between the number of

  2. Plasma ficolin levels and risk of nephritis in Danish patients with systemic lupus erythematosus

    DEFF Research Database (Denmark)

    Tanha, Nima; Pilely, Katrine; Faurschou, Mikkel

    2017-01-01

    Given the scavenging properties of ficolins, we hypothesized that variation in the plasma concentrations of the three ficolins may be associated with development of lupus nephritis (LN), type of LN, end-stage renal disease (ESRD), and/or mortality among patients with systemic lupus erythematosus...

  3. Interstitial nephritis of slaughtered pigs in the State of Mato Grosso, Brazil

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    João X. Oliveira Filho

    2012-04-01

    Full Text Available This study evaluated histological lesions in kidney samples from pigs with nephritis in two slaughterhouses in the State of Mato Grosso, Brazil. Four hundred samples were subjected to histology, anti-porcine circovirus type 2 (PCV2 immunohistochemistry (IHC, anti-Leptospira sp. immunofluorescence (IF, and polymerase chain reaction (PCR for PCV2, porcine parvovirus (PPV, and Torque teno virus type 1 and 2 (TTV1, TTV2 detection. Histological lesions were found in 81% of the samples, and mononuclear interstitial nephritis was the most frequent lesion (77.50%. A follicular pattern was observed in 40.97% of the interstitial nephritis lesions. PCV2, PPV, TTV1, and TTV2 were identified in the kidneys by PCR in 27.25%, 28.50%, 94%, and 87.5% of the samples, respectively. Leptospira sp. was not detected through IF. Infection by PCV2 (PCR and the presence of histological lesions (P=0.008 and giant cells (P=0.0016 were significantly associated. An association was observed between the TTV2-TTV1 co-infection (P<0.0001 and the risk for pathogenesis. These findings indicated that PCV2, PPV, TTV1, and TTV2 were widely distributed among pigs in the local farms and that the presence of these agents should be considered in the differential diagnosis of kidneys with interstitial nephritis in pigs.

  4. [Therapeutic effect of total glucosides of paeony on lupus nephritis in MRL/lpr mice].

    Science.gov (United States)

    Ding, Zhao-Xia; Yang, Shao-Feng; Wu, Qi-Fu; Lu, Ying; Chen, Yu-Yao; Nie, Xiao-Li; Jie, Hong-Yu; Qi, Jing-Min; Wang, Fan-Sheng

    2011-04-01

    To observe the therapeutic effect of total glucosides of paeony (TGP) on lupus nephritis (LN) in MRL/lpr mice. MRL/lpr mice with lupus nephritis were randomized into model group and TGP group. The urinary protein content was detected using Coomassie brilliant blue, and the serum levels of IgG anti-double-stranded DNA (dsDNA) antibodies and antinuclear antibodies (ANA) were measured by enzyme-linked immunosorbent assay (ELISA). The changes in the renal pathology were examined microscopically, and the spleen and thymus were weighed to calculate the spleen and thymus indexes. At 15 and 30 days after TGP administration, the urinary protein content in the TGP group was significantly lower than that in the model group (PTGP treatment significantly lowered the serum levels of anti-dsDNA antibodies and ANA and the weight and index of spleen (PTGP treatment, the urinary protein content and the levels of anti-dsDNA antibodies and ANA decreased significantly at 15 and 30 days after TGP administration (PTGP administration, the urinary protein content was significantly lowered in the TGP group as compared to that at 15 days (PTGP can reduce urinary protein content and serum levels of anti-dsDNA antibodies and ANA, and lessen renal pathology in MRL/lpr mice with lupus nephritis, suggesting its therapeutic effect on lupus nephritis.

  5. Pregnancy complications in a patient with systemic lupus erythematosus and lupus nephritis

    DEFF Research Database (Denmark)

    Bisgaard, Helene; Jacobsen, Søren; Tvede, Niels

    2014-01-01

    A woman with systemic lupus erythematosus (SLE) and lupus nephritis had two pregnancies which both resulted in complications known to be associated with SLE, i.e. late abortion, preterm delivery and pre-eclampsia. We conclude that disease quiescence is important for a successful outcome...

  6. Clearing the complexity: immune complexes and their treatment in lupus nephritis

    Directory of Open Access Journals (Sweden)

    Catherine Toong

    2011-01-01

    Full Text Available Catherine Toong1, Stephen Adelstein1, Tri Giang Phan21Department of Clinical Immunology, Royal Prince Alfred Hospital, Missenden Rd, Camperdown, NSW, Australia; 2Immunology Program, Garvan Institute of Medical Research and St. Vincent’s Clinical School, University of New South Wales, Darlinghurst, NSW, AustraliaAbstract: Systemic lupus erythematosus (SLE is a classic antibody-mediated systemic autoimmune disease characterised by the development of autoantibodies to ubiquitous self-antigens (such as antinuclear antibodies and antidouble-stranded DNA antibodies and widespread deposition of immune complexes in affected tissues. Deposition of immune complexes in the kidney results in glomerular damage and occurs in all forms of lupus nephritis. The development of nephritis carries a poor prognosis and high risk of developing end-stage renal failure despite recent therapeutic advances. Here we review the role of DNA-anti-DNA immune complexes in the pathogenesis of lupus nephritis and possible new treatment strategies aimed at their control.Keywords: immune complex, systemic lupus erythematosus, nephritis, therapy

  7. Nucleosomes and histones are present in glomerular deposits in human lupus nephritis

    NARCIS (Netherlands)

    vanBruggen, MCJ; Kramers, C; Walgreen, B; Elema, JD; Kallenberg, CGM; vandenBorn, J; Smeenk, RJT; Assmann, KJM; Muller, S; Monestier, M; Berden, JHM

    Background. Recently we showed that antinuclear autoantibodies complexed to nucleosomes can bind to heparan sulphate (HS) in the glomerular basement membrane (GEM) via the histone part of the nucleosome. Histones have been identified in glomerular deposits in human and murine lupus nephritis. In

  8. High risk of ischemic heart disease in patients with lupus nephritis

    DEFF Research Database (Denmark)

    Faurschou, Mikkel; Mellemkjaer, Lene; Starklint, Henrik

    2011-01-01

    Abstract OBJECTIVE: To investigate the occurrence of ischemic heart disease (IHD) in a cohort of 104 Danish patients with biopsy-proven lupus nephritis (LN). METHODS: Information on all hospitalizations in Denmark for IHD between 1977 and 2006 was obtained from the Danish National Hospital Regist...

  9. Serial non-invasive assessment of antibody induced nephritis in mice using positron emission tomography.

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    Guiyang Hao

    Full Text Available Mouse models of experimental anti-glomerular basement membrane (anti-GBM nephritis provide an analytical tool for studying spontaneous lupus nephritis. The potential of Positron Emission Tomography (PET was evaluated using 2-deoxy-2-[(18F]fluoro-d-glucose (FDG as a probe to monitor the progression of anti-GBM induced nephritis in a mouse model. The imaging results were compared to conventional measures of renal function and pathological changes. Serum and urinary vascular cell adhesion molecule-1 (VCAM-1 levels were used as measures of endothelial cell activation and inflammation. Following a challenge with anti-glomerular antibodies, mice exhibited peak changes in serum creatinine, proteinuria, and glomerulonephritis score at 14 days post-challenge (p.c.. In contrast, VCAM levels peaked at day 7 p.c. On dynamic PET images (0-60 min of day 7, kidneys of the anti-GBM nephritis mice demonstrated a unique pattern of FDG uptake. Compared to the time activity curve (TAC prior to challenge, a rightward shift was observed after the challenge. By day 10 p.c., kidney FDG uptake was lower than baseline and remained so until the study ended at 21 days p.c. During this time frame measures of renal dysfunction remained high but VCAM-1 levels declined. These changes were accompanied by an increase in kidney volume as measured by Computed Tomography (CT and intra-abdominal fluid collection. Our results suggest that FDG-PET-CT can be used as a non-invasive imaging tool to longitudinally monitor the progression of renal disease activity in antibody mediated nephritis and the magnitude of renal FDG retention correlates better with early markers of renal inflammation than renal dysfunction.

  10. Modulation of interferon-induced genes by lipoxin analogue in anti-glomerular basement membrane nephritis.

    Science.gov (United States)

    Ohse, Takamoto; Ota, Tatsuru; Kieran, Niamh; Godson, Catherine; Yamada, Koei; Tanaka, Tetsuhiro; Fujita, Toshiro; Nangaku, Masaomi

    2004-04-01

    Immune complex deposition is associated with the accumulation of neutrophils, which play an important role in the various immune-mediated diseases. A novel anti-inflammatory agent, the lipoxin A (LXA) analogue (15-epi-16-(FPhO)-LXA-Me)), a stable synthetic analogue of aspirin-triggered 15-epi-lipoxin A4 (ATLa), was used in experimental anti-glomerular basement membrane (GBM) antibody nephritis in mice. ATLa was administered before the induction of the disease, and 2 h later, the animals were killed. ATLa reduced the infiltrating neutrophils and nitrotyrosine staining in glomeruli. Subsequent changes of gene expression in the early phase were evaluated, and 5674 genes were present under the basal conditions in kidneys from normal mice; 54 upregulated genes and 25 downregulated genes were detected in anti-GBM nephritis. Eighteen of these upregulated genes were those induced by IFN-gamma. Real-time quantitative PCR analysis confirmed the results of the microarrays. To investigate a role of IFN-gamma in neutrophil infiltration, anti-GBM nephritis was induced in IFN-gamma knockout mice. The number of infiltrating neutrophils in these mice did not differ from those in wild-type mice. Also examined were CD11b expression on neutrophils from mice treated with ATLa by flow cytometry, but suppression of this adhesion molecule was not observed. Neutrophil infiltration was successfully inhibited by ATLa in the early phase of murine anti-GBM nephritis. Microarray analysis detected the change of mRNA expression in anti-GBM nephritis and demonstrated amelioration of various genes by ATLa, which may provide a clue to the development of novel therapeutic approaches in immune renal injury.

  11. A Longitudinal Analysis of Outcomes of Lupus Nephritis in an International Inception Cohort Using a Multistate Model Approach

    DEFF Research Database (Denmark)

    Hanly, John G; Su, Li; Urowitz, Murray B

    2016-01-01

    OBJECTIVE: To study bidirectional change and predictors of change in estimated glomerular filtration rate (GFR) and proteinuria in lupus nephritis (LN) using a multistate modeling approach. METHODS: Patients in the Systemic Lupus International Collaborating Clinics inception cohort were classifie...

  12. [Clinical guideline for the treatment of lupus nephritis and single-centre results of mycofenolate mofetil among patients with lupus nephritis in the National Institute of Rheumatology and Physiotherapy, Budapest].

    Science.gov (United States)

    Szabó, Melinda Zsuzsanna; Kiss, Emese

    2016-08-01

    The authors present the latest guideline for the treatment of lupus nephritis and their own single-centre results with mycofenolate mofetil treated lupus nephritis. Lupus nephritis and mainly its proliferative form is a frequent and potentially life-threatening manifestation of systemic lupus erythematosus that can lead to end-stage renal disease. The treatment of lupus nephritis greatly improved in the last decades; mycofenolate mofetil has become an alternative of cyclophosphamide both in remission induction and as a maintenance regimen as well in the treatment of Class III and IV glomerulonephritis. The authors ordered mycofenolate mofetil for 25 patients with lupus nephritis so far. Histologically most of them had Class III (A/C) or IV (A) glomerulonephritis (30-30%), and only 16% of the patients had renal impairment at that time. Mycofenolate mofetil given after glucocorticoid and cyclophosphamide induction therapy reduced the daily proteinuria from 3.18 grs to 1.06 grs. Complete remission could be achieved in 24% and partial remission in 48% of the patients. The authors conclude that mycofenolate mofetil is effective in the therapy of lupus nephritis. Orv. Hetil., 2016, 157(35), 1385-1393.

  13. Combination Therapy With Pulse Cyclophosphamide Plus Corticosteroids Improves Renal Outcome In Patients With Lupus Nephritis

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    H. Mansouri Torghabeh

    2005-08-01

    Full Text Available Background: The prognosis of SLE is int1uenced by the onset of glomerulonephtitis. Clinical ttials in lupus nephritis have demonstrated that cyclophosphamide therapy is the superior regimen in the management oflupus nephritis for preserving renal function.Objective:The purpose of this study is to define the outcome of renal function with bolus pu lses of cyclophosphamide and steroid according to our protocol and also to determine an appropriate pattern of treatment of lupus nephritis. Methods: In this open-label clinical triaL to evaluate the results, the short-term prognosis and the rate of complications of an immunosuppressive regimen with corticosteroids and cyclophosphamide, twenty-five patients with biopsy-proven lupus nephritis were studied. Treatment was structured in 4 phases: I Induction with bolus methylprednisolone and cyclophosphamide. 2 Maintenance with oral prednisolone for 4 weeks and monthly cyclophosphamide pulses for 6 months. 3 Tapeting with reduction of prednisolone by 10% each month and continuing cyclophosphamide every other month till one year and for the second year every 3 months. 4 Discontinuation with oral prednisolone slowly tapered to the least effective daily dose and cyclophosphamide discontinued after 2 yr of therapy. We defined primary outcome measures according to these criteria: renal function return to normal limits or become stable, regression of systemic and local inflammatory symptoms. urine protein excretion h1lling below 0.3 gr/ elL or by at least SOo/c. RBC cast disappearance, C3, C4, Hb, and ESR return to notmallimits. Result: Twenty-three patients wi th lupus nephritis completed our therapeutic protocol. Renal biopsy was perfonned in 22 cases and indicated type IV in 20 patients (95.2%, and type V in 2 patients. After an average of 4+ 1.95 months 22 patients achieved remission (95.65% and only one case remained non-responsive. She became pregnant in her fourth month of therapy. Significant

  14. Total glucosides of paeony attenuate renal tubulointerstitial injury in STZ-induced diabetic rats: role of Toll-like receptor 2.

    Science.gov (United States)

    Zhang, Wei; Zhao, Li; Su, Shuang-Quan; Xu, Xing-Xin; Wu, Yong-Gui

    2014-01-01

    Accumulating evidence suggested that macrophages induce tubulointerstitial injury. Total glucosides of paeony (TGP), extracted from Paeonia lactiflora, has presented anti-inflammatory activities in diabetic kidney disease. This research will investigate the protective effect of TGP on renal tubulointerstitium and its mechanism in streptozotocin-induced diabetic rats. TGP was administered orally at a dose of 50, 100, and 200 mg·kg(-1)·d(-1) for 8 weeks. Tubulointerstitial injury was quantified, followed by immunohistochemistry analysis of renal α-smooth muscle actin (α-SMA), E-cadherin (E-cad) expression, nuclear factor kappa B (NF-κB)-p-p-65(+), Toll-like receptor (TLR)2(+), and ED-1(+) cell infiltration in renal tubulointerstitium. Renal TLR2(+) macrophages were detected by double immunohistochemical staining. Western blotting was used to detect the TLR2 expression. Histologically, there was marked accumulation of TLR2(+), NF-κB-p-p-65(+), ED-1(+) cells, and ED-1(+)TLR2(+) cells (macrophages) in the diabetic kidney and TGP treatment could alleviate it. Accompanying with that, the tubulointerstitial injury was ameliorated, α-SMA expression was lower, and E-cad expression was higher compared with the diabetic rats. Western blot analysis showed that the expression of TLR2 protein was significantly increased in the kidney of the diabetic rats, whereas TGP treatment reduced it. Our study showed that TGP could prevent renal tubulointerstitium injury in diabetic rats through a mechanism that may be at least partly correlated with suppression of increased macrophage infiltration and the expression of TLR2.

  15. Mesenchymal stem cell-derived microparticles ameliorate peritubular capillary rarefaction via inhibition of endothelial-mesenchymal transition and decrease tubulointerstitial fibrosis in unilateral ureteral obstruction.

    Science.gov (United States)

    Choi, Hoon Young; Lee, Hyun Gyu; Kim, Beom Seok; Ahn, Sun Hee; Jung, Ara; Lee, Mirae; Lee, Jung Eun; Kim, Hyung Jong; Ha, Sung Kyu; Park, Hyeong Cheon

    2015-03-11

    Microparticles (MPs) derived from kidney-derived mesenchymal stem cells (KMSCs) have recently been reported to ameliorate rarefaction of peritubular capillaries (PTC) in ischemic kidneys via delivery of proangiogenic effectors. This study aimed to investigate whether KMSC-derived MPs show anti-fibrotic effects by ameliorating endothelial-to-mesenchymal transition (EndoMT) in human umbilical vein endothelial cells (HUVEC) in vitro and by preserving PTC in kidneys with unilateral ureteral obstruction (UUO) in vivo. MPs isolated from the supernatants of KMSC were co-cultured with HUVEC to assess their in vitro biologic effects on endothelial cells. Mice were treated with MPs via the tail vein after UUO injury to assess their anti-fibrotic and PTC sparing effects. Renal tubulointerstitial damage and inflammatory cell infiltration were examined with Masson's trichrome, F4/80 and α-smooth muscle actin (α-SMA) staining and PTC rarefaction index was determined by CD31 staining. KMSC-derived MPs significantly ameliorated EndoMT and improved in vitro proliferation of TGF-β1 treated HUVEC. In vivo administration of KMSC-derived MPs significantly inhibited EndoMT of PTC endothelial cells and improved PTC rarefaction in UUO kidneys. Furthermore, administration of KMSC-derived MPs inhibited inflammatory cell infiltration as well as tubulointerstitial fibrosis in UUO mice as demonstrated by decreased F4/80 and α-SMA-positive cells and Masson's trichrome staining, respectively. Our results suggest that KMSC-derived MPs ameliorate PTC rarefaction via inhibition of EndoMT and protect against progression of renal damage by inhibiting tubulointerstitial fibrosis.

  16. MBL2 gene variants coding for mannose-binding lectin deficiency are associated with increased risk of nephritis in Danish patients with systemic lupus erythematosus

    DEFF Research Database (Denmark)

    Tanha, N; Troelsen, L; From Hermansen, M-L

    2014-01-01

    .2-5.5) higher risk of developing nephritis, and their risk of death after 10 years was 6.0 times increased (95% CI: 1.0-36). MBL serum levels below 100 ng/ml were associated with a 2.0 (95% CI: 1.2-3.4; p = 0.007) increased risk of developing nephritis. ESRD and histological class of nephritis were...

  17. Necrotizing suppurative nephritis in a Japanese black feedlot steer due to Proteus mirabilis infection.

    Science.gov (United States)

    Abe, Tadatsugu; Iizuka, Ayako; Kojima, Hirokazu; Kimura, Kumiko; Shibahara, Tomoyuki; Haritani, Makoto

    2017-04-05

    A Japanese black feedlot steer suddenly died after exhibiting astasia and cramping of the extremities. Necropsy of the animal revealed that the right kidney was enlarged and pale with severe nephrolithiasis. The urinary bladder displayed mucosal hemorrhage. Upon bacteriological investigation, Proteus mirabilis was isolated from the liver, spleen, right kidney, lungs and urine. Histopathological examination revealed necrotizing suppurative nephritis with the presence of numerous gram-negative bacilli and fibrinous suppurative cystitis with no bacilli. Immunohistochemical analysis revealed that the bacteria and cytoplasm of the macrophages stained positively with P. mirabilis antiserum. Electron microscopy revealed the presence of numerous bacteria in the renal tubules. To our knowledge, this is the first report describing the histopathological aspects of nephritis caused by P. mirabilis in cattle.

  18. Lupus Nephritis in Asia: Clinical Features and Management.

    Science.gov (United States)

    Yap, Desmond Y H; Chan, Tak Mao

    2015-09-01

    Lupus nephritis (LN) is a common and severe organ involvement manifesting itself in systemic lupus erythematosus (SLE). There is a considerable difference in prevalence, severity, treatment response and outcomes between Asian LN patients and LN patients from other racial backgrounds. Asian SLE patients have a higher prevalence of LN than Caucasian SLE patients and often present with a more severe disease. Increasing data from genetic studies, accompanied by progress in high-throughput genotyping, have advanced our knowledge about genetic predispositions that might partly contribute to the clinical variations observed. Corticosteroids combined with either cyclophosphamide (CYC) or mycophenolic acid (MPA) is the current standard-of-care induction regimen for severe LN irrespective of race or ethnicity. However, the preference for MPA or CYC, and possibly the optimum dose for MPA, is influenced by the patient's origin. Also, there is an insufficient evidence base for reduced-dose intravenous CYC in Asian patients. Health economics and access to prompt diagnosis and treatment are still challenging issues in some Asian regions. The former represents a significant obstacle limiting the access of patients to MPA despite the proven efficacy of the drug as an induction agent and its superiority over azathioprine (AZA) in preventing disease flares when used for long-term maintenance immunosuppression. Calcineurin inhibitors such as tacrolimus deserve further investigation in view of their additional effect on podocytes by reducing proteinuria and the promising data from Asian patients. Despite considerable advances in the clinical management of LN over the past few decades with resultant improvements in patients' outcomes, there are still knowledge gaps and unmet clinical needs. Asia has made substantial contributions to the evidence base that guides clinical management and continues to offer invaluable opportunities for research pursuits. Treatment responses and clinical

  19. Semi-quantitative evaluation of gallium-67 scintigraphy in lupus nephritis

    International Nuclear Information System (INIS)

    Lin Wanyu; Hsieh Jihfang; Tsai Shihchuan; Lan Joungliang; Cheng Kaiyuan; Wang Shyhjen

    2000-01-01

    Within nuclear medicine there is a trend towards quantitative analysis. Gallium renal scan has been reported to be useful in monitoring the disease activity of lupus nephritis. However, only visual interpretation using a four-grade scale has been performed in previous studies, and this method is not sensitive enough for follow-up. In this study, we developed a semi-quantitative method for gallium renal scintigraphy to find a potential parameter for the evaluation of lupus nephritis. Forty-eight patients with lupus nephritis underwent renal biopsy to determine World Health Organization classification, activity index (AI) and chronicity index (CI). A delayed 48-h gallium scan was also performed and interpreted by visual and semi-quantitative methods. For semi-quantitative analysis of the gallium uptake in both kidneys, regions of interest (ROIs) were drawn over both kidneys, the right forearm and the adjacent spine. The uptake ratios between these ROIs were calculated and expressed as the ''kidney/spine ratio (K/S ratio)'' or the ''kidney/arm ratio (K/A ratio)''. Spearman's rank correlation test and Mann-Whitney U test were used for statistical analysis. Our data showed a good correlation between the semi-quantitative gallium scan and the results of visual interpretation. K/S ratios showed a better correlation with AI than did K/A ratios. Furthermore, the left K/S ratio displayed a better correlation with AI than did the right K/S ratio. In contrast, CI did not correlate well with the results of semi-quantitative gallium scan. In conclusion, semi-quantitative gallium renal scan is easy to perform and shows a good correlation with the results of visual interpretation and renal biopsy. The left K/S ratio from semi-quantitative renal gallium scintigraphy displays the best correlation with AI and is a useful parameter in evaluating the disease activity in lupus nephritis. (orig.)

  20. Increased Granulocyte Heparanase Activity in Neutrophils from Patients with Lupus Nephritis and Idiopathic Membranous Nephropathy.

    Science.gov (United States)

    Szymczak, Maciej; Kuźniar, Jakub; Kopeć, Wacław; Żabińska, Marcelina; Marchewka, Zofia; Kościelska-Kasprzak, Katarzyna; Klinger, Marian

    2017-02-01

    Heparanase is a β-glucuronidase that cleaves sugar chains of heparan sulfate proteoglycans. It is believed that heparanase may be involved in the pathogenesis of proteinuria. The aim of this study was to assess the significance of heparanase in the pathogenesis of particular glomerulonephritis types. The evaluation of heparanase activity in serum, urine, and granulocytes and superoxide dismutase (SOD) activity in granulocytes of patients with lupus nephritis (n = 17), membranous nephropathy (n = 11), IgA nephropathy (n = 12), focal and segmental glomerulosclerosis (n = 18), mesangiocapillary glomerulonephritis (n = 12) and in 19 healthy volunteers were performed. The heparanase activity in granulocytes of patients with lupus nephritis and membranous nephropathy was higher than heparanase activity in granulocytes in the control group (p = 0.02 in both cases). This is the first observation of this phenomenon. There was no difference between SOD activity in granulocytes of patients with all assessed types of glomerulonephritis and the control group. A positive correlation between heparanase activity in urine and double-strain DNA antibodies (r = 0.51; p = 0.04), and reverse correlations between heparanase in urine and hemolytic activity of the complement (r = -0.57; p = 0.03) in the lupus nephritis group, and between heparanase activity in granulocytes and serum total protein level (r = -0.69; p = 0.02) in membranous nephropathy were observed. Increase in heparanase activity without changes in superoxide dismutase activity in the granulocytes from patients with lupus nephritis and membranous nephropathy was observed. It may be used as one of the markers of these disease activities.

  1. Acute interstitial nephritis induced by intermittent use of Rifampicin in patient with Brucellosis

    International Nuclear Information System (INIS)

    Salih, S. Bin; Kharal, M.; Qahtani, M.; Dahneem, L.; Nohair, S.

    2008-01-01

    Acute oliguric renal failure (ARF) developed in a patient 2 days after she was started on intermittent anti-Brucella therapy including rifampicin. The clinical picture was compatible with acute allergic interstitial nephritis. Renal histology revealed mainly acute tubular necrosis with mild tubulo-intertitial mononuclear cellular infiltrate. Intermittent therapy, as in our patient, has been the major factor in the development of rifampicin induced ARF in cases reviewed in literature. (author)

  2. The serum levels of connective tissue growth factor in patients with systemic lupus erythematosus and lupus nephritis.

    Science.gov (United States)

    Wang, F-M; Yu, F; Tan, Y; Liu, G; Zhao, M-H

    2014-06-01

    The expression of connective tissue growth factor mRNA in human kidneys may serve as an early marker for lupus nephritis progression. Therefore, we speculated that connective tissue growth factor may be involved in the pathogenesis of systemic lupus erythematosus and lupus nephritis. In this study, we set out to investigate the associations between serum connective tissue growth factor levels and clinicopathological features of patients with systemic lupus erythematosus and lupus nephritis. Serum samples from patients with non-renal systemic lupus erythematosus, renal biopsy-proven lupus nephritis and healthy control subjects were detected by enzyme-linked immunosorbent assay for serum connective tissue growth factor levels. The associations between connective tissue growth factor levels and clinicopathological features of the patients were further analysed. The levels of serum connective tissue growth factor in patients with non-renal systemic lupus erythematosus and lupus nephritis were both significantly higher than those in the normal control group (34.14 ± 12.17 ng/ml vs. 22.8 ± 3.0 ng/ml, plupus erythematosus and lupus nephritis group (34.14 ± 12.17 ng/ml vs. 44.1 ± 46.8 ng/ml, p = 0.183). Serum connective tissue growth factor levels were significantly higher in lupus nephritis patients with the following clinical manifestations, including anaemia (51.3 ± 51.4 ng/ml vs. 23.4 ± 9.7 ng/ml, plupus nephritis (63.3 ± 63.4 ng/ml vs. 38.3 ± 37.9 ng/ml, p = 0.035, respectively). Serum connective tissue growth factor levels were negatively associated with estimated glomerular filtration rate (r = -0.46, plupus nephritis (plupus and correlated with chronic renal interstitial injury and doubling of serum creatinine in patients with lupus nephritis. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  3. Cell death in the pathogenesis of systemic lupus erythematosus and lupus nephritis.

    Science.gov (United States)

    Mistry, Pragnesh; Kaplan, Mariana J

    2017-12-01

    Nephritis is one of the most severe complications of systemic lupus erythematosus (SLE). One key characteristic of lupus nephritis (LN) is the deposition of immune complexes containing nucleic acids and/or proteins binding to nucleic acids and autoantibodies recognizing these molecules. A variety of cell death processes are implicated in the generation and externalization of modified nuclear autoantigens and in the development of LN. Among these processes, apoptosis, primary and secondary necrosis, NETosis, necroptosis, pyroptosis, and autophagy have been proposed to play roles in tissue damage and immune dysregulation. Cell death occurs in healthy individuals during conditions of homeostasis yet autoimmunity does not develop, at least in part, because of rapid clearance of dying cells. In SLE, accelerated cell death combined with a clearance deficiency may lead to the accumulation and externalization of nuclear autoantigens and to autoantibody production. In addition, specific types of cell death may modify autoantigens and alter their immunogenicity. These modified molecules may then become novel targets of the immune system and promote autoimmune responses in predisposed hosts. In this review, we examine various cell death pathways and discuss how enhanced cell death, impaired clearance, and post-translational modifications of proteins could contribute to the development of lupus nephritis. Published by Elsevier Inc.

  4. Impact of the ALMS and MAINTAIN trials on the management of lupus nephritis.

    Science.gov (United States)

    Morris, Heather K; Canetta, Pietro A; Appel, Gerald B

    2013-06-01

    Current treatment of lupus nephritis consists of both induction and maintenance therapy, with the latter being designed to consolidate remissions and prevent relapses. Long-term maintenance treatment with intravenous cyclophosphamide was effective but associated with considerable toxicity. A small but well-designed controlled trial found that for post-induction maintenance therapy, both oral mycophenolate mofetil (MMF) and oral azathioprine were superior in efficacy and had reduced toxicity than a regimen of continued every third month intravenous cyclophosphamide. Although these oral agents were rapidly accepted and utilized as maintenance medications, their usage was based on scant evidence and there were no comparisons between the two. Recently, two relatively large, randomized, well-controlled, multicenter trials dealing with maintenance therapy for severe lupus nephritis have been completed. The Aspreva Lupus Management Study (ALMS) maintenance and MAINTAIN nephritis trials provide important information regarding the comparative efficacy and safety of MMF and azathioprine as maintenance therapies, as well as information on the effect of dosage and duration of treatment with these agents.

  5. Mesenchymal Stem Cells Control Complement C5 Activation by Factor H in Lupus Nephritis

    Directory of Open Access Journals (Sweden)

    Haijun Ma

    2018-06-01

    Full Text Available Lupus nephritis (LN is one of the most severe complications of systemic lupus erythematosus (SLE caused by uncontrolled activation of the complement system. Mesenchymal stem cells (MSCs exhibit clinical efficacy for severe LN in our previous studies, but the underlying mechanisms of MSCs regulating complement activation remain largely unknown. Here we show that significantly elevated C5a and C5b-9 were found in patients with LN, which were notably correlated with proteinuria and different renal pathological indexes of LN. MSCs suppressed systemic and intrarenal activation of C5, increased the plasma levels of factor H (FH, and ameliorated renal disease in lupus mice. Importantly, MSCs transplantation up-regulated the decreased FH in patients with LN. Mechanistically, interferon-α enhanced the secretion of FH by MSCs. These data demonstrate that MSCs inhibit the activation of pathogenic C5 via up-regulation of FH, which improves our understanding of the immunomodulatory mechanisms of MSCs in the treatment of lupus nephritis. Keywords: Lupus nephritis, C5, MSCs, FH

  6. Autosomal Dominant Tubulointerstitial Kidney Disease: Clinical Presentation of Patients With ADTKD-UMOD and ADTKD-MUC1.

    Science.gov (United States)

    Ayasreh, Nadia; Bullich, Gemma; Miquel, Rosa; Furlano, Mónica; Ruiz, Patricia; Lorente, Laura; Valero, Oliver; García-González, Miguel Angel; Arhda, Nisrine; Garin, Intza; Martínez, Víctor; Pérez-Gómez, Vanessa; Fulladosa, Xavier; Arroyo, David; Martínez-Vea, Alberto; Espinosa, Mario; Ballarín, Jose; Ars, Elisabet; Torra, Roser

    2018-05-18

    Autosomal dominant tubulointerstitial kidney disease (ADTKD) is a rare underdiagnosed cause of end-stage renal disease (ESRD). ADTKD is caused by mutations in at least 4 different genes: MUC1, UMOD, HNF1B, and REN. Retrospective cohort study. 56 families (131 affected individuals) with ADTKD referred from different Spanish hospitals. Clinical, laboratory, radiologic, and pathologic data were collected, and genetic testing for UMOD, MUC1, REN, and HNF1B was performed. Hyperuricemia, ultrasound findings, renal histology, genetic mutations. Age at ESRD, rate of decline in estimated glomerular filtration rate. ADTKD was diagnosed in 25 families (45%), 9 carried UMOD pathogenic variants (41 affected members), and 16 carried the MUC1 pathogenic mutation c.(428)dupC (90 affected members). No pathogenic variants were identified in REN or HNF1B. Among the 77 individuals who developed ESRD, median age at onset of ESRD was 51 years for those with ADTKD-MUC1 versus 56 years (P=0.1) for those with ADTKD-UMOD. Individuals with the MUC1 duplication presented higher risk for developing ESRD (HR, 2.24; P=0.03). The slope of decline in estimated glomerular filtration rate showed no significant difference between groups (-3.0mL/min/1.73m 2 per year in the ADTKD-UMOD group versus -3.9mL/min/1.73m 2 per year in the ADTKD-MUC1 group; P=0.2). The prevalence of hyperuricemia was significantly higher in individuals with ADTKD-UMOD (87% vs 54%; P=0.006). Although gout occurred more frequently in this group, the difference was not statistically significant (24% vs 7%; P=0.07). Relatively small Spanish cohort. MUC1 analysis limited to cytosine duplication. The main genetic cause of ADTKD in our Spanish cohort is the MUC1 pathogenic mutation c.(428)dupC. Renal survival may be worse in individuals with the MUC1 mutation than in those with UMOD mutations. Clinical presentation does not permit distinguishing between these variants. However, hyperuricemia and gout are more frequent in individuals

  7. Galectin-3 binding protein links circulating microparticles with electron dense glomerular deposits in lupus nephritis.

    Science.gov (United States)

    Nielsen, C T; Østergaard, O; Rekvig, O P; Sturfelt, G; Jacobsen, S; Heegaard, N H H

    2015-10-01

    A high level of galectin-3-binding protein (G3BP) appears to distinguish circulating cell-derived microparticles in systemic lupus erythematosus (SLE). The aim of this study is to characterize the population of G3BP-positive microparticles from SLE patients compared to healthy controls, explore putative clinical correlates, and examine if G3BP is present in immune complex deposits in kidney biopsies from patients with lupus nephritis. Numbers of annexin V-binding and G3BP-exposing plasma microparticles from 56 SLE patients and 36 healthy controls were determined by flow cytometry. Quantitation of microparticle-associated G3BP, C1q and immunoglobulins was obtained by liquid chromatography tandem mass spectrometry (LC-MS/MS). Correlations between microparticle-G3BP data and clinical parameters were analyzed. Co-localization of G3BP with in vivo-bound IgG was examined in kidney biopsies from one non-SLE control and from patients with class IV (n = 2) and class V (n = 1) lupus nephritis using co-localization immune electron microscopy. Microparticle-G3BP, microparticle-C1q and microparticle-immunoglobulins were significantly (P microparticle populations could be discerned by flow cytometry, including two subpopulations that were significantly increased in SLE samples (P = 0.01 and P = 0.0002, respectively). No associations of G3BP-positive microparticles with clinical manifestations or disease activity were found. Immune electron microscopy showed co-localization of G3BP with in vivo-bound IgG in glomerular electron dense immune complex deposits in all lupus nephritis biopsies. Both circulating microparticle-G3BP numbers as well as G3BP expression are increased in SLE patients corroborating G3BP being a feature of SLE microparticles. By demonstrating G3BP co-localized with deposited immune complexes in lupus nephritis, the study supports cell-derived microparticles as a major autoantigen source and provides a new understanding of the origin of

  8. Tubulointerstitial damage as the major pathological lesion in endemic chronic kidney disease among farmers in North Central Province of Sri Lanka.

    Science.gov (United States)

    Nanayakkara, Shanika; Komiya, Toshiyuki; Ratnatunga, Neelakanthi; Senevirathna, S T M L D; Harada, Kouji H; Hitomi, Toshiaki; Gobe, Glenda; Muso, Eri; Abeysekera, Tilak; Koizumi, Akio

    2012-05-01

    Chronic kidney disease of uncertain etiology (CKDu) in North Central Province of Sri Lanka has become a key public health concern in the agricultural sector due to the dramatic rise in its prevalence and mortality among young farmers. Although cadmium has been suspected as a causative pathogen, there have been controversies. To date, the pathological characteristics of the disease have not been reported. Histopathological observations of 64 renal biopsies obtained at Anuradhapura General Hospital from October 2008 to July 2009 were scored according to Banff 97 Working Classification of Renal Allograft pathology. The correlations between the histological observations and clinical parameters were statistically analyzed. Interstitial fibrosis and tubular atrophy with or without nonspecific interstitial mononuclear cell infiltration was the dominant histopathological observation. Glomerular sclerosis, glomerular collapse, and features of vascular pathology such as fibrous intimal thickening and arteriolar hyalinosis were also common. Although hypertension was identified as one of the common clinical features among the cases, it did not influence the histopathological lesions in all the cases. This study concludes that tubulointerstitial damage is the major pathological lesion in CKDu. Exposure(s) to an environmental pathogen(s) should be systematically investigated to elucidate such tubulointerstitial damage in CKDu.

  9. Anti-pentraxin 3 auto-antibodies might be protective in lupus nephritis: a large cohort study.

    Science.gov (United States)

    Yuan, Mo; Tan, Ying; Pang, Yun; Li, Yong-Zhe; Song, Yan; Yu, Feng; Zhao, Ming-Hui

    2017-11-01

    Anti-pentraxin 3 (PTX3) auto-antibodies were found to be associated with the absence of renal involvement in systemic lupus erythematosus (SLE). This study is to investigate the prevalence of anti-PTX3 auto-antibodies and their clinical significance based on a large Chinese lupus nephritis cohort. One hundred and ninety-six active lupus nephritis patients, 150 SLE patients without clinical renal involvement, and 100 healthy controls were enrolled. Serum anti-PTX3 auto-antibodies and PTX3 levels were screened by enzyme-linked immunosorbent assay (ELISA). The associations between anti-PTX3 auto-antibodies and clinicopathological parameters in lupus nephritis were further analyzed. Anti-PTX3 auto-antibodies were less prevalent in active lupus nephritis patients compared with SLE without renal involvement (19.4% (38/196) versus 40.7% (61/150), p auto-antibodies were negatively correlated with proteinuria in lupus nephritis (r = -.143, p = .047). The levels of proteinuria, serum creatinine, and the prevalence of thrombotic microangiopathy were significantly higher in patients with higher PTX3 levels (≥3.207 ng/ml) and without anti-PTX3 auto-antibodies compared with patients with lower PTX3 levels (auto-antibodies (4.79 (3.39-8.28) versus 3.95 (1.78-7.0), p = .03; 168.84 ± 153.63 versus 101.44 ± 47.36, p = .01; 34.1% (14/41) versus 0% (0/9), p = .04; respectively). Anti-PTX3 auto-antibodies were less prevalent in active lupus nephritis patients compared with SLE without renal involvement and associated with less severe renal damage, especially with the combined evaluation of serum PTX3 levels.

  10. Induction of passive Heymann nephritis in complement component 6-deficient PVG rats.

    Science.gov (United States)

    Spicer, S Timothy; Tran, Giang T; Killingsworth, Murray C; Carter, Nicole; Power, David A; Paizis, Kathy; Boyd, Rochelle; Hodgkinson, Suzanne J; Hall, Bruce M

    2007-07-01

    Passive Heymann nephritis (PHN), a model of human membranous nephritis, is induced in susceptible rat strains by injection of heterologous antisera to rat renal tubular Ag extract. PHN is currently considered the archetypal complement-dependent form of nephritis, with the proteinuria resulting from sublytic glomerular epithelial cell injury induced by the complement membrane attack complex (MAC) of C5b-9. This study examined whether C6 and MAC are essential to the development of proteinuria in PHN by comparing the effect of injection of anti-Fx1A antisera into PVG rats deficient in C6 (PVG/C6(-)) and normal PVG rats (PVG/c). PVG/c and PVG/C6(-) rats developed similar levels of proteinuria at 3, 7, 14, and 28 days following injection of antisera. Isolated whole glomeruli showed similar deposition of rat Ig and C3 staining in PVG/c and PVG/C6(-) rats. C9 deposition was abundant in PVG/c but was not detected in PVG/C6(-) glomeruli, indicating C5b-9/MAC had not formed in PVG/C6(-) rats. There was also no difference in the glomerular cellular infiltrate of T cells and macrophages nor the size of glomerular basement membrane deposits measured on electron micrographs. To examine whether T cells effect injury, rats were depleted of CD8+ T cells which did not affect proteinuria in the early heterologous phase but prevented the increase in proteinuria associated with the later autologous phase. These studies showed proteinuria in PHN occurs without MAC and that other mechanisms, such as immune complex size, early complement components, CD4+ and CD8+ T cells, disrupt glomerular integrity and lead to proteinuria.

  11. IRF4 Deficiency Abrogates Lupus Nephritis Despite Enhancing Systemic Cytokine Production

    Science.gov (United States)

    Lech, Maciej; Weidenbusch, Marc; Kulkarni, Onkar P.; Ryu, Mi; Darisipudi, Murthy Narayana; Susanti, Heni Eka; Mittruecker, Hans-Willi; Mak, Tak W.

    2011-01-01

    The IFN-regulatory factors IRF1, IRF3, IRF5, and IRF7 modulate processes involved in the pathogenesis of systemic lupus and lupus nephritis, but the contribution of IRF4, which has multiple roles in innate and adaptive immunity, is unknown. To determine a putative pathogenic role of IRF4 in lupus, we crossed Irf4-deficient mice with autoimmune C57BL/6-(Fas)lpr mice. IRF4 deficiency associated with increased activation of antigen-presenting cells in C57BL/6-(Fas)lpr mice, resulting in a massive increase in plasma levels of TNF and IL-12p40, suggesting that IRF4 suppresses cytokine release in these mice. Nevertheless, IRF4 deficiency completely protected these mice from glomerulonephritis and lung disease. The mice were hypogammaglobulinemic and lacked antinuclear and anti-dsDNA autoantibodies, revealing the requirement of IRF4 for the maturation of plasma cells. As a consequence, Irf4-deficient C57BL/6-(Fas)lpr mice neither developed immune complex disease nor glomerular activation of complement. In addition, lack of IRF4 impaired the maturation of Th17 effector T cells and reduced plasma levels of IL-17 and IL-21, which are cytokines known to contribute to autoimmune tissue injury. In summary, IRF4 deficiency enhances systemic inflammation and the activation of antigen-presenting cells but also prevents the maturation of plasma cells and effector T cells. Because these adaptive immune effectors are essential for the evolution of lupus nephritis, we conclude that IRF4 promotes the development of lupus nephritis despite suppressing antigen-presenting cells. PMID:21742731

  12. Trimethoprim-sulfamethoxazole induced acute interstitial nephritis in renal allografts; clinical course and outcome.

    LENUS (Irish Health Repository)

    Garvey, J P

    2009-11-01

    Acute interstitial nephritis (AIN) secondary to trimethoprim-sulfamethoxazole (TMP-SMX) is well documented as a cause of acute renal failure in native kidneys. TMP-SMX is the standard prophylactic agent against pneumocystis carinii (PCP) used in the early post-transplant period, however, it has to date only been indirectly associated with AIN in renal allografts. DESIGN, SETTING, PARTICIPANTS AND MEASUREMENTS: We describe eleven renal transplant patients with acute allograft dysfunction in whom a transplant biopsy demonstrated primary histopathologic features of allergic AIN, all of whom were receiving TMP-SMX in addition to other medications known to cause AIN.

  13. Semi-quantitative evaluation of gallium-67 scintigraphy in lupus nephritis

    Energy Technology Data Exchange (ETDEWEB)

    Lin Wanyu [Dept. of Nuclear Medicine, Taichung Veterans General Hospital, Taichung (Taiwan); Dept. of Radiological Technology, Chung-Tai College of Medical Technology, Taichung (Taiwan); Hsieh Jihfang [Section of Nuclear Medicine, Chi-Mei Foundation Hospital, Yunk Kang City, Tainan (Taiwan); Tsai Shihchuan [Dept. of Nuclear Medicine, Show Chwan Memorial Hospital, Changhua (Taiwan); Lan Joungliang [Dept. of Internal Medicine, Taichung Veterans General Hospital, Taichung (Taiwan); Cheng Kaiyuan [Dept. of Radiological Technology, Chung-Tai College of Medical Technology, Taichung (Taiwan); Wang Shyhjen [Dept. of Nuclear Medicine, Taichung Veterans General Hospital, Taichung (Taiwan)

    2000-11-01

    Within nuclear medicine there is a trend towards quantitative analysis. Gallium renal scan has been reported to be useful in monitoring the disease activity of lupus nephritis. However, only visual interpretation using a four-grade scale has been performed in previous studies, and this method is not sensitive enough for follow-up. In this study, we developed a semi-quantitative method for gallium renal scintigraphy to find a potential parameter for the evaluation of lupus nephritis. Forty-eight patients with lupus nephritis underwent renal biopsy to determine World Health Organization classification, activity index (AI) and chronicity index (CI). A delayed 48-h gallium scan was also performed and interpreted by visual and semi-quantitative methods. For semi-quantitative analysis of the gallium uptake in both kidneys, regions of interest (ROIs) were drawn over both kidneys, the right forearm and the adjacent spine. The uptake ratios between these ROIs were calculated and expressed as the ''kidney/spine ratio (K/S ratio)'' or the ''kidney/arm ratio (K/A ratio)''. Spearman's rank correlation test and Mann-Whitney U test were used for statistical analysis. Our data showed a good correlation between the semi-quantitative gallium scan and the results of visual interpretation. K/S ratios showed a better correlation with AI than did K/A ratios. Furthermore, the left K/S ratio displayed a better correlation with AI than did the right K/S ratio. In contrast, CI did not correlate well with the results of semi-quantitative gallium scan. In conclusion, semi-quantitative gallium renal scan is easy to perform and shows a good correlation with the results of visual interpretation and renal biopsy. The left K/S ratio from semi-quantitative renal gallium scintigraphy displays the best correlation with AI and is a useful parameter in evaluating the disease activity in lupus nephritis. (orig.)

  14. Transverse myelitis in a patient with severe Lupus Nephritis: A casereport

    International Nuclear Information System (INIS)

    Mitwalli, Ahmad H.; Memon, Nawaz Ali; Abu-Aisha, H.; Al-Wakeel, Jamal S.; Tarif, N.; Askar, A.; Hammad, D.

    2002-01-01

    We report here a case of severe lupus nephritis, Raynaud's phenomenon,digital gangrene and optic neuritis who, developed acute transverse myelitis(ATM). SLE can present virtually with any complication in the central nervoussystem (CNS) and ATM is a rare but serious manifestation. It is noteworthythat ATM developed in this patient while she was on intravenouscyclophosphamide (IVC) therapy having already finished six doses of monthlyinfusions of 10 mg/kg body weight. The patient responded well tomethyl-prednisolone pulse therapy, IVC and plasmapheresis. She recoveredfully and doing well after nine months of follow-up. (author)

  15. Radiation nephritis following total-body irradiation and cyclophosphamide in preparation for bone marrow transplantation

    International Nuclear Information System (INIS)

    Bergstein, J.; Andreoli, S.P.; Provisor, A.J.; Yum, M.

    1986-01-01

    Two children prepared for bone marrow transplantation with total-body irradiation and cyclophosphamide developed hypertension, microscopic hematuria, proteinuria, diminished renal function, and anemia six months after transplantation. Light microscopy of the kidneys revealed mesangial expansion, glomerular capillary wall thickening, and lumenal thrombosis. Electron microscopy demonstrated widening of the subendothelial space due to the deposition of amorphous fluffy material. In one patient, immunofluorescence microscopy revealed glomerular capillary wall deposition of fibrin and immunoglobulins. The clinical and histologic findings support the diagnosis of radiation nephritis. Patients prepared for bone marrow transplantation with total-body irradiation and cyclophosphamide should be followed closely after transplantation for the development of hypertension, proteinuria, and renal insufficiency

  16. Nephritogenic antigen determinants in epidermal and renal basement membranes of kindreds with Alport-type familial nephritis.

    OpenAIRE

    Kashtan, C; Fish, A J; Kleppel, M; Yoshioka, K; Michael, A F

    1986-01-01

    We probed epidermal basement membranes (EBM) of acid-urea denatured skin from members of kindreds with Alport-type familial nephritis (FN) for the presence of antigens reactive with Goodpasture sera (GPS) and serum (FNS) from an Alport patient who developed anti-glomerular basement membrane (GBM) nephritis in a renal allograft. By immunoblotting, GPS reacted primarily with the 28,000 molecular weight (mol wt) monomer but also the 24,000 mol wt and 26,000 mol wt monomers of the noncollagenous ...

  17. Clinical profile of patients with biopsy proven lupus nephritis at a tertiary care hospital from Northern Pakistan, 1995 to 2012.

    Science.gov (United States)

    Ali, Akhtar; Mehmood, Anjum; Ali, Muhammad Usman

    2017-01-01

    TTo highlight the clinical spectrum of biopsy-proven lupus nephritis by analysing any variations in its histological subtypes across gender, varying age groups, serum creatinine levels and anti-double stranded deoxyribonucleic acid levels. This retrospective, observational study was conducted at the Lady Reading Hospital in collaboration with the Fauji Foundation Hospital, Peshawar, Pakistan, and comprised patient records of biopsy-proven lupus nephritis from 1995 to 2012. The cases were analysed according to clinical presentations and histological pattern of systemic lupus erythematosus nephritis. EpiData 3.1 and SPSS 17 were used for data analyses. Of the 2,000 renal biopsies performed, lupus nephritis was found in 74(3.7%) cases. Of them, 63(85.1%) were females and 11(14.9%) males. The mean age of the cases was 23.88±9.73 years (range: 10-55 years). Class IV lupus nephritis was seen in 38(51.4%) patients, followed by Class II in 15(20.3%), Class III in 10(13.5%), Class V and VI in 4(5.4%) each and Class I in 3(4.1%). Out of the combined Class III and IV cases, 25(52.08%) had serum creatinine levels of >1.2 mg/dL, whereas positive anti-double stranded deoxyribonucleic acid titers up to 50 IU/L were seen in all of the 48(100%) such patients. Overall, microscopic haematuria was found in 52(70.3%) cases, followed by arthralgia in 40(54.1%). Moreover, 32(50.8%) females and 6(54.5%) males had Type IV nephritis. Class VI lupus nephritis, in particular, were significantly more prominent in 31-40 years of age group when compared to other histological subtypes and age groups (p=0.0096, odds ratio: 23.25, 95% confidence interval: 2.15-251.21). Female predominance was observed in all histological sub-types of lupus nephritis. Class IV lupus was the most common histological pattern. Microscopic haematuria was the most common clinical presentation.

  18. Interferon-γ production by tubulointerstitial human CD56bright natural killer cells contributes to renal fibrosis and chronic kidney disease progression.

    Science.gov (United States)

    Law, Becker M P; Wilkinson, Ray; Wang, Xiangju; Kildey, Katrina; Lindner, Mae; Rist, Melissa J; Beagley, Kenneth; Healy, Helen; Kassianos, Andrew J

    2017-07-01

    Natural killer (NK) cells are a population of lymphoid cells that play a significant role in mediating innate immune responses. Studies in mice suggest a pathological role for NK cells in models of kidney disease. In this study, we characterized the NK cell subsets present in native kidneys of patients with tubulointerstitial fibrosis, the pathological hallmark of chronic kidney disease. Significantly higher numbers of total NK cells (CD3 - CD56 + ) were detected in renal biopsies with tubulointerstitial fibrosis compared with diseased biopsies without fibrosis and healthy kidney tissue using multi-color flow cytometry. At a subset level, both the CD56 dim NK cell subset and particularly the CD56 bright NK cell subset were elevated in fibrotic kidney tissue. However, only CD56 bright NK cells significantly correlated with the loss of kidney function. Expression of the tissue-retention and -activation molecule CD69 on CD56 bright NK cells was significantly increased in fibrotic biopsy specimens compared with non-fibrotic kidney tissue, indicative of a pathogenic phenotype. Further flow cytometric phenotyping revealed selective co-expression of activating receptor CD335 (NKp46) and differentiation marker CD117 (c-kit) on CD56 bright NK cells. Multi-color immunofluorescent staining of fibrotic kidney tissue localized the accumulation of NK cells within the tubulointerstitium, with CD56 bright NK cells (NKp46 + CD117 + ) identified as the source of pro-inflammatory cytokine interferon-γ within the NK cell compartment. Thus, activated interferon-γ-producing CD56 bright NK cells are positioned to play a key role in the fibrotic process and progression to chronic kidney disease. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

  19. Mechanisms involved in the p62-73 idiopeptide-modulated delay of lupus nephritis in SNF(1) mice.

    Science.gov (United States)

    Nyland, J F; Stoll, M L; Jiang, F; Feng, F; Gavalchin, J

    2012-12-01

    The F(1) progeny of the (SWR × NZB) cross develop a lupus-like disease with high serum titers of autoantibodies, and increased frequency and severity of immune complex-mediated glomerulonephritis in females. In previous work, we found that an idiotypic peptide corresponding to aa62-73 (p62-73) of the heavy chain variable region of autoantibody 540 (Id(LN)F(1)) induced the proliferation of p62-73 idiotype-reactive T cell clones. Further, monthly immunization of pre-nephritic SNF(1) female mice with p62-73 resulted in decreased nephritis and prolonged life spans. Here we show that this treatment modulated proliferative responses to Id(LN)F(1) antigen, including a reduction in the population of idiopeptide-presenting antigen-presenting cells (APCs), as early as two weeks after immunization (10 weeks of age). Th1-type cytokine production was increased at 12 weeks of age. The incidence and severity of nephritis was reduced by 14 weeks compared to controls. Clinical indicators of nephritis, specifically histological evidence of glomerulonephritis and urine protein levels, were reduced by 20 weeks. Together these data suggest that events involved in the mechanism(s) whereby p62-73 immunization delayed nephritis occurred early after immunization, and involved modulation of APCs, B and T cell populations.

  20. Economic evaluation of lupus nephritis in the Systemic Lupus International Collaborating Clinics inception cohort using a multistate model approach

    DEFF Research Database (Denmark)

    Barber, Megan R W; Hanly, John G; Su, Li

    2018-01-01

    OBJECTIVE: Little is known about the long-term costs of lupus nephritis (LN). These were compared between patients with and without LN based on multistate modelling. METHODS: Patients from 32 centres in 11 countries were enrolled in the Systemic Lupus International Collaborating Clinics (SLICC...

  1. Comparative clinical characteristics and natural history of three variants of sclerosing cholangitis: IgG4-related SC, PSC/AIH and PSC alone.

    Science.gov (United States)

    Lian, Min; Li, Bo; Xiao, Xiao; Yang, Yue; Jiang, Pan; Yan, Li; Sun, Chunyan; Zhang, Jun; Wei, Yiran; Li, Yanmei; Chen, Weihua; Jiang, Xiang; Miao, Qi; Chen, Xiaoyu; Qiu, Dekai; Sheng, Li; Hua, Jing; Tang, Ruqi; Wang, Qixia; Eric Gershwin, M; Ma, Xiong

    2017-08-01

    There is increased interest and recognition of the clinical variants of Sclerosing Cholangitis (SC) namely IgG4-SC, PSC/AIH overlap and PSC. For most Centers, the characteristic of IgG4-SC has not been thoroughly clinically compared with other sclerosing cholangitis variants. Further there are relatively few PSC/AIH overlap patients and the clinical outcome is not well characterized, especially for the PSC/AIH overlap syndrome. Our objective herein is to clarify the differences and similarities of the natural history of IgG4-SC, the PSC/AIH overlap and PSC alone. We also place in perspective the diagnostic value of serum IgG4 for IgG4-SC and investigate biomarkers for predicting the prognosis of sclerosing cholangitis. In this study, we took advantage of our large and well-defined patient cohort to perform a retrospective cohort study including 57 IgG4-SC, 36 PSC/AIH overlap patients, and 55 PSC patients. Firstly, as expected, we noted significant differences among immunoglobulin profiles and all patients exhibited similar cholestatic profiles at presentation. Cirrhotic events were found in 20 of total 57 IgG4-SC, 15 of 36 PSC/AIH overlap, and 18 of 55 PSC patients. Serum IgG4 was elevated in 92.65% of IgG4-SC patients with an 86% sensitivity and 98% specificity for diagnosis. IgG4-SC patients had a better treatment response at 6-month and 1-year than PSC/AIH patients, while the latter responded better with steroids than PSC patients. Importantly the adverse outcome-free survival of IgG4-SC patients was reduced, unlike earlier reports, and therefore similar to the PSC/AIH overlap syndrome. Serum IgG and total bilirubin were useful to predict long-term survival of IgG4-SC and PSC/AIH, respectively. In conclusion, serum IgG4≧1.25 ULN shows an excellent predictability to distinguish IgG4-SC among SC patients. IgG4-SC appears to be immune-mediated inflammatory process, while PSC/AIH overlap more tends to be cholestatic disease. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Increases in IgE, Eosinophils, and Mast Cells Can be Used in Diagnosis and to Predict Relapse of IgG4-Related Disease.

    Science.gov (United States)

    Culver, Emma L; Sadler, Ross; Bateman, Adrian C; Makuch, Mateusz; Cargill, Tamsin; Ferry, Berne; Aalberse, Rob; Barnes, Eleanor; Rispens, Theo

    2017-09-01

    IgG subclass 4-related disease (IgG4-RD) is characterized by increased serum levels of IgG4 and infiltration of biliary, pancreatic, and other tissues by IgG4-positive plasma cells. We assessed the prevalence of allergy and/or atopy, serum, and tissue IgE antibodies, and blood and tissue eosinophils in patients with IgG4-RD. We investigated the association between serum IgE and diagnosis and relapse of this disease. We performed a prospective study of 48 patients with IgG4-RD, 42 patients with an increased serum level of IgG4 with other inflammatory and autoimmune conditions (disease control subjects), and 51 healthy individuals (healthy control subjects) recruited from Oxford, United Kingdom from March 2010 through March 2014, and followed for a median of 41 months (range, 3-73 months). Serum levels of immunoglobulin were measured at diagnosis, during steroid treatment, and at disease relapse for patients with IgG4-RD; levels at diagnosis were compared with baseline levels of control subjects. Allergen-specific IgEs were measured using the IgE ImmunoCAP. Levels and distribution of IgG4 and IgE antibodies in lymphoid, biliary, and pancreatic tissues from patients with IgG4-RD and disease control subjects were measured by immunohistochemistry. We analyzed data using the Spearman rank correlation and receiver operating characteristic curves. Serum levels of IgG4 increased to 1.4 g/L or more, and IgE increased to 125 kIU/L or more, in 81% and 54% of patients with IgG4-RD, respectively, compared with 6% and 16% of healthy control subjects (P IgG4-RD versus 9% of healthy control subjects (P = .004). Of patients with IgG4-RD, 63% had a history of allergy and 40% had a history of atopy with an IgE-specific response; these values were 60% and 53% in patients with increased serum levels of IgE (P 480 kIU/L distinguished patients with IgG4-RD from disease control subjects with 86% specificity, 36% sensitivity, and a likelihood ratio of 3.2. Level of IgE at diagnosis >380 kIU/L identified patients with disease relapse with 88% specificity, 64% sensitivity, and a likelihood ratio of 5.4. IgE-positive mast cells and eosinophilia were observed in lymphoid, biliary, and pancreatic tissue samples from 50% and 86% of patients with IgG4-RD, respectively. In a prospective study, we associated IgG4-RD with allergy, atopy, eosinophilia, increased serum levels of IgE, and IgE-positive mast cells in lymphoid, biliary, and pancreatic tissue. An IgE-mediated allergic response therefore seems to develop in most patients with IgG4-RD; levels of IgE might be used in diagnosis and predicting relapse. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

  3. IgG4-related disease involving polyserous effusions with elevated serum interleukin-6 levels: a case report and literature review.

    Science.gov (United States)

    Tong, Xiang; Bai, Min; Wang, Weiya; Han, Qingbing; Tian, Panwen; Fan, Hong

    2017-08-01

    Immunoglobulin G4-related disease (IgG4-RD) is a recently described immune-mediated fibroinflammatory disease with a characteristic histopathologic appearance that can affect various organs. We report a 43-year-old Chinese female patient with IgG4-RD involving polyserous effusions with reports of worsening exertional dyspnea for 3 months. Laboratory blood tests revealed that serum interleukin (IL)-6, carbohydrate antigens (CA-199 and CA-125), and alpha-fetoprotein levels were significantly increased, but serum IgG4 levels were normal. Repeat pleural effusion and ascite analysis showed lymphocyte-predominant exudates. In addition, computed tomography scan showed massive pleural effusion in the right pleural cavity, abdominal effusion, and some pericardial effusion with a partial compression atelectasis. Further, medical thoracoscopy was performed to examine the pleural cavity and found multiple nodules on the pleura and partly thickened pleura with a reddish color. Histopathologic and immunohistochemical examination revealed marked lymphocytes and IgG4-positive plasma cell infiltration. The patient was finally diagnosed with IgG4-RD according to the comprehensive diagnostic criteria, although the patient presented similar serological and pathological manifestations of Castleman disease (CD). Our case suggests that IgG4-RD may be one of the causes of polyserous effusions and shows the difficulties in differentiating between IgG4-RD and CD.

  4. Efficacy between high and medium doses of glucocorticoid therapy in remission induction of IgG4-related diseases: a preliminary randomized controlled trial.

    Science.gov (United States)

    Wu, Qingjun; Chang, Jie; Chen, Hua; Chen, Yu; Yang, Hongxian; Fei, Yunyun; Zhang, Panpan; Zeng, Xiaofeng; Zhang, Fengchun; Zhang, Wen

    2017-05-01

    In order to evaluate the efficacy and safety of high versus medium doses of glucocorticoid therapy in remission induction of immunoglobulin G4-related disease (IgG4-RD), we set up a randomized controlled study. Newly diagnosed IgG4-RD patients were randomly assigned to two groups: high doses of prednisone (0.8-1.0 mg/kg/day) and medium doses (0.5-0.6 mg/kg/day). Patients were assessed at weeks 0, 4, 12 and 24. The primary outcome was the remission rate at week 24. The secondary endpoints included IgG4-RD responder index (IgG4-RD RI), IgG and IgG4 levels. Twenty cases in each group finished the study. At week 24, the total response rates were 95% and 80% in high and medium dose groups, respectively. There was no significant difference between the two groups. IgG4-RD RI reduced from 14.9 to 3.0 in the high dose group, while in the medium dose group it was from 13.1 to 3.2. At week 24, the average level of IgG4 reduced from 1576 to 324 mg/dL and from 1445 to 684 mg/dL in the two groups, respectively. Relapsed patients had higher baseline IgG4-RD RI. There was no severe adverse effect shown in both groups. The effect of remission induction was similar in high and medium glucocorticoid groups. However, patients with more organs involved and higher IgG4-RD RI score at baseline might get more benefit with high dose glucocorticoid for remission induction. © 2017 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.

  5. Fibrosis of the thyroid gland caused by an IgG4-related sclerosing disease: three years of follow-up.

    Science.gov (United States)

    Oriot, P; Amraoui, A; Rousseau, E; Malvaux, P; Dechambre, S; Delcourt, A

    2014-12-01

    Immunoglobulin G4-related sclerosing disease (IgG4-RSD) represents a recently identified inflammatory disorder in which infiltration of IgG4 plasma cells causes fibrosis in organs. While IgG4-RSD is well documented in the pancreas and other organs, it is poorly characterized in the thyroid gland. We report a case of a 48-year-old female with a fibrotic thyroid mass associated with a retroperitoneal fibrosis. Diagnosed early as Riedel disease, the high serum IgG4, immunohistopathology and decreased fibrosis with corticosteroid therapy, finally confirm for the first time, the origin of IgG4-RSD fibrosis of the thyroid.

  6. Clinical significance of determination of changes of serum ferritin, MMP-2 and MMP-9 levels and after transfusion of red blood cells in patients with chronic nephritis

    International Nuclear Information System (INIS)

    Yuan Haitao; Li Xinhua; He Haoming

    2010-01-01

    Objective: To explore the changes of serum Ferritin, MMP-2 and MMP-9 contents after transfusion of red blood cells in patients with chronic nephritis. Methods: Serum Ferritin (with RIA) and serum MMP-2, MMP-9 (with ELISA) levels were measured in 32 patients with chronic nephritis both before and after a course of transfusion of red blood cells and 35 controls. Results: Before transfusion, the serum Ferritin, MMP-9 levels in the patients were significantly lower than those in controls (P 0.05). Conclusion: Determination of serum Ferritin, MMP-2 and MMP-9 levels is clinically useful for management of patients with chronic nephritis. (authors)

  7. Clinical significance of estimation of changes in serum SF, VEGF and HGF levels and after transfusion of red blood cells in patients with chronic nephritis

    International Nuclear Information System (INIS)

    Mu Peidong; He Haoming

    2011-01-01

    Objective: To observe the changes of serum SF, VEGF and HGF levels and after transfusion of red blood cells (RBC) in patients with chronic nephritis. Methods: Serum SF (with RIA) and serum VEGF, HGF (with ELISA) levels were measured in 30 patients with chronic nephritis both before and after a course of transfusion of RBC and 35 controls. Results: Before transfusion the serum SF levels in the patients were significantly lower than those in controls (P 0.05). Conclusion: Determination of serum SF, VEGF and HGF levels were clinically useful for the progress, prognosis and judgement of chronic nephritis. (authors)

  8. Comparative transcriptional profiling of 3 murine models of SLE nephritis reveals both unique and shared regulatory networks.

    Directory of Open Access Journals (Sweden)

    Ramalingam Bethunaickan

    Full Text Available To define shared and unique features of SLE nephritis in mouse models of proliferative and glomerulosclerotic renal disease.Perfused kidneys from NZB/W F1, NZW/BXSB and NZM2410 mice were harvested before and after nephritis onset. Affymetrix based gene expression profiles of kidney RNA were analyzed using Genomatix Pathway Systems and Ingenuity Pathway Analysis software. Gene expression patterns were confirmed using real-time PCR.955, 1168 and 755 genes were regulated in the kidneys of nephritic NZB/W F1, NZM2410 and NZW/BXSB mice respectively. 263 genes were regulated concordantly in all three strains reflecting immune cell infiltration, endothelial cell activation, complement activation, cytokine signaling, tissue remodeling and hypoxia. STAT3 was the top associated transcription factor, having a binding site in the gene promoter of 60/263 regulated genes. The two strains with proliferative nephritis shared a macrophage/DC infiltration and activation signature. NZB/W and NZM2410 mice shared a mitochondrial dysfunction signature. Dominant T cell and plasma cell signatures in NZB/W mice reflected lymphoid aggregates; this was the only strain with regulatory T cell infiltrates. NZW/BXSB mice manifested tubular regeneration and NZM2410 mice had the most metabolic stress and manifested loss of nephrin, indicating podocyte loss.These findings identify shared inflammatory mechanisms of SLE nephritis that can be therapeutically targeted. Nevertheless, the heterogeneity of effector mechanisms suggests that individualized therapy might need to be based on biopsy findings. Some common mechanisms are shared with non-immune-mediated renal diseases, suggesting that strategies to prevent tissue hypoxia and remodeling may be useful in SLE nephritis.

  9. Lupus Nephritis

    Science.gov (United States)

    ... in men and most often strikes during the child-bearing years. Nine out of 10 people who have lupus are women. Lupus is also more common in people of African or Asian background. African Americans and Asian Americans ...

  10. Interstitial nephritis

    Science.gov (United States)

    ... lungs (pulmonary edema) Common tests include: Arterial blood gases Blood chemistry BUN and blood creatinine levels Complete ... 2018, A.D.A.M., Inc. Duplication for commercial use must be authorized in writing by ADAM ...

  11. [Collagen nephritis].

    Science.gov (United States)

    Lago, N R; Bulos, M J; Monserrat, A J

    1997-01-01

    Fibrillar collagen in the glomeruli is considered specific of the nail-patella syndrome. A new nephropathy with diffuse intraglomerular deposition of type III collagen without nail and skeletal abnormalities has been described. We report the case of a 26-year-old woman who presented persistent proteinuria, hematuria, deafness without nail and skeletal abnormalities. The renal biopsy showed focal and segmental glomerulosclerosis by light microscopy. The electron microscopy revealed the presence of massive fibrillar collagen within the mesangial matriz and the basement membrane. This is the first patient reported in our country. We emphasize the usefulness of electron microscopy in the study of glomerular diseases.

  12. Interstitial Nephritis

    Science.gov (United States)

    ... A reaction to a medicine, such as certain antibiotics. Too much of certain medicines. These include diuretics (water pills) or pain relievers, such as acetaminophen, aspirin, or a non-steroidal anti-inflammatory drug (NSAID). Unbalanced levels of certain nutrients in ...

  13. Reduced Incidence of Slowly Progressive Heymann Nephritis in Rats Immunized With a Modified Vaccination Technique

    Directory of Open Access Journals (Sweden)

    Arpad Z. Barabas

    2006-01-01

    Full Text Available A slowly progressive Heymann nephritis (SPHN was induced in three groups of rats by weekly injections of a chemically modified renal tubular antigen in an aqueous medium. A control group of rats received the chemically unmodified version of the antigen in an aqueous solution. One group of SPHN rats were pre- and post-treated with weekly injections of IC made up of rKF3 and rarKF3 IgM antibody at antigen excess (MIC (immune complexes [ICs] containing sonicated ultracentrifuged [u/c] rat kidney fraction 3 [rKF3] antigen and IgM antibodies specific against the antigen, at slight antigen excess. One group of SPHN rats were post-treated with MIC 3 weeks after the induction of the disease and one group of SPHN animals received no treatment. The control group of rats received pre- and post-treatment with sonicated u/c rKF3.

  14. DRESS with delayed onset acute interstitial nephritis and profound refractory eosinophilia secondary to Vancomycin

    Directory of Open Access Journals (Sweden)

    O'Meara Paloma

    2011-10-01

    Full Text Available Abstract Background Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS is a relatively rare clinical entity; even more so in response to vancomycin. Methods Case report. Results We present a severe case of vancomycin-induced DRESS syndrome, which on presentation included only skin, hematological and mild liver involvement. The patient further developed severe acute interstitial nephritis, eosinophilic pneumonitis, central nervous system (CNS involvement and worsening hematological abnormalities despite immediate discontinuation of vancomycin and parenteral corticosteroids. High-dose corticosteroids for a prolonged period were necessary and tapering of steroids a challenge due to rebound-eosinophilia and skin involvement. Conclusion Patients with DRESS who are relatively resistant to corticosteroids with delayed onset of certain organ involvement should be treated with a more prolonged corticosteroid tapering schedule. Vancomycin is increasingly being recognized as a culprit agent in this syndrome.

  15. Quaternary epitopes of α345(IV) collagen initiate Alport post-transplant anti-GBM nephritis

    DEFF Research Database (Denmark)

    Olaru, Florina; Luo, Wentian; Wang, Xu-Ping

    2013-01-01

    Alport post-transplant nephritis (APTN) is an aggressive form of anti-glomerular basement membrane disease that targets the allograft in transplanted patients with X-linked Alport syndrome. Alloantibodies develop against the NC1 domain of α5(IV) collagen, which occurs in normal kidneys, including...... of alloantibodies against allogeneic collagen IV. Some alloantibodies targeted alloepitopes within α5NC1 monomers, shared by α345NC1 and α1256NC1 hexamers. Other alloantibodies specifically targeted alloepitopes that depended on the quaternary structure of α345NC1 hexamers. In Col4a5-null mice, immunization...... with native forms of allogeneic collagen IV exclusively elicited antibodies to quaternary α345NC1 alloepitopes, whereas alloimmunogens lacking native quaternary structure elicited antibodies to shared α5NC1 alloepitopes. These results imply that quaternary epitopes within α345NC1 hexamers may initiate...

  16. Acute kidney injury with granulomatous interstitial nephritis and vasculitis revealing sarcoidosis

    Directory of Open Access Journals (Sweden)

    Amel Harzallah

    2017-01-01

    Full Text Available Sarcoidosis is an inflammatory disease that affects mostly the lungs and lymph glands. Renal involvement is rare and especially vasculitis. We report a case who presented an acute kidney failure and had sarcoidosis with vasculitis and nodular splenic involvement. A 35-year-old woman presenting a Lofgren syndrome was hospitalized for acute renal failure with cervical lymphadenopathy without other clinical findings. Laboratory data disclosed elevated angiotensin converting enzyme serum level. Abdominal ultrasound showed a multinodular spleen. Renal histology revealed granulomatous interstitial nephritis with necrotizing vasculitis. Outcome was favorable after the institution of high dose corticosteroids along with cyclophosphamide. Renal involvement is rare in sarcoidosis. However, the diagnostic delay should be avoided to improve the outcome.

  17. Acute kidney injury with granulomatous interstitial nephritis and vasculitis revealing sarcoidosis.

    Science.gov (United States)

    Harzallah, Amel; Kaaroud, Hayet; Boubaker, Karima; Barbouch, Samia; Goucha, Rim; Hamida, Fethi Ben; Abdallah, Taieb Ben

    2017-01-01

    Sarcoidosis is an inflammatory disease that affects mostly the lungs and lymph glands. Renal involvement is rare and especially vasculitis. We report a case who presented an acute kidney failure and had sarcoidosis with vasculitis and nodular splenic involvement. A 35-year-old woman presenting a Lofgren syndrome was hospitalized for acute renal failure with cervical lymphadenopathy without other clinical findings. Laboratory data disclosed elevated angiotensin converting enzyme serum level. Abdominal ultrasound showed a multinodular spleen. Renal histology revealed granulomatous interstitial nephritis with necrotizing vasculitis. Outcome was favorable after the institution of high dose corticosteroids along with cyclophosphamide. Renal involvement is rare in sarcoidosis. However, the diagnostic delay should be avoided to improve the outcome.

  18. Interdisciplinary care for adequate adherence totreatment in patients with lupus nephritis

    Directory of Open Access Journals (Sweden)

    Gladys Gaviria-García

    2016-02-01

    Full Text Available The review is based on the contribution that each discipline should provide the patient for a holistic care, which include medical assessment, monitoring and counselling as emotional support, assessment and nutritional monitoring as a key element in core requirements, physical activity that optimize the quality of life, social activities that can enter the individual in active groups, follow-up by nurses to the fulfillment of the ordered drug treatment, car care and orientation education to the family. The novelty of this proposal is to basically carry out care of the interdisciplinary team for treatment adherence. This review concluded that patients with lupus nephritis (NL treated after assessment and follow-up holistic, such as system monitoring and adherence to the treatment of comprehensive care, provides better quality of life, and minimizes the risks of complication of the patient, avoiding recurrent hospitalizations.

  19. Toll-like receptor activation in the pathogenesis of lupus nephritis.

    Science.gov (United States)

    Lorenz, Georg; Lech, Maciej; Anders, Hans-Joachim

    2017-12-01

    The pathogenesis of systemic lupus erythematosus (SLE) and lupus nephritis is complex but no longer enigmatic. Much progress has been made to on the polygenetic origin of lupus in identifying gene variants that permit the loss of tolerance against nuclear autoantigens. Along the same line in about 50% of lupus patients additional genetic weaknesses promote immune complex glomerulonephritis and filtration barrier dysfunction. Here we briefly summarize the pathogenesis of SLE with a focus on loss of tolerance and the role of toll-like receptors in the "pseudo"-antiviral immunity concept of systemic lupus. In addition, we discuss the local role of Toll-like receptors in intrarenal inflammation and kidney remodeling. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Clinical outcomes in children with Henoch-Schönlein purpura nephritis without crescents.

    Science.gov (United States)

    Delbet, Jean Daniel; Hogan, Julien; Aoun, Bilal; Stoica, Iulia; Salomon, Rémi; Decramer, Stéphane; Brocheriou, Isabelle; Deschênes, Georges; Ulinski, Tim

    2017-07-01

    Henoch-Schönlein purpura is the most common vasculitis in children. Its long-term prognosis depends on renal involvement. The management of Henoch-Schönlein purpura nephritis (HSPN) remains controversial. This study reports the prognosis of children with HSPN presenting with class 2 International Study of Kidney Disease in Children (ISKDC) nephritis. All children with HSPN class 2 diagnosed between 1995 and 2015 in four pediatric nephrology centers were included, and clinical and biological data were collected from the medical files. The primary endpoint was proteinuria remission defined as a proteinuria 3 g/L, 52% proteinuria between 1 and 3 g/L, and 18% proteinuria <1 g/L. Forty-seven percent of patients received orally treatment with steroids alone, 37% received methylprednisolone pulses followed by steroids orally, 18% received no steroids. Although 85% reached remission during follow-up, 12% did not maintain complete remission over time so that only 75% remained in complete remission by the end of the follow-up. Univariate analysis found a higher likelihood of remission in patients with higher proteinuria at disease onset (p = 0.009). This trend was not found in the multivariate analysis after adjusting for treatments, as patients with higher proteinuria were most often treated with steroids. Our study shows that one fourth of patients with HSPN class 2 remain proteinuric and thus carry the risk of developing chronic kidney disease over the long term. This finding, together with the better outcome of patients treated with steroids, is in favor of using high-dose steroids orally or IV in these patients.

  1. The Steroids in the Maintenance of Remission of Proliferative Lupus Nephritis (SIMPL Pilot Trial

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    Lauren Galbraith

    2014-11-01

    Full Text Available Background: Patients with proliferative lupus nephritis are at risk of frequent relapses. Whether low- dose prednisone prevents relapses is uncertain. Objectives: We undertook a pilot RCT to determine the feasibility of a larger trial. Design: Pilot randomized controlled trial. Setting: Single center Canadian outpatient nephrology clinic. Patients: Participants with systemic lupus erythematosus (SLE and a history of class III or IV lupus nephritis that achieved at least partial remission and remained on prednisone were eligible. Measurements: Feasibility: proportion of eligible patients randomized and adherence to tapering regimen. Clinical: occurrence of renal or major non-renal flare of SLE. Methods: We conducted a blinded, two-parallel-group randomized controlled trial of prednisone 7.5 mg/day (continuation compared to a matching placebo (withdrawal. Results: Of nineteen eligible patients screened, 15 (79% were recruited and randomized; 8 to prednisone continuation and seven to withdrawal. All participants adhered to the tapering protocol to their assigned withdrawal or low-dose maintenance target. Over 36 months, the primary outcome occurred in four (50% patients in the continuation group (three renal and one major non-renal flare, compared with one patient (14% in the withdrawal group (one renal flare. Three participants (38% in the continuation group had minor flares, while no patients in the withdrawal group did. Limitations: This pilot RCT was small and not designed to assess the efficacy or safety of maintenance with low-dose prednisone. Conclusions: The high proportion of eligible patients recruited, and success of protocol adherence suggest a large trial of prednisone maintenance therapy compared to withdrawal is feasible. Trial registration: Current Controlled Trials ISRCTN31327267.

  2. Decay-accelerating factor 1 deficiency exacerbates leptospiral-induced murine chronic nephritis and renal fibrosis.

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    María F Ferrer

    Full Text Available Leptospirosis is a global zoonosis caused by pathogenic Leptospira, which can colonize the proximal renal tubules and persist for long periods in the kidneys of infected hosts. Here, we characterized the infection of C57BL/6J wild-type and Daf1-/- mice, which have an enhanced host response, with a virulent Leptospira interrogans strain at 14 days post-infection, its persistence in the kidney, and its link to kidney fibrosis at 90 days post-infection. We found that Leptospira interrogans can induce acute moderate nephritis in wild-type mice and is able to persist in some animals, inducing fibrosis in the absence of mortality. In contrast, Daf1-/- mice showed acute mortality, with a higher bacterial burden. At the chronic stage, Daf1-/- mice showed greater inflammation and fibrosis than at 14 days post-infection and higher levels at all times than the wild-type counterpart. Compared with uninfected mice, infected wild-type mice showed higher levels of IL-4, IL-10 and IL-13, with similar levels of α-smooth muscle actin, galectin-3, TGF-β1, IL-17, IFN-γ, and lower IL-12 levels at 90 days post-infection. In contrast, fibrosis in Daf1-/- mice was accompanied by high expression of α-smooth muscle actin, galectin-3, IL-10, IL-13, and IFN-γ, similar levels of TGF-β1, IL-12, and IL-17 and lower IL-4 levels. This study demonstrates the link between Leptospira-induced murine chronic nephritis with renal fibrosis and shows a protective role of Daf1.

  3. Serum levels of adiponectin and leptin as biomarkers of proteinuria in lupus nephritis.

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    Valeria Diaz-Rizo

    Full Text Available There are controversial results about the role of serum leptin and adiponectin levels as biomarkers of the severity of proteinuria in lupus nephritis.The aim of this study was to evaluate the relationship between serum leptin and adiponectin levels with severity of proteinuria secondary to lupus nephritis (LN.In a cross-sectional study, 103 women with systemic lupus erythematosus (SLE were evaluated for kidney involvement. We compared 30 SLE patients with LN, all of them with proteinuria, versus 73 SLE patients without renal involvement (no LN. A comprehensive set of clinical and laboratory variables was assessed, including serum levels of leptin and adiponectin by ELISA. Multivariate analyses were used to adjust for potential confounders associated with proteinuria in LN.We found higher adiponectin levels in the LN group compared with the no LN group (20.4 ± 10.3 vs 15.6 ± 7.8 μg/mL; p = 0.02, whereas no differences were observed in leptin levels (33.3 ± 31.4 vs 22.5 ± 25.5 ng/mL; p = 0.07. Severity of proteinuria correlated with an increase in adiponectin levels (r = 0.31; p = 0.001, but no correlation was observed with leptin. Adiponectin levels were not related to anti-dsDNA or anti-nucleosome antibodies. In the logistic regression, adiponectin levels were associated with a high risk of proteinuria in SLE (OR = 1.06; 95% CI 1.01-1.12; p = 0.02. Instead, leptin was not associated with LN.These findings indicate that adiponectin levels are useful markers associated with proteinuria in LN. Further longitudinal studies are required to identify if these levels are predictive of renal relapse.

  4. Angiotensin-converting enzyme insertion/deletion gene polymorphism in Egyptian children with systemic lupus erythematosus: a possible relation to proliferative nephritis.

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    Hammad, A; Yahia, S; Laimon, W; Hamed, S M; Shouma, A; Shalaby, N M; Abdel-Hady, D; Ghanem, R; El-Farahaty, R M; El-Bassiony, S R; Hammad, E M

    2017-06-01

    Introduction Angiotensin-converting enzyme (ACE) is crucial in the pathogenesis of systemic lupus erythematosus through angiotensin II which regulates vascular tone and endothelial functions. Objectives To study the frequency of ACE insertion/deletion (I/D) gene polymorphism in Egyptian children with systemic lupus erythematosus and its possible relation to the renal pathology in cases with lupus nephritis. Subjects and methods The frequency of ACE gene insertion/deletion polymorphism genotypes was determined in 78 Egyptian children with systemic lupus erythematosus and compared to a matched group of 140 healthy controls using polymerase chain reaction. Results The DD genotype of the ACE gene was higher in systemic lupus erythematosus patients when compared to controls ( Plupus erythematosus patients in comparison to controls ( P lupus nephritis group, the DD genotype was significantly higher in those with proliferative lupus nephritis when compared to those with non-proliferative lupus nephritis ( P = 0.02; OR = 1.45; 95% CI = 1.4-1.6). Also, patients with proliferative lupus nephritis showed a higher frequency of the D allele ( P lupus erythematosus and occurrence of proliferative nephritis in Egyptian children.

  5. Whole-exome sequencing reveals genetic variants associated with chronic kidney disease characterized by tubulointerstitial damages in North Central Region, Sri Lanka.

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    Nanayakkara, Shanika; Senevirathna, S T M L D; Parahitiyawa, Nipuna B; Abeysekera, Tilak; Chandrajith, Rohana; Ratnatunga, Neelakanthi; Hitomi, Toshiaki; Kobayashi, Hatasu; Harada, Kouji H; Koizumi, Akio

    2015-09-01

    The familial clustering observed in chronic kidney disease of uncertain etiology (CKDu) characterized by tubulointerstitial damages in the North Central Region of Sri Lanka strongly suggests the involvement of genetic factors in its pathogenesis. The objective of the present study is to use whole-exome sequencing to identify the genetic variants associated with CKDu. Whole-exome sequencing of eight CKDu cases and eight controls was performed, followed by direct sequencing of candidate loci in 301 CKDu cases and 276 controls. Association study revealed rs34970857 (c.658G > A/p.V220M) located in the KCNA10 gene encoding a voltage-gated K channel as the most promising SNP with the highest odds ratio of 1.74. Four rare variants were identified in gene encoding Laminin beta2 (LAMB2) which is known to cause congenital nephrotic syndrome. Three out of four variants in LAMB2 were novel variants found exclusively in cases. Genetic investigations provide strong evidence on the presence of genetic susceptibility for CKDu. Possibility of presence of several rare variants associated with CKDu in this population is also suggested.

  6. Barriers to Medication Decision Making in Women with Lupus Nephritis: A Formative Study using Nominal Group Technique.

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    Singh, Jasvinder A; Qu, Haiyan; Yazdany, Jinoos; Chatham, Winn; Dall'era, Maria; Shewchuk, Richard M

    2015-09-01

    To assess the perspectives of women with lupus nephritis on barriers to medication decision making. We used the nominal group technique (NGT), a structured process to elicit ideas from participants, for a formative assessment. Eight NGT meetings were conducted in English and moderated by an expert NGT researcher at 2 medical centers. Participants responded to the question: "What sorts of things make it hard for people to decide to take the medicines that doctors prescribe for treating their lupus kidney disease?" Patients nominated, discussed, and prioritized barriers to decisional processes involving medications for treating lupus nephritis. Fifty-one women with lupus nephritis with a mean age of 40.6 ± 13.3 years and disease duration of 11.8 ± 8.3 years participated in 8 NGT meetings: 26 African Americans (4 panels), 13 Hispanics (2 panels), and 12 whites (2 panels). Of the participants, 36.5% had obtained at least a college degree and 55.8% needed some help in reading health materials. Of the 248 responses generated (range 19-37 responses/panel), 100 responses (40%) were perceived by patients as having relatively greater importance than other barriers in their own decision-making processes. The most salient perceived barriers, as indicated by percent-weighted votes assigned, were known/anticipated side effects (15.6%), medication expense/ability to afford medications (8.2%), and the fear that the medication could cause other diseases (7.8%). Women with lupus nephritis identified specific barriers to decisions related to medications. Information relevant to known/anticipated medication side effects and medication cost will form the basis of a patient guide for women with systemic lupus erythematosus, currently under development.

  7. Value of HLA-DR genotype in systemic lupus erythematosus and lupus nephritis: a meta-analysis.

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    Niu, Zhili; Zhang, Pingan; Tong, Yongqing

    2015-01-01

    Human leukocyte antigen (HLA)-DRB1 allele polymorphisms have been reported to be associated with systemic lupus erythematosus (SLE) susceptibility, but the results of these previous studies have been inconsistent. The purpose of the present study was to systematically summarize and explore whether specific HLA-DRB1 alleles confer susceptibility or resistance to SLE and lupus nephritis. This review was guided by the preferred reporting items for systematic reviews and meta-analyses (PRISMA) approach. A comprehensive search was made for articles from PubMed, Medline, Elsevier Science, Springer Link and Cochrane Library database. A total of 25 case-control studies on the relationship between gene polymorphism of HLA-DRB l and SLE were performed and data were analyzed and processed using Review Manager 5.2 and Stata 11.0. At the allelic level, HLA-DR4, DR11 and DR14 were identified as protective factors for SLE (0.79 [0.69,0.91], P  0.05). DR4 and 11 (OR, 0.55 [0.39, 0.79], P  0.05; 0.90 [0.64, 1.27], P > 0.05; 0.61 [0.36, 1.03], P > 0.05, respectively) were not statistically significant between the lupus nephritis and control groups. The HLA-DR4, DR11, DR14 alleles might be protective factors for SLE and HLA-DR3, DR9, DR15 were potent risk factors. In addition, HLA-DR4 and DR11 alleles might be protective factors for lupus nephritis and DR3 and DR15 suggest a risk role. These results proved that HLA-DR3, DR15, DR4 and DR11 might be identified as predictors for lupus nephritis and SLE. © 2014 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

  8. Immune profile and Epstein-Barr virus infection in acute interstitial nephritis: an immunohistochemical study in 78 patients.

    LENUS (Irish Health Repository)

    Mansur, Abdurrezagh

    2011-01-01

    Acute interstitial nephritis (AIN) is a common cause of acute kidney injury and is characterised by a dense interstitial cellular infiltrate, which has not been well defined. Previous studies have demonstrated a correlation between Epstein-Barr virus (EBV) infection and AIN. The purpose of our study was to define the nature of the interstitial immune infiltrate and to investigate the possibility of renal infection with EBV.

  9. Characterization of Novel PI3Kδ Inhibitors as Potential Therapeutics for SLE and Lupus Nephritis in Pre-Clinical Studies.

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    Haselmayer, Philipp; Camps, Montserrat; Muzerelle, Mathilde; El Bawab, Samer; Waltzinger, Caroline; Bruns, Lisa; Abla, Nada; Polokoff, Mark A; Jond-Necand, Carole; Gaudet, Marilène; Benoit, Audrey; Bertschy Meier, Dominique; Martin, Catherine; Gretener, Denise; Lombardi, Maria Stella; Grenningloh, Roland; Ladel, Christoph; Petersen, Jørgen Søberg; Gaillard, Pascale; Ji, Hong

    2014-01-01

    SLE is a complex autoimmune inflammatory disease characterized by pathogenic autoantibody production as a consequence of uncontrolled T-B cell activity and immune-complex deposition in various organs, including kidney, leading to tissue damage and function loss. There is a high unmet need for better treatment options other than corticosteroids and immunosuppressants. Phosphoinositol-3 kinase δ (PI3Kδ) is a promising target in this respect as it is essential in mediating B- and T-cell function in mouse and human. We report the identification of selective PI3Kδ inhibitors that blocked B-, T-, and plasmacytoid dendritic cell activities in human peripheral blood and in primary cell co-cultures (BioMAP(®)) without detecting signs of undesired toxicity. In an IFNα-accelerated mouse SLE model, our PI3Kδ inhibitors blocked nephritis development, whether administered at the onset of autoantibody appearance or the onset of proteinuria. Disease amelioration correlated with normalized immune cell numbers in the spleen, reduced immune-complex deposition as well as reduced inflammation, fibrosis, and tissue damage in the kidney. Improvements were similar to those achieved with a frequently prescribed drug for lupus nephritis, the potent immunosuppressant mycophenolate mofetil. Finally, we established a pharmacodynamics/pharmacokinetic/efficacy model that revealed that a sustained PI3Kδ inhibition of 50% is sufficient to achieve full efficacy in our disease model. These data demonstrate the therapeutic potential of PI3Kδ inhibitors in SLE and lupus nephritis.

  10. A Study on Clinical and Pathologic Features in Lupus Nephritis with Mainly IgA Deposits and a Literature Review

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    Liu Hongyan

    2013-01-01

    Full Text Available Objective. To study the clinical and pathologic features of systemic lupus erythematosus (SLE that has atypical lupus nephritis (LN with mainly IgA deposits. Methods. We searched the SLE patients who had nephritis with mainly IgA deposits in our hospital and selected the information including clinical manifestations, laboratory tests, treatments, and prognosis. Results. From January 2009 to June 2012, 5 patients were definitely diagnosed as SLE according to both 1982 and 2009 ACR classification criteria. But renal biopsy showed that all cases had mainly IgA deposits and were free of IgG, C1q, and fibrinogen-related antigen deposits under immunofluorescent microscopy, which did not match with typical LN. There were 2 males and 3 females, aging from 31 to 64 years and with an average of years. The 5 cases had multiple-system involvements, mainly the renal system. Compared to primary IgAN, the atypical LN showed some differences: older than primary IgAN, more women than men, no previous infection history, lower incidence of serum IgA elevation, and ACL positive rate as high as 100%. Conclusion. Nephritis with mainly IgAN deposits, as an atypical LN, may be a special subtype of SLE.

  11. Integrative medicine for managing the symptoms of lupus nephritis: A protocol for systematic review and meta-analysis.

    Science.gov (United States)

    Choi, Tae-Young; Jun, Ji Hee; Lee, Myeong Soo

    2018-03-01

    Integrative medicine is claimed to improve symptoms of lupus nephritis. No systematic reviews have been performed for the application of integrative medicine for lupus nephritis on patients with systemic lupus erythematosus (SLE). Thus, this review will aim to evaluate the current evidence on the efficacy of integrative medicine for the management of lupus nephritis in patients with SLE. The following electronic databases will be searched for studies published from their dates of inception February 2018: Medline, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL), as well as 6 Korean medical databases (Korea Med, the Oriental Medicine Advanced Search Integrated System [OASIS], DBpia, the Korean Medical Database [KM base], the Research Information Service System [RISS], and the Korean Studies Information Services System [KISS]), and 1 Chinese medical database (the China National Knowledge Infrastructure [CNKI]). Study selection, data extraction, and assessment will be performed independently by 2 researchers. The risk of bias (ROB) will be assessed using the Cochrane ROB tool. This systematic review will be published in a peer-reviewed journal and disseminated both electronically and in print. The review will be updated to inform and guide healthcare practice and policy. PROSPERO 2018 CRD42018085205.

  12. Angiotensin-converting enzyme (ACE) gene insertion/deletion polymorphism is not a risk factor for hypertension in SLE nephritis.

    Science.gov (United States)

    Negi, Vir S; Devaraju, Panneer; Gulati, Reena

    2015-09-01

    SLE is a systemic autoimmune disease with high prevalence of hypertension. Around 40-75 % of SLE patients develop nephritis, a major cause of hypertension and mortality. Angiotensin-converting enzyme (ACE) maintains the blood pressure and blood volume homeostasis. An insertion/deletion (I/D) polymorphism in intron 16 of ACE gene was reported to influence the development of hypertension, nephritis, and cardiovascular diseases in different ethnic populations. Despite compelling evidence for the high prevalence of hypertension in individuals with SLE, underlying factors for its development are not well studied. With this background, we analyzed the influence of ACE insertion/deletion polymorphism on susceptibility to SLE, development of nephritis and hypertension, other clinical features and autoantibody phenotype in South Indian SLE patients. Three hundred patients with SLE and 460 age and sex similar ethnicity matched individuals were included as patients and healthy controls, respectively. The ACE gene insertion/deletion polymorphism was analyzed by PCR. Insertion (I) and deletion (D) alleles were observed to be equally distributed among patients (57 and 43 %) and controls (59 and 41 %), respectively. The mutant (D) allele did not confer significant risk for SLE (II vs. ID: p = 0.4, OR 1.15, 95 % CI 0.8-1.6; II vs. DD: p = 0.34, OR 1.22, 95 % CI 0.8-1.85). There was no association of the ACE genotype or the allele with development of lupus nephritis (II vs. ID: p = 0.19, OR 1.41, 95 % CI 0.84-2.36; II vs. DD: p = 0.41, OR 0.74, 95 % CI 0.38-1.41) or hypertension (II vs. ID: p = 0.85, OR 0.9, 95 % CI 0.43-1.8; II vs. DD: p = 0.66, OR 1.217, 95 % CI 0.5-2.8). The presence of mutant allele (D) was not found to influence any clinical features or autoantibody phenotype. The insertion/deletion polymorphism of the ACE gene is not a genetic risk factor for SLE and does not influence development of hypertension or lupus nephritis in South Indian

  13. Urinary Transforming Growth Factor-beta 1 as a marker of response to immunosuppressive treatment, in patients with crescentic nephritis

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    Sotsiou Florentia

    2005-12-01

    Full Text Available Abstract Background Crescentic nephritis is characterized by formation of cellular crescents that soon become fibrotic and result in irreversible damage, unless an effective immunosuppressive therapy is rapidly commenced. TGF-β1 is involved in the development of crescents through various pathways. The aim of this study was to identify whether the determination of urinary TGF-β1 levels in patients with crescentic nephritis could be used as a marker of response to treatment. Methods Fifteen patients with crescentic nephritis were included in the study. The renal expression of TGF-β1 was estimated in biopsy sections by immunohistochemistry and urinary TGF-β1 levels were determined by quantitative sandwich enzyme immunoassay (EIA. TGF-β1 levels were determined at the time of renal biopsy, before the initiation of immunosuppressive treatment (corticosteroids, cyclophosphamide and plasma exchange. Twelve patients with other types of proliferative glomerulonephritis and ten healthy subjects were used as controls. Results Improvement of renal function with immunosuppressive therapy was observed in 6 and stabilization in 4 patients (serum creatinine from 3.2 ± 1.5 to 1.4 ± 0.1 mg/dl and from 4.4 ± 1.2 to 4.1 ± 0.6 mg/dl, respectively. In 5 patients, with severe impairment of renal function who started on dialysis, no improvement was noted. The main histological feature differentiating these 5 patients from others with improved or stabilized renal function was the percentage patients with poor response to treatment were the percentage of glomeruli with crescents and the presence of ruptured Bowman's capsule and glomerular necrosis. Urinary TGF-β1 levels were significantly higher in patients who showed no improvement of renal function with immunosuppressive therapy (930 ± 126 ng/24 h vs. 376 ± 84 ng/24 h, p 1 was identified in crescents and tubular epithelial cells, whereas a significant correlation of TGF-β1 immunostaining with the presence

  14. An integrative study of the genetic, social and environmental determinants of chronic kidney disease characterized by tubulointerstitial damages in the North Central Region of Sri Lanka.

    Science.gov (United States)

    Nanayakkara, Shanika; Senevirathna, S T M L D; Abeysekera, Tilak; Chandrajith, Rohana; Ratnatunga, Neelakanthi; Gunarathne, E D L; Yan, Junxia; Hitomi, Toshiaki; Muso, Eri; Komiya, Toshiyuki; Harada, Kouji H; Liu, Wanyang; Kobayashi, Hatasu; Okuda, Hiroko; Sawatari, Hideyuki; Matsuda, Fumihiko; Yamada, Ryo; Watanabe, Takao; Miyataka, Hideki; Himeno, Seiichiro; Koizumi, Akio

    2014-01-01

    Previous investigations on chronic kidney disease of unknown etiology characterized by tubulointerstitial damages (CKDu) in the North Central Region (NCR) of Sri Lanka have supported the involvement of social, environmental and genetic factors in its pathogenesis. We conducted a social-environmental-and-genetic epidemiology study on a male population in NCR to investigate the genetic and environmental contributors. We recruited 311 case-series patients and 504 control candidates. Of the 504 control candidates, 218 (43%) were eliminated because of the presence of hypertension, proteinuria, high HbA1c, high serum creatinine or high alpha-1 microglobulin in urine. None of 18 metals measured (μg//) in urine, including Cd, As and Pb, showed significantly higher concentrations in cases compared with controls. As speciation results showed that 75-80% of total urinary As was in the form of arsenobetaine, which is non-toxic to humans. None of the metal concentrations in drinking water samples exceeded guideline values. A genome-wide association study (GWAS) was conducted to determine the genetic contributors. The GWAS yielded a genome-wide significant association with CKDu for a single nucleotide polymorphism (SNP; rs6066043; p=5.23 × 10(-9) in quantitative trait locus analysis; p=3.73 × 10(-9) in dichotomous analysis) in SLC13A3 (sodium-dependent dicarboxylate transporter member 3). The population attributable fraction and odds ratio for this SNP were 50% and 2.13. Genetic susceptibility was identified as the major risk factor for CKDu. However, 43% of the apparently healthy male population suffers from non-communicable diseases, suggesting their possible influence on CKDu progression.

  15. iRhom2 promotes lupus nephritis through TNF-α and EGFR signaling.

    Science.gov (United States)

    Qing, Xiaoping; Chinenov, Yurii; Redecha, Patricia; Madaio, Michael; Roelofs, Joris Jth; Farber, Gregory; Issuree, Priya D; Donlin, Laura; Mcllwain, David R; Mak, Tak W; Blobel, Carl P; Salmon, Jane E

    2018-04-02

    Lupus nephritis (LN) often results in progressive renal dysfunction. The inactive rhomboid 2 (iRhom2) is a newly identified key regulator of A disintegrin and metalloprotease 17 (ADAM17), whose substrates, such as TNF-α and heparin-binding EGF (HB-EGF), have been implicated in the pathogenesis of chronic kidney diseases. Here, we demonstrate that deficiency of iRhom2 protects the lupus-prone Fcgr2b-/- mice from developing severe kidney damage without altering anti-double-stranded DNA (anti-dsDNA) Ab production by simultaneously blocking HB-EGF/EGFR and TNF-α signaling in the kidney tissues. Unbiased transcriptome profiling of kidneys and kidney macrophages revealed that TNF-α and HB-EGF/EGFR signaling pathways are highly upregulated in Fcgr2b-/- mice, alterations that were diminished in the absence of iRhom2. Pharmacological blockade of either TNF-α or EGFR signaling protected Fcgr2b-/- mice from severe renal damage. Finally, kidneys from LN patients showed increased iRhom2 and HB-EGF expression, with interstitial HB-EGF expression significantly associated with chronicity indices. Our data suggest that activation of iRhom2/ADAM17-dependent TNF-α and EGFR signaling plays a crucial role in mediating irreversible kidney damage in LN, thereby uncovering a target for selective and simultaneous dual inhibition of 2 major pathological pathways in the effector arm of the disease.

  16. Mechanisms and kinetics for platelet and neutrophil localization in immune complex nephritis

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    Johnson, R.J.; Alpers, C.E.; Pruchno, C.; Schulze, M.; Baker, P.J.; Pritzl, P.; Couser, W.G. (Univ. of Washington, Seattle (USA))

    1989-11-01

    We have previously reported that both neutrophils (PMNs) and platelets mediate proteinuria in a model of subendothelial immune complex (IC) nephritis (GN) in the rat. In order to understand the interaction of PMNs and platelets in this model, we quantitated the uptake of {sup 111}In-labelled platelets in glomeruli and correlated this with the number of PMNs observed histologically at 10 and 30 minutes, 1, 4 and 24 hours following induction of GN. Platelet accumulation was biphasic with a major peak at 10 minutes and a minor peak at four hours. Early platelet accumulation was complement dependent, and PMN-independent. PMN accumulation occurred after the initial platelet influx, peaking at one and four hours, was complement dependent, but was not affected by platelet depletion. Complement depletion significantly reduced proteinuria. This is the first documentation that platelet accumulation in glomeruli in IC GN is complement dependent. In addition, the enhancement of PMN-mediated injury by the platelet in this model does not involve effects of platelets on PMN localization, thus implying a functional interaction between these cells within the glomerulus.

  17. The contribution of the programmed cell death machinery in innate immune cells to lupus nephritis.

    Science.gov (United States)

    Tsai, FuNien; Perlman, Harris; Cuda, Carla M

    2017-12-01

    Systemic lupus erythematosus (SLE) is a chronic multi-factorial autoimmune disease initiated by genetic and environmental factors, which in combination trigger disease onset in susceptible individuals. Damage to the kidney as a consequence of lupus nephritis (LN) is one of the most prevalent and severe outcomes, as LN affects up to 60% of SLE patients and accounts for much of SLE-associated morbidity and mortality. As remarkable strides have been made in unlocking new inflammatory mechanisms associated with signaling molecules of programmed cell death pathways, this review explores the available evidence implicating the action of these pathways specifically within dendritic cells and macrophages in the control of kidney disease. Although advancements into the underlying mechanisms responsible for inducing cell death inflammatory pathways have been made, there still exist areas of unmet need. By understanding the molecular mechanisms by which dendritic cells and macrophages contribute to LN pathogenesis, we can improve their viability as potential therapeutic targets to promote remission. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Protocol renal biopsy in patients with lupus nephritis: a single center experience.

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    Singh, Ametashver; Ghosh, Rabindranath; Kaur, Prabhjeet; Golay, Vishal; Pandey, Rajendra; Roychowdhury, Arpita

    2014-07-01

    Renal biopsy plays an indispensable role in the diagnosis and management of patients with lupus nephritis (LN). A number of studies have evaluated the role of a repeat biopsy in case of disease relapse or treatment unresponsiveness. We studied 40 patients with LN with renal biopsies performed at baseline and after six months of therapy. The baseline and protocol biopsies were compared with respect to histological class transformation, crescents, tubular atrophy, interstitial fibrosis and glomerulosclerosis. We also compared serum creatinine, hemoglobin, systemic lupus erythematosus disease activity index (SLEDAI) scores, 24-h urine protein excretion and C3levels as well as activity index (AI) and chronicity index (CI) at baseline and at six months. Comparison of means was made by paired t test, McNemar test and marginal homogeneity test (multinomial data). Histological class transformation was seen in 10 patients (25%). Intra-class progression to greater chronicity was seen in 10 other patients (25%).There was an increase in glomerulosclerosis, tubular atrophy, interstitial fibrosis and a reduction in cellularity, crescent formation and wire loop lesions in the protocol biopsy. A decline in AI (6.05 vs. 2.50, P protocol biopsy. Our study shows a trend toward greater chronicity in protocol biopsies in LN.

  19. Clozapine-induced interstitial nephritis - a rare but important complication: a case report

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    Hunter Robert

    2009-08-01

    Full Text Available Abstract Introduction Given the limited range of effective drug treatments for patients with schizophrenia, increasing numbers of patients, often termed 'treatment-resistant' are prescribed clozapine. While the induction of neutropenia or agranulocytosis by clozapine is well appreciated, other rare potentially fatal adverse reactions may also occur including acute interstitial nephritis as reported in this case. Case presentation A 57-year-old Caucasian woman with treatment-resistant chronic schizophrenia developed acute renal failure following initiation of treatment with clozapine. The adverse reaction occurred after only four doses of the drug had been administered (titrated from 12.5 to 25 mg per day. After clozapine had been withdrawn, the patient's renal function returned to normal with no other changes to medication. The patient had been exposed to clozapine about 4 years previously when she had developed a similar reaction. Conclusion Renal reactions to clozapine are extremely rare but, if not recognized promptly, may prove fatal. Psychiatrists need to be aware of this possible complication when clozapine is initiated.

  20. Retracted Association of STAT4 gene polymorphism with systemic lupus erythematosus / lupus nephritis risk.

    Science.gov (United States)

    Zhou, Tian-Biao; Jiang, Zong-Pei; Qin, Yuan-Han; Zhou, Jia-Fan

    2014-04-16

    The association of STAT4 gene polymorphism with systemic lupus erythematosus (SLE) / lupus nephritis (LN) results from the published studies is still conflicting. This meta-analysis was performed to evaluate the relationship between STAT4 rs7574865, rs16833431, rs11889341, rs8179673, rs10168266, rs7582694, rs3821236, rs7601754 gene polymorphism and SLE / LN, and to explore whether STAT4 gene polymorphism could become a predictive marker for SLE / LN risk. Association studies were identified from the databases of PubMed, Embase, Cochrane Library and CBM-disc (China Biological Medicine Database) as of September 1, 2013, and eligible investigations were synthesized using meta-analysis method. 24 investigations were identified for the analysis of association between STAT4 gene polymorphism and SLE, consisting of 31190 patients with SLE and 43940 controls. In STAT4 rs7574865, there was a marked association between T allele or TT genotype and SLE susceptibility (T: OR=1.53, 95% CI: 1.30-1.79, Prs7574865 gene polymorphism was not associated with the LN risk. Our results indicate that T allele or TT homozygous is a significant risk genetic molecular marker to predict the SLE susceptibility and GG genotype is a valuable marker to against the SLE risk, but the association was not found for LN. However, more investigations are required to further clarify the association of the T allele or TT homozygous with SLE / LN susceptibility. This article is protected by copyright. All rights reserved.

  1. Clinical evaluation of determination the changes on serum IL-2, IL-4 and IFN-γ levels after treatment in pediatric patients with acute nephritis

    International Nuclear Information System (INIS)

    Zhou Hong; Hu Yan; Wei Guoyu; Liu Ya

    2011-01-01

    Objective: To explore the clinical evaluation of the changes of determination of serum IL-2, IL-4 and IFN-γ levels after treatment in pediatric patients with acute nephritis. Methods: Serum IL-2 (with RIA), IL-4, IFN-γ (with ELISA) levels were determined both before and after treatment in 32 pediatric patients with acute nephritis and 35 normal controls. Results: The serum IL-4, IFN-γ levels were significantly higher in the patients than those in controls before treatment (P 0.05). Serum IL-2 levels were negatively correlated with IL-4, IFN-γ levels (r=-0.5536, -0.6012, P<0.01). Conclusion: Interaction of the serum IL-2, IL-4 and IFN-γ also participated in the pathogenesis of acute nephritis in pediatric patients, monitoring the changes of their serum levels was helpful for the management of the diseases and provider important clinical value. (authors)

  2. Clinical significance of determination of changes of serum IGF-II, GM-CSF and TNF-α levels after treatment in children with acute nephritis

    International Nuclear Information System (INIS)

    Xu Xiaoyan; Zhou Hong; Xu Weiqin; Li Xinghua

    2008-01-01

    Objective: To explore the clinical significance of determination of changes of serum IGF-II, GM-CSF and TNF- α levels after treatment in children with acute nephritis. Methods: Serum IGF-II, GM-CSF and TNF-α levels (with RIA) were measured in 31 pediatric patients with acute nephritis and 35 controls. Results: Before treatment, the serum IGF-II, GM-CSF and TNF-α levels in the patients were significantly higher than those in controls (P< O.01). After treatment for 3 months, the serum IGF-II, GM-CSF and TNF-α levels, though markedly corrected, remained significantly higher than those in controls (P<0.05). Conclusion: Determination of changes of serum IGF-II, GM-CSF and TNF-α contents after treatment might be of prognostic importance in pediatric patients with acute nephritis. (authors)

  3. Clinical significance of determination of changes of serum TNF-α and plasma VEGF contents after treatment in pediatric patients with acute nephritis

    International Nuclear Information System (INIS)

    Ding Guomin

    2008-01-01

    Objective: To investigate the serum TNF-α and plasma VEGF levels after treatment in pediatric patients with acute nephritis. Methods: Serum TNF-α levels (with RIA) and plasma VEGF levels (with ELISA) were determined in 32 pediatric patients with acute nephritis both before and after treatment as well as in 35 controls. Results: Before treatment the serum TNF-α and plasma VEGF levels in the patients were significantly higher than those in the controls (P<0.01). After one month of treatment with combined traditional Chinese and western medicine, the levels though dropped markedly, still remained significantly higher than those in controls (P<0.05). Conclusion: Development of acute nephritis in pediatric patients was closely related to the serum TNF-α and plasma VEGF levels. (authors)

  4. Endogenous interleukin (IL)-17A promotes pristane-induced systemic autoimmunity and lupus nephritis induced by pristane.

    Science.gov (United States)

    Summers, S A; Odobasic, D; Khouri, M B; Steinmetz, O M; Yang, Y; Holdsworth, S R; Kitching, A R

    2014-06-01

    Interleukin (IL)-17A is increased both in serum and in kidney biopsies from patients with lupus nephritis, but direct evidence of pathogenicity is less well established. Administration of pristane to genetically intact mice results in the production of autoantibodies and proliferative glomerulonephritis, resembling human lupus nephritis. These studies sought to define the role of IL-17A in experimental lupus induced by pristane administration. Pristane was administered to wild-type (WT) and IL-17A(-/-) mice. Local and systemic immune responses were assessed after 6 days and 8 weeks, and autoimmunity, glomerular inflammation and renal injury were measured at 7 months. IL-17A production increased significantly 6 days after pristane injection, with innate immune cells, neutrophils (Ly6G(+)) and macrophages (F4/80(+)) being the predominant source of IL-17A. After 8 weeks, while systemic IL-17A was still readily detected in WT mice, the levels of proinflammatory cytokines, interferon (IFN)-γ and tumour necrosis factor (TNF) were diminished in the absence of endogenous IL-17A. Seven months after pristane treatment humoral autoimmunity was diminished in the absence of IL-17A, with decreased levels of immunoglobulin (Ig)G and anti-dsDNA antibodies. Renal inflammation and injury was less in the absence of IL-17A. Compared to WT mice, glomerular IgG, complement deposition, glomerular CD4(+) T cells and intrarenal expression of T helper type 1 (Th1)-associated proinflammatory mediators were decreased in IL-17A(-/-) mice. WT mice developed progressive proteinuria, but functional and histological renal injury was attenuated in the absence of IL-17A. Therefore, IL-17A is required for the full development of autoimmunity and lupus nephritis in experimental SLE, and early in the development of autoimmunity, innate immune cells produce IL-17A. © 2014 British Society for Immunology.

  5. Glutathione S Transferases Polymorphisms Are Independent Prognostic Factors in Lupus Nephritis Treated with Cyclophosphamide.

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    Alexandra Audemard-Verger

    Full Text Available To investigate association between genetic polymorphisms of GST, CYP and renal outcome or occurrence of adverse drug reactions (ADRs in lupus nephritis (LN treated with cyclophosphamide (CYC. CYC, as a pro-drug, requires bioactivation through multiple hepatic cytochrome P450s and glutathione S transferases (GST.We carried out a multicentric retrospective study including 70 patients with proliferative LN treated with CYC. Patients were genotyped for polymorphisms of the CYP2B6, CYP2C19, GSTP1, GSTM1 and GSTT1 genes. Complete remission (CR was defined as proteinuria ≤0.33g/day and serum creatinine ≤124 µmol/l. Partial remission (PR was defined as proteinuria ≤1.5g/day with a 50% decrease of the baseline proteinuria value and serum creatinine no greater than 25% above baseline.Most patients were women (84% and 77% were Caucasian. The mean age at LN diagnosis was 41 ± 10 years. The frequency of patients carrying the GST null genotype GSTT1-, GSTM1-, and the Ile→105Val GSTP1 genotype were respectively 38%, 60% and 44%. In multivariate analysis, the Ile→105Val GSTP1 genotype was an independent factor of poor renal outcome (achievement of CR or PR (OR = 5.01 95% CI [1.02-24.51] and the sole factor that influenced occurrence of ADRs was the GSTM1 null genotype (OR = 3.34 95% CI [1.064-10.58]. No association between polymorphisms of cytochrome P450s gene and efficacy or ADRs was observed.This study suggests that GST polymorphisms highly impact renal outcome and occurrence of ADRs related to CYC in LN patients.

  6. Inhibition of sphingosine kinase-2 in a murine model of lupus nephritis.

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    Ashley J Snider

    Full Text Available Sphingosine-1-phosphate (S1P, a potent bioactive lipid, is emerging as a central mediator in inflammation and immune responses. We have previously implicated S1P and its synthetic enzyme sphingosine kinase (SK in inflammatory and autoimmune disorders, including inflammatory bowel disease and rheumatoid arthritis. Generation of S1P requires phosphorylation of sphingosine by SK, of which there are two isoforms. Numerous studies have implicated SK1 in immune cell trafficking, inflammation and autoimmune disorders. In this study, we set out to determine the role of SK and S1P in lupus nephritis (LN. To this end, we examined S1P and dihydro-S1P (dh-S1P levels in serum and kidney tissues from a mouse model of LN. Interestingly dh-S1P was significantly elevated in serum and kidney tissue from LN mice, which is more readily phosphorylated by SK2. Therefore, we employed the use of the specific SK2 inhibitor, ABC294640 in our murine model of LN. Treatment with ABC294640 did not improve vascular or interstitial pathology associated with LN. However, mice treated with the SK2 inhibitor did demonstrate decreases in glomerular pathology and accumulation of B and T cells in the spleen these were not statistically different from lpr mice treated with vehicle. LN mice treated with ABC294640 did not have improved urine thromboxane levels or urine proteinuria measurements. Both S1P and dh-S1P levels in circulation were significantly reduced with ABC294640 treatment; however, dh-S1P was actually elevated in kidneys from LN mice treated with ABC294640. Together these data demonstrate a role for SKs in LN; however, they suggest that inhibition of SK1 or perhaps both SK isoforms would better prevent elevations in S1P and dh-S1P and potentially better protect against LN.

  7. Serious Infections among Adult Medicaid Beneficiaries with Systemic Lupus Erythematosus and Lupus Nephritis

    Science.gov (United States)

    Feldman, Candace H.; Hiraki, Linda T.; Winkelmayer, Wolfgang C.; Marty, Francisco M.; Franklin, Jessica M.; Kim, Seoyoung C.; Costenbader, Karen H.

    2015-01-01

    Objective While serious infections are significant causes of morbidity and mortality in systemic lupus erythematosus (SLE), the epidemiology in a nationwide cohort of SLE and lupus nephritis (LN) patients has not been examined. Methods Using the Medicaid Analytic eXtract (MAX) database, 2000-2006, we identified patients 18-64 years with SLE and a subset with LN. We ascertained hospitalized serious infections using validated algorithms, and 30-day mortality rates. We used Poisson regression to calculate infection incidence rates (IR), and multivariable Cox proportional hazards models to calculate hazard ratios (HR) for first infection, adjusted for sociodemographics, medication use, and a SLE-specific risk adjustment index. Results We identified 33,565 patients with SLE and 7,113 with LN. There were 9,078 serious infections in 5,078 SLE patients and 3,494 infections in 1,825 LN patients. The infection IR per 100 person-years was 10.8 in SLE and 23.9 in LN. In adjusted models, in SLE, we observed increased risks of infection among males compared to females (HR 1.33, 95% CI 1.20-1.47), in Blacks compared to Whites (HR 1.14, 95% CI 1.06-1.21), and glucocorticoid users (HR 1.51, 95% CI 1.43-1.61) and immunosuppressive users (HR 1.11, 95% CI 1.03-1.20) compared with non-users. Hydroxychloroquine users had a reduced risk of infection compared to non-users (HR 0.73, 95% CI 0.68-0.77). The 30-day mortality rate per 1,000 person-years among those hospitalized with infections was 21.4 in SLE and 38.7 in LN. Conclusion In this diverse, nationwide cohort of SLE patients, we observed a substantial burden of serious infections with many subsequent deaths. PMID:25772621

  8. Elevated Subclinical Double-Stranded DNA Antibodies and Future Proliferative Lupus Nephritis

    Science.gov (United States)

    Lee, Jessica J.; Prince, Lisa K.; Baker, Thomas P.; Papadopoulos, Patricia; Edison, Jess; Abbott, Kevin C.

    2013-01-01

    Summary Background and objectives Elevated anti–double-stranded DNA (dsDNA) antibody and C-reactive protein are associated with proliferative lupus nephritis (PLN). Progression of quantitative anti-dsDNA antibody in patients with PLN has not been compared with that in patients with systemic lupus erythematosus (SLE) without LN before diagnosis. The temporal relationship between anti-dsDNA antibody and C-reactive protein elevation has also not been evaluated. Design, setting, participants, & measurements This case-control Department of Defense Serum Repository (established in 1985) study compared longitudinal prediagnostic quantitative anti-dsDNA antibody and C-reactive protein levels in 23 patients with biopsy-proven PLN (Walter Reed Army Medical Center, 1993–2009) with levels in 21 controls with SLE but without LN matched for patient age, sex, race, and age of serum sample. The oldest (median, 2601 days; 25%, 1245 days, 75%, 3075 days), the second to last (368; 212, 635 days), and the last (180; 135, 477 days) serum sample before diagnosis were analyzed. Results More patients with PLN had an elevated anti-dsDNA antibody level than did the matched controls at any point (78% versus 5%; P4 years (33% versus 0%; P=0.04) before diagnosis. A rate of increase >1 IU/ml per year (70% versus 0%; P<0.001) was most specific for PLN. The anti-dsDNA antibody levels increased before C-reactive protein did in most patients with an antecedent elevation (92% versus 8%; P<0.001). Conclusions Elevated anti-dsDNA antibody usually precedes both clinical and subclinical evidence of proliferative LN, which suggests direct pathogenicity. Absolute anti-dsDNA antibody level and rate of increase could better establish risk of future PLN in patients with SLE. PMID:23833315

  9. Drug-induced acute interstitial nephritis: A clinicopathological study and comparative trial of steroid regimens

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    R Ramachandran

    2015-01-01

    Full Text Available Steroids are used in the management of drug-induced acute interstitial nephritis (AIN. The present study was undertaken to compare the efficacy of pulse methyl prednisolone with oral prednisolone in the treatment of drug-induced AIN. Patients with biopsy-proven AIN with a history of drug intake were randomized to oral prednisolone (Group 1 1 mg/kg for 3 weeks or a pulse methyl prednisolone (Group II 30 mg/kg for 3 days followed by oral prednisolone 1 mg/kg for 2 weeks, tapered over 3 weeks. Kidney biopsy scoring was done for interstitial edema, infiltration and tubular damage. The response was reported as complete remission (CR (improvement in estimated glomerular filtration rate [eGFR] to ≥60 ml/min/1.73 m 2 , partial remission (PR (improvement but eGFR <60 ml/min/1.73 m 2 or resistance (no CR/PR. A total of 29 patients, Group I: 16 and Group II: 13 were studied. Offending drugs included nonsteroidal anti-inflammatory drugs, herbal drugs, antibiotics, diuretic, rifampicin and omeprazole. There was no difference in the baseline parameters between the two groups. The biopsy score in Groups I and II was 5.9 ΁ 1.1 and 5.1 ΁ 1.2, respectively. At 3 months in Group I, eight patients each (50% achieved CR and PR. In Group II, 8 (61% achieved CR and 5 (39% PR. This was not significantly different. Percentage fall in serum creatinine at 1 week (56% was higher in CR as compared to (42% those with PR. ( P = 0.14. Patients with neutrophil infiltration had higher CR compared to patients with no neutrophil infiltration ( P = 0.01. Early steroid therapy, both oral and pulse steroid, is equally effective in achieving remission in drug-induced AIN.

  10. Profiling analysis of circulating microRNA in peripheral blood of patients with class IV lupus nephritis.

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    Elkin Navarro-Quiroz

    Full Text Available Renal involvement in Systemic Lupus Erythematous (SLE patients is one of the leading causes of morbidity and a significant contributor to mortality. It's estimated that nearly 50% of SLE individuals develop kidney disease in the first year of the diagnosis. Class IV lupus nephritis (LN-IV is the class of lupus nephritis most common in Colombian patients with SLE. Altered miRNAs expression levels have been reported in human autoimmune diseases including lupus. Variations in the expression pattern of peripheral blood circulating miRNAs specific for this class of lupus nephritis could be correlated with the pathophysiological status of this group of individuals. The aim of this study was to evaluate the relative abundance of circulating microRNAs in peripheral blood from Colombian patients with LN-IV. Circulating miRNAs in plasma of patients with diagnosis of LN-IV were compared with individuals without renal involvement (LNN group and healthy individuals (CTL group. Total RNA was extracted from 10 ml of venous blood and subsequently sequenced using Illumina. The sequences were processed and these were analyzed using miRBase and Ensembl databases. Differential gene expression analysis was carried out with edgeR and functional analysis were done with DIANA-miRPath. Analysis was carried out using as variables of selection fold change (≥2 o ≤-2 and false discovery rate (0.05. We identified 24 circulating microRNAs with differential abundance between LN-IV and CTL groups, fourteen of these microRNAs are described for the first time to lupus nephritis (hsa-miR-589-3p, hsa-miR-1260b, hsa-miR-4511, hsa-miR-485-5p, hsa-miR-584-5p, hsa-miR-543, hsa-miR-153-3p, hsa-miR-6087, hsa-miR-3942-5p, hsa-miR-7977, hsa-miR-323b-3p, hsa-miR-4732-3p and hsa-miR-6741-3p. These changes in the abundance of miRNAs could be interpreted as alterations in the miRNAs-mRNA regulatory network in the pathogenesis of LN, preceding the clinical onset of the disease. The findings

  11. IgA nephropathy and Henoch-Schönlein nephritis in adults : with special reference to factors affecting outcome

    OpenAIRE

    Rauta, Virpi

    2006-01-01

    IgA nephropathy (IgAN) is the most common primary glomerulonephritis. In one third of the patients the disease progresses, and they eventually need renal replacement therapy. IgAN is in most cases a slowly progressing disease, and the prediction of progression has been difficult, and the results of studies have been conflicting. Henoch-Schönlein nephritis (HSN) is rare in adults, and prediction of the outcome is even more difficult than in IgAN. This study was conducted to evaluate the c...

  12. Effects of Integrated Traditional Chinese and Western Medicine for the Treatment of Lupus Nephritis: A Meta-Analysis of Randomized Trials

    Directory of Open Access Journals (Sweden)

    Mingli Heng

    2016-01-01

    Full Text Available After a thorough search through the database as CNKI database, VIP database, Wanfang database, PubMed, and Cochrane Library, the clinical experimental articles have been selected out on the effects of Integrated Traditional Chinese and Western Medicine on the treatment of lupus nephritis. A meta-analysis was carried out in terms of clinical efficacy criteria and safety criteria by RevMan 5.3 software. Based on the results, we cautiously conclude that Integrated Traditional Chinese and Western Medicine used for lupus nephritis could improve the clinical efficacy while at same time lower the 24-hour urine protein, serum creatinine, and adverse drug reactions.

  13. Assessment of urinary TWEAK levels in Mexican patients with untreated lupus nephritis: An exploratory study

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    Fabiola Reyes-Martínez

    2018-03-01

    Full Text Available Objectives: Urinary levels of TWEAK (uTWEAK may be correlated with the degree of lupus nephritis (LN activity. Our objective was to determine the sensitivity and specificity of uTWEAK in Mexican patients with untreated active lupus nephritis. Methods: An exploratory study was performed; four groups of patients were analyzed as follows: 1 patients with systemic lupus erythematosus (SLE without renal activity (SLE-LN, 2 patients with SLE with renal activity (SLE + LN, 3 patients with other types of glomerulopathy (glomerulonephritis, GMN, 4 and healthy patients (controls. Results: In all, 44 patients, with an average age of 35.9 ± 11.5 years, were evaluated. uTWEAK levels were higher in patients with SLE + LN compared with patients in the other groups: SLE + LN 12.88 ± 8.33, SLE-LN 3.12 ± 2.31, GMN 4.36 ± 2.31 and controls 2.41 ± 1.94 pg/mg Cr (p = 0.007. A total of 72.7% of the cases had renal activity index scores above 12, and 90.9% of the cases had scores of chronicity below 6 points. Receiver Operating Characteristic (ROC curve analysis revealed that uTWEAK levels above 4.91 pg/mg Cr had a sensitivity of 81% and a specificity of 75% for the diagnosis of renal activity due to lupus, with an area under the curve of 0.876 (95% CI: 0.75–0.99. However, no significant correlation was observed between the levels of uTWEAK and the histological findings specific to the activity and chronicity associated with SLE. Conclusions: Our study revealed that uTWEAK can adequately distinguish renal activity due to lupus, but cannot predict the degree of histological activity in Mexican patients with active lupus nephropathy. Resumen: Objetivos: Los niveles urinarios de TWEAK (uTWEAK pueden correlacionarse con el grado de actividad de nefritis lúpica (NL. Nuestro objetivo fue determinar la sensibilidad y especificidad de los uTWEAK en pacientes mexicanos con NL activa sin

  14. Acute Kidney Injury, Recurrent Seizures, and Thrombocytopenia in a Young Patient with Lupus Nephritis: A Diagnostic Dilemma

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    Hector Alvarado Verduzco

    2016-01-01

    Full Text Available Introduction. Posterior reversible encephalopathy syndrome (PRES is a constellation of clinical and radiologic findings. Fluctuations in blood pressure, seizures, and reversible brain MRI findings mainly in posterior cerebral white matter are the main manifestations. PRES has been associated with multiple conditions such as autoimmune disorders, pregnancy, organ transplant, and thrombotic microangiopathy (TMA. Case Presentation. A 22-year-old woman with history of Systemic Lupus Erythematous complicated with chronic kidney disease secondary to lupus nephritis class IV presented with recurrent seizures and uncontrolled hypertension. She was found to have acute kidney injury and thrombocytopenia. Repeat kidney biopsy showed diffuse endocapillary and extracapillary proliferative and membranous lupus nephritis (ISN-RPS class IV-G+V and endothelial swelling secondary to severe hypertension but no evidence of TMA. Brain MRI showed reversible left frontal and parietal lesions that resolved after controlling the blood pressure, making PRES the diagnosis. Conclusion. PRES is an important entity that must be recognized and treated early due to the potential reversibility in the early stages. Physicians must have high suspicion for these unusual presentations. We present a case where performing kidney biopsy clinched the diagnosis in our patient with multiple confounding factors.

  15. Nephritogenic antigen determinants in epidermal and renal basement membranes of kindreds with Alport-type familial nephritis.

    Science.gov (United States)

    Kashtan, C; Fish, A J; Kleppel, M; Yoshioka, K; Michael, A F

    1986-10-01

    We probed epidermal basement membranes (EBM) of acid-urea denatured skin from members of kindreds with Alport-type familial nephritis (FN) for the presence of antigens reactive with Goodpasture sera (GPS) and serum (FNS) from an Alport patient who developed anti-glomerular basement membrane (GBM) nephritis in a renal allograft. By immunoblotting, GPS reacted primarily with the 28,000 molecular weight (mol wt) monomer but also the 24,000 mol wt and 26,000 mol wt monomers of the noncollagenous globular domain (NC1) of type IV collagen from normal human GBM, while FNS identified only the 26,000-mol wt monomer. FNS reacted with EBM of 12 controls and nine unaffected male kindred members but not EBM of eight affected males. Five affected females exhibited interrupted reactivity of FNS with EBM. GPS showed variable reactivity with EBM and was not discriminating with respect to Alport-type FN. FNS did not stain renal basement members of five affected males. However, the EBM, tubular basement membrane, and Bowman's capsules of affected males contained antigens reactive with GPS. These immunochemical studies suggest that the FNS antigen is distinct from Goodpasture antigen(s). The expression of FNS antigen located on the NC1 domain of type IV collagen is altered in basement membranes of patients with Alport-type FN, and the distribution of this antigenic anomaly within kindreds suggests X-linked dominant transmission of a defective gene.

  16. Successful Prednisolone Therapy in Elderly Patients with Severe Forms of Henoch–Schönlein Purpura Nephritis

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    Saiko Kato-Okada

    2015-01-01

    Full Text Available Introduction Recently, Henoch–Schönlein purpura (HSP has been observed in elderly people, although it was believed to be uncommon in these subjects. The increased risks of developing end-stage renal disease (ESRD in adults in comparison with children were highlighted by different studies; however, limited data are available on the treatment of HSP nephritis in adults. Methods Between 2002 and 2008, five elderly Japanese patients (>65 years old (mean age, 68 years, ranging from 65 to 72 with severe forms of HSP nephritis were entered into a prospective study to evaluate prednisolone therapy on the outcome of nephropathy in terms of clinical symptoms and histopathological changes. The patients were considered at risk of developing chronic renal failure when they presented with a nephrotic syndrome and crescentic glomeruli. Results At the last follow-up, 4–10 years after initiation of the therapy, four patients had clinically recovered and one died of lung cancer. No patients developed ESRD. The clinical outcome seemed to be correlated with glomerular activity (massive proteinuria and crescent formation. In spite of a relatively large dose of prednisolone, a few adverse effects, such as insomnia and skin lesions, were observed. Discussion Our preliminary small study suggests that renal outcome as well as survival of elderly patients with severe forms of HSP might be altered by aggressive prednisolone therapy.

  17. ESRD from lupus nephritis in the United States, 1995-2010.

    Science.gov (United States)

    Sexton, Donal J; Reule, Scott; Solid, Craig; Chen, Shu-Cheng; Collins, Allan J; Foley, Robert N

    2015-02-06

    While ESRD from lupus nephritis (ESLN) increased in the United States after the mid-1990s and racial disparities were apparent, current trends are unknown. Retrospective US Renal Data System data (n=1,557,117) were used to calculate standardized incidence ratios (standardized to 1995-1996) and outcomes of ESLN (n=16,649). For events occurring after initiation of RRT, follow-up ended on June 30, 2011. Overall ESLN rates (95% confidence intervals [95% CIs]) in 1995-1996 were 3.1 (2.9 to 3.2) cases per million per year. Rates were higher for subgroups characterized by African-American race (11.1 [95% CI, 10.3 to 11.9]); other race (4.9 [95% CI, 4.0 to 5.8]); female sex (4.9 [95% CI, 4.6 to 5.2]); and ages 20-29 years (4.9 [95% CI, 4.4 to 5.4]), 30-44 years (4.6 [95% CI, 4.2 to 5.0]), and 45-64 years (4.0 [95% CI, 3.7 to 4.4]). Standardized incidence ratios for the overall population in subsequent biennia were 1.19 (1.14 to 1.24) in 1997-1998, 1.17 (1.12 to 1.22) in 1999-2000, 1.17 (1.12 to 1.22) in 2001-2002, 1.21 (1.16 to 1.26) in 2003-2004, 1.18 (1.13 to 1.23) in 2005-2006, 1.16 (1.11 to 1.21) in 2007-2008, and 1.05 (1.01 to 1.09) in 2009-2010, respectively. During a median (interquartile range) follow-up of 4.4 (6.3) years, 42.6% of patients with ESLN died, 45.3% were listed for renal transplant, and 28.7% underwent transplantation. Patients with ESLN were more likely than matched controls to be listed for and to undergo transplantation, and mortality rates were similar. Among patients with ESLN, African Americans were less likely to undergo transplantation (adjusted hazard ratio, 0.54 [0.51 to 0.58]) and more likely to die prematurely (adjusted hazard ratio, 1.23 [1.17 to 1.30]). While ESLN appears to have stopped increasing in the last decade, racial disparities in outcomes persist. Copyright © 2015 by the American Society of Nephrology.

  18. Prevalence, incidence, and demographics of systemic lupus erythematosus and lupus nephritis from 2000 to 2004 among children in the US Medicaid beneficiary population.

    Science.gov (United States)

    Hiraki, Linda T; Feldman, Candace H; Liu, Jun; Alarcón, Graciela S; Fischer, Michael A; Winkelmayer, Wolfgang C; Costenbader, Karen H

    2012-08-01

    To investigate the nationwide prevalence, incidence, and sociodemographics of systemic lupus erythematosus (SLE) and lupus nephritis among children in the US Medicaid beneficiary population. Children ages 3 years to Classification of Diseases, Ninth Revision [ICD-9] code of 710.0 for SLE, each >30 days apart) were identified from the US Medicaid Analytic eXtract database from 2000 to 2004. This database contains all inpatient and outpatient Medicaid claims for 47 US states and the District of Columbia. Lupus nephritis was identified from ≥2 ICD-9 billing codes for glomerulonephritis, proteinuria, or renal failure, each recorded >30 days apart. The prevalence and incidence of SLE and lupus nephritis were calculated among Medicaid-enrolled children overall and within sociodemographic groups. Of the 30,420,597 Medicaid-enrolled children during these years, 2,959 were identified as having SLE. The prevalence of SLE was 9.73 (95% confidence interval [95% CI] 9.38-10.08) per 100,000 Medicaid-enrolled children. Among the children with SLE, 84% were female, 40% were African American, 25% were Hispanic, 21% were White, and 42% resided in the South region of the US. Moreover, of the children with SLE, 1,106 (37%) had lupus nephritis, representing a prevalence of 3.64 (95% CI 3.43-3.86) per 100,000 children. The average annual incidence of SLE was 2.22 cases (95% CI 2.05-2.40) and that of lupus nephritis was 0.72 cases (95% CI 0.63-0.83) per 100,000 Medicaid enrollees per year. The prevalence and incidence rates of SLE and lupus nephritis increased with age, were higher in girls than in boys, and were higher in all non-White racial/ethnic groups. In the current study, the prevalence and incidence rates of SLE among Medicaid-enrolled children in the US are high compared to studies in other populations. In addition, these data represent the first population-based estimates of the prevalence and incidence of lupus nephritis in the US to date. Copyright © 2012 by the American

  19. The safety of isotretinoin in patients with lupus nephritis: a comprehensive review.

    Science.gov (United States)

    Miziołek, Bartosz; Bergler-Czop, Beata; Stańkowska, Anna; Brzezińska-Wcisło, Ligia

    2017-03-01

    Oral isotretinoin (13-cis-retinoinc acid) is a derivative of vitamin A and belongs to the first generation of retinoids, which act as synthetic isomers of retinoic acid (RA). It is a very effective agent in a treatment of acne vulgaris; however, multiple side effects related to therapy with retinoids preclude the use of isotretinoin in less severe acne vulgaris. A significant limitation for the administration of isotretinoin appears in case of concomitant kidney disease with a special attention regarding the safety of the agent in patients with lupus nephritis (LN). The aim of this review is an assessment of the safety of isotretinoin for the treatment of acne vulgaris in patients with LN. We searched both MEDLINE and SCOPUS databases, as well as several dermatological textbooks, to present all limitations and benefits of therapy with isotretinoin or its isomer (ATRA) for patients with kidney diseases. Several mouse models of SLE revealed a significant modulatory influence of retinoids on autoimmune injury of the glomerular unit. Retinoids were demonstrated to affect mononuclear cell infiltrations of renal tissue allowing for a reduction in the overall glomerular damage. Presumptively, they can affect a synthesis of autoantibodies significantly limiting their deposition in the glomerular unit. Moreover, retinoids were also shown to affect the synthesis of different cytokines specific both for lymphocytes Th1 (IL-2, IL-12, INFγ) ant Th2 (IL-4, IL-10). The influence of retinoids on the course of LN seems to be more multidimensional than only restricted to immune aspects and these synthetic RA isomers manifest also antiproteinuric activity in comparable extent to steroidal agents. The agents were demonstrated to counteract a loss of podocytes after the injury of the glomerular unit. They can promote a differentiation of renal progenitor cells (RPCs) within the Bowman capsule into mature podocytes leading to regeneration of podocyte number. Additionally, retinoids can

  20. Role of MYH9 and APOL1 in African and non-African populations with lupus nephritis

    DEFF Research Database (Denmark)

    Lin, C P; Adrianto, I; Lessard, C J

    2012-01-01

    ) and African-Americans (AAs) (N = 407). Multiple peaks of association exceeding a Bonferroni corrected P-value of P ...Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by autoantibody production and organ damage. Lupus nephritis (LN) is one of the most severe manifestations of SLE. Multiple studies reported associations between renal diseases and variants in the non-muscle myosin...... heavy chain 9 (MYH9) and the neighboring apolipoprotein L 1 (APOL1) genes. We evaluated 167 variants spanning MYH9 for association with LN in a multiethnic sample. The two previously identified risk variants in APOL1 were also tested for association with LN in European-Americans (EAs) (N = 579...

  1. Ultraviolet light-denatured DNA/anti-ultraviolet light-denatured DNA immune-complex nephritis in rabbits

    International Nuclear Information System (INIS)

    Sweny, P.

    1980-01-01

    Two groups of preimmunized rabbits were studied during a 3-month course of daily intravenous injections of uv DNA in amounts sufficient to neuralize circulating antibody. One group was given high-molecular-weight uv DNA, and the other group, US uv DNA. Rabbits receiving US uv DNA formed potentially more damaging immune complexes, since this group of animals developed greater rises in blood urea and greater falls in C3. Both groups of animals developed evidence of immune complex-mediated glomerular nephritis as evidenced by heavy granular deposits of IgG and C3 in the glomeruli. The results suggest that immune complexes formed with US uv DNA may be more nephrotoxic

  2. Chronic liver disease and subchronic nephritis in a male warty chameleon (Furcifer verrucosus with transient hyperglycaemia – case report

    Directory of Open Access Journals (Sweden)

    Zdeněk Knotek

    2011-01-01

    Full Text Available A two-year old male warty chameleon (Furcifer verrucosus weighing 160 g was presented for veterinary examination following 4 weeks of decreased ability to catch insects with the tongue and difficulty in swallowing the prey. Non-invasive endoscopy did not reveal any macroscopic changes of the oral cavity mucosa or the cranial part of the esophagus. Dorsoventral and laterolateral plain and contrast radiographs revealed enlargement of the medial part of the liver without any visible abnormalities in the regions of the esophagus, stomach or small intestine. Abnormalities in the plasma chemistry profile included transient hyperglycaemia (52.68–57.18 mmol/l and hyperuricaemia (452.70–622.20 μmol/l. The chameleon was examined at 7, 20 and 22 weeks after initial examination. Its body weight decreased to 120 g. A blood profile revealed normoglycaemia (16.37–10.22 mmol/l and hyperphosphataemia (2.92–3.06 mmol/l at the last three examinations. The chameleon died suddenly 33 days after the final examination. Necropsy revealed the presence of a large liver cyst, filled with fluid. The liver had lost all of its normal structure. The kidneys showed a large area with fibrosis and multiple uric acid tophi. The post mortem findings were defined as liver with fatty degeneration and moderate fibrotic changes with large cyst, subchronic nephritis with uric acid tophi, and mineralization in the myocardium. This paper describes the first documented case of transient hyperglycaemia in a warty chameleon (Furcifer verrucosus associated with chronic liver disease and subchronic nephritis.

  3. Inducible nitric oxide synthase gene polymorphisms are associated with a risk of nephritis in Henoch-Schönlein purpura children.

    Science.gov (United States)

    Jiang, Jue; Duan, Wuqiong; Shang, Xu; Wang, Hua; Gao, Ya; Tian, Peijun; Zhou, Qi

    2017-08-01

    Henoch-Schönlein purpura (HSP) is the most common form of systemic small-vessel vasculitis in children, and HSP nephritis (HSPN) is a major complication of HSP and is the primary cause of morbidity and mortality. Previous studies have suggested that inducible nitric oxide synthase (iNOS) may play an important role in the pathogenesis of HSP. In this study, we performed a detailed analysis to investigate the potential association between iNOS polymorphisms and the risk of HSP and the tendency for children with HSP to develop HSPN in a Chinese Han population. A promoter pentanucleotide repeat (CCTTT)n and 10 functional single-nucleotide polymorphisms (SNPs) from 532 healthy controls and 513 children with HSP were genotyped using the MassARRAY system and GeneScan. The results suggested that the allelic and genotypic frequencies of the rs3729508 polymorphism were nominally associated with susceptibility to HSP. In addition, there was a significant difference in the allelic distribution of the (CCTTT)12 repeats and rs2297518 between the HSP children with and without nephritis; the HSP children with nephritis exhibited a significantly higher frequency of the (CCTTT)12 repeats and A allele of rs2297518 than the HSP children without nephritis (P FDR  = 0.033, OR = 1.624, 95% CI = 1.177-2.241 and P FDR  = 0.030, OR = 1.660, 95% CI = 1.187-2.321, respectively). Our results support that iNOS polymorphisms are associated with the risk of HSP and may strongly contribute to the genetic basis of individual differences in the progression to nephritis among children with HSP in the Chinese Han population. What is Known: • The etiology of HSP is unknown, but the genetic factors may play an important role in the pathogenesis of HSP. • iNOS could contribute to the development and clinical manifestations of HSP, and this has not been studied extensively so far. What is New: • Our results support that iNOS polymorphisms not only are associated with HSP risk but also

  4. Membrane targeting and secretion of mutant uromodulin in familial juvenile hyperuricemic nephropathy

    NARCIS (Netherlands)

    Jennings, Paul; Aydin, Sonia; Kotanko, Peter; Lechner, Judith; Lhotta, Karl; Williams, Sian; Thakker, Rajesh V; Pfaller, Walter

    Familial juvenile hyperuricemic nephropathy (FJHN) is an autosomal dominant genetic disorder that is characterized by hyperuricemia, gout, and tubulointerstitial nephritis. FJHN is caused by mutations in the UMOD gene, which encodes for uromodulin, the most abundant urinary protein. Herein is

  5. Henoch-Schönlein purpura nephritis occurring postpartum in a patient with anti-PL-7 anti-synthetase syndrome.

    Science.gov (United States)

    Nagai, Kojiro; Kishi, Jun; Morizumi, Shun; Minakuchi, Jun; Bando, Yoshimi; Nishioka, Yasuhiko; Doi, Toshio

    2017-09-01

    A 37-year-old pregnant woman developed purpura which was subsequently diagnosed as Henoch-Schönlein purpura (HSP). After childbirth, the patient developed proteinuria and hematuria. Further examination revealed that the HSP nephritis (HSPN) was associated with anti-threonyl-tRNA synthetase anti-synthetase syndrome. The onset of HSPN during pregnancy or after childbirth is rare. Moreover, to our knowledge, this is the first case to describe renal involvement in anti-synthetase syndrome.

  6. Circulating chromatin-anti-chromatin antibody complexes bind with high affinity to dermo-epidermal structures in murine and human lupus nephritis

    DEFF Research Database (Denmark)

    Fismen, S; Hedberg, A; Fenton, K A

    2009-01-01

    Murine and human lupus nephritis are characterized by glomerular deposits of electron-dense structures (EDS). Dominant components of EDS are chromatin fragments and IgG antibodies. Whether glomerular EDS predispose for similar deposits in skin is unknown. We analysed (i) whether dermo-epidermal i......Murine and human lupus nephritis are characterized by glomerular deposits of electron-dense structures (EDS). Dominant components of EDS are chromatin fragments and IgG antibodies. Whether glomerular EDS predispose for similar deposits in skin is unknown. We analysed (i) whether dermo......-epidermal immune complex deposits have similar molecular composition as glomerular deposits, (ii) whether chromatin fragments bind dermo-epidermal structures, and (iii) whether deposits in nephritic glomeruli predispose for accumulation of similar deposits in skin. Paired skin and kidney biopsies from nephritic...... (NZBxNZW)F1 and MRL-lpr/lpr mice and from five patients with lupus nephritis were analysed by immunofluorescence, immune electron microscopy (IEM) and co-localization TUNEL IEM. Affinity of chromatin fragments for membrane structures was determined by surface plasmon resonance. Results demonstrated (i...

  7. Preeclampsia in pregnancies complicated by systemic lupus erythematosus (SLE) nephritis: prophylactic treatment with multidisciplinary approach are important keys to prevent adverse obstetric outcomes.

    Science.gov (United States)

    Mecacci, Federico; Simeone, Serena; Cirami, Calogero Lino; Cozzolino, Mauro; Serena, Caterina; Rambaldi, Marianna Pina; Gallo, Pamela; Emmi, Lorenzo; Cammelli, Daniele; Mello, Giorgio; Matucci Cerinic, Marco

    2017-11-27

    Systemic lupus erythematosus (SLE) commonly affects women of childbearing age. Hypertension, antiphospholipid syndrome, and lupus nephritis are risk factors for adverse maternal/fetal outcome. The aim of this retrospective cohort study is to compare pregnancy outcomes in patients with and without SLE nephritis, using a multidisciplinary approach and a broad prophylaxis protocol. Data were collected from 86 pregnancies complicated by SLE. Twenty-seven women with nephropathy before pregnancy stated as the study group and 59 formed the control group. Each group received a prophylactic treatment based on their clinical characteristics. Results were expressed as mean ± SD, percentage and χ 2 -test (significant values when p 1.2 mg/dL, which was related to a risk 1.25 times higher than the risk observed in patients with serum creatinine approach in a tertiary care center and a broad prophylactic treatment protocol to patients affected by SLE and complicated by nephritis may definitively foster a successful pregnancy.

  8. Association of anti C1q and ds-DNA levels with the pathogenesis of Lupus Nephritis among SLE patients

    Directory of Open Access Journals (Sweden)

    Zara Sohail

    2018-02-01

    Full Text Available Background: Lupus nephritis (LN is the most common and serious complication associated with SLE and it results in significant morbidity and mortality. It is known by several studies that patients of LN have higher levels of anti-dsDNA and anti-C1q compared with SLE patients without renal involvement. The current study was designed to determine and compare the level of anti-dsDNA and anti-C1q in patients of SLE with and without lupus nephritis in the Pakistani population. This current study was also aimed at providing proof that anti-C1q levels are more prominent in LN/non-LN SLE as compared to anti-dsDNA. This project may help in the determination of results in Pakistan and contribute to the further confirmation of the sensitivity of anti-C1q. Method: The patient samples were collected from Sheikh Zayed hospital, Lahore. These patients were clinically diagnosed by the Rheumatologists as SLE and LN positive on the basis of ACR and SLEDAI scoring criteria. This study was performed and samples were analyzed in the Department of Medical and Laboratory Sciences, Imperial College of Business Study, Lahore on the patient’s serum by ELISA technique. Result: About 38% (12 patients with LN were positive for anti-dsDNA and 31% (9 SLE patients without LN were positive whereas about 38.7% (12 were anti-dsDNA negative in LN cases and 58.6% (17 in SLE without LN. In case of anti-C1q 100% (31 of these LN patients were positive and 93.1% (27 patients SLE without LN showed positive anti C1q results. Only 6.9% (2 patients showed negative results for anti-C1q in LN negative patients Conclusion: The higher levels of anti-C1q suggest that it may be a better diagnostic marker for LN than that of anti-dsDNA and that it can be helpful in the prognosis of SLE patients.

  9. Do classic blood biomarkers of JSLE identify active lupus nephritis? Evidence from the UK JSLE Cohort Study.

    Science.gov (United States)

    Smith, E M D; Jorgensen, A L; Beresford, M W

    2017-10-01

    Background Lupus nephritis (LN) affects up to 80% of juvenile-onset systemic lupus erythematosus (JSLE) patients. The value of commonly available biomarkers, such as anti-dsDNA antibodies, complement (C3/C4), ESR and full blood count parameters in the identification of active LN remains uncertain. Methods Participants from the UK JSLE Cohort Study, aged modeling, with stepAIC function applied to select a final model. Receiver-operating curve analysis was used to assess diagnostic accuracy. Results A total of 370 patients were recruited; 191 (52%) had active LN and 179 (48%) had inactive LN. Binary logistic regression modeling demonstrated a combination of ESR, C3, white cell count, neutrophils, lymphocytes and IgG to be best for the identification of active LN (area under the curve 0.724). Conclusions At best, combining common classic blood biomarkers of lupus activity using multivariate analysis provides a 'fair' ability to identify active LN. Urine biomarkers were not included in these analyses. These results add to the concern that classic blood biomarkers are limited in monitoring discrete JSLE manifestations such as LN.

  10. Outcome of lupus nephritis in childhood onset SLE in North and Central India: single-centre experience over 25 years.

    Science.gov (United States)

    Srivastava, P; Abujam, B; Misra, R; Lawrence, A; Agarwal, V; Aggarwal, A

    2016-04-01

    Childhood SLE (cSLE) has a higher prevalence of lupus nephritis (LN), and there are ethnic variations in response to treatment as well as outcome of LN. There are limited data on long-term outcome of LN in cSLE from the Indian subcontinent. Retrospective analysis of case records of patients with cSLE (satisfying revised American College of Rheumatology (ACR) 1997 criteria for diagnosis) and age of onset Collaborating Clinics (SLICC)/ACR damage score was 0.79 ± 1.13. Actuarial ESRD-free survival at five, 10 and 15 years was 91.1%, 79% and 76.2%, and five-, 10- and 15-year renal survival was 93.8%, 87.1% and 84%, respectively. Although multiple factors individually predicted poor outcome (death/ESRD), only raised serum creatinine at onset (R square = 0.65, p ≤ 0.0001) and damage accrual (R square = 0.62, p ≤ 0.0001) remained significant on multivariate analysis. Eleven (8.2%) children died during the follow-up period, and infections were the leading cause of mortality. Long-term outcome of LN in cSLE in our cohort was better than previous reports from India. However, a high rate of major infection still remains the leading cause of mortality. © The Author(s) 2015.

  11. The Involvement of MicroRNAs in Modulation of Innate and Adaptive Immunity in Systemic Lupus Erythematosus and Lupus Nephritis

    Science.gov (United States)

    Köhler, Paulina; von Rauchhaupt, Ekaterina

    2018-01-01

    Noncoding RNAs (ncRNAs), including microRNAs (miRNAs), represent a family of RNA molecules that do not translate into protein. Nevertheless, they have the ability to regulate gene expression and play an essential role in immune cell differentiation and function. MicroRNAs were found to be differentially expressed in various tissues, and changes in their expression have been associated with several pathological processes. Yet, their roles in systemic lupus erythematosus (SLE) and lupus nephritis (LN) remain to be elucidated. Both SLE and LN are characterized by a complex dysfunction of the innate and adaptive immunity. Recently, significant findings have been made in understanding SLE through the use of genetic variant identification and expression pattern analysis and mouse models, as well as epigenetic analyses. Abnormalities in immune cell responses, cytokine and chemokine production, cell activation, and apoptosis have been linked to a unique expression pattern of a number of miRNAs that have been implicated in the immune pathogenesis of this autoimmune disease. The recent evidence that significantly increased the understanding of the pathogenesis of SLE drives a renewed interest in efficient therapy targets. This review aims at providing an overview of the current state of research on the expression and role of miRNAs in the immune pathogenesis of SLE and LN. PMID:29854836

  12. Warfarin-induced toxic epidermal necrolysis in combination therapy of Henoch-Schönlein purpura nephritis: a case report.

    Science.gov (United States)

    Kasahara, Katsuaki; Gotoh, Yoshimitsu; Kuroyanagi, Yoshiyuki; Nagano, China

    2017-07-14

    Toxic epidermal necrolysis (TEN) is a rare life-threatening condition almost exclusively attributed to drugs. The main etiologic factors for TEN are sulphonamides, anticonvulsants, and antibiotics; however, there are no published reports of warfarin causing TEN. We present the case of a 3-year-old patient who developed TEN while receiving treatment for Henoch-Schönlein purpura nephritis (HSPN). With multiple-drug therapy comprising prednisolone, mizoribine, dipyridamole, and warfarin, it is difficult to detect which drug is the causative agent. While in most cases, diagnosis of the causative drug is based on clinical history without a lymphocyte transformation test (LTT), we performed the test three times and identified the causative drug as warfarin at the late phase. We continued HSPN treatment without warfarin, and results showed good renal function without life-threatening complications. To our knowledge, this is the first report about TEN caused by warfarin. Repeated LTTs could be useful for identifying TEN-causative drugs even in the late phase.

  13. The Involvement of MicroRNAs in Modulation of Innate and Adaptive Immunity in Systemic Lupus Erythematosus and Lupus Nephritis.

    Science.gov (United States)

    Honarpisheh, Mohsen; Köhler, Paulina; von Rauchhaupt, Ekaterina; Lech, Maciej

    2018-01-01

    Noncoding RNAs (ncRNAs), including microRNAs (miRNAs), represent a family of RNA molecules that do not translate into protein. Nevertheless, they have the ability to regulate gene expression and play an essential role in immune cell differentiation and function. MicroRNAs were found to be differentially expressed in various tissues, and changes in their expression have been associated with several pathological processes. Yet, their roles in systemic lupus erythematosus (SLE) and lupus nephritis (LN) remain to be elucidated. Both SLE and LN are characterized by a complex dysfunction of the innate and adaptive immunity. Recently, significant findings have been made in understanding SLE through the use of genetic variant identification and expression pattern analysis and mouse models, as well as epigenetic analyses. Abnormalities in immune cell responses, cytokine and chemokine production, cell activation, and apoptosis have been linked to a unique expression pattern of a number of miRNAs that have been implicated in the immune pathogenesis of this autoimmune disease. The recent evidence that significantly increased the understanding of the pathogenesis of SLE drives a renewed interest in efficient therapy targets. This review aims at providing an overview of the current state of research on the expression and role of miRNAs in the immune pathogenesis of SLE and LN.

  14. Renal lesions associated with autoimmune pancreatitis: CT findings

    International Nuclear Information System (INIS)

    Triantopoulou, Charikleia; Maniatis, Petros; Siafas, Ioannis; Papailiou, John; Malachias, George; Anastopoulos, John

    2010-01-01

    Background: Autoimmune pancreatitis (AIP) is a chronic inflammatory condition characterized by IgG4-positive plasma cells. Recent evidence suggests that it is a systemic disease affecting various organs. Tubulointerstitial nephritis has been reported in association with AIP. Purpose: To investigate the incidence and types of renal involvement in patients with AIP. Material and Methods: Eighteen patients with no history of renal disease and a diagnosis of AIP (on the basis of histopathologic findings or a combination of characteristic imaging features, increased serum IgG4 levels, and response to steroid treatment) were included. All patients underwent computed tomography (CT) imaging and follow-up ranged from 6 months to 2 years. CT images were reviewed for the presence of renal lesions. Results: Seven patients had renal involvement (38.8%). None of the lesions was visible on non-contrast-enhanced CT scan. Parenchymal lesions appeared as multiple nodules showing decreased enhancement (four cases). Pyelonephritis, lymphoma, and metastases were considered in the differential diagnosis. An ill-defined low-attenuation mass-like lesion was found in one patient, while diffuse thickening of the renal pelvis wall was evident in the last two cases. Renal lesions regressed in all patients after steroid treatment, the larger one leaving a fibrous cortical scar. Conclusion: Different types of renal lesions in patients with AIP are relatively common, appearing as multiple nodules with decreased enhancement. These findings support the proposed concept of an IgG4-related systemic disease. Autoimmune disease should be suspected in cases of renal involvement in association with pancreatic focal or diffuse enlargement.

  15. Renal lesions associated with autoimmune pancreatitis: CT findings

    Energy Technology Data Exchange (ETDEWEB)

    Triantopoulou, Charikleia; Maniatis, Petros; Siafas, Ioannis; Papailiou, John (CT and Radiology Dept., ' Konstantopouleion' General Hospital, Athens (Greece)), e-mail: ctriantopoulou@gmail.com; Malachias, George; Anastopoulos, John (Radiology Dept., ' Sismanogleio' General Hospital, Athens (Greece))

    2010-07-15

    Background: Autoimmune pancreatitis (AIP) is a chronic inflammatory condition characterized by IgG4-positive plasma cells. Recent evidence suggests that it is a systemic disease affecting various organs. Tubulointerstitial nephritis has been reported in association with AIP. Purpose: To investigate the incidence and types of renal involvement in patients with AIP. Material and Methods: Eighteen patients with no history of renal disease and a diagnosis of AIP (on the basis of histopathologic findings or a combination of characteristic imaging features, increased serum IgG4 levels, and response to steroid treatment) were included. All patients underwent computed tomography (CT) imaging and follow-up ranged from 6 months to 2 years. CT images were reviewed for the presence of renal lesions. Results: Seven patients had renal involvement (38.8%). None of the lesions was visible on non-contrast-enhanced CT scan. Parenchymal lesions appeared as multiple nodules showing decreased enhancement (four cases). Pyelonephritis, lymphoma, and metastases were considered in the differential diagnosis. An ill-defined low-attenuation mass-like lesion was found in one patient, while diffuse thickening of the renal pelvis wall was evident in the last two cases. Renal lesions regressed in all patients after steroid treatment, the larger one leaving a fibrous cortical scar. Conclusion: Different types of renal lesions in patients with AIP are relatively common, appearing as multiple nodules with decreased enhancement. These findings support the proposed concept of an IgG4-related systemic disease. Autoimmune disease should be suspected in cases of renal involvement in association with pancreatic focal or diffuse enlargement.

  16. Blood oxygen level dependent magnetic resonance imaging for detecting pathological patterns in lupus nephritis patients: a preliminary study using a decision tree model.

    Science.gov (United States)

    Shi, Huilan; Jia, Junya; Li, Dong; Wei, Li; Shang, Wenya; Zheng, Zhenfeng

    2018-02-09

    Precise renal histopathological diagnosis will guide therapy strategy in patients with lupus nephritis. Blood oxygen level dependent (BOLD) magnetic resonance imaging (MRI) has been applicable noninvasive technique in renal disease. This current study was performed to explore whether BOLD MRI could contribute to diagnose renal pathological pattern. Adult patients with lupus nephritis renal pathological diagnosis were recruited for this study. Renal biopsy tissues were assessed based on the lupus nephritis ISN/RPS 2003 classification. The Blood oxygen level dependent magnetic resonance imaging (BOLD-MRI) was used to obtain functional magnetic resonance parameter, R2* values. Several functions of R2* values were calculated and used to construct algorithmic models for renal pathological patterns. In addition, the algorithmic models were compared as to their diagnostic capability. Both Histopathology and BOLD MRI were used to examine a total of twelve patients. Renal pathological patterns included five classes III (including 3 as class III + V) and seven classes IV (including 4 as class IV + V). Three algorithmic models, including decision tree, line discriminant, and logistic regression, were constructed to distinguish the renal pathological pattern of class III and class IV. The sensitivity of the decision tree model was better than that of the line discriminant model (71.87% vs 59.48%, P decision tree model was equivalent to that of the line discriminant model (63.87% vs 63.73%, P = 0.939) and higher than that of the logistic regression model (63.87% vs 38.0%, P decision tree model was greater than that of the line discriminant model (0.765 vs 0.629, P Decision tree models constructed using functions of R2* values may facilitate the prediction of renal pathological patterns.

  17. Urinary neutrophil gelatinase-associated lipocalin for diagnosis and estimating activity in lupus nephritis: a meta-analysis.

    Science.gov (United States)

    Fang, Y G; Chen, N N; Cheng, Y B; Sun, S J; Li, H X; Sun, F; Xiang, Y

    2015-12-01

    Urinary neutrophil gelatinase-associated lipocalin (uNGAL) is relatively specific in lupus nephritis (LN) patients. However, its diagnostic value has not been evaluated. The aim of this review was to determine the value of uNGAL for diagnosis and estimating activity in LN. A comprehensive search was performed on PubMed, EMBASE, Web of Knowledge, Cochrane electronic databases through December 2014. Meta-analysis of sensitivity and specificity was performed with a random-effects model. Additionally, summary receiver operating characteristic (SROC) curves and area under the curve (AUC) values were calculated. Fourteen studies were selected for this review. With respect to diagnosing LN, the pooled sensitivity and specificity were 73.6% (95% confidence interval (CI), 61.9-83.3) and 78.1% (95% CI, 69.0-85.6), respectively. The SROC-AUC value was 0.8632. Regarding estimating LN activity, the pooled sensitivity and specificity were 66.2% (95% CI, 60.4-71.7) and 62.1% (95% CI, 57.9-66.3), respectively. The SROC-AUC value was 0.7583. In predicting renal flares, the pooled sensitivity and specificity were 77.5% (95% CI, 68.1-85.1) and 65.3% (95% CI, 60.0-70.3), respectively. The SROC-AUC value was 0.7756. In conclusion, this meta-analysis indicates that uNGAL has relatively fair sensitivity and specificity in diagnosing LN, estimating LN activity and predicting renal flares, suggesting that uNGAL is a potential biomarker in diagnosing LN and monitoring LN activity. © The Author(s) 2015.

  18. Economic evaluation of lupus nephritis in the Systemic Lupus International Collaborating Clinics inception cohort using a multistate model approach.

    Science.gov (United States)

    Barber, Megan R W; Hanly, John G; Su, Li; Urowitz, Murray B; Pierre, Yvan St; Romero-Diaz, Juanita; Gordon, Caroline; Bae, Sang-Cheol; Bernatsky, Sasha; Wallace, Daniel J; Isenberg, David A; Rahman, Anisur; Ginzler, Ellen M; Petri, Michelle; Bruce, Ian N; Fortin, Paul R; Gladman, Dafna D; Sanchez-Guerrero, Jorge; Ramsey-Goldman, Rosalind; Khamashta, Munther A; Aranow, Cynthia; Mackay, Meggan; Alarcón, Graciela S; Manzi, Susan; Nived, Ola; Jönsen, Andreas; Zoma, Asad A; van Vollenhoven, Ronald F; Ramos-Casals, Manuel; Ruiz-Irastorza, Guillermo; Sam Lim, S; Kalunian, Kenneth C; Inanc, Murat; Kamen, Diane L; Peschken, Christine A; Jacobsen, Soren; Askanase, Anca; Theriault, Chris; Farewell, Vernon; Clarke, Ann E

    2017-11-28

    Little is known about the long-term costs of lupus nephritis (LN). These were compared between patients with and without LN based on multistate modelling. Patients from 32 centres in 11 countries were enrolled in the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort within 15 months of diagnosis and provided annual data on renal function, hospitalizations, medications, dialysis, and selected procedures. LN was diagnosed by renal biopsy or the American College of Rheumatology classification criteria. Renal function was assessed annually using estimated glomerular filtration rate (eGFR) or proteinuria (ePrU). A multistate model was used to predict 10-year cumulative costs by multiplying annual costs associated with each renal state by the expected state duration. 1,545 patients participated, 89.3% female, mean age at diagnosis 35.2 years (SD 13.4), 49.0% Caucasian, and mean follow up 6.3 years (SD 3.3). LN developed in 39.4% by the end of follow up. Ten-year cumulative costs were greater in those with LN and an eGFR 60 ml/min) or with LN and ePrU > 3 g/d ($84 040 versus $20 499 if no LN and ePrU < 0.25 g/d). Patients with eGFR < 30 ml/min incurred 10-year costs 15-fold higher than those with normal eGFR. By estimating the expected duration in each renal state and incorporating associated annual costs, disease severity at presentation can be used to anticipate future healthcare costs. This is critical knowledge for cost-effectiveness evaluations of novel therapies. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  19. Efficacy of Intravenous Cyclophosphamide Pulse Therapy for P-Glycoprotein-expressing B Cell-associated Active True Renal Lupus Vasculitis in Lupus Nephritis

    Science.gov (United States)

    Kawabe, Akio; Tsujimura, Shizuyo; Saito, Kazuyoshi; Tanaka, Yoshiya

    2017-01-01

    True renal lupus vasculitis (TRLV), a vascular lesion usually associated with proliferative lupus nephritis (LN), is resistant to conventional treatments. The expression of P-glycoprotein (P-gp) on activated lymphocytes causes drug resistance. We herein report a patient with TRLV, minimal change LN, overexpression of P-gp on peripheral B cells, and accumulation of P-gp+ B cells at the site of TRLV. High-dose corticosteroids combined with intravenous cyclophosphamide pulse therapy resulted in clinical remission and the long-term normal renal function. PMID:28626187

  20. Co-Positivity for Anti-dsDNA, -Nucleosome and -Histone Antibodies in Lupus Nephritis Is Indicative of High Serum Levels and Severe Nephropathy.

    Directory of Open Access Journals (Sweden)

    Jinfeng Yang

    Full Text Available To characterize the significance of correlated autoantibodies in systemic lupus erythematosus (SLE and its complication lupus nephritis (LN in a large cohort of patients.Clinical data were statistically analyzed in 1699 SLE patients with or without nephritis who were diagnosed and treated during 2002-2013 in the northeast region of China. Reactivity to a list of 16 autoantibodies was detected by the serum test Euroline ANA profile (IgG. Serum titers of the anti-nucleosome autoantibodies were measured by ELISA assays. Kidney biopsies were examined by pathologists. Immune complex deposition was identified by immunohistochemistry stain.Simultaneous positivity of anti-dsDNA, -nucleosome and -histone antibodies (3-pos was prevalent in SLE patients with LN compared to Non-renal SLE patients (41% vs 11%, p< 0.001. Significant correlations were found between any two of the above three anti-nucleosome antibodies in LN patients. In comparison to non-3-pos cohorts, 3-pos patients with LN had significantly higher serum levels of the three antibodies and more active disease; was associated with type IV disease; suffered from more severe renal damages; received more intensive treatment and had worse disease outcome. The serum levels of these three autoantibodies in 3-pos LN patients were significantly decreased when they underwent clinical recovery.Simultaneous reactivity to anti-dsDNA, -nucleosome and -histone antibodies by Euroline ANA profile (IgG may indicate severe nephropathy in patients with SLE.

  1. Long-term post-marketing surveillance of mizoribine for the treatment of lupus nephritis: Safety and efficacy during a 3-year follow-up

    Directory of Open Access Journals (Sweden)

    Nobuyuki Yagi

    2014-05-01

    Full Text Available Objective: To determine the safety and efficacy of long-term use of mizoribine by undertaking a 3-year post-marketing surveillance study. Methods: Subjects were all lupus nephritis patients newly treated with mizoribine between 1 October 2003 and 30 September 2005 at contracted study sites. Results: Mizoribine was administered to 881 lupus nephritis patients in the safety analysis set consisting of 946 patients recruited from 281 contracted study sites after satisfying the eligibility criteria. There were 301 events of adverse drug reactions that were observed in 196 (20.7% of the 946 subjects. There were 34 events of serious adverse drug reactions in 31 patients (3.2%. No deterioration in hematological and biochemical test values was observed, but immunological testing showed significant improvements in C3, CH50, and anti-DNA antibody titers. The negative rate of proteinuria also increased over time. The median steroid dosage was 15 mg/day at the commencement of treatment, but was reduced to 10 mg/day at 12 months and 8 mg/day at 36 months. Conclusion: The findings of the 3-year long-term drug use surveillance study indicated that mizoribine can be used over the long term with relatively few adverse drug reactions, suggesting its suitability for use in maintenance drug therapy.

  2. Association of polymorphic variants of PTPN22, TNF and VDR genes in children with lupus nephritis: A study in Colombian family triads.

    Science.gov (United States)

    Garavito, Gloria; Egea, Eduardo; Fang, Luis; Malagón, Clara; Olmos, Carlos; González, Luz; Guarnizo, Pilar; Aroca, Gustavo; López, Guillermo; Iglesias, Antonio

    2017-06-01

    Systemic lupus erythematosus is an autoimmune disease in which the severity varies according to race, sex and age of onset. This variation is also observed in the genetic markers associated with the disease, including PTPN22, VDR and TNF genes. The genetic stratification in different populations worldwide can influence the variability. To analyze the heritability of PTPN22, VDR and TNF genetic variants and their association with pediatric lupus nephritis in Colombian families. We conducted a family-based study including 46 triads (case, father and mother). The variants rs2476601 of PTPN22; rs361525 and rs1800629 of TNF, and TaqI [rs731236], ApaI [rs7975232], BsmI [rs1544410] and FokI [rs2228570] of VDR were genotyped by qPCR. The effects of overtransmission of the risk allele from parents to children and linkage disequilibrium at the VDR and TNF loci were estimated. We found that allele A of rs2476601 in PTPN22 was distributed among 8.69 % (n=16) of the parents and 19.5 % (n=18) of the cases; this allele was overtransmitted from parents to children 17 times more often than the G allele (p=0.028). TNF and VDR polymorphisms did not exhibit transmission disequilibrium. VDR TaqI, ApaI and BsmI variants exhibited linkage disequilibrium. These findings showed an association between the PTPN22 rs2476601 polymorphism and pediatric lupus nephritis due to its overtransmission in the group of families studied.

  3. A large-sized bubbling appearance of the glomerular basement membrane in a patient with pulmonary limited AL amyloidosis and a past history of lupus nephritis.

    Science.gov (United States)

    Suga, Norihiro; Miura, Naoto; Uemura, Yuko; Nakamura, Toshinobu; Morita, Hiroyuki; Banno, Shogo; Imai, Hirokazu

    2011-12-01

    We report an unusual pathological finding, a large-sized bubbling appearance of the glomerular basement membrane (GBM), in a patient with pulmonary limited AL amyloidosis and a past history of lupus nephritis. The first renal biopsy specimen from 10 years ago, when systemic lupus erythematosus was diagnosed, demonstrated mild mesangial proliferation and subepithelial deposits (WHO classification: III + V). Light microscopy of the current biopsy using periodic acid methenamine silver (PAMS) stain demonstrated a large-sized bubbling appearance of the GBM; however, very weak immunoglobulin and complement deposition was observed in immunofluorescence studies. Routine electron microscopy demonstrated partial subendothelial expansion with electron-lucent materials, but no electron-dense deposits or amyloid fibrils. Electron microscopy with PAMS stain revealed electron-lucent endothelial scalloping, including some cellular components and microspheres in the GBM; however, it is not clear if these materials are derived from endothelial cells. One possibility is that these unique findings represent a recovery phase of lupus membranous nephritis; another is that these findings correspond to a new disease entity.

  4. Cardiovascular risk in lupus nephritis: Do renal disease-related and other traditional risk factors play a role?

    Directory of Open Access Journals (Sweden)

    Inoshi Atukorala

    2015-01-01

    Full Text Available This study was performed to evaluate the prevalence of thickened carotid intima media thickness (CIMT in a Sri Lankan cohort of lupus nephritis (LN patients and to identify associations between traditional cardiovascular disease (CVD and LN-related risk factors with increased CIMT. Consecutive patients with biopsy-proven LN were evaluated for conventional CVD risk factors, renal parameters and extent of organ involvement in this cross-sectional study. Current disease activity and damage were assessed by the British Isles Lupus Activity Group (BILAG score and the Systemic Lupus International Collaborative Clinics/American College of Rheumatology (SLICC/ACR damage index, respectively. CIMT was assessed by B Mode grey scale ultrasonography. Increased CIMT was defined as CIMT more than the 75th percentile based on cutoffs from the "Carotid Atherosclerosis Progression Study." Forty patients (98% female, with a mean age of 38 years (age range of 20-50 and of South Asian descent, were evaluated. The mean duration of disease of 6.15 years (SD = 4.66. The overall prevalence of cardiovascular events was low and included previous acute coronary syndromes in 7.5%, stable angina in 5%, cerebrovascular accidents in 7.5% and transient ischemic attacks in 2.5% of the patients; 72.5% had hypertension (HTN [mean blood pressure (BP 140/80 mm Hg]; 32.5% had dyslipidemias (mean serum cholesterol 5.9; SD = 5.6 and 25% had diabetes (mean blood sugar 103.7; SD = 15.6. Forty percent were obese and 20% were overweight (Asian cutoffs. Increased CIMT (57.5% and atherosclerotic plaques (15.36% indicated a high CVD risk in this cohort. Diabetes (P = 0.016, HTN (P = 0.002, dyslipidemia (P = 0.002 and obesity (P = 0.048 were associated with thickened CIMT. The only LN-related risk factor associated with thickened CIMT (P <0.05 was the SLICC/ACR damage index. The independent predictors of thickened CIMT determined by logistic regression analysis were HTN and dyslipidemia.

  5. Epidemiology and sociodemographics of systemic lupus erythematosus and lupus nephritis among US adults with Medicaid coverage, 2000-2004.

    Science.gov (United States)

    Feldman, Candace H; Hiraki, Linda T; Liu, Jun; Fischer, Michael A; Solomon, Daniel H; Alarcón, Graciela S; Winkelmayer, Wolfgang C; Costenbader, Karen H

    2013-03-01

    Systemic lupus erythematosus (SLE) and lupus nephritis (LN) disproportionately affect individuals who are members of racial/ethnic minority groups and individuals of lower socioeconomic status (SES). This study was undertaken to investigate the epidemiology and sociodemographics of SLE and LN in the low-income US Medicaid population. We utilized Medicaid Analytic eXtract data, with billing claims from 47 states and Washington, DC, for 23.9 million individuals ages 18-65 years who were enrolled in Medicaid for >3 months in 2000-2004. Individuals with SLE (≥3 visits >30 days apart with an International Classification of Diseases, Ninth Revision [ICD-9] code of 710.0) and with LN (≥2 visits with an ICD-9 code for glomerulonephritis, proteinuria, or renal failure) were identified. We calculated SLE and LN prevalence and incidence, stratified by sociodemographic category, and adjusted for number of American College of Rheumatology (ACR) member rheumatologists in the state and SES using a validated composite of US Census variables. We identified 34,339 individuals with SLE (prevalence 143.7 per 100,000) and 7,388 (21.5%) with LN (prevalence 30.9 per 100,000). SLE prevalence was 6 times higher among women, nearly double in African American compared to white women, and highest in the US South. LN prevalence was higher among all racial/ethnic minority groups compared to whites. The areas with lowest SES had the highest prevalence; areas with the fewest ACR rheumatologists had the lowest prevalence. SLE incidence was 23.2 per 100,000 person-years and LN incidence was 6.9 per 100,000 person-years, with similar sociodemographic trends. In this nationwide Medicaid population, there was sociodemographic variation in SLE and LN prevalence and incidence. Understanding the increased burden of SLE and its complications in this low-income population has implications for resource allocation and access to subspecialty care. Copyright © 2013 by the American College of Rheumatology.

  6. IgA Nephropathy and Henoch-Schoenlein Purpura Nephritis: Aberrant Glycosylation of IgA1, Formation of IgA1-Containing Immune Complexes, and Activation of Mesangial Cells

    DEFF Research Database (Denmark)

    Novak, J.; Moldoveanu, Z.; Renfrow, M.B.

    2007-01-01

    IgA1 in the circulation and glomerular deposits of patients with IgA nephropathy (IgAN) is aberrantly glycosylated; the hinge-region O-linked glycans are galactose-deficient. The circulating IgA1 of patients with Henoch-Schoenlein purpura nephritis (HSPN) has a similar defect. This aberrancy...

  7. Pulmonary haemorrhage and nephritis

    African Journals Online (AJOL)

    1983-04-30

    Apr 30, 1983 ... trachea was central, the chest was dull to percussion anteriorly and there were bronchial ... The venous pressure was normal. Heart sounds were ... A catheter urine specimen showed scanty red cells, occasional pus cells and ..... ces in penetration. Professor G.R. Keeton: The natural history of GPS is va-.

  8. A benzenediamine derivate FC-99 attenuates lupus nephritis in MRL/lpr mice via inhibiting myeloid dendritic cell-secreted BAFF.

    Science.gov (United States)

    Ji, Jianjian; Xu, Jingjing; Li, Fanlin; Li, Xiaojing; Gong, Wei; Song, Yuxian; Dou, Huan; Hou, Yayi

    2016-05-01

    Myeloid dendritic cells (DCs) can produce B-cell-activating factor (BAFF) that modulates survival and differentiation of B cells and plays a pivotal role in the pathogenesis of systemic lupus erythematosus (SLE). Toll-like receptor 4 (TLR4) signaling has important functions in the process of BAFF production. Our previous study showed that a benzenediamine derivate FC-99 possesses anti-inflammation activity and directly interacts with interleukin-1 receptor-associated kinase 4 (IRAK4), which was a pivotal molecule in TLR4 signaling. In this study, we demonstrated that FC-99 attenuated lupus nephritis in the MRL/lpr mice. FC-99 also decreased the levels of total immunoglobulin G (IgG), total IgG2a and IgM in sera, as well as the activation of B cells in the spleens of MRL/lpr mice. Moreover, FC-99 inhibited abnormal activation of myeloid DCs in spleens and reduced the levels of BAFF in sera, spleens, and kidneys of MRL/lpr mice. Furthermore, upon TLR4 stimulation with lipopolysaccharide in vitro, FC-99 inhibited IRAK4 phosphorylation, as well as the activation and BAFF production in murine bone marrow-derived DCs. These data indicate that FC-99 attenuates lupus nephritis in MRL/lpr mice via inhibiting DC-secreted BAFF, suggesting that FC-99 may be a potential therapeutic candidate for the treatment of SLE. © The Author 2016. Published by ABBS Editorial Office in association with Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences.

  9. Protective Effect of Hydroxychloroquine on Renal Damage in Patients with Lupus Nephritis: Data from LUMINA, a Multiethnic U.S. Cohort

    Science.gov (United States)

    Pons-Estel, Guillermo J.; Alarcón, Graciela S.; McGwin, Gerald; Danila, Maria I.; Zhang, Jie; Bastian, Holly M.; Reveille, John D.; Vilá, Luis M.

    2010-01-01

    Objective To assess if hydroxychloroquine can delay renal damage development in lupus nephritis patients. Methods Lupus nephritis patients (n=256) from LUMINA (n=635), a multiethnic cohort of African Americans, Hispanics and Caucasians, age ≥16 years, disease duration ≤5 years at baseline (T0) were studied. Renal damage was defined per the SLICC Damage Index (≥1 of the following lasting at least six months: estimated/measured glomerular filtration rate hydroxychloroquine use and renal damage (as defined, or omitting proteinuria) was estimated using Cox proportional regression analyses adjusting for potentially confounders. Kaplan-Meier survival curves based on hydroxychloroquine intake or World Health Organization (WHO) Class glomerulonephritis were also derived. Results Sixty-three (31.0%) of 203 patients developed renal damage over a mean (standard deviation) disease duration of 5.2 (3.5) years. The most frequent renal damage domain item was proteinuria. Hydroxychloroquine-takers (79.3%) exhibited a lower frequency of WHO Class IV glomerulonephritis, lower disease activity and received lower glucocorticoid doses than non-takers. After adjusting for confounders, hydroxychloroquine was protective of renal damage occurrence in full (HR=0.12; 95% CI 0.02-0.97; p=0.0464) and reduced (HR=0.29; 95%CI 0.13-0.68; p=0.0043) models. Omitting proteinuria provided comparable results. The cumulative probability of renal damage occurrence was higher in hydroxychloroquine non-takers and in WHO Class IV glomerulonephritis (phydroxychloroquine in retarding renal damage occurrence in SLE is still evident. PMID:19479701

  10. Sialylated Autoantigen-Reactive IgG Antibodies Attenuate Disease Development in Autoimmune Mouse Models of Lupus Nephritis and Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    Yannic C. Bartsch

    2018-06-01

    Full Text Available Pro- and anti-inflammatory effector functions of IgG antibodies (Abs depend on their subclass and Fc glycosylation pattern. Accumulation of non-galactosylated (agalactosylated; G0 IgG Abs in the serum of rheumatoid arthritis and systemic lupus erythematosus (SLE patients reflects severity of the diseases. In contrast, sialylated IgG Abs are responsible for anti-inflammatory effects of the intravenous immunoglobulin (pooled human serum IgG from healthy donors, administered in high doses (2 g/kg to treat autoimmune patients. However, whether low amounts of sialylated autoantigen-reactive IgG Abs can also inhibit autoimmune diseases is hardly investigated. Here, we explore whether sialylated autoantigen-reactive IgG Abs can inhibit autoimmune pathology in different mouse models. We found that sialylated IgG auto-Abs fail to induce inflammation and lupus nephritis in a B cell receptor (BCR transgenic lupus model, but instead are associated with lower frequencies of pathogenic Th1, Th17 and B cell responses. In accordance, the transfer of small amounts of immune complexes containing sialylated IgG Abs was sufficient to attenuate the development of nephritis. We further showed that administration of sialylated collagen type II (Col II-specific IgG Abs attenuated the disease symptoms in a model of Col II-induced arthritis and reduced pathogenic Th17 cell and autoantigen-specific IgG Ab responses. We conclude that sialylated autoantigen-specific IgG Abs may represent a promising tool for treating pathogenic T and B cell immune responses in autoimmune diseases.

  11. Sobresaturacion urinaria del Oxalato de Calcio más alla de la Nefrolitiasis: La relación con el daño tubulointersticial Urinary calcium oxalate supersaturation beyond nephrolithiasis: Relationship with tubulointerstitial damage

    Directory of Open Access Journals (Sweden)

    J. E. Toblli

    2003-04-01

    Full Text Available Numerosos estudios han demostrado que el producto de la actividad iónica (PAI de oxalato de calcio (OxCa en la orina, como indicador de sobresaturación (SS urinaria, es mayor en pacientes formadores de cálculos que en sujetos normales. Más allá de la relación entre SS urinaria del OxCa y litogénesis, la exposición de OxCa al epitelio tubular puede ocasionar lesiones en la célula tubular y en el intersticio renal. Nuestro objetivo fue evaluar la posible relación entre SS urinaria de OxCa y el daño tubulointersticial (TI en un modelo animal de hiperoxaluria. Durante cuatro semanas, ratas Sprague-Dawley machos, divididas en dos grupos recibieron: grupo 1 Control [G1], (n= 8 agua, grupo 2 [G2], (n = 8 etilenglicol (ETG al 1% en el agua de beber. La SS urinaria de OxCa se valoró mediante el PAI del OxCa. Las lesiones TI se analizaron al finalizar el estudio por microscopía óptica e inmunohistoquímica. El G2 (ETG presentó valores mayores (pA number of studies have demonstrated that the urinary ion activity product (IAP of calcium oxalate (CaOx, as an index of urinary CaOx supersaturation (SS, is higher in renal stone formers than in normal subjects. Besides, the relation between CaOx SS and lithogenesis, crystal CaOx exposition can produce tubular cell as well as renal interstitial lesions. The aim of our study was to evaluate the possible relationship between CaOx SS and tubulointerstitial (TI damage in an animal model of hyperoxaluria. During four weeks, male Sprague-Dawley rats received: G1 (n=8 control regular water, and G2 (n= 8 1% ethylene glycol (ETG (precursor for oxalates in drinking water. In order to evaluate urinary CaOx SS, IAP assessed by Tisselius formula was performed. At the end of the study, renal lesions were evaluated by light microscopy and immunohistochemistry. Animals from G2 (ETG presented higher (p< 0.01 values of: a urinary oxalate excretion; b urinary CaOx SS; c crystalluria score; d proteinuria; and lower (p

  12. Glomerulonefrite lúpica: estudo da evolução a longo prazo Lupus nephritis: a long term follow-up

    Directory of Open Access Journals (Sweden)

    R. S. Martins

    2000-06-01

    Full Text Available OBJETIVO: Estudar a apresentação clínica e a evolução de pacientes portadores de glomerulonefrite lúpica. CASUÍSTICA E MÉTODOS: Foram estudados 37 pacientes portadores de glomerulonefrite lúpica, atendidos pela Disciplina de Nefrologia - Faculdade de Medicina de Botucatu, com seguimento médio de 52,4 ± 13,3 meses. Os dados foram obtidos através do levantamento retrospectivo dos prontuários. RESULTADOS: A idade média foi de 26,05 ± 11,12 anos, com predomínio do sexo feminino (84% sendo que a glomerulonefrite classe IV foi a mais freqüente (80%. No início do seguimento a média da creatinina sérica foi de 1,74 ± 1,15 mg/dl, e a da proteinúria de 24h foi de 2,62 ± 2.89 g. Cinqüenta e um porcento dos pacientes com creatinina sérica elevada apresentaram, durante o seguimento, diminuição desses valores. Dentre diferentes variáveis estudadas, à época da biopsia renal, (idade, sexo, proteinúria, presença de hipertensão arterial e creatinina sérica a única que se associou com pior prognóstico foi a elevação da creatinina sérica. Remissão da síndrome nefrótica ocorreu em 65% das vezes. A sobrevida atuarial foi de 96%, 82%, 70% e 70% em 1, 5, 10 e 12 anos. Cinco pacientes desenvolveram insuficiência renal crônica terminal e sete morreram, sendo infecção a principal causa de óbito (57% CONCLUSÃO: Em pacientes com nefropatia lúpica, o aumento da creatinina sérica, à época da biópsia, se associou com o desenvolvimento de insuficiência renal crônica ao fim do seguimento e a principal causa de óbito foi processo infeccioso.PURPOSE: To evaluate and the long term course of patients with lupus nephritis, METHOD: Thirty seven patients with lupus nephritis followed in a referral, tertiary care center of a developing country (Brazil were studied. The length of follow up was 52.4 + 13.3 months and mean age was 26.05 +11.12 years. 84% of the patients were females and class IV nephritis was found to be the most

  13. Association of endothelial nitric oxide synthase gene polymorphism with the risk of Henoch-Schönlein purpura/Henoch-Schönlein purpura nephritis.

    Science.gov (United States)

    Zhong, Weiqiang; Zhou, Tian-Biao; Jiang, Zongpei

    2015-04-01

    Association between endothelial nitric oxide synthase (eNOS) gene polymorphism and Henoch-Schönlein purpura (HSP)/Henoch-Schönlein purpura nephritis (HSPN) risk is still controversial. A meta-analysis was performed to evaluate the association between eNOS gene polymorphism and HSP/HSPN susceptibility. A predefined literature search and selection of eligible relevant studies were performed to collect data from electronic database. Three articles were identified for the analysis of association between eNOS gene polymorphism and HSPN/HSP risk. eNOS G894T gene polymorphism was not associated with HSPN susceptibility and the risk of patients with HSP developing into HSPN. Interestingly, eNOS G894T T allele and GG genotype were associated with HSP susceptibility, but not the TT genotype. eNOS T786C TT genotype was associated with HSPN susceptibility, but not C allele and CC genotype. Furthermore, eNOS T786C gene polymorphism was not associated with HSP risk and the risk of patients with HSP developing into HSPN. In conclusion, eNOS T786C TT genotype was associated with and eNOS G894T T allele and GG genotype were associated with HSP susceptibility. However, more studies should be performed in the future.

  14. A clinico-pathological study of lupus nephritis based on the International Society of Nephrology-Renal Pathology Society 2003 classification system.

    Science.gov (United States)

    Satish, Suchitha; Deka, Pallavi; Shetty, Manjunath Sanjeev

    2017-01-01

    Lupus nephritis (LN) is a major complication of systemic lupus erythematosus (SLE). Renal involvement is a major determinant of the prognosis of SLE. The histological classification of LN is a key factor in determining the renal survival of patients with LN. Prompt recognition and treatment of renal disease are important, as early response to therapy is correlated with better outcome and renal biopsy plays an important role in achieving this. The objective of this study was to correlate the clinical and laboratory findings with histopathological classes of LN as per the 2003 International Society of Nephrology-Renal Pathology Society (ISN/RPS) classification system. Fifty-six patients with SLE, undergoing a renal biopsy for renal dysfunction were studied. The comparison of data from multiple groups was made by Pearson's Chi-square test and between two groups by independent samples t -test. The values of P renal biopsy. Since renal morphology may predict long-term prognosis, and no clinical or laboratory feature uniformly predicts prognosis, it is important to study the constellation of features in LN for better patient management.

  15. Changing patterns in clinical-histological presentation and renal outcome over the last five decades in a cohort of 499 patients with lupus nephritis.

    Science.gov (United States)

    Moroni, Gabriella; Vercelloni, Paolo Gilles; Quaglini, Silvana; Gatto, Mariele; Gianfreda, Davide; Sacchi, Lucia; Raffiotta, Francesca; Zen, Margherita; Costantini, Gloria; Urban, Maria Letizia; Pieruzzi, Federico; Messa, Piergiorgio; Vaglio, Augusto; Sinico, Renato Alberto; Doria, Andrea

    2018-05-05

    To evaluate changes in demographic, clinical and histological presentation, and prognosis of lupus nephritis (LN) over time. We studied a multicentre cohort of 499 patients diagnosed with LN from 1970 to 2016. The 46-year follow-up was subdivided into three periods (P): P1 1970-1985, P2 1986-2001 and P3 2002-2016, and patients accordingly grouped based on the year of LN diagnosis. Predictors of patient and renal survival were investigated by univariate and multivariate proportional hazards Cox regression analyses. Survival curves were compared using the log-rank test. A progressive increase in patient age at the time of LN diagnosis (ppresentation progressively decreased (pClinical presentation of LN has become less severe in the last years, leading to a better long-term renal survival. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  16. Chinese herbal medicine for the treatment of Henoch-Schönlein purpura nephritis in children: A prospective cohort study protocol.

    Science.gov (United States)

    Zhang, Jun; Lv, Jing; Pang, Shuang; Bai, Xiaohong; Yuan, Fang; Wu, Yubin; Jiang, Hong; Yang, Guanqi; Zhang, Shaoqing

    2018-06-01

    Henoch-Schönlein purpura nephritis (HSPN) involves the renal impairment of Henoch-Schönlein purpura and can easily relapse into life-threatening late nephropathy in severe cases. Although there is a lack of validated evidence for its effectiveness, Chinese herbal medicine (CHM) is one of the most commonly used methods in China to treat HSPN. It is thus need to report the protocol of a prospective cohort trial using CHM to investigate the effectiveness, safety and advantages for children with HSPN. This large, prospective, multicenter cohort study started in May 2015 in Shenyang. Six hundred children diagnosed with HSPN were recruited from 3 institutions and are followed-up every 2 to 4 weeks till May 2020. Detailed information of participants includes general information, history of treatment, physical examination, and symptoms of TCM is taken face-to-face at baseline. This study has received ethical approval from the ethics committee of institutional review board of the Affiliated Hospital of Liaoning University of Traditional Chinese Medicine (No.2016CS(KT)-002-01). Articles summarizing the primary results and ancillary analyses will be published in peer-reviewed journals. Clinical Trials Registration: NCT02878018.

  17. Significance of changes of the plasma levels of nitricoxide, endothelin and atrial natriuretic peptide in patients with lupus nephritis complicated with renal failure and receiving hemodialysis

    International Nuclear Information System (INIS)

    Zhang Jie; Shen Dongbo; Li Yijin

    2009-01-01

    Objective: To investigate the clinical significance of changes of plasma levels of nitricoxide(NO), endothelin (ET) and atrial natriuretic peptide (ANP) before and after hemodialysis in lupus nephritis(LN) patients with renal failure. Methods: Plasma NO (with biochemistry) and ET, ANP(with RIA) levels were measured in 32 lupus patients with renal failure both before and after a course of hemodialysis and 32 controls. Results: The plasma levels of NO, ET and ANP in the 32 LN patients with renal failure were significant higher than those in controls (P<0.05) before hemodialysis, the NO, ET and ANP levels were positively correlated with the BUN and creatinine levels. After a course of hemodialysis, plasma NO and ANP decreased significantly (P<0.05), but no significant changes were observed in plasma ET levels. Conclusion: The plasma level of NO, ET and ANP could help to assess the damage of renal function and hemodialysis could lower the level of NO and ANP in LN patients with renal failure. (authors)

  18. Post-marketing surveillance study of the long-term use of mizoribine for the treatment of lupus nephritis: 2-Year results.

    Science.gov (United States)

    Takeuchi, Tsutomu; Okada, Kenya; Yoshida, Hisao; Yagi, Nobuyuki

    2018-01-01

    To understand the status of mizoribine use in patients with lupus nephritis (LN) and to collect safety- and efficacy-related data on 2-year treatment with mizoribine. A continuous survey was conducted between March 2010 and July 2015. The analysis set included 559 patients (mean age 39.5 years, females 82.6%, mean duration of systemic lupus erythematosus (SLE) 8.4 years, mean duration of LN 5.9 years). Renal function was satisfactory for 6 months, but worsened from 12 months, with significant worsening at 24 months. By the ACR 2006 remission criteria (eGFR >60), at 24 months, 26.5% of patients achieved complete remission, and 63.3% achieved complete or partial remission. The urine protein to creatinine ratio decreased significantly. The SLE Disease Activity Index 2000 score decreased significantly at 12 and 24 months. Overall, 98 (17.5%) patients experienced 124 adverse drug reactions (ADRs); 3.6% experienced serious ADRs. Mizoribine was used with a steroid in 99.3% and an immunosuppressant in 51.2%; tacrolimus was used in 43.8%. The oral steroid dosage decreased from baseline to 24 months. The incidence of ADRs was not significantly different with concomitant tacrolimus use. The results suggest that long-term mizoribine is safe and effective, even when used with tacrolimus.

  19. RENAL SAFETY OF PROTON PUMP INHIBITORS

    Directory of Open Access Journals (Sweden)

    A. I. Dyadyk

    2017-01-01

    Full Text Available Proton pump inhibitors are a widely used in clinical practice, and are taken by millions of patients around the world for a long time. While proton pump inhibitors are well-tolerated class of drugs, the number of publications has been raised about adverse renal effects, specially their association with acute tubulointerstitial nephritis. It is one of the leading causes of acute renal injury and have catastrophic long-term consequences called chronic kidney disease. In this review, we consider epidemiology, pathogenesis, diagnostic criteria (including biopsy and morphological pattern, clinical manifestations and treatment of proton pump inhibitors-induced acute tubulointerstitial nephritis. A subclinical course without classical manifestations of a cell-mediated hypersensitivity reaction (fever, skin rash, eosinophilia, arthralgia is characteristic of acute tubulointerstitial nephritis. Increased serum creatinine, decreased glomerular filtration rate, electrolyte disorders, pathological changes in urine tests are not highly specific indicators, but allow to suspect the development of acute tubulointerstitial nephritis. The “gold” standard of diagnosis is the intravital morphological examination of the kidney tissue. Timely diagnosis and immediate discontinuation of the potentially causative drug is the mainstay of therapy and the first necessary step in the early management of suspected or biopsy-proven drug-induced acute tubulointerstitial nephritis. The usage of proton pump inhibitors should be performed only on strict indications with optimal duration of treatment and careful monitoring of kidney function. Multiple comorbidities (older age, heart failure, diabetes, cirrhosis, chronic kidney disease, hypovolemia increase potential nephrotoxicity. Awareness of this iatrogenic complication will improve diagnosis of proton pump inhibitors-induced acute tubulointerstitial nephritis by multidisciplinary specialists and increase the possibility

  20. An unusual renal manifestation of chronic HBV infection.

    Science.gov (United States)

    Aravindan, Ananthakrishnapuram; Yong, Jim; Killingsworth, Murray; Strasser, Simone; Suranyi, Michael

    2010-08-01

    Hepatitis B viral infection is usually a self-limiting disease in immunocompetent individuals. Chronic infection can be seen in up to 5% of infected patients. Renal manifestations of chronic HBV infection are usually glomerular. We describe here an uncommon presentation of a patient with chronic HBV infection with very high viral load and rapidly progressive renal failure. Renal biopsy showed features of tubulointerstitial nephritis and tubular epithelial inclusion bodies suggestive of HBV infection. Entecavir treatment slowed down the progression of his renal disease. Tubulointerstitial nephritis should be considered as a part of the differential diagnosis in patients with HBV infection. Early antiviral treatment may halt the progression of renal disease.

  1. Fc RIIA Genotypes and Its Association with Anti-C1q Autoantibodies in Lupus Nephritis (LN Patients from Western India

    Directory of Open Access Journals (Sweden)

    Vandana Pradhan

    2010-01-01

    Full Text Available To identify Fc RIIA genotypes in Systemic Lupus Erythematosus (SLE patients and their association with anti-C1q antibodies. Methods. Fc RIIA genotyping was done in eighty Indian SLE patients and eighty healthy controls using allele-specific PCR. Anti-C1q antibodies were measured by ELISA. Results. LN patients showed higher SLEDAI (6–32 as compared to SLE patients without renal manifestations and had SLEDAI between 6–23. Fc RIIA polymorphic frequency in SLE patients was R131/H131 (67.5%, R131/R131 (20% and H131/ H131 (12.5% as against that of normal population (62.5%, 10%, and 27.5%, respectively. Sixty two patients (77.5% showed positivity for anti-C1q antibodies. LN patients showed elevated levels of anti-C1q antibodies (258.2u/ml±38.5U/mL as compared to SLE patients without nephritis (134.6±24.6 U/mL. Among anti-C1q positive patients, 71% had R131/H131 genotype, 22.6% had R131/R131 and remaining 6.4%, patients had H131/H131 genotype. All anti-C1q positive patients with R131/R131 genotype had elevated levels of anti-C1q antibodies (>100 U/ml, whereas among anti-C1q negative patients, none had R131/R131 genotype. Conclusion. This first report on Indian SLE patients supports the hypothesis that Fc RIIA R131 variant over expression may constitute a susceptibility factor for development of severe SLE manifestations in LN patients.

  2. CD147/basigin limits lupus nephritis and Th17 cell differentiation in mice by inhibiting the interleukin-6/STAT-3 pathway.

    Science.gov (United States)

    Maeda, Kayaho; Kosugi, Tomoki; Sato, Waichi; Kojima, Hiroshi; Sato, Yuka; Kamimura, Daisuke; Kato, Noritoshi; Tsuboi, Naotake; Yuzawa, Yukio; Matsuo, Seiichi; Murakami, Masaaki; Maruyama, Shoichi; Kadomatsu, Kenji

    2015-05-01

    Interleukin-17 (IL-17)-producing T cells (Th17 cells) play critical roles in the pathogenesis of immune-related diseases, including systemic lupus erythematosus. However, the fundamental mechanism regulating Th17 cell differentiation is not fully understood. Recently, we demonstrated that plasma levels of CD147/basigin (Bsg) in patients with lupus nephritis (LN) were closely associated with disease activity. but the molecular mechanism involving Bsg has been elusive. Here, we addressed the role of Bsg in the pathogenesis of LN. Injections of pristane (2,6,10,14-tetramethylpentadecane [TMPD]) were administered to Bsg(-/-) or Bsg(+/+) mice to induce LN. The mice were killed 6 months after being injected, for histologic and biochemical analyses of the kidneys and spleens. Pristane induced LN more strikingly in Bsg(-/-) mice than in Bsg(+/+) mice, even though humoral autoimmunity was similarly increased in both genotypes. The increased number of Th17, but not Th1, Treg cells, was augmented in Bsg(-/-) mice. The expression of IL-17 was also increased in the kidneys of Bsg(-/-) mice, in proportion to LN disease activity. Furthermore, treatment with anti-IL-17 antibody reduced LN disease activity in Bsg(-/-) mice. Complementary to these phenotypes of Bsg(-/-) mice, Bsg expression was enhanced in activated CD4+ T cells in vivo and in vitro. Bsg deficiency selectively augmented in vitro differentiation of naive CD4+ T cells to Th17 cells and STAT-3 phosphorylation during this differentiation. Moreover, STAT-3 phosphorylation was suppressed by crosslinking of Bsg with its antibody. Bsg plays an indispensable role in Th17 cell differentiation as a negative regulator by suppressing the IL-6/STAT-3 pathway. © 2015, American College of Rheumatology.

  3. Renal vascular lesions as a marker of poor prognosis in patients with lupus nephritis. Gruppo Italiano per lo Studio della Nefrite Lupica (GISNEL).

    Science.gov (United States)

    Banfi, G; Bertani, T; Boeri, V; Faraggiana, T; Mazzucco, G; Monga, G; Sacchi, G

    1991-08-01

    The frequency of renal vascular lesions (RVL) and their relevance in the progression of renal damage were evaluated by the Pathology Group of the "Gruppo Italiano per lo Studio della Nefrite Lupica" (GISNEL). Of 285 patients with lupus nephritis collected from 20 nephrology centers in Italy and classified according to World Health Organization (WHO) criteria, 79 cases (27.7%) with RVL were identified and classified as follows: (1) lupus vasculopathy (n = 27); (2) hemolytic-uremic syndrome/thrombotic thrombocytopenic purpura (HUS/TTP) malignant hypertension-like lesions (n = 24); (3) vasculitis (n = 8); (4) arterio-arteriosclerosis (n = 20). At the time of renal biopsy, patients with RVL had mean serum creatinine levels significantly higher than patients without RVL (201.8 +/- 195.9 mumol/L [2.2 +/- 2.2 mg/dL] v 108.1 +/- 108.0 mumol/L [1.2 +/- 1.2 mg/dL]; P less than 0.01). Hypertension was more frequent in patients with RVL than in those without (68.4% v 30.5%; P less than 0.01). The probability of kidney survival assessed according to the Kaplan-Meier method at 5 and 10 years was, respectively, 74.3% +/- 5.9% and 58.0% +/- 8.9% in patients with RVL, compared with 89.6% +/- 2.7% and 85.9% +/- 3.7% in patients without RVL. However, the two groups did not differ significantly as regards overall survival, the probability of survival at 5 and 10 years being 86.5% +/- 4.5% and 78.8% +/- 6.6% in patients with RVL and 92.2% +/- 2.2% and 83.3% +/- 4.4% in patients without RVL.(ABSTRACT TRUNCATED AT 250 WORDS)

  4. Role of P-glycoprotein on CD69+CD4+ cells in the pathogenesis of proliferative lupus nephritis and non-responsiveness to immunosuppressive therapy.

    Science.gov (United States)

    Tsujimura, Shizuyo; Adachi, Tomoko; Saito, Kazuyoshi; Tanaka, Yoshiya

    2017-01-01

    P-glycoprotein (P-gp) expression on activated lymphocytes in systemic lupus erythematosus (SLE) plays a role in active efflux of intracellular drugs, resulting in drug resistance. The role of P-gp-expressing lymphocytes in the pathogenesis of SLE remains unclear. The aim of this study was to determine the importance of P-gp + CD4 + cells in organ manifestations in refractory SLE. The proportion of P-gp + CD4 + cells was determined by flow cytometry in peripheral blood of patients with SLE (n=116) and healthy adults (n=10). Renal biopsy specimens were examined by immunohistochemistry for P-gp expression. CD69 is a marker of CD4 cell activation. The proportion of both P-gp-expressing CD4 + cells and CD69-expressing CD4 + cells in peripheral blood was higher in SLE than control. The proportion of P-gp + CD69 + CD4 + cells correlated with Systemic Lupus Erythematosus Disease Activity Index and was higher in poor responders to corticosteroids. Furthermore, the proportion of P-gp + CD69 + CD4 + cells was significantly higher in proliferative lupus nephritis (LN) with poor response to corticosteroids. The efficacy of immunosuppressive therapy depended on the regulation of the proportion of P-gp + CD69 + CD4 + cells. Marked accumulation of P-gp + CD4 + cells in renal interstitial tissue and high proportion of peripheral P-gp + CD69 + CD4 + cells were noted in patients with proliferative LN. The results showed high proportion of P-gp + CD69 + CD4 + cells in peripheral blood and their accumulation in renal tissue in patients with proliferative LN refractory to CS therapy, suggesting that P-gp expression on activated CD4 + T cells is a potentially useful marker for refractoriness to treatment and a novel target for treatment.

  5. Altered expression of signalling lymphocyte activation molecule receptors in T-cells from lupus nephritis patients-a potential biomarker of disease activity.

    Science.gov (United States)

    Stratigou, Victoria; Doyle, Anne F; Carlucci, Francesco; Stephens, Lauren; Foschi, Valentina; Castelli, Marco; McKenna, Nicola; Cook, H Terence; Lightstone, Liz; Cairns, Thomas D; Pickering, Matthew C; Botto, Marina

    2017-07-01

    The aim was to investigate whether the signalling lymphocyte activation molecule (SLAM) signalling pathways contribute to LN and whether SLAM receptors could be valuable biomarkers of disease activity. Peripheral blood mononuclear cells from 30National Research Ethics Service SLE patients with biopsy-proven LN were analysed by flow cytometry. Clinical measures of disease activity were assessed. The expression of the SLAM family receptors on T-cell subpopulations [CD4, CD8 and double negative (DN) T cells] was measured and compared between lupus patients with active renal disease and those in remission. The frequency of CD8 T cells expressing SLAMF3, SLAMF5 and SLAMF7 was significantly lower in LN patients who were in remission. In contrast, these subsets were similar in patients with active renal disease and in healthy individuals. Patients with active nephritis had an increased percentage of circulating monocytes, consistent with a potential role played by these cells in glomerular inflammation. Changes in the frequency of DN T cells positive for SLAMF2, SLAMF4 and SLAMF7 were observed in lupus patients irrespective of the disease activity. We detected alterations in the cellular expression of the SLAM family receptors, but these changes were less obvious and did not reveal any specific pattern. The percentage of DN T cells expressing SLAMF6 could predict the clinical response to B-cell depletion in patients with LN. Our study demonstrates altered expression of the SLAM family receptors in SLE T lymphocytes. This is consistent with the importance of the SLAM-associated pathways in lupus pathogenesis. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology.

  6. CD4+ T helper cells and regulatory T cells in active lupus nephritis: an imbalance towards a predominant Th1 response?

    Science.gov (United States)

    Mesquita, D; Kirsztajn, G Mastroianni; Franco, M F; Reis, L A; Perazzio, S F; Mesquita, F V; Ferreira, V da Silva; Andrade, L E Coelho; de Souza, A W Silva

    2018-01-01

    The objective of this study was to evaluate the frequency of CD4 + T cell subsets in peripheral blood mononuclear cells (PBMC), urine and renal tissue from patients with lupus nephritis (LN). PBMC and urinary cells were collected from 17 patients with active LN, 20 disease controls (DC) with primary glomerulonephritis and 10 healthy controls (HC) and were analysed by flow cytometry with markers for T helper type 1 (Th1), Th2, Th17 and regulatory T cells (T reg ) cells. T cell subsets were assessed by immunohistochemistry from LN biopsy specimens from 12 LN patients. T cell subtypes in PBMC were re-evaluated at 6 months of therapy. CD4 + T cells were decreased in PBMC in LN compared with DC and HC (P = 0·0001). No differences were observed in urinary CD4 + T cell subsets between LN and DC. The frequency of urinary Th17 cells was higher in patients with non-proliferative than in proliferative LN (P = 0·041). CD3 + and T-box 21 ( Tbet+) cells were found in glomeruli and interstitium of LN patients, while forkhead box protein 3 (FoxP3), retinoid-related orphan receptor gamma (ROR-γ) and GATA binding protein 3 (GATA-3) were present only in glomeruli. Th1 cells in PBMC were correlated negatively with urinary Th1 cells (Rho = -0·531; P = 0·028) and with T bet in renal interstitium (Rho = -0·782; P = 0·004). At 6 months, LN patients showed an increase in Th17 cells in PBMC. In conclusion, the inverse association between Th1 cells from PBMC and urinary/renal tissue indicate a role for Th1 in LN pathophysiology. Urinary Th17 cells were associated with less severe LN, and Th17 increased in PBMC during therapy. Urinary CD4 + T cells were not different between LN and DC. © 2017 British Society for Immunology.

  7. Cranioectodermal Dysplasia : A Probable Ciliopathy

    NARCIS (Netherlands)

    Konstantinidou, Anastasia E.; Fryssira, Helen; Sifakis, Stavros; Karadimas, Charalampos; Kaminopetros, Petros; Agrogiannis, Georgios; Velonis, Stylianos; Nikkels, Peter G. J.; Patsouris, Efstratios

    2009-01-01

    Cranioectodermal dysplasia (CED), also known as Sensenbrenner syndrome, is a rare autosomal recessive genetic disorder characterized by typical craniofacial, skeletal and ectodermal defects, and tubulointerstitial nephritis leading to early end-stage renal failure. We report on a new familial case

  8. Renal impairment in patients with inflammatory bowel disease: association with aminosalicylate therapy?

    NARCIS (Netherlands)

    Elseviers, M. M.; D'Haens, G.; Lerebours, E.; Plane, C.; Stolear, J. C.; Riegler, G.; Capasso, G.; van Outryve, M.; Mishevska-Mukaetova, P.; Djuranovic, S.; Pelckmans, P.; de Broe, M. E.

    2004-01-01

    In recent years, several case reports have been published suggesting an association between the use of 5-aminosalicylic acid (5-ASA) in patients with inflammatory bowel disease (IBD) and the development of chronic tubulo-interstitial nephritis. Apart from lesions associated to 5-ASA treatment,

  9. Evolution of IgA nephropathy into anaphylactoid purpura in six cases--further evidence that IgA nephropathy and Henoch-Schonlein purpura nephritis share common pathogenesis.

    Science.gov (United States)

    Kamei, Koichi; Ogura, Masao; Sato, Mai; Ito, Shuichi; Ishikura, Kenji

    2016-05-01

    As the morphological and immunohistochemical manifestations of immunoglobulin A (IgA) nephropathy and Henoch-Schonlein purpura nephritis (HSPN) are very similar, they are considered to share a common pathogenesis. Although HSPN usually develops after the appearance of anaphylactoid purpura, we have encountered patients whose renal symptoms preceded purpura. We reviewed the clinical courses of patients who were first diagnosed with IgA nephropathy, but developed purpura later, at the National Center for Child Health and Development in Tokyo, Japan. Of the 53 patients who were diagnosed with primary IgA nephropathy at our institute during the study period (March 2002 to July 2015), six (11 %) developed anaphylactoid purpura after the diagnosis of primary IgA nephropathy and therefore met the inclusion criteria. Duration between the onset of nephritis and subsequent appearance of purpura ranged from 5 months to 14 years. One patient reached end-stage renal failure due to IgA nephropathy and developed purpura after renal transplantation. All renal biopsies performed before the appearance of purpura showed mesangial proliferation with predominant IgA deposits. Urinary findings deteriorated in three patients after the appearance of purpura, including one patient who developed rapidly progressive glomerulonephritis. Renal biopsy findings worsened in two patients. At the last observation, two patients showed mild renal insufficiency. Our clinical experience and previous reports support the argument that IgA nephropathy and HSPN are different manifestations of a single disease. Hence, it is acceptable to consider that they are variants of a single disease.

  10. Rationale and design of the RIACT–study: a multi-center placebo controlled double blind study to test the efficacy of RItuximab in Acute Cellular tubulointerstitial rejection with B-cell infiltrates in renal Transplant patients: study protocol for a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Schiffer Lena

    2012-10-01

    Full Text Available Abstract Background Acute kidney allograft rejection is a major cause for declining graft function and has a negative impact on the long-term graft survival. The majority (90% of acute rejections are T-cell mediated and, therefore, the anti-rejection therapy targets T-cell-mediated mechanisms of the rejection process. However, there is increasing evidence that intragraft B-cells are also important in the T-cell-mediated rejections. First, a significant proportion of patients with acute T-cell-mediated rejection have B-cells present in the infiltrates. Second, the outcome of these patients is inferior, which has been related to an inferior response to the conventional anti-rejection therapy. Third, treatment of these patients with an anti-CD20 antibody (rituximab improves the allograft outcome as reported in single case observations and in one small study. Despite the promise of these observations, solid evidence is required before incorporating this treatment option into a general treatment recommendation. Methods/Design The RIACT study is designed as a randomized, double-blind, placebo-controlled, parallel group multicenter Phase III study. The study examines whether rituximab, in addition to the standard treatment with steroid-boli, leads to an improved one-year kidney allograft function, compared to the standard treatment alone in patients with acute T-cell mediated tubulointerstitial rejection and significant B-cell infiltrates in their biopsies. A total of 180 patients will be recruited. Discussion It is important to clarify the relevance of anti-B cell targeting in T-cell mediated rejection and answer the question whether this novel concept should be incorporated in the conventional anti-rejection therapy. Trial registration Clinical trials gov. number: NCT01117662

  11. Blood oxygen level-dependent magnetic resonance imaging for detecting pathological patterns in patients with lupus nephritis: a preliminary study using gray-level co-occurrence matrix analysis.

    Science.gov (United States)

    Shi, Huilan; Jia, Junya; Li, Dong; Wei, Li; Shang, Wenya; Zheng, Zhenfeng

    2018-01-01

    Objective Blood oxygen level-dependent magnetic resonance imaging (BOLD MRI) is a noninvasive technique useful in patients with renal disease. The current study was performed to determine whether BOLD MRI can contribute to the diagnosis of renal pathological patterns. Methods BOLD MRI was used to obtain functional magnetic resonance parameter R2* values. Gray-level co-occurrence matrixes (GLCMs) were generated for gray-scale maps. Several GLCM parameters were calculated and used to construct algorithmic models for renal pathological patterns. Results Histopathology and BOLD MRI were used to examine 12 patients. Two GLCM parameters, including correlation and energy, revealed differences among four groups of renal pathological patterns. Four Fisher's linear discriminant formulas were constructed using two variables, including the correlation at 45° and correlation at 90°. A cross-validation test showed that the formulas correctly predicted 28 of 36 samples, and the rate of correct prediction was 77.8%. Conclusions Differences in the texture characteristics of BOLD MRI in patients with lupus nephritis may be detected by GLCM analysis. Discriminant formulas constructed using GLCM parameters may facilitate prediction of renal pathological patterns.

  12. Extended follow-up of the CYCLOFA-LUNE trial comparing two sequential induction and maintenance treatment regimens for proliferative lupus nephritis based either on cyclophosphamide or on cyclosporine A.

    Science.gov (United States)

    Závada, J; Sinikka Pesicková, S; Rysavá, R; Horák, P; Hrncír, Z; Lukác, J; Rovensky, J; Vítová, J; Havrda, M; Rychlík, I; Böhmova, J; Vlasáková, V; Slatinská, J; Zadrazil, J; Olejárová, M; Tegzova, D; Tesar, V

    2014-01-01

    Objective To evaluate the extended follow-up of the CYCLOFA-LUNE trial, a randomized prospective trial comparing two sequential induction and maintenance treatment regimens for proliferative lupus nephritis based either on cyclophosphamide (CPH) or cyclosporine A (CyA). Patients and methods Data for kidney function and adverse events were collected by a cross-sectional survey for 38 of 40 patients initially randomized in the CYCLOFA-LUNE trial. Results The median follow-up time was 7.7 years (range 5.0-10.3). Rates of renal impairment and end-stage renal disease, adverse events (death, cardiovascular event, tumor, premature menopause) did not differ between the CPH and CyA group, nor did mean serum creatinine, 24 h proteinuria and SLICC damage score at last follow-up. Most patients in both groups were still treated with glucocorticoids, other immunosuppressant agents and blood pressure lowering drugs. Conclusion An immunosuppressive regimen based on CyA achieved similar clinical results to that based on CPH in the very long term.

  13. 4G/5G plasminogen activator inhibitor-1 and -308 A/G tumor necrosis factor-α promoter gene polymorphisms in Argentinean lupus patients: focus on lupus nephritis.

    Science.gov (United States)

    Muñoz, Sebastián Andrés; Aranda, Federico; Allievi, Alberto; Orden, Alberto Omar; Perés Wingeyer, Silvia; Trobo, Rosana; Alvarez, Analía; Eimon, Alicia; Barreira, Juan Carlos; Schneeberger, Emilce; Dal Pra, Fernando; Sarano, Judith; Hofman, Julio; Chamorro, Julián; de Larrañaga, Gabriela

    2014-02-01

    We investigated the relationship between the 4G/5G plasminogen activator inhibitor (PAI-1) and -308 A/G tumor necrosis factor-α (TNF-α) polymorphisms and the clinical and biochemical features of systemic lupus erythematosus (SLE) in an Argentinean patient cohort. A total of 402 patients were studied, including 179 SLE patients and 223 healthy individuals. PCR-RLFP was used to determine the genotypes of the 4G/5G PAI-1 and -308 A/G TNF-α polymorphisms. SLE patients with lupus nephritis (LN) (n = 86) were compared with patients without LN (n = 93). Additionally, LN patients were divided into proliferative LN and non-proliferative LN groups according to the results of the renal biopsies. No significant differences were noted in the genotype distributions or allele frequencies of these TNF-α and PAI-1 polymorphisms between SLE patients and controls. There were higher numbers of criteria for SLE, more lupus flares and higher damage scores in LN patients, but there were similar frequencies of anti-phospholipid antibody (APA) positivity and anti-phospholipid syndrome. No significant difference was noted for any studied variable between the proliferative LN and non-proliferative LN groups except for the presence of APA. We found no significant differences in the TNF-α and PAI-1 genotype distributions or allele frequencies between groups. We found that the -308 A/G TNF-α and 4G/5G PAI-1 polymorphisms are not associated with susceptibility to SLE in an Argentinean population. We also did not find any association between the presence of any specific allele or genotype and the development of LN in SLE patients. Finally, no association was noted between either of the two polymorphisms and the severity of renal disease.

  14. Comparative effects of n-3, n-6 and n-9 unsaturated fatty acid-rich diet consumption on lupus nephritis, autoantibody production and CD4+ T cell-related gene responses in the autoimmune NZBWF1 mouse.

    Directory of Open Access Journals (Sweden)

    James J Pestka

    Full Text Available Mortality from systemic lupus erythematosus (SLE, a prototypical autoimmune disease, correlates with the onset and severity of kidney glomerulonephritis. There are both preclinical and clinical evidence that SLE patients may benefit from consumption of n-3 polyunsaturated fatty acids (PUFA found in fish oil, but the mechanisms remain unclear. Here we employed the NZBWF1 SLE mouse model to compare the effects of dietary lipids on the onset and severity of autoimmune glomerulonephritis after consuming: 1 n-3 PUFA-rich diet containing docosahexaenoic acid-enriched fish oil (DFO, 2 n-6 PUFA-rich Western-type diet containing corn oil (CRN or 3 n-9 monounsaturated fatty acid (MUFA-rich Mediterranean-type diet containing high oleic safflower oil (HOS. Elevated plasma autoantibodies, proteinuria and glomerulonephritis were evident in mice fed either the n-6 PUFA or n-9 MUFA diets, however, all three endpoints were markedly attenuated in mice that consumed the n-3 PUFA diet until 34 wk of age. A focused PCR array was used to relate these findings to the expression of 84 genes associated with CD4+ T cell function in the spleen and kidney both prior to and after the onset of the autoimmune nephritis. n-3 PUFA suppression of autoimmunity in NZBWF1 mice was found to co-occur with a generalized downregulation of CD4+ T cell-related genes in kidney and/or spleen at wk 34. These genes were associated with the inflammatory response, antigen presentation, T cell activation, B cell activation/differentiation and leukocyte recruitment. Quantitative RT-PCR of representative affected genes confirmed that n-3 PUFA consumption was associated with reduced expression of CD80, CTLA-4, IL-10, IL-18, CCL-5, CXCR3, IL-6, TNF-α and osteopontin mRNAs in kidney and/or spleens as compared to mice fed n-6 PUFA or n-9 MUFA diets. Remarkably, many of the genes identified in this study are currently under consideration as biomarkers and/or biotherapeutic targets for SLE and other

  15. Lupus and Kidney Disease (Lupus Nephritis)

    Science.gov (United States)

    ... disease. Your family history and things in your environment such as infections, viruses, toxic chemicals or pollutants ( ... to show how well your kidneys are filtering wastes Check for antiphospholipid antibodies and anti-nuclear antibodies (ANA) at least once during your disease. ...

  16. Prognostic significance of repeat biopsy in lupus nephritis: Histopathologic worsening and a short time between biopsies is associated with significantly increased risk for end stage renal disease and death.

    Science.gov (United States)

    Arriens, Cristina; Chen, Sixia; Karp, David R; Saxena, Ramesh; Sambandam, Kamalanathan; Chakravarty, Eliza; James, Judith A; Merrill, Joan T

    2017-12-01

    Approximately half of patients with systemic lupus erythematosus (SLE) develop lupus nephritis (LN), a major cause of morbidity and early mortality in that disease. Prolonged renal inflammation is associated with irreversible kidney damage which confers a 30% risk of end stage renal disease (ESRD), making early, aggressive treatment mandatory. Failure to achieve therapeutic response or recurrence of renal flare often prompts repeat biopsy. However, the role of repeat biopsy in determining long-term renal prognosis remains controversial. For this reason repeat biopsies are usually not utilized unless clinical evidence of refractory or recurrent disease is already present, despite known mismatches between clinical and biopsy findings. The current study quantifies the degree to which histopathologic worsening between first and second biopsies and duration between them predicts ESRD and death. Medical records of 141 LN patients with more than one biopsy were obtained from a single large urban medical center. Cases were attained using billing codes for diagnosis and procedures from 1/1999-1/2015. Biopsy worsening was defined as unfavorable histopathologic classification transitions and/or increased chronicity; if neither were present, the patient was defined as non-worsening. We used Cox proportional hazard models to study the relationship between ESRD and survival adjusting for covariates which included age at first biopsy, gender, race, initial biopsy class, and initial induction therapy. Of 630 patients screened, 141 had more than one biopsy. Advancing chronicity was detected in 48 (34.0%) and a renal class switch to worse grade of pathology was found in 54 (38.3%). At least one of these adverse second biopsy features was reported in 79 (56.0%) patients. Five years following initial biopsy, 28 (35.4%) of those with worsening histopathology on second biopsy developed ESRD, compared to 6 (9.7%) of non-worsening patients and 10 (12.7%) of patients with worsening

  17. 莫西沙星和左氧氟沙星致急性肾小管间质肾病%Acute interstitial nephritis caused by moxifloxacin and levofloxacin

    Institute of Scientific and Technical Information of China (English)

    李颖慧; 杭永付; 梁雁

    2016-01-01

    A 31-year-old male patient received an oral moxifloxacin 0. 4 g once daily for respiratory infection and after 3 days of treatment,his symptoms were not improved and appeared urine decrease. Moxifloxacin was stopped and changed into levofloxacin 0. 2 g twice daily by mouth. After 8 days of treatment,the patient's symptoms was not improved apparently and appeared urinary protein( + ),5-10 erythrocytes/ high magnification( HP),3-5 white blood cells/ HP,serum creatinine 419 μmol/ L. Renal biopsy showed acute tubular interstitial nephropathy. Drug-induced acute interstitial nephritis-induced by moxifloxacin and levofloxacin was considered. Levofloxacin was stopped and an IV infusion of methylpred-nisolone 250 mg once daily was given,and 3 days later,it was changed into oral prednison 40 mg once daily. After 7 days of treatment,the patient' s blood creatinine was 168 mol/ L,urea 13. 6 mmol/ L, glomerular filtration rate 45. 8 ml/ min/ 1. 73 m2 . The patient got better and was discharged. At 2 months of follow up,the patient's blood creatinine was 119 μmol/ L and urea was 6. 2 mmol/ L.%1例31岁男性患者因呼吸道感染给予莫西沙星0.4 g、1次/ d 口服,用药3 d 病情无改善并出现尿量减少;换用左氧氟沙星0.2 g、2次/ d 口服,用药8 d 病情仍无明显好转,且出现尿蛋白(+),5~10个红细胞/ HP,3~5个白细胞/ HP,Scr 419μmol/ L。肾活检示急性肾小管间质肾病。考虑可能为莫西沙星和左氧氟沙星引起的急性间质性肾炎。停用左氧氟沙星,给予甲泼尼龙250 mg、1次/ d 静脉滴注;3 d 后改为泼尼松40 mg、1次/ d 口服。治疗7 d 后患者 Scr 降至168μmol/ L,尿素13.6 mmol/ L,eGFR 45.8 ml·min-1·1.73 m-2。2个月后复查,患者 Scr 119μmol/ L,尿素6.2 mmol/ L。

  18. Distal renal tubular acidosis as a cause of osteomalacia in a patient with primary Sjögren's syndrome

    Directory of Open Access Journals (Sweden)

    Jovelić Aleksandra

    2005-01-01

    Full Text Available Background. One half of the patients with primary Sjögren’s syndrome has extraglandular manifestations, including renal involvement. The most frequent renal lesion is tubulo-interstitial nephritis, which manifests clinically as distal tubular acidosis and may result in the development of osteomalacia. Case report. In a 29 - year-old female patient, with bilateral nephrolithiasis, the diagnosis of primary Sjögren’s syndrome, tubulo-interstitial nephritis, distal renal tubular acidosis, and hypokalemia were established. She was treated for hypokalemia. Two years later she developed bone pains and muscle weakness, she wasn’t able to walk, her proximal muscles and pelvic bones were painful, with radiological signs of pelvic bones osteopenia and pubic bones fractures. The diagnosis of osteomalacia was established and the treatment started with Schol’s solution, vitamin D and calcium. In the following two months, acidosis was corrected, and the patient started walking. Conclusion. In our patient with primary Sjögren’s syndrome and interstitial nephritis, osteomalacia was a result of the long time decompensate acidosis, so the correction of acidosis, and the supplementation of vitamin D and calcium were the integral part of the therapy.

  19. A case of scrub typhus requiring maintenance hemodialysis

    Directory of Open Access Journals (Sweden)

    Dae-Yeon Kim

    2013-12-01

    Full Text Available Renal failure caused by scrub typhus is known to be reversible. In most cases, renal function is almost fully restored after appropriate antibiotic treatment. A 71-year-old man was diagnosed with scrub typhus complicated by renal failure. A renal biopsy revealed histopathologic findings consistent with acute tubulointerstitial nephritis. Renal function did not improve 18 months after discharge and the patient required continuous hemodialysis. Although severe renal failure requiring dialysis is a rare complication of scrub typhus, we describe a case of scrub typhus requiring maintenance hemodialysis. To the best of our knowledge, this is the first such report.

  20. Successful treatment of thrombotic microangiopathy associated with dengue infection: A case report and literature review.

    Science.gov (United States)

    Nieto-Ríos, John Fredy; Álvarez Barreneche, María Fernanda; Penagos, Sara Catalina; Bello Márquez, Diana Carolina; Serna-Higuita, Lina Maria; Ramírez Sánchez, Isabel Cristina

    2018-02-01

    Dengue infection has been associated with multiple renal complications, including glomerulonephritis, acute tubular necrosis, tubulointerstitial nephritis, and thrombotic microangiopathy (TMA), this last one being a rare complication of dengue, with only a few reported cases. TMA associated with dengue can be explained by an alteration in the activity of the enzyme ADAMTS13, leading to thrombotic thrombocytopenic purpura; or it can be secondary to direct or indirect endothelial injury by the virus, which leads to hemolytic uremic syndrome. Here, we present a case of severe TMA, not related to ADAMTS13, which was clearly associated with dengue infection. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. NGAL (Lcn2) monomer is associated with tubulointerstitial damage in chronic kidney disease.

    Science.gov (United States)

    Nickolas, Thomas L; Forster, Catherine S; Sise, Meghan E; Barasch, Nicholas; Solá-Del Valle, David; Viltard, Melanie; Buchen, Charles; Kupferman, Shlomo; Carnevali, Maria Luisa; Bennett, Michael; Mattei, Silvia; Bovino, Achiropita; Argentiero, Lucia; Magnano, Andrea; Devarajan, Prasad; Mori, Kiyoshi; Erdjument-Bromage, Hediye; Tempst, Paul; Allegri, Landino; Barasch, Jonathan

    2012-09-01

    The type and the extent of tissue damage inform the prognosis of chronic kidney disease (CKD), but kidney biopsy is not a routine test. Urinary tests that correlate with specific histological findings might serve as surrogates for the kidney biopsy. We used immunoblots and ARCHITECT-NGAL assays to define the immunoreactivity of urinary neutrophil gelatinase-associated lipocalin (NGAL) in CKD, and we used mass spectroscopy to identify associated proteins. We analyzed kidney biopsies to determine whether specific pathological characteristics associated with the monomeric NGAL species. Advanced CKD urine contained the NGAL monomer as well as novel complexes of NGAL. When these species were separated, we found a significant correlation between the NGAL monomer and glomerular filtration rate (r=-0.53, P<0.001), interstitial fibrosis (mild vs. severe disease; mean 54 vs. 167 μg uNGAL/g Cr, P<0.01), and tubular atrophy (mild vs. severe disease; mean 54 vs. 164 μg uNGAL/g Cr, P<0.01). Monospecific assays of the NGAL monomer demonstrated a correlation with histology that typifies progressive, severe CKD.

  2. Dual effect of chemokine CCL7/MCP-3 in the development of renal tubulointerstitial fibrosis

    NARCIS (Netherlands)

    Gonzalez, Julien; Mouttalib, Sofia; Delage, Christine; Calise, Denis; Maoret, Jean-Jose; Pradere, Jean-Philippe; Klein, Julie; Buffin-Meyer, Benedicte; Van der Veen, Betty; Charo, Israel F.; Heeringa, Peter; Duchene, Johan; Bascands, Jean-Loup; Schanstra, Joost-Peter

    2013-01-01

    Most end-stage renal disease kidneys display accumulation of extracellular matrix (ECM) in the renal tubular compartment (tubular interstitial fibrosis - TIF) which is strongly correlated with the future loss of renal function. Although inflammation is a key event in the development of TIF, it can

  3. Ambulatory blood pressure and tubulointerstitial injury in patients with IgA nephropathy.

    Science.gov (United States)

    Haruhara, Kotaro; Tsuboi, Nobuo; Koike, Kentaro; Kanzaki, Go; Okabayashi, Yusuke; Miyazaki, Yoichi; Kawamura, Tetsuya; Ogura, Makoto; Yokoo, Takashi

    2015-12-01

    Few studies have been conducted to assess the ambulatory blood pressure (ABP) in IgA nephropathy (IgAN) patients. This study aimed to determine the relationships between ABP and renal histopathological findings assessed using the Oxford classification (OC) and the Japanese classification (JC), which have recently established histopathological criteria for IgAN. This cross-sectional study included biopsy-diagnosed IgAN patients, in whom both a renal biopsy and ABP measurement were performed. The histopathological findings were assessed using the OC and the JC and were analyzed in relation to the ABP. A total of 111 IgAN patients were included. The score of interstitial fibrosis and tubular atrophy (T score) using the OC was a significantly associated factor with both the daytime and nighttime ABP values. In contrast, the other histopathological scores, including mesangial hypercellularity, endocapillary hypercellularity and segmental glomerulosclerosis, did not show significant associations with the ABP. The histological grade (H-grade) using the JC, which was based on the sum of injured glomeruli, was associated with the daytime ABP, but not with the nighttime ABP. The associations between the T score using the OC (%) and the daytime and nighttime ABP values were independent of age, gender, renal function, proteinuria and the use of antihypertensive medications, whereas the H-grade using the JC (%) did not show significant associations after adjusting for these clinical parameters. These results suggest that the T score using the OC is the most relevant renal histopathological parameter associated with abnormalities of circadian blood pressure in IgAN patients.

  4. César Augusto Restrepo Valencia, Consuelo Vélez Álvarez Abstract Objective. To evaluate the effectiveness of calcineurin ciclosporin and tacrolimus inhibitors to induce remission in patients with refractory lupus nephritis. Patients, materials and methods. Patients with lupus nephritis class IV-G who despite receiving therapy with high doses of steroid and with a cytostatic (cyclophosphamide or mycophenolate for 3 months had not been able to induce some kind of remission.The exclusion criteria were creatinine levels greater than 3 mg / dl, pregnancy, previous history of exposure to calcineurin inhibitors, cancer, active infections, uncontrolled hypertension, and negligence with medication intake. The recommended dose of cyclosporine was 3 mg / kg / day and tacrolimus 0.1 mg / kg / day, in joint with prednisone 0.3 mg / kg / day, cyclophosphamide 1 mg / kg / day or mycophenolate mofetil 1 gram every 12 hours. The cyclophosphamide was administered only during 6 months, after which it was changed to azathioprine at doses of 1 mg / kg / day. Still, mycophenolate was continued at the same dose. All patients completed a minimum period of 12 months follow-up, it was considered that patients achieved partial remission when proteinuria decreased by 50% of the baseline value or its value decreased to less than 1 gram in 24 hours, decrease of leukocytes count and red blood cells in urine of 50%, and creatinine values were stable. A complete remission was considered when there was a reduction in proteinuria in a value less than 300 mg per 24 hours, urinary sediment with less than 3 red blood cells, less than 5 leukocyte for each high power microscopic field, and a creatinine value reduction by 50% or reaching a normal value. Results. Twelve patients met the inclusion criteria and initiated the calcineurin inhibitor protocol. Two presented accelerated deterioration in their function and required chronic dialysis therapy. Ten patients with active treatment completed 12 months

    Directory of Open Access Journals (Sweden)

    César Augusto Restrepo Valencia

    2014-10-01

    Full Text Available Objective: To evaluate the effectiveness of calcineurin ciclosporin and tacrolimus inhibitors to induce remission in patients with refractory lupus nephritis. Patients, materials and methods: Patients with lupus nephritis class IV-G who despite receiving the rapy with high doses of steroid and with a cytostatic (cyclophosphamide or mycophenolate for 3 months had not been able to induce some kind of remission.The exclusion criteria were creatinine levels greater than 3 mg / dl, pregnancy, previous history of exposure to calcineurin inhibitors, cancer, active infections, uncontrolled hypertension, and negligence with medication intake. The recommended dose of cyclosporine was 3 mg / kg / day and tacrolimus 0.1 mg / kg / day, in joint with prednisone 0.3 mg / kg / day, cyclophosphamide 1 mg / kg / day or mycophenolate mofetil 1 gram every 12 hours. The cyclophosphamide was administered only during 6 months, after which it was changed to azathioprine at doses of 1 mg / kg / day. Still, mycophenolate was continued at the same dose. All patients completed a minimum period of 12 months follow-up, it was considered that patients achieved partial remission when proteinuria decreased by 50% of the baseline value or its value decreased to less than 1 gram in 24 hours, decrease of leukocytes count and red blood cells in urine of 50%, and creatinine values were stable. A complete remission was considered when there was a reduction in proteinuria in a value less than 300 mg per 24 hours, urinary sediment with less than 3 red blood cells, less than 5 leukocyte for each high power microscopic field, and a creatinine value reduction by 50% or reaching a normal value. Results: Twelve patients met the inclusion criteria and initiated the calcineurin inhibitor protocol. Two presented accelerated deterioration in their function and required chronic dialysis therapy. Ten patients with active treatment completed 12 months of followup, of which 4 (40% had partial

  5. Nanoemulsion formulation of Abatacept for lupus nephritis therapy

    African Journals Online (AJOL)

    Tropical Journal of Pharmaceutical Research June 2017; 16 (6): 1205-1213. ISSN: 1596-5996 (print); .... been approved for the treatment of rheumatoid arthritis and juvenile inflammatory arthritis, and is being tested for the treatment of several.

  6. Hyperreninemic hypertension secondary to radiation nephritis in a child

    International Nuclear Information System (INIS)

    Hulbert, W.C. Jr.; Ettinger, L.J.; Wood, B.P.; Anderson, V.M.; Putnam, T.C.; Rabinowitz, R.

    1985-01-01

    Radiation injury to the kidney, first reported almost eighty years ago, may vary from subclinical changes in renal blood flow or enzyme activity to clinically significant hypertension and/or renal failure. A child with radiation-induced hyperreninemic hypertension was cured by nephrectomy. The microscopic, subclinical, and clinical changes of irradiation injury are reviewed. The etiology of radiation-induced hypertension, methods of radioprotection, and early detection of radiation renal damage are discussed

  7. Lupus nephritis . Part ll. A clinicopathological correlation and study ...

    African Journals Online (AJOL)

    ... often with uncommon pathogens, were the most important causes of death. Serum creatinine values and creatinine clearance at the time of biopsy or ... persistent hypertension, histological classification IV, and high activity scores were ...

  8. A Predictive Model for Estimation Risk of Proliferative Lupus Nephritis

    Directory of Open Access Journals (Sweden)

    Dong-Ni Chen

    2018-01-01

    Conclusion: This study developed and validated a model including demographic and clinical indices to evaluate the probability of presenting proliferative LN to guide therapeutic decisions and outcomes.

  9. Lupus nephritis: An approach to diagnosis and treatment in South ...

    African Journals Online (AJOL)

    In all patients, treatment should include adjunctive therapies such as renin angiotensin aldosterone system .... Switching to an alternative agent is recommended for ... gastritis, cataracts, avascular necrosis of femur, cushingoid appearance.

  10. Transient nephritis during resolution phase of acute virale hepatitis E

    OpenAIRE

    Arden, Amir David

    2009-01-01

    Hepatitis E Virus is a causative agent of hepatitis. Viral E hepatitis is responsible for various clinical manifestations. However, immune reactions due to hepatitis E virus are rarely encountered. A case of membranoproliferative glomerulonephritis associated with hepatitis E virus is reported her.

  11. Correlation between cytomegalovirus infection and Raynaud's phenomenon in lupus nephritis.

    Science.gov (United States)

    Stratta, P; Canavese, C; Ciccone, G; Santi, S; Quaglia, M; Ghisetti, V; Marchiaro, G; Barbui, A; Fop, F; Cavallo, R; Piccoli, G

    1999-06-01

    Relationships between viruses and autoimmune diseases such as systemic lupus erythematosus (SLE) are still elusive. Recent reports demonstrated the association of some viral infections with peculiar clinical events in the general population, such as cytomegalovirus (CMV) with arterial damage and Parvovirus B19 (PV-B19) with hematologic abnormalities. We planned to look for this kind of viral imprinting in SLE, hypothesizing that traces of specific features of some viral infections might be found in some subsets of seropositive SLE patients. In 60 SLE patients recruited at our nephrologic center, serology for CMV, PV-B19, Epstein-Barr virus viral capsid antigen (EBV-VCA), Epstein-Barr nuclear antigen (EBNA) and Epstein-Barr virus early antigen (EBV-EA) was performed. chi2 and ANOVA were employed to compare the frequency and titers of antiviral antibodies in SLE patients with groups of transplant, hemodialysis and blood donor subjects. chi2, Fisher's test, Bonferroni and Scheffe's test were employed to compare the different biochemical/clinical features between seropositive and seronegative SLE patients. Univariate and multivariate analysis (logistic regression models) were employed to evaluate the odds ratio (OR) of different risk factors for vascular events (including Raynaud's phenomenon, deep venous thrombosis) and hematologic abnormalities (including severe anemia, leukopenia and thrombocytopenia). Anti-CMV (82%), anti-PV-B19 (60%), anti-EBV-VCA (92%) and EBV-EA (45%) IgG antibodies were frequent in SLE, with higher prevalence in comparison with the blood donor group and higher titers in comparison with transplant and hemodialysis groups. CMV seropositivity was a highly significant risk factor for Raynaud's phenomenon (OR +alpha in univariate and multivariate analysis = 13.51 using a correction of 0.5 in case of a zero event), but not for venous vascular events (OR = 1.31). An increased though not significant risk factor was found for antiphospholipid antibodies (OR = 2.71, p = 0.19), while the presence of nephrotic syndrome during the follow-up was a significant protective factor (OR = 0.15, p = 0.035). There was no significantly increased OR for PV-B19 seropositivity in cases with severe anemia (OR = 2.09, p = 0. 29). No significant associations were found with the status of EBV reactivation. In conclusion, our results support the hypothesis that viral infection may imprint the course of SLE leading to specific clinical subsets (i.e. CMV and 'vascular' SLE, with more frequent Raynaud's phenomenon and a less frequent typical histological renal picture responsible for nephrotic syndrome). Further prospective studies are justified to validate these correlations, mainly dealing with associations between acute viral infections and vascular events, thus eventually leading to a better understanding of mutual relationships between viruses and SLE.

  12. Detection of avian nephritis virus and chicken astrovirus in Nigerian ...

    African Journals Online (AJOL)

    2012-02-28

    Feb 28, 2012 ... rate, late maturity and high degree of adaptability to prevailing climatic .... ultraviolet transillumination. ... 2 500 bp were clearly visible in 4 of the 5 gut content samples .... productivity and poor performance generally associated.

  13. Progression of Tubulointerstitial Fibrosis and the Chronic Kidney Disease Phenotype – Role of Risk Factors and Epigenetics

    Directory of Open Access Journals (Sweden)

    Timothy D. Hewitson

    2017-08-01

    Full Text Available Although the kidney has capacity to repair after mild injury, ongoing or severe damage results in scarring (fibrosis and an associated progressive loss of kidney function. However, despite its universal significance, evidence highlights a population based heterogeneity in the trajectory of chronic kidney disease (CKD in these patients. To explain the heterogeneity of the CKD phenotype requires an understanding of the relevant risk factors for fibrosis. These factors include both the extrinsic nature of injury, and intrinsic factors such as age, gender, genetics, and perpetual activation of fibroblasts through priming. In many cases an additional level of regulation is provided by epigenetic mechanisms which integrate the various pro-fibrotic and anti-fibrotic triggers in fibrogenesis. In this review we therefore examine the various molecular and structural changes of fibrosis, and how they are influenced by extrinsic and intrinsic factors. Our aim is to provide a unifying hypothesis to help explain the transition from acute to CKD.

  14. [Cavitating lung lesions in the course of ANCA-associated vasculitis: differential diagnostic aspects].

    Science.gov (United States)

    Kirchner, J; Raab, H P; Länger, F; Wigand, R; Mitrou, P; Jacobi, V

    1998-05-01

    Antineutrophil cytoplasmatic antibodies (ANCA)-associated vasculitides (Wegener's granulomatosis, microscopic polyangiitis, Churg-Strauss syndrome) show quite variable courses. Clinical features of the full blown generalized systemic vasculitis are usually found in the respiratory tract and the kidney. Pulmonary involvement of Wegener's granulomatosis shows commonly nodules and cavitations but also diffuse alveolar hemorrhage. We report the case of a 57 year-old man suffering from dyspnea, thoracal pain, arthralgia, purpura, scleritis and tinitus. Specimen of the kidney showed segmental glomerulosclerosis and tubulointerstitial nephritis. Because of the presence of cANCA Wegener's disease was assumed. Pulmonary infiltrates developed under immunosuppressive treatment with cyclophosphamid. As differential diagnosis of the pulmonary infiltrates, we considered invasive pulmonary aspergillosis as well as infiltrates due to Wegener's granulomatosis. In spite of maximal therapeutic management of patient died of respiratory and cardiovascular failure. The findings at autopsy showed distinct invasive pulmonary aspergillosis and perifocal hemorrhage.

  15. Spectrum of pathological lesions in acute renal failure

    International Nuclear Information System (INIS)

    Kazi, J.I.; Mubarak, M.; Akhter, F.; Ahmed, E.; Naqvi, R.; Naqvi, S.A.; Rizvi, S.A.H.

    2003-01-01

    Objective: To determine the spectrum of pathological lesions in percutaneous renal biopsies of patients with acute renal failure (ARF) and to compare our findings with reported literature. Results: A total of 158 patients were studied. Of these 57 were males and 101 females. Mean age of the patients in this series were 30.7 years with a range of 6 to 75 years. Of these 61 (38.6%) had acute tubular necrosis, 36 (22.7%) acute cortical necrosis and 49(31%) patients had various types of glomerculonephriits (GN). Eight patients (5%) had acute tubulointerstitial nephritis, 3(1.8%) acute pyelonephritis and one patient had mucormycosis. Conclusion: This study showed that even in the selected population of biopsied ARF cases, there was a high prevalence of ischemic renal disease. A substantial number of cases in unexplained ARF on renal biopsy were due to various forms of glomerulonephritis. (author)

  16. Acute Kidney Injury Complicated Epstein-Barr Virus Infection in Infancy

    Directory of Open Access Journals (Sweden)

    Gamze Ozgurhan

    2015-01-01

    Full Text Available Infectious mononucleosis is an acute lymphoproliferative disorder caused by the Epstein-Barr virus (EBV and seen most commonly in children and young adults. Clinical presentation of the disease is characterized by fever, tonsillopharyngitis, lymphadenopathy, and hepatosplenomegaly, whereas serological findings of this benign disorder include positive heterophilic antibody formation (transient increase in heterophilic antibodies and prominence of hematological lymphocytosis of more than 10% of atypical lymphocytes. An EBV infection is usually asymptomatic in childhood, but acute kidney injury can be a rare complication during its course. Most cases recover from the disease completely. Early recognition of EBV infection and estimation of its complication are important for its prognosis. In light of previous literature, we discuss the case evaluated as an EBV infection complicated by acute kidney injury in early childhood and results of tubulointerstitial nephritis shown on a renal biopsy that was later diagnosed as an EBV infection by serological examination.

  17. Anatomo-pathological and epidemiological analysis of urinary tract lesions in dogs

    Directory of Open Access Journals (Sweden)

    Carolina da Fonseca Sapin

    2016-01-01

    Full Text Available ABSTRACT: In dogs, diseases of the urinary tract are common and can be caused by disorders of varied etiology. The objective of this study was to classify qualitatively and quantitatively urinary tract lesions of 363 dogs, which were classified according to its anatomical distribution and etiology. The data was obtained from the revision of 36 years of protocols from the Regional Laboratory of Diagnosis (LRD/UFPel and it represents 4.0% of diagnoses from a total of 8980 for that period and species. Renal injury accounted for 93.1% of cases, with 309 being primary kidney lesions; from which the main lesions were the tubulointerstitial nephritis (142 cases often associated with Leptospirosis (47. Injuries of lower urinary tract accounted for 6.9% of the cases where acute cystitis stands out (19. In this study, renal failure, acute or chronic, represented an important cause of death in dogs.

  18. Contrast-enhanced 18F-fluorodeoxyglucose positron emission tomography/computed tomography in immunoglobulin G4-related retroperitoneal fibrosis

    International Nuclear Information System (INIS)

    Sharma, Punit; Chatterjee, Piyali

    2015-01-01

    Immunoglobulin G4 (IgG4)-related disease encompasses a wide variety of immune disorders previously thought be distinct. IgG4-related retroperitoneal fibrosis is one such entity. Metabolic imaging with 18 F-fluorodeoxyglucose ( 18 F-FDG) positron emission tomography/computed tomography (PET/CT) can be useful in the management of IgG4-related retroperitoneal fibrosis. We here discuss the case of 63-year-old male with IgG4-related retroperitoneal fibrosis and the role, 18 F-FDG PET/CT played in his management

  19. Appendiceal immunoglobulin G4-related disease mimicking appendiceal tumor or appendicitis: A case report

    International Nuclear Information System (INIS)

    Kim, Hyun Soo; Kang, Won Kyung; Chung, Dong Jin

    2016-01-01

    Immunoglobulin G4 (IgG4)-related disease is an autoimmune disease that forms tumorous lesions. Several cases involving various organs are reported, however, IgG4-related disease involving appendix has not been reported yet. In this report, we presented a case of IgG4-related disease of appendix, which raised a suspicion of appendiceal tumor or usual appendicitis and, therefore, led to unnecessary surgical resection. IgG4-related disease should be considered in the differential diagnosis for a mass-like swelling of the appendix, in order to avoid unnecessary surgery

  20. Appendiceal immunoglobulin G4-related disease mimicking appendiceal tumor or appendicitis: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hyun Soo; Kang, Won Kyung; Chung, Dong Jin [Yeouido St. Mary' s Hospital, The Catholic University of Korea, Seoul (Korea, Republic of)

    2016-02-15

    Immunoglobulin G4 (IgG4)-related disease is an autoimmune disease that forms tumorous lesions. Several cases involving various organs are reported, however, IgG4-related disease involving appendix has not been reported yet. In this report, we presented a case of IgG4-related disease of appendix, which raised a suspicion of appendiceal tumor or usual appendicitis and, therefore, led to unnecessary surgical resection. IgG4-related disease should be considered in the differential diagnosis for a mass-like swelling of the appendix, in order to avoid unnecessary surgery.

  1. Does hypokalemia contribute to acute kidney injury in chronic laxative abuse?

    Directory of Open Access Journals (Sweden)

    Eun-Young Lee

    2015-06-01

    Full Text Available Prolonged hypokalemia from chronic laxative abuse is recognized as the cause of chronic tubulointerstitial disease, known as “hypokalemic nephropathy,” but it is not clear whether it contributes to acute kidney injury (AKI. A 42-year-old woman with a history of chronic kidney disease as a result of chronic laxative abuse from a purging type of anorexia nervosa (AN-P, developed an anuric AKI requiring hemodialysis and a mild AKI 2 months later. Both episodes of AKI involved severe to moderate hypokalemia (1.2 and 2.7 mmol/L, respectively, volume depletion, and mild rhabdomyolysis. The histologic findings of the first AKI revealed the remnants of acute tubular necrosis with advanced chronic tubulointerstitial nephritis and ischemic glomerular injury. Along with these observations, the intertwined relationship among precipitants of recurrent AKI in AN-P is discussed, and then we postulate a contributory role of hypokalemia involved in the pathophysiology of the renal ischemia-induced AKI.

  2. Immunoglobulin G4-related prostatitis: a case-control study focusing on clinical and pathologic characteristics

    NARCIS (Netherlands)

    Buijs, Jorie; Maillette de Buy Wenniger, Lucas; van Leenders, Geert; Verheij, Joanne; van Onna, Ilze; Hansen, Bettina; van Heerde, Marianne; Krak, Nanda; Beuers, Ulrich; Bruno, Marco; van Buuren, Henk

    2014-01-01

    To evaluate the occurrence and histopathologic characteristics of immunoglobulin G4 (IgG4)-related prostatic involvement in patients diagnosed with autoimmune pancreatitis. Nine cases of IgG4-related prostatitis were identified among 117 men in the autoimmune pancreatitis and IgG4-associated

  3. Immunoglobulin G4-related prostatitis: A case-control study focusing on clinical and pathologic characteristics

    NARCIS (Netherlands)

    J. Buijs (Jorie); L. Maillette De Buy Wenniger (Lucas); G.J.H.L. Leenders (Geert); J. Verheij (Joanne); I. van Onna (Ilze); B.E. Hansen (Bettina); M. van Heerde (Marianne); N.C. Krak (Nanda); U. Beuers (Ulrich); M.J. Bruno (Marco); H.R. van Buuren (Henk)

    2014-01-01

    markdownabstractOBJECTIVE To evaluate the occurrence and histopathologic characteristics of immunoglobulin G4 (IgG4)- related prostatic involvement in patients diagnosed with autoimmune pancreatitis. METHODS Nine cases of IgG4-related prostatitis were identified among 117 men in the

  4. Immunoglobulin G4-related dacyroadenitis presenting as bilateral chorioretinal folds from severely enlarged lacrimal glands

    Directory of Open Access Journals (Sweden)

    Toru Kurokawa

    2018-03-01

    Conclusions and importance: This is the first account of chorioretinal fold formation by severely enlarged lacrimal glands appearing in IgG4-related dacryoadenitis. Chorioretinal fold formation by an enlarged lacrimal gland occurring bilaterally may represent a basis for suspecting IgG4-related dacryoadenitis. Prompt treatment is recommended for patients presenting with very large lacrimal glands to avoid visual impairment.

  5. Current clinical research of immunoglobulin G4-related orbital disease

    Directory of Open Access Journals (Sweden)

    Yang Wang

    2016-05-01

    Full Text Available Immunoglobulin G4-related disease(IgG4-related diseasehas received lots of attention in medical community as a recently recognized fibro-inflammatory condition. It is characterized by infiltration of IgG4-immunopositive plasmacytes and concentration of elevated serum IgG4. IgG4-related disease shows organ enlargement or nodular/hyperplastic lesions in various organs including the pancreas, hepatobiliary tract and orbit, which is called IgG4-related orbital disease. The diagnostic criteria for IgG4-related disease and IgG4-related orbital disease has recently been established, which is based on clinical, imaging and histopathologic features of the orbital lesions. Besides, attention should be drawn to the differentiation from other diseases. The treatment is empirical including corticosteroids, immunosuppressive drugs, radiotherapy, and rituximab. This article reviews clinical progression of IgG4-related orbital disease.

  6. Expression of T helper 17 cells and interleukin 17 in lupus nephritis patients

    Directory of Open Access Journals (Sweden)

    Nayera Z. Saber

    2017-07-01

    Conclusion: Peripheral blood Th17 cell frequencies and IL-17 in urine are highly linked to LN in SLE and are promising markers of disease activity in LN. Both are valuable targets for future therapeutic applications.

  7. Post-radiation nephritis. Study of the renal consequences of splenic irradiation for lymphoma

    International Nuclear Information System (INIS)

    Le Bourgeois, J.P.; Godefroy, D.; Di Paolo, M.; Parmentier, C.; Tubiana, M.

    1975-01-01

    The left kidney consequences of splenic irradiation in 40 patients with lymphomas were studied. The renal work-up performed before irradiation and every six months afterwards includes: blood pressure, biological tests, IV P and 179 Hg neohydrine renal scan. Computer scan data processing showed a partial disfunction of left kidney in 16 patients with 18 month-follow up. Renal disfunction appeared within 8 to 10 months following spleen irradiation. During that period no clinical or radiological abnormalities were observed [fr

  8. Isolated HBsAg positivity in a Mexican patient with newly diagnosed lupus nephritis

    Directory of Open Access Journals (Sweden)

    Guillermo Delgado-García

    2017-01-01

    Conclusions: Isolated HBsAg positivity may result from multiple causes, one of which is cross-reactivity. To the best of our knowledge, this is the first report of a false-positive reading using CMIA technique in an active lupus patient. It is reasonable to stress that lupus patients with a positive screening for HBV should undergo a confirmatory assay (such as genomic detection, since this diagnosis may have important therapeutic implications.

  9. 75 FR 35492 - Guidance for Industry on Lupus Nephritis Caused By Systemic Lupus Erythematosus-Developing...

    Science.gov (United States)

    2010-06-22

    ... Communication, Outreach and Development (HFM-40), Center for Biologics Evaluation and Research (CBER), Food and...: The Food and Drug Administration (FDA) is announcing the availability of a guidance for industry... the Division of Drug Information, Center for Drug Evaluation and Research, Food and Drug...

  10. ِAssessment of lupus nephritis by measuring urinary retinol binding ...

    African Journals Online (AJOL)

    Ehab

    Background: Renal disease is a common manifestation of systemic lupus erythematosus (SLE). Both glomerular and ... Objective: The study was aimed to assess the urinary RPB level in SLE patients with and without evidence of .... Twenty-one patients were receiving prednisone (1-2 mg/Kg/day) either alone (n= 13) or.

  11. Lupus nephritis: prolonged immunoadsorption (IAS) reduces proteinuria and stabilizes global disease activity.

    Science.gov (United States)

    Stummvoll, Georg H; Schmaldienst, Sabine; Smolen, Josef S; Derfler, Kurt; Biesenbach, Peter

    2012-02-01

    Systemic lupus erythematosus (SLE) is characterized by pathogenic autoantibodies, which can be removed by extracorporeal procedures. While previous studies have shown short-term efficacy of immunoadsorption (IAS) in SLE, no information on long-term benefit and safety is available. IAS was offered to patients with highly active renal disease when conventional therapy had failed. Eleven patients entered the prolonged IAS programme and were followed for up to 10 years (mean 6.4 ± 3.5). Efficacy of IAS was determined by reduction in proteinuria (primary outcome), global disease activity [SLE Disease Activity Index (SLEDAI)] and anti-double-stranded DNA (anti-dsDNA) levels (secondary outcomes). Full/partial remission was defined as ≤ 0.5/≤ 1.0 g/day for proteinuria, ≤ 5/≤ 8 for SLEDAI and ≤ 25/≤ 50 IU/mL for anti-dsDNA levels. We further assessed flares, infections, malignancies and procedure-related adverse events. Short-term IAS (≤ 1 year) resulted in a significant reduction of proteinuria (9.2 ± 3.7 to 2.3 ± 2.4, P = 0.0001), disease activity (SLEDAI 19 ± 8 to 4 ± 2, P = 0.0004) and dsDNA levels (168 ± 205 to 45 ± 34, P = 0.001). In patients without remission after 1 year (n = 5), prolonged IAS decreased proteinuria from 4.3 ± 2.4 to 0.5 ± 0.4 g/day, P = 0.02. At the end of observation, complete remission in proteinuria was achieved in seven patients (64%) and partial remission in two (18%) additional patients. One patient flared and was discontinued; in all other patients, disease activity and anti-dsDNA stabilized at remission levels. Flares (0.28 ± 0.30) and infections (0.66 ± 0.70 per patient/year) were relatively uncommon; no malignancies, anaphylactic or orthostatic adverse events were observed. IAS is effective in short-term use but prolonged IAS can provide additional therapeutic benefit while showing an acceptable safety profile. The vast majority of initially therapy-refractory patients met the remission criteria at the end of observation.

  12. The risk of cardiovascular morbidity and cardiovascular mortality in systemic lupus erythematosus and lupus nephritis

    DEFF Research Database (Denmark)

    Hermansen, Marie-Louise; Lindhardsen, Jesper; Torp-Pedersen, Christian

    2017-01-01

    Objective: . To assess the role of LN as a risk factor for myocardial infarction (MI), stroke and cardiovascular mortality (CVM) in patients with SLE. Methods: . The study was conducted using individual-level data from multiple nationwide registers. We identified a cohort of patients diagnosed wi...

  13. Deposition of nucleosomal antigens (histones and DNA) in the epidermal basement membrane in human lupus nephritis.

    NARCIS (Netherlands)

    Grootscholten, C.; Bruggen, M.C.J. van; Pijl, J.W. van der; Jong, E.M.G.J. de; Ligtenberg, G.; Derksen, R.H.W.M.; Berden, J.H.M.

    2003-01-01

    OBJECTIVE: Antinuclear autoantibodies complexed to nucleosomes can bind to heparan sulfate (HS) in the glomerular basement membrane. This binding is due to the binding of the positively charged histones to the strongly anionic HS. Nucleosomes and histones have been identified in glomerular deposits

  14. Acute kidney injury with granulomatous interstitial nephritis and vasculitis revealing sarcoidosis

    OpenAIRE

    Amel Harzallah; Hayet Kaaroud; Karima Boubaker; Samia Barbouch; Rim Goucha; Fethi Ben Hamida; Taieb Ben Abdallah

    2017-01-01

    Sarcoidosis is an inflammatory disease that affects mostly the lungs and lymph glands. Renal involvement is rare and especially vasculitis. We report a case who presented an acute kidney failure and had sarcoidosis with vasculitis and nodular splenic involvement. A 35-year-old woman presenting a Lofgren syndrome was hospitalized for acute renal failure with cervical lymphadenopathy without other clinical findings. Laboratory data disclosed elevated angiotensin converting enzyme serum level. A...

  15. Lupus Nephritis in Males: Clinical Features, Course, and Prognostic Factors for End-Stage Renal Disease

    Directory of Open Access Journals (Sweden)

    Andrés Urrestarazú

    2017-09-01

    Discussion: LN in males usually presents as nephrotic syndrome, and type IV LN is the most frequent form. An estimated glomerular filtration rate < 60 ml/min at the time of renal biopsy is associated with poor renal outcomes. There were no differences in remission or progression of LN in males when compared with a cohort of female patients with LN.

  16. Autoantibodies against Modified Histone Peptides in SLE Patients Are Associated with Disease Activity and Lupus Nephritis

    NARCIS (Netherlands)

    Dieker, J.W.; Berden, J.H.; Bakker, M.A.; Briand, J.P.; Muller, S.; Voll, R.; Sjowall, C.; Herrmann, M.; Hilbrands, L.B.; Vlag, J. van der

    2016-01-01

    Persistent exposure of the immune system to death cell debris leads to autoantibodies against chromatin in patients with systemic lupus erythematosus (SLE). Deposition of anti-chromatin/chromatin complexes can instigate inflammation in multiple organs including the kidney. Previously we identified

  17. Intravenous immunoglobulin therapy in a patient with lupus serositis and nephritis.

    Science.gov (United States)

    Meissner, M; Sherer, Y; Levy, Y; Chwalinska-Sadowska, H; Langevitz, P; Shoenfeld, Y

    2000-01-01

    The use of intravenous immunoglobulin (IVIg) has been reported as an immunomodulating agent in several autoimmune diseases, including systemic lupus erythematosus (SLE). Herein we report a SLE patient with severe clinical presentation that included pericarditis, pleural effusion, nephrotic range proteinuria, leukopenia, and lymphopenia. The patient received one course of high-dose IVIg (2.8 g/kg body weight), and within a week of post-IVIg therapy, her condition significantly improved. One-month post-IVIg there were decreased proteinuria, elevated leukocytes and lymphocytes count, decrease in antinuclear and anti-dsDNA antibodies, and disappearance of pericarditis and pleuritis. This case demonstrates the efficacy of IVIg in severe SLE with various clinical manifestations.

  18. Lack of passive transfer of renal tubulointerstitial disease by serum or monoclonal antibody specific for renal tubular antigens in the mouse.

    Science.gov (United States)

    Evans, B D; Dilwith, R L; Balaban, S L; Rudofsky, U H

    1988-01-01

    Mice immunized with rabbit renal basement membranes form autoantibodies to their kidney glomerular and tubular basement membranes (GBM/TBM). Development of renal tubular disease (RTD) consists of deposition of autoantibodies along the GBM/TBM with the inter- and intratubular accumulation of lymphocytes and macrophages and destruction of the TBM. Transfer of this disease in mice with either serum or monoclonal antibodies, however, has been difficult to demonstrate and, therefore, attempts were made to confirm a report that RTD is passively transferred by anti-TBM autoantibodies. Using the revised protocol in this later report, we found that 12 weeks after transfer autoantibodies were deposited along the GBM and/or TBM of the recipients, yet RTD was not observed. Although qualitative and quantitative characteristics of the antibody may play a role in the pathogenesis in the murine model of RTD, we could not obtain evidence to support and confirm this study.

  19. Rethinking Ormond’s Disease

    Science.gov (United States)

    Khosroshahi, Arezou; Carruthers, Mollie N.; Stone, John H.; Shinagare, Shweta; Sainani, Nisha; Hasserjian, Robert P.; Deshpande, Vikram

    2013-01-01

    Abstract Idiopathic retroperitoneal fibrosis (RPF) is a periaortic sclerotic disease that encases adjacent retroperitoneal structures, particularly the ureters. A subset of idiopathic RPF cases can be associated with IgG4-related disease, but the frequency of this association is not clear. We selected 23 cases of idiopathic RPF and identified IgG4-related RPF cases based on the presence of IgG4+ plasma cells in the tissue, using an IgG4/IgG ratio cutoff of >40%. We then compared the IgG4-related RPF patients and the non-IgG4-related RPF patients in terms of both the presence of histopathologic features typical of IgG4-related disease and the simultaneous occurrence (or history) of other organ manifestations typical of IgG4-related disease. The IgG4-related RPF and non-IgG4-related RPF groups were also analyzed in terms of clinical, laboratory, and radiologic features and treatment review. We identified 13 cases of IgG4-related RPF (57% of the total cohort). The distinguishing features of IgG4-related RPF were histopathologic and extra-organ manifestations of IgG4-related disease. The IgG4-related RPF patients were statistically more likely than non-IgG4-related RPF patients to have retroperitoneal biopsies showing lymphoplasmacytic infiltrate (p = 0.006), storiform fibrosis (p = 0.006), or tissue eosinophilia (p = 0.0002). Demographics of the 2 groups, including a middle-aged, male predominance (mean age, 58 yr; 73% male), were similar. IgG4-related disease accounts for a substantial percentage of patients with “idiopathic” RPF. Histopathologic features such as storiform fibrosis, obliterative phlebitis, and tissue eosinophilia are critical to identifying this disease association. Extraretroperitoneal manifestations of IgG4-related disease are also often present among patients with IgG4-related RPF. Elevated IgG4/total IgG ratios in tissue biopsies are more useful than the number of IgG4+ plasma cells per high-power field in cases of RPF that are highly fibrotic. PMID:23429355

  20. The Significance of Serum beta2-Microglobulin Measurement in Various Renal Diseases

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    Koong, Sung Soo; Oh, Ha Yong; Han, Jin Suk; Lee, Jung Sang [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    1985-03-15

    To evaluate change of serum beta{sub 2}-microglobulin concentration (sbeta{sub 2}-MG) and the usefulness of sbeta{sub 2}-MG and sbeta{sub 2}-MG/serum creatinine concentration (sCr) ratio in various renal diseases, sbeta{sub 2}-MG and sCr were measured in 25 normal controls and 90 patients of various renal diseases (16 cases of glomerulonephritis, 12 cases of acute renal failure, 8 cases of chronic renal failure, 24 cases of nephrotic syndrome, 15 cases of tubulointerstitial diseases and 15 cases of lupus nephritis) using Phadebas beta{sub 2}-Micro Test kits. The results were as follows; 1) In normal control, the mean value of sbeta{sub 2}-MG was 1.65+-0.41 mg/l and the mean value of sbeta{sub 2}-MG/sCr ratio was 0.14+-0.05. 2) In various renal diseases, the mean value of sbeta{sub 2}-MG was 6.74+-5.47 mg/l. The mean value of sbeta{sub 2}-MG/sCr ratio was 0.24+-0.11 and significantly elevated than that of normal contro1. (P<0.05). 3) The correlation between sbeta-2-MG and sCr in glomerular and tubulointerstitial disease was log sbeta{sub 2}-MG=0.90 log sCr-0.48 and its correlation coefficient was 0.78 (P<0.05). 4) In glomerular disease, the correlation between sbeta{sub 2}-MG and sCr was log sbeta{sub 2}-MG=0.89 log sCr-0.46 (r-0.76) and in tubulointerstitial disease, it was log sbeta{sub 2}-MG=0.95 1og sCr-0.59 (r-0.87). There was no significant difference between the two groups (p<0.05). 5) Among 32 cases of glomerular and tubulointerstitial disease patients, whose sCr was within normal range, 17 cases showed elevated sbeta{sub 2}-MG. The mean values of sbeta{sub 2}-MG/sCr ratio in these patients was 0.30+-0.14 and significantly elevated than that of normal control (p<0.05). 6) In 15 cases of lupus nephritis, 12 cases showed elevated sbeta{sub 2}-MG with normal sCr and 12 cases showed elevated sbeta{sub 2}-MG/sCr ratio. With above results, It was found that the sbeta{sub 2}-MG can be used as an index of glomerular filtration rate as in the case of sCr and thats

  1. The clinical and pathological characteristics of nephropathies in connective tissue diseases in the Japan Renal Biopsy Registry (J-RBR).

    Science.gov (United States)

    Ichikawa, Kazunobu; Konta, Tsuneo; Sato, Hiroshi; Ueda, Yoshihiko; Yokoyama, Hitoshi

    2017-12-01

    In connective tissue diseases, a wide variety of glomerular, tubulointerstitial, and vascular lesions of the kidney are observed. Nonetheless, recent information is limited regarding renal lesions in connective tissue diseases, except in systemic lupus erythematosus (SLE). In this study, we used a nationwide database of biopsy-confirmed renal diseases in Japan (J-RBR) (UMIN000000618). In total, 20,523 registered patients underwent biopsy between 2007 and 2013; from 110 patients with connective tissue diseases except SLE, we extracted data regarding the clinico-pathological characteristics of the renal biopsy. Our analysis included patients with rheumatoid arthritis (RA) (n = 52), Sjögren's syndrome (SjS) (n = 35), scleroderma (n = 10), mixed connective tissue disease (MCTD; n = 5), anti-phospholipid syndrome (APS; n = 3), polymyositis/dermatomyositis (PM/DM; n = 1), Behçet's disease (n = 1) and others (n = 3). The clinico-pathological features differed greatly depending on the underlying disease. The major clinical diagnosis was nephrotic syndrome in RA; chronic nephritic syndrome with mild proteinuria and reduced renal function in SjS; rapidly progressive nephritic syndrome in scleroderma. The major pathological diagnosis was membranous nephropathy (MN) and amyloidosis in RA; tubulointerstitial nephritis in SjS; proliferative obliterative vasculopathy in scleroderma; MN in MCTD. In RA, most patients with nephrosis were treated using bucillamine, and showed membranous nephropathy. Using the J-RBR database, our study revealed that biopsy-confirmed cases of connective tissue diseases such as RA, SjS, scleroderma, and MCTD show various clinical and pathological characteristics, depending on the underlying diseases and the medication used.

  2. Tumefactive immunoglobulin G4-related disease involving the dura mater: A case report and literature review

    International Nuclear Information System (INIS)

    Lee, Jeong Hoon; Lee, Ji Hoon; Ko, Yong; Paik, Seoung Sam; Lee, Young Jun; Park, Dong Woo

    2015-01-01

    Immunoglobulin G4 (IgG4)-related disease is a well-known disorder characterized by an inflammatory reaction with an increase in the number of IgG4-positive plasma cells associated with sclerosis. IgG4-related disease often affects the dura mater with a pattern of diffuse thickening when the central nervous system is involved. However, some nodular dural thickening requires discrimination from tumors because of obviously different treatment options. We report of a case of IgG4-related disease with tumefactive dural involvement

  3. Osteomalacia complicating renal tubular acidosis in association with Sjogren′s syndrome

    Directory of Open Access Journals (Sweden)

    Zohra El Ati

    2014-01-01

    Full Text Available Renal involvement in Sjogren′s syndrome (SS is not uncommon and may precede other complaints. Tubulointerstitial nephritis is the most common renal disease in SS and may lead to renal tubular acidosis (RTA, which in turn may cause osteomalacia. Nevertheless, osteomalacia rarely occurs as the first manifestation of a renal tubule disorder due to SS. We herewith describe a 43-year-old woman who was admitted to our hospital for weakness, lumbago and inability to walk. X-ray of the long bones showed extensive demineralization of the bones. Laboratory investigations revealed chronic kidney disease with serum creatinine of 2.3 mg/dL and creatinine clearance of 40 mL/min, hypokalemia (3.2 mmol/L, hypophosphatemia (0.4 mmol/L, hypocalcemia (2.14 mmol/L and hyperchloremic metabolic acidosis (chlorine: 114 mmol/L; alkaline reserve: 14 mmol/L. The serum alkaline phosphatase levels were elevated. The serum levels of 25-hydroxyvitamin D and 1,25-dihydroxy vitamin D were low and borderline low, respectively, and the parathyroid hormone level was 70 pg/L. Urinalysis showed inappropriate alkaline urine (urinary PH: 7, glycosuria with normal blood glucose, phosphaturia and uricosuria. These values indicated the presence of both distal and proximal RTA. Our patient reported dryness of the mouth and eyes and Schirmer′s test showed xerophthalmia. An accessory salivary gland biopsy showed changes corresponding to stage IV of Chisholm and Masson score. Kidney biopsy showed diffuse and severe tubulo-interstitial nephritis with dense lymphoplasmocyte infiltrates. Sicca syndrome and renal interstitial infiltrates indicated SS as the underlying cause of the RTA and osteomalacia. The patient received alkalinization, vitamin D (Sterogyl ®, calcium supplements and steroids in an initial dose of 1 mg/kg/day, tapered to 10 mg daily. The prognosis was favorable and the serum creatinine level was 1.7 mg/dL, calcium was 2.2 mmol/L and serum phosphate was 0.9 mmol/L.

  4. Frequency, clinicopathological features and phylogenetic analysis of feline morbillivirus in cats in Istanbul, Turkey.

    Science.gov (United States)

    Yilmaz, Huseyin; Tekelioglu, Bilge K; Gurel, Aydin; Bamac, Ozge E; Ozturk, Gulay Y; Cizmecigil, Utku Y; Altan, Eda; Aydin, Ozge; Yilmaz, Aysun; Berriatua, Eduardo; Helps, Chris R; Richt, Juergen A; Turan, Nuri

    2017-12-01

    Objectives The aim of the study was to investigate feline morbillivirus (FmoPV) frequency, phylogeny and associated pathology in cats in Istanbul, Turkey. Methods Samples from sick (n = 96) and dead ( n = 15) cats were analysed using reverse transcription PCR. Blood and urine analyses and histopathology were also performed. Results FmoPV RNA was detected in six cats (5.4%), including three sick (in the urine) and three dead cats (tissues). A significantly greater proportion of FmoPV RNA-positive cats had street access compared with non-infected cats. Blood samples from the morbillivirus-positive cats were negative for morbillivirus RNA. Tubular parenchymal cells, lymphoid and plasma cells in kidney and hepatocytes, lymphoid and plasma cells in liver from dead cats were also positive by immunohistochemistry for the viral N protein. Two FmoPV-positive cats were also positive for feline coronavirus RNA and one cat for feline immunodeficiency virus RNA and feline leukaemia virus proviral DNA. Phylogenetic analysis of the six FmoPV-positive cats showed that the strains were grouped into cluster D and had high similarity (98.5-100%) with strains from Japan and Germany. In the three FmoPV RNA-positive sick cats, respiratory, urinary and digestive system signs were observed as well as weight loss, fever and depression in some cats. Similar clinical signs were also seen in the morbillivirus RNA-negative sick cats. FmoPV RNA-positive cats had lower median red blood cell count, haemoglobin, albumin, albumin/globulin and urobilinogen and higher alanine transaminase, alkaline phosphatase and bilirubin compared with non-infected cats. Significant histopathology of FmoPV RNA-positive dead cats included tubulointerstitial nephritis characterised by severe granular and vacuolar degeneration of the epithelial cells of the cortical and medullary tubules as well as mononuclear cell infiltrates. Widespread lymphoid cell infiltrates were detected in the renal cortex and medullary

  5. Osteomalacia complicating renal tubular acidosis in association with Sjogren's syndrome.

    Science.gov (United States)

    El Ati, Zohra; Fatma, Lilia Ben; Boulahya, Ghada; Rais, Lamia; Krid, Madiha; Smaoui, Wided; Maiz, Hedi Ben; Beji, Soumaya; Zouaghi, Karim; Moussa, Fatma Ben

    2014-09-01

    Renal involvement in Sjogren's syndrome (SS) is not uncommon and may precede other complaints. Tubulointerstitial nephritis is the most common renal disease in SS and may lead to renal tubular acidosis (RTA), which in turn may cause osteomalacia. Nevertheless, osteomalacia rarely occurs as the first manifestation of a renal tubule disorder due to SS. We herewith describe a 43-year-old woman who was admitted to our hospital for weakness, lumbago and inability to walk. X-ray of the long bones showed extensive demineralization of the bones. Laboratory investigations revealed chronic kidney disease with serum creatinine of 2.3 mg/dL and creatinine clearance of 40 mL/min, hypokalemia (3.2 mmol/L), hypophosphatemia (0.4 mmol/L), hypocalcemia (2.14 mmol/L) and hyperchloremic metabolic acidosis (chlorine: 114 mmol/L; alkaline reserve: 14 mmol/L). The serum alkaline phosphatase levels were elevated. The serum levels of 25-hydroxyvitamin D and 1,25-dihydroxy vitamin D were low and borderline low, respectively, and the parathyroid hormone level was 70 pg/L. Urinalysis showed inappropriate alkaline urine (urinary PH: 7), glycosuria with normal blood glucose, phosphaturia and uricosuria. These values indicated the presence of both distal and proximal RTA. Our patient reported dryness of the mouth and eyes and Schirmer's test showed xerophthalmia. An accessory salivary gland biopsy showed changes corresponding to stage IV of Chisholm and Masson score. Kidney biopsy showed diffuse and severe tubulo-interstitial nephritis with dense lymphoplasmocyte infiltrates. Sicca syndrome and renal interstitial infiltrates indicated SS as the underlying cause of the RTA and osteomalacia. The patient received alkalinization, vitamin D (Sterogyl ®), calcium supplements and steroids in an initial dose of 1 mg/kg/day, tapered to 10 mg daily. The prognosis was favorable and the serum creatinine level was 1.7 mg/dL, calcium was 2.2 mmol/L and serum phosphate was 0.9 mmol/L.

  6. Deceased donor organ transplantation with expanded criteria donors: a single-center experience from India.

    Science.gov (United States)

    Goplani, K R; Firoz, A; Ramakrishana, P; Shah, P R; Gumber, M R; Patel, H V; Vanikar, A V; Trivedi, H L

    2010-01-01

    Deceased donor organ transplantation (DDOT) accounts for DKT) and 19 single (SKT). Fourteen donors had hypertension, a cerebrovascular accident as the cause of death, 9 had both, and 4 had diabetes. Mean donor age was 70.3 +/- 8.9 years. Decisions on the procedure were based upon frozen section biopsy in 13 of 21 donors. Mean DKT donor age was 76 +/- 9.7 years versu 64 +/- 5.7 years of SKT donors. The native kidney diseases were chronic glomerulonephritis (n = 14), diabetic nephropathy (n = 7), tubulointerstitial nephritis (n = 4) and polycystic kidney disease, focal segmental glomerulosclerosis, lupus nephritis and patchy cortical necrosis, (n = 1 each). Mean recipient age of DKT versus SKT was 43.5 versus 42.3 years. All recipients received rabbit anti-thymocyte globulin, followed by steroid, mycophenolate mofetil/calcinueurin inhibitor. Over a mean follow-up of 341 days, the mean serum creatinine (SCr) of 25/29 patients was 1.60 mg/dL (range, 1.0-2.6). The mean SCr of SKT patients was 1.59 +/- 0.63 mg/dL and of DKT, 1.62 +/- 0.48 mg/dL. Ten patients had delayed graft function and 11 had biopsy proven acute tubular necrosis. Seven (24%) patients had rejection (grade 3 Banff update '05, type IA; 4, type 2A); 6 responded to antirejection; 1 graft was lost at 7 months due to chronic rejection. Three (10.3%) patients were lost, 1 each due to AMI, sepsis, and CMV disease. In the circumstances of organ shortage, DDOT with expanded criteria donor is a feasible option.

  7. An immunoglobulin G-4 related sclerosing disease of the small bowel: CT and small bowel series findings

    International Nuclear Information System (INIS)

    Ko, Young Hwan; Hwang, Dae Hyun; Min, Seon Jeong; Woo, Ji Young; Kim, Jeong Won; Hong, Hye Sook; Yang, Ik; Lee, Yul

    2013-01-01

    Immunoglobulin G4 (IgG4)-related sclerosing disease is rare and is known to involve various organs. We present a case of histologically proven IgG4-related sclerosing disease of the small bowel with imaging findings on computed tomography (CT) and small bowel series. CT showed irregular wall thickening, loss of mural stratification and aneurysmal dilatation of the distal ileum. Small bowel series showed aneurysmal dilatations, interloop adhesion with traction and abrupt angulation.

  8. Immunoglobulin G4-related disease: autoimmune pancreatitis and extrapancreatic manifestations

    Directory of Open Access Journals (Sweden)

    Daniel Alvarenga Fernandes

    2016-04-01

    Full Text Available Abstract We present a case of immunoglobulin G4 (IgG4-related disease with pancreatic and extrapancreatic involvement, including the biliary and renal systems. Given the importance of imaging methods for the diagnosis of IgG4-related disease and its differentiation from pancreatic adenocarcinoma, we emphasize important abdominal computed tomography and magnetic resonance imaging findings related to this recently recognized systemic autoimmune disease.

  9. Tubuloreticular Inclusions in the Absence of Systemic Lupus Erythematosus and HIV Infection: A Report of Three Pediatric Cases

    Directory of Open Access Journals (Sweden)

    Ayah Elmaghrabi

    2017-06-01

    Full Text Available Tubuloreticular inclusions (TRIs are subcellular structures located within the cisternae of endoplasmic reticulum. Formation of TRIs has been linked to the exposure of excess interferon (IFN, either from endogenous or exogenous sources. In renal disease, TRIs have been most commonly associated with systemic lupus erythematosus (SLE, and human immunodeficiency virus-associated nephropathy (HIVAN. Case reports of patients with renal biopsies showing TRIs without underlying SLE or HIV are infrequent in adults, and to our knowledge none have been reported in children. We report 3 pediatric cases in which the renal biopsy showed TRIs on electron microscopy without underlying SLE or HIV infection. The first patient presented at 2 years of age with nephrotic syndrome and renal failure. His renal biopsy revealed focal segmental glomerulosclerosis and TRIs. The second patient presented at 6 months of age with infantile nephrotic syndrome, and his renal biopsy revealed membranous glomerulopathy and TRIs. The last patient presented at 4 years of age with acute kidney injury of unclear etiology leading to chronic kidney disease. Her biopsy revealed acute and chronic tubulointerstitial nephritis with TRIs. Despite extensive evaluation in all 3 patients, including testing for HIV infection and SLE, we could not identify an underlying etiology to explain the presence of TRIs. In conclusion, renal biopsy with TRIs in the absence of underling SLE and HIV remains obscure. We propose a possible role for excess IFN triggered by an abnormal immune response to common viral infections in the formation of TRIs and renal injury.

  10. The protective effect of curcumin against lithium-induced nephrotoxicity in rats

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    Mohammad Shaterpour

    2017-08-01

    Full Text Available Lithium is an element which has been used as salts of chloride or carbonate for many years in the treatment of some psychological disorders such as mania, bipolar or schizophrenic diseases. Chronic application of lithium may induce some serious nephropathies such as natriuresis, renal tubular acidosis, tubulointerstitial nephritis progression to progressive chronic kidney disease and hypercalcemia and, most commonly, nephrogenic diabetes insipidus. Curcumin is an antioxidant derived from Curcuma longa (turmeric or curcuma which has the ability to react directly with reactive species and up-regulation of many cytoprotective and antioxidant proteins. The preventive roles of curcumin in nephropathies were reported, but there was little information on the protective effect of curcumin against lithium-induced nephrotoxicity. In this study, male Wistar rats divided into five groups of six each and were treated as follows: group1; animals were received lithium chloride as 2 mmol/kg, group 2; animals were received normal saline (0, 5%, group 3; animals were received curcumin (200 mg/kg, group 4 animals were received curcumin plus lithium and group 5; animals were received solvent intraperitoneally for three weeks. Then the animals were killed and biochemical parameters of blood were assayed and histopathological assessment was performed. The results have shown that curcumin significantly improved the biochemicals (BUN, creatinine, malondialdehyde. Curcumin prevented significantly the histological parameters that were changed by lithium administration in rats. Our results provide new insights into beneficial usages of curcumin in chronic nephrotoxicity induced by lithium salts.

  11. Natural Infections With Pigeon Paramyxovirus Serotype 1: Pathologic Changes in Eurasian Collared-Doves ( Streptopelia decaocto) and Rock Pigeons ( Columba livia) in the United States.

    Science.gov (United States)

    Isidoro-Ayza, M; Afonso, C L; Stanton, J B; Knowles, S; Ip, H S; White, C L; Fenton, H; Ruder, M G; Dolinski, A C; Lankton, J

    2017-07-01

    Pigeon paramyxovirus serotype 1 (PPMV-1) is a globally distributed, virulent member of the avian paramyxovirus serotype 1 serogroup that causes mortality in columbiformes and poultry. Following introduction into the United States in the mid-1980s, PPMV-1 rapidly spread causing numerous mortality events in Eurasian collared-doves ( Streptopelia decaocto) (ECDOs) and rock pigeons ( Columba livia) (ROPIs). The investigators reviewed pathological findings of 70 naturally infected, free-ranging columbiforms from 25 different mortality events in the United States. Immunohistochemistry targeting PPMV-1 nucleoprotein was used to determine the tissue distribution of the virus in a subset of 17 birds from 10 of the studied outbreaks. ECDOs (61 birds) and ROPIs (9 birds) were the only species in which PPMV-1-associated disease was confirmed by viral isolation and presence of histologic lesions. Acute to subacute tubulointerstitial nephritis and necrotizing pancreatitis were the most frequent histologic lesions, with immunolabeling of viral antigen in renal tubular epithelial cells and pancreatic acinar epithelium. Lymphoid depletion of bursa of Fabricius and spleen was common, but the presence of viral antigen in these organs was inconsistent among infected birds. Hepatocellular necrosis was occasionally present with immunolabeling of hypertrophic Kupffer cells, and immunopositive eosinophilic intracytoplasmic inclusion bodies were present in hepatocytes of 1 ECDO. Immunopositive lymphocytic choroiditis was present in 1 ECDO, while lymphocytic meningoencephalitis was frequent in ROPIs in absence of immunolabeling. This study demonstrates widespread presence of PPMV-1 antigen in association with histologic lesions, confirming the lethal potential of this virus in these particular bird species.

  12. Relative efficacy of casein or soya protein combined with palm or safflower-seed oil on hyperuricaemia in rats.

    Science.gov (United States)

    Lo, Hui-Chen; Wang, Yao-Horng; Chiou, Hue-Ying; Lai, Shan-Hu; Yang, Yu

    2010-07-01

    Diets that ameliorate the adverse effects of uric acid (UA) on renal damage deserve attention. The effects of casein or soya protein combined with palm or safflower-seed oil on various serum parameters and renal histology were investigated on hyperuricaemic rats. Male Wistar rats administered with oxonic acid and UA to induce hyperuricaemia were fed with casein or soya protein plus palm- or safflower-seed oil-supplemented diets. Normal rats and hyperuricaemic rats with or without allopurinol treatment (150 mg/l in drinking water) were fed with casein plus maize oil-supplemented diets. After 8 weeks, allopurinol treatment and soya protein plus safflower-seed oil-supplemented diet significantly decreased serum UA in hyperuricaemic rats (one-way ANOVA; P soya protein and casein attenuated hyperuricaemia-induced decreases in serum albumin and insulin, respectively (two-way ANOVA; P soya protein significantly decreased renal NO and nitrotyrosine and palm oil significantly decreased renal nitrotyrosine, TNF-alpha and interferon-gamma and increased renal transforming growth factor-beta. Casein with safflower-seed oil significantly attenuated renal tubulointerstitial nephritis, crystals and fibrosis. Comparing casein v. soya protein combined with palm or safflower-seed oil, the results support that casein with safflower-seed oil may be effective in attenuating hyperuricaemia-associated renal damage, while soya protein with safflower-seed oil may be beneficial in lowering serum UA and TAG.

  13. Systemic sarcoidosis complicated of acute renal failure: about 12 cases.

    Science.gov (United States)

    Mahfoudhi, Madiha; Mamlouk, Habiba; Turki, Sami; Kheder, Adel

    2015-01-01

    The sarcoidosis is a systemic granulomatosis affecting most frequently the lungs and the mediastinum. An acute renal failure reveals exceptionally this disease. It's a retrospective study implicating 12 cases of sarcoidosis complicated of acute renal failure. The aim of this study is to determine epidemiological, clinical, biological and histological profile in these cases and then to indicate the interest to consider the diagnosis of sarcoidosis in cases of unexplained renal failure. Extra-renal complications, therapeutic modalities and the outcome were determined in all patients. Our series involved 12 women with an average age of 40 years. Biological investigations showed an abnormal normocalcemia in 7 cases, a hypercalcemia in 5 cases, a hypercalciuria in 10 cases and polyclonal hypergammaglobulinemia in 7 cases. An acute renal failure was found in all patients with a median creatinin of 520 umol/L. For all patients, the renal echography was normal however, the kidney biopsy showed tubulo-interstitial nephritis. The extra-renal signs highlighting pulmonary interstitial syndrome in 5 cases, a sicca syndrome in 4 cases, mediastinal lymph nodes in 2 cases, a lymphocytic alveolitis in 3 cases, an anterior granulomatous uveitis in 2 cases and a polyarthritis in 5 cases. Five patients benefited of hemodialysis. The treatment consisted of corticosteroid in all cases. The follow up was marked by complete resolution of clinical and biological signs. The diagnosis of renal sarcoidosis must be done quickly to prevent renal failure.

  14. Ectopic germinal center and megalin defect in primary Sjogren syndrome with renal Fanconi syndrome.

    Science.gov (United States)

    Wang, Jing; Wen, Yubing; Zhou, Mengyu; Shi, Xiaoxiao; Jiang, Lanping; Li, Mingxi; Yu, Yang; Li, Xuemei; Li, Xuewang; Zhang, Wen; Lundquist, Andrew L; Chen, Limeng

    2017-06-02

    This study reports the clinical and pathological features of 12 cases of primary Sjogren syndrome (pSS) with renal involvement presenting with proximal tubular dysfunction in a single center, and investigates the possible correlation of ectopic germinal center formation and megalin/cubilin down-expression. Clinical and pathological records were reviewed. Immunohistochemistry was carried out to detect megalin, cubilin, CD21 and IL-17 expression. Patients presented with different degrees of proximal renal tubule lesion and decreased estimated glomerular filtration rate (eGFR). Renal biopsy revealed tubulointerstitial nephritis, with tubular epithelial cell degeneration, tubular atrophy, interstitial inflammation and focal fibrosis. Immunohistochemistry revealed decreased expression of megalin and cubilin, two important multiligand protein receptors on the brush border of proximal tubular epithelial cells. IL-17 secreted by Th17 subtype effector T cells was diffusely detected in the renal proximal tubule, with a negative correlation of IL-17 and megalin expression. In addition, ectopic germinal centers characterized by CD21 + follicular dendritic cells were present in the renal interstitium. In patients with a decreased eGFR, treatment with 4 weeks of glucocorticoid therapy resulted in an improved eGFR in 75% of patients. We report 12 cases of pSS characterized by Fanconi syndrome. The decreased megalin and cubilin expression may contribute to the proximal tubular reabsorption defect, possibly secondary to Th17 infiltration and formation of ectopic germinal centers.

  15. Renal flagellate infections in reptiles: 29 cases.

    Science.gov (United States)

    Juan-Sallés, Caries; Garner, Michael M; Nordhausen, Robert W; Valls, Xavier; Gallego, Miguel; Soto, Sara

    2014-03-01

    Renal infection with flagellated protozoa was retrospectively evaluated in 29 reptiles, including 12 turtles, 7 tortoises, and 6 chameleons; overall, 20 species of reptiles were represented. Most cases presented with nonspecific clinical signs or a combination of several concurrent diseases. Nineteen of 29 reptiles had tubulointerstitial nephritis associated with flagellates, and this lesion was considered contributory to death in 15 cases, although concurrent diseases were frequent. Infection was invasive into the renal interstitium in three reptiles due to tubular rupture and in one chameleon also spread to adjacent tissues, coelomic cavity, and blood vessels due to renal rupture. Cytologic or ultrastructural evaluation of trophozoites in two cases was consistent with diplomonad flagellates. Renal disease was often complicated with soft-tissue mineralization and/or gout. Gastrointestinal and cloacal infection with flagellates and inflammation were frequent in reptiles in which the digestive tract was available for histopathologic examination, and this supports the possibility of infections ascending the urinary tract from the cloaca. Renal disease associated with flagellate protozoa is rare in vertebrates but appears to be relevant in reptiles, particularly chelonians and chameleons.

  16. Acute renal failure due to mesangial proliferative glomerulonephritis in a pregnant woman with primary Sjögren's syndrome.

    Science.gov (United States)

    Adam, Fatma Ulku; Torun, Dilek; Bolat, Filiz; Zumrutdal, Aysegul; Sezer, Siren; Ozdemir, Fatma Nurhan

    2006-02-01

    The most common form of renal involvement in Sjögren's syndrome (SS) is tubulointerstitial nephritis. Renal dysfunction is usually mild and subclinical. Glomerulonephritis (GMN) is rare in patients with SS. We report a 28-year-old multigravida patient with primary Sjögren's syndrome (pSS) and associated manifestations, who presented with acute renal failure in the 20th week of her fifth pregnancy. The complaints and clinical findings, positive Schirmer's test, findings of dry eye on ophthalmologic examination, and the salivary gland biopsy were compatible with SS. The patient exhibited no other clinical or laboratory findings indicative of other collagenous disease and/or rheumatoid arthritis. She refused renal biopsy, hesitating for fear of fetal loss; thus, based on the clinical and laboratory findings indicating rapidly progressive GMN and vasculitis, prednisolone, plasmapheresis, and one dose of cyclophosphamide were administered during the pregnancy. Hemodialysis five times weekly was performed. At the 28th week of gestation, she underwent a cesarean section due to early rupture of membranes and fetal distress. A healthy male boy was delivered. The renal biopsy performed 2 weeks after labor revealed mesangial proliferative glomerulonephritis. After the fourth cyclophosphamide treatment, her urinary output increased and she was discharged from the hemodialysis program. She remains in follow-up at our outpatient clinic free of hemodialysis for 4 months. This is the first report of mesangial proliferative GMN requiring dialysis in a pregnant pSS patient that has featured good maternal and fetal outcomes.

  17. End-stage renal disease in both husband and wife in Taiwan.

    Science.gov (United States)

    Chang, C-H; Fang, Y-W; Chen, H-S

    2009-10-01

    The incidence and prevalence of end-stage renal disease (ESRD) are extremely high in Taiwan. It is an interesting fact that both the husband and wife in some families of Taiwan suffer from ESRD. Therefore, we attempted to identify the potential risk factors of such couples. This is a retrospective observational study. Six couples receiving maintenance dialysis in our hospital from 1996 to 2006 were enrolled in this study. Detailed medical history; drugs history including over-the-counter drugs (OCD), analgesics and herbal remedies; occupational history and onset of transitional cell carcinoma (TCC) were recorded. These data are correlated with pre-dialysis laboratory findings. The outcomes of dialysis and TCC were also recorded and analyzed. Two males were Chinese herbal medicine practitioners. All the patients (12/12) had taken Chinese herbs and most of them (10/12) had also taken OCD (especially cold remedies and analgesics). We found all of them had bilateral contracted kidneys, mild proteinuria and trace glucosuria. One patient's renal biopsy revealed Chinese herb nephropathy. Four patients (33%) suffered from TCC. Three patients expired during follow up due to hyperkalemia, extensive TCC and suicide, respectively. The prevalence of Chinese herbs or compound analgesics abuse is high in couples with ESRD. The clinical features and high incidence of TCC are compatible with drug related chronic tubulointerstitial nephritis. Abuse of offending agents should be considered as a risk factor in family members with ESRD.

  18. Natural infections with pigeon paramyxovirus serotype 1: Pathologic changes in Eurasian collared-doves (Streptopelia decaocto) and rock pigeons (Columba livia) in the United States

    Science.gov (United States)

    Isidoro Ayza, Marcos; Afonso, C.L.; Stanton, J.B.; Knowles, Susan N.; Ip, Hon S.; White, C. LeAnn; Fenton, Heather; Ruder, M.G.; Dolinski, A. C.; Lankton, Julia S.

    2017-01-01

    Pigeon paramyxovirus serotype 1 (PPMV-1) is a globally distributed, virulent member of the avian paramyxovirus serotype 1 serogroup that causes mortality in columbiformes and poultry. Following introduction into the United States in the mid-1980s, PPMV-1 rapidly spread causing numerous mortality events in Eurasian collared-doves (Streptopelia decaocto) (ECDOs) and rock pigeons (Columba livia) (ROPIs). The investigators reviewed pathological findings of 70 naturally infected, free-ranging columbiforms from 25 different mortality events in the United States. Immunohistochemistry targeting PPMV-1 nucleoprotein was used to determine the tissue distribution of the virus in a subset of 17 birds from 10 of the studied outbreaks. ECDOs (61 birds) and ROPIs (9 birds) were the only species in which PPMV-1-associated disease was confirmed by viral isolation and presence of histologic lesions. Acute to subacute tubulointerstitial nephritis and necrotizing pancreatitis were the most frequent histologic lesions, with immunolabeling of viral antigen in renal tubular epithelial cells and pancreatic acinar epithelium. Lymphoid depletion of bursa of Fabricius and spleen was common, but the presence of viral antigen in these organs was inconsistent among infected birds. Hepatocellular necrosis was occasionally present with immunolabeling of hypertrophic Kupffer cells, and immunopositive eosinophilic intracytoplasmic inclusion bodies were present in hepatocytes of 1 ECDO. Immunopositive lymphocytic choroiditis was present in 1 ECDO, while lymphocytic meningoencephalitis was frequent in ROPIs in absence of immunolabeling. This study demonstrates widespread presence of PPMV-1 antigen in association with histologic lesions, confirming the lethal potential of this virus in these particular bird species.

  19. Renal disease and mitochondrial genetics.

    Science.gov (United States)

    Rötig, Agnès

    2003-01-01

    Respiratory chain (RC) deficiencies have long been regarded as neuromuscular diseases mainly originating from mutations in the mitochondrial DNA. Oxidative phosphorylation, i.e. adenosine triphosphate (ATP) synthesis-coupled electron transfer from substrate to oxygen through the RC, does not occur only in the neuromuscular system. Therefore, a RC deficiency can theoretically give rise to any symptom, in any organ or tissue, at any age and with any mode of inheritance, owing to the dual genetic origin of RC enzymes (nuclear DNA and mitochondrial DNA). Mitochondrial diseases can give rise to various syndromes or association, namely, neurologic and neuromuscular diseases, cardiac, renal, hepatic, hematological and endocrin or dermatological presentations. The most frequent renal symptom is proximal tubular dysfunction with a more or less complete de Toni-Debre-Fanconi Syndrome. A few patients have been reported with tubular acidosis, Bartter Syndrome, chronic tubulointerstitial nephritis or nephrotic syndrome. The diagnosis of a RC deficiency is difficult when only renal symptoms are present, but should be easier when another, seemingly unrelated symptom is observed. Metabolic screening for abnormal oxidoreduction status in plasma, including lactate/pyruvate and ketone body molar ratios, can help to identify patients for further investigations. These include the measurement of oxygen consumption by mitochondria and the assessment of mitochondrial respiratory enzyme activities by spectrophotometric studies. Any mode of inheritance can be observed: sporadic, autosomal dominant or recessive, or maternal inheritance.

  20. Bartter syndrome presenting as poor weight gain and abdominal mass in an infant.

    Science.gov (United States)

    Heffernan, Annie; Steffensen, Thora S; Gilbert-Barness, Enid; Perlman, Sharon

    2008-01-01

    Bartter syndrome, a group of disorders that encompasses multiple genetic defects with similar clinical presentation, has been divided into six different genotypes, according to different genetic defects, and into three main clinical variants (or phenotypes). Classic laboratory findings in all variants include hypochloremia, hypokalemia, and metabolic alkalosis with excessive excretion of chloride and potassium. Classic Bartter syndrome, neonatal Bartter syndrome, and Gitelman syndrome are the three main clinical variants. Classic Bartter syndrome and neonatal Bartter syndrome have defects in genes that affect transport channels in the ascending loop of Henle, where as in Gitleman syndrome the defect occurs in the transport channels of the distal convoluted tubule. Classic Bartter syndrome and neonatal Bartter syndrome have similar presenting symptoms, potential outcomes, and treatment, but different ages at presentation. Gitelman syndrome, a more benign condition than the other clinical variants, has the classic hallmark finding of hypomagnesemia and low to normal excretion of calcium. This differentiates it from the classic and neonatal variants of the disease. With early diagnosis and proper treatment, Bartter syndrome has a good prognosis. But failure to identify it can lead to tubulointerstitial nephritis and renal failure. We present a case of a 6-month-old boy with Bartter syndrome who presented with poor weight gain and an abdominal mass.