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Sample records for human iga nephropathy

  1. IgA Nephropathy

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    ... Health Information Kidney Disease IgA Nephropathy Related Topics Section Navigation Kidney Disease Acquired Cystic Kidney Disease Amyloidosis & ... for a Child with Kidney Disease Ectopic Kidney Medullary Sponge Kidney Kidney Dysplasia Kidney Failure Choosing a ...

  2. IgA nephropathy enigma.

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    Mestecky, Jiri; Novak, Jan; Moldoveanu, Zina; Raska, Milan

    2016-11-01

    IgA nephropathy (IgAN) is the leading cause of primary glomerulonephritis in the world. The disease is characterized by the presence of IgA-containing immune complexes in the circulation and in mesangial deposits with ensuing glomerular injury. Although in humans there are two IgA subclasses, only IgA1 molecules are involved. The exclusivity of participation of IgA1 in IgAN prompted extensive structural and immunological studies of the unique hinge region (HR) of IgA1, which is absent in otherwise highly homologous IgA2. HR of IgA1 with altered O-glycans serves as an antigen recognized by autoantibodies specific for aberrant HR glycans leading to the generation of nephritogenic immune complexes. However, there are several unresolved questions concerning the phylogenetic origin of human IgA1 HR, the structural basis of its antigenicity, the origin of antibodies specific for HR with altered glycan moieties, the regulatory defects in IgA1 glycosylation pathways, and the potential approaches applicable to the disease-specific interventions in the formation of nephritogenic immune complexes. This review focuses on the gaps in our knowledge of molecular and cellular events that are involved in the immunopathogenesis of IgAN.

  3. Gluten exacerbates IgA nephropathy in humanized mice through gliadin-CD89 interaction.

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    Papista, Christina; Lechner, Sebastian; Ben Mkaddem, Sanae; LeStang, Marie-Bénédicte; Abbad, Lilia; Bex-Coudrat, Julie; Pillebout, Evangéline; Chemouny, Jonathan M; Jablonski, Mathieu; Flamant, Martin; Daugas, Eric; Vrtovsnik, François; Yiangou, Minas; Berthelot, Laureline; Monteiro, Renato C

    2015-08-01

    IgA1 complexes containing deglycosylated IgA1, IgG autoantibodies, and a soluble form of the IgA receptor (sCD89), are hallmarks of IgA nephropathy (IgAN). Food antigens, notably gluten, are associated with increased mucosal response and IgAN onset, but their implication in the pathology remains unknown. Here, an IgAN mouse model expressing human IgA1 and CD89 was used to examine the role of gluten in IgAN. Mice were given a gluten-free diet for three generations to produce gluten sensitivity, and then challenged for 30 days with a gluten diet. A gluten-free diet resulted in a decrease of mesangial IgA1 deposits, transferrin 1 receptor, and transglutaminase 2 expression, as well as hematuria. Mice on a gluten-free diet lacked IgA1-sCD89 complexes in serum and kidney eluates. Disease severity depended on gluten and CD89, as shown by reappearance of IgAN features in mice on a gluten diet and by direct binding of the gluten-subcomponent gliadin to sCD89. A gluten diet exacerbated intestinal IgA1 secretion, inflammation, and villous atrophy, and increased serum IgA1 anti-gliadin antibodies, which correlated with proteinuria in mice and patients. Moreover, early treatment of humanized mice with a gluten-free diet prevented mesangial IgA1 deposits and hematuria. Thus, gliadin-CD89 interaction may aggravate IgAN development through induction of IgA1-sCD89 complex formation and a mucosal immune response. Hence, early-stage treatment with a gluten-free diet could be beneficial to prevent disease.

  4. Crescentic IgA nephropathy.

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    Abuelo, J G; Esparza, A R; Matarese, R A; Endreny, R G; Carvalho, J S; Allegra, S R

    1984-11-01

    We report five cases of crescentic IgA nephropathy. All are males, 16-60 years of age. One case each came to medical attention with uremia, nephrotic syndrome, and gross hematuria; two cases presented with microhematuria and proteinuria on routine urinalysis. All had hypertension, azotemia (serum creatinine 1.6-9.4 mg/dl), proteinuria (greater than 6 g/24 hr in four cases), hypoalbuminemia (less than 3 g/dl), and hematuria (gross in two cases). All progressed to end-stage renal failure renal failure ending in dialysis (three cases) or death from unrelated causes (two cases). Prednisone, 60 mg/day for 1 month in two patients (with two 1-g doses of iv methylprednisolone in 1 case) did not improve the serum creatinine level, but one patient subsequently experienced a less rapid fall in renal function. A crescentic glomerulonephritis was present in all biopsies (crescents in 31-80% of glomeruli; mean, 50%). The size and stage of the crescents were variable. Numerous glomeruli had focal or diffuse sclerosis. In all cases, there was a 3 or 4+ deposition of IgA. Low-intensity staining for IgG and IgM was noted in four and three patients, respectively. On electron microscopy, dense granular mesangial deposits were noted in all cases and in four patients capillary subepithelial deposits were also observed. This form of IgA nephropathy is not common, but some studies indicate that it may occur in about 5% of patients with IgA nephropathy.

  5. Vibration Induces BAFF Overexpression and Aberrant O-Glycosylation of IgA1 in Cultured Human Tonsillar Mononuclear Cells in IgA Nephropathy

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    Muyao Ye

    2016-01-01

    Full Text Available Objective. To investigate the influence of in vitro vibratory stimulation of human tonsillar mononuclear cells (TMCs. Methods. Fourteen IgA nephropathy (IgAN patients with chronic tonsillitis (CT and 12 CT patients with no renal pathology were enrolled. Group A TMCs were collected after 24 hours of culture and used to determine baseline levels. TMCs in groups B, C, D, E, and F were exposed to vibratory stimulation (60 Hz for 0 (as the control group, 1, 3, 5, and 10 minutes, respectively. Results. Baseline concentrations of B-cell-activation factor (BAFF and IgA1, BAFF mRNA expression, and aberrant O-glycosylation IgA1 level were higher in the IgAN group as compared to that in the CT group, and all increased after vibratory stimulation. Baseline mRNA expressions of core β1,3-galactosyltransferase (C1GALT1 and core β1,3GalT-specific molecular chaperone (Cosmc were lower in the IgAN group; the levels decreased further after vibratory stimulation. Conclusion. In patients with IgAN, vibratory stimulation of TMCs appears to induce IgA1 secretion through activation of BAFF release and to aberrant O-glycosylation IgA1 by suppressing C1GALT1 and Cosmc expression. In vitro vibratory stimulation of human TMCs mimics the vibratory simulation of palatine tonsils produced by vocal cords during phonation.

  6. IgA nephropathy and infections.

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    Rollino, Cristiana; Vischini, Gisella; Coppo, Rosanna

    2016-08-01

    In this paper we concentrate on the role of infections in IgA nephropathy both from a pathogenetic and clinic point of view. The current hypotheses as regards the role of infections in the pathogenesis of IgA nephropathy are: (a) role of particular pathogens, (b) chronic exposure to mucosal infections, (c) abnormal handling of commensal microbes (gut microbiota). We also focus on particular infections reported in association with classic IgA nephropathy (HIV, malaria, Chlamydia, Lyme disease), as well as on IgA dominant-infection-associated glomerulonephritis. This is a unique form of glomerulonephritis, where IgA deposition is dominant. It is mostly recognized in old, diabetic patients and in association with staphylococcal infection.

  7. Immune regulation in IgA nephropathy

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    Eijgenraam, Jan-Willem

    2008-01-01

    IgA nephropathy (IgAN) is the most common form of glomerulonephritis worldwide. The hallmark of the disease is depositions of polymeric IgA1 in the mesangium of the glomeuli. These depositions will lead to inflammation in the kidneys and eventually to deterioration of renal function. The

  8. Immune regulation in IgA nephropathy

    NARCIS (Netherlands)

    Eijgenraam, Jan-Willem

    2008-01-01

    IgA nephropathy (IgAN) is the most common form of glomerulonephritis worldwide. The hallmark of the disease is depositions of polymeric IgA1 in the mesangium of the glomeuli. These depositions will lead to inflammation in the kidneys and eventually to deterioration of renal function. The pathogenesi

  9. Gluten and IgA nephropathy: you are what you eat?

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    Cheung, Chee Kay; Barratt, Jonathan

    2015-08-01

    Although extensively studied, the relationship between dietary antigens-in particular, gluten-and IgA nephropathy remains unclear. Using a double transgenic mouse model of IgA nephropathy that expresses both human IgA1 and human CD89, Papista et al. report that a gluten-free diet protects against the development of IgA deposition and glomerular injury, and that these events occur with the introduction of dietary gluten.

  10. Behcet's disease and IgA nephropathy.

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    Altay, Mustafa; Secilmis, Sema; Unverdi, Selman; Ceri, Mevlut; Duranay, Murat

    2012-07-01

    Although Behçet's disease (BD) is a kind of systemic disease, renal involvement is rare, especially IgA nephropathy (IgAN). Renal manifestations in BD range from mild urinary abnormalities to glomerulonephritis with persistent renal failure, which includes minimal change disease, proliferative glomerulonephritis, rapidly crescentic glomerulonephritis, renal amyloidosis and IgA nephropathy. Amyloidosis seems to be the most common type of renal lesion in BD, and several cases of nephrotic syndrome secondary to amyloidosis have been documented. Co-occurrence of BD and IgA nephropathy has only been reported in only few cases. We describe two patients with the rare association of BD and IgAN. We suggested that it is important to periodically perform renal function assessment in patients with BD, through urinalysis and measurement of serum creatinine for detecting any abnormality and providing an early adequate treatment.

  11. Proliferation and Cytokine Production of Human Mesangial Cells Stimulated by Secretory IgA Isolated from Patients with IgA Nephropathy

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    Yan Liang

    2015-07-01

    Full Text Available Background/Aims: IgA nephropathy (IgAN is the most common form of primary glomerulonephritis, and often aggravates by mucosal infection. Secretory IgA (SIgA is the dominant immunoglobulin in mucosal immunity, and is deposited in the mesangium in IgAN. The biological effects of SIgA on mesangial cells are poorly understood. Methods: Deposition of SIgA in frozen renal sections from IgAN patients was detected and the association between deposition of SIgA and patients characteristics was analyzed. The biological effects of SIgA and polymeric IgA (pIgA on human renal mesangial cells were compared. We also studied the molecular mechanism of microRNA regulating the inflammatory effects of SIgA on mesangial cells. Results: Fifty-five of 176 patients had SIgA deposition with higher incidence of infection history and hematuria, lower serum cystatin C, β2 microglobulin, blood urea nitrogen and T-grade in the Oxford classification, compared with patients without SIgA deposition. SIgA stimulated mesangial cells at a higher ratio of proliferation and higher production of interleukin (IL-6, IL-8, monocyte chemotactic protein 1, transforming growth factor-β1 and fibronectin, compared with SIgA from healthy volunteers. The proliferation and cytokines production in mesangial cells stimulated by SIgA were significantly lower than that stimulated by pIgA. miR-16 targeted the 3′-untranslated region of IL-6 and suppressed its translation in mesangial cells induced by SIgA. Conclusions: The biological effects of SIgA on mesangial cells differ from those of pIgA. SIgA stimulates mesangial cell proliferation and production of proinflammatory cytokines. IL-6 production is regulated by miR-16 in mesangial cells.

  12. The Role of TNF Superfamily Member 13 in the Progression of IgA Nephropathy.

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    Han, Seung Seok; Yang, Seung Hee; Choi, Murim; Kim, Hang-Rae; Kim, Kwangsoo; Lee, Sangmoon; Moon, Kyung Chul; Kim, Joo Young; Lee, Hajeong; Lee, Jung Pyo; Jung, Ji Yong; Kim, Sejoong; Joo, Kwon Wook; Lim, Chun Soo; Kang, Shin-Wook; Kim, Yon Su; Kim, Dong Ki

    2016-11-01

    TNF superfamily member 13 (TNFSF13) has been identified as a susceptibility gene for IgA nephropathy in recent genetic studies. However, the role of TNFSF13 in the progression of IgA nephropathy remains unresolved. We evaluated two genetic polymorphisms (rs11552708 and rs3803800) and plasma levels of TNFSF13 in 637 patients with IgA nephropathy, and determined the risk of ESRD according to theses variable. Neither of the examined genetic polymorphisms associated with a clinical outcome of IgA nephropathy. However, high plasma levels of TNFSF13 increased the risk of ESRD. To explore the causal relationship and underlying mechanism, we treated B cells from patients (n=21) with or without recombinant human TNFSF13 (rhTNFSF13) and measured the expression of IgA and galactose-deficient IgA (GdIgA) using ELISA and flow cytometry. Treatment with rhTNFSF13 significantly increased the total IgA level among B cells, and TNFSF13 receptor blockade abrogated this increase. Furthermore, the absolute levels of GdIgA increased with rhTNFSF13 treatment, but the total IgA-normalized levels did not change. Both RNA sequencing and quantitative PCR results showed that rhTNFSF13 did not alter the expression of glycosyltransferase enzymes. These results suggest that high plasma TNFSF13 levels associate with a worse prognosis of IgA nephropathy through the relative increase in GdIgA levels.

  13. Biomarkers in IgA nephropathy: relationship to pathogenetic hits

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    Hastings, Margaret Colleen; Moldoveanu, Zina; Suzuki, Hitoshi; Berthoux, Francois; Julian, Bruce A; Sanders, John T; Renfrow, Matthew B; Novak, Jan; Wyatt, Robert J

    2015-01-01

    Introduction IgA nephropathy, the most prevalent glomerular disease in the world, requires a renal biopsy for diagnosis. Reliable biomarkers are needed for the non-invasive diagnosis of this disease and to more fully delineate its natural history and risk for progression. Areas covered In this review, the authors examine serum levels of galactose-deficient IgA1 (Gd-IgA1) and glycan-specific IgG and IgA autoantibodies that are integral to pathogenesis of IgA nephropathy. They also explore biomarkers related to alternative and lectin pathways of complement activation and serum and urinary peptide biomarkers detected by mass spectrometric methods. The literature search included review of all publications having IgA nephropathy in the title that were cited in PubMed and Scopus over the past 10 years and a non-systematic review of abstracts published for the annual meetings of the American Society of Nephrology and the International Symposia on IgA Nephropathy. Expert opinion Serum Gd-IgA1 level and glycan-specific autoantibody levels are prime candidates to become diagnostic biomarkers for IgA nephropathy because of their central role in the earliest stages of disease pathogenesis. Assays for serum levels of complement proteins C3 and factor H are readily available in clinical practice and deserve continued study, either alone or in tandem with total serum IgA or serum Gd-IgA1 levels, as prognostic biomarkers for patients with IgA nephropathy. Urinary peptidomic data are also reviewed because this approach can successfully differentiate patients with IgA nephropathy from healthy controls and from patients with other forms of renal disease. PMID:24175678

  14. Role of IgA receptors in the pathogenesis of IgA nephropathy.

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    Lechner, Sebastian M; Papista, Christina; Chemouny, Jonathan M; Berthelot, Laureline; Monteiro, Renato C

    2016-02-01

    Immunoglobulin A nephropathy (IgAN) or Berger's disease is the most common form of primary glomerulonephritis in the world and one of the first causes of end-stage renal failure. IgAN is characterized by the accumulation of immune complexes containing polymeric IgA1 in mesangial areas. The pathogenesis of this disease involves the deposition of polymeric and hypogalactosylated IgA1 (Gd-IgA1) in the mesangium. Quantitative and structural changes of Gd-IgA1 play a key role in the development of the disease due to functional abnormalities of two IgA receptors: the FcαRI (CD89) expressed by blood myeloid cells and the transferrin receptor (CD71) on mesangial cells. Abnormal Gd-IgA1 induces release of soluble CD89, which participates in the formation of circulating IgA1 complexes. These complexes are trapped by CD71 that is overexpressed on mesangial cells in IgAN patients together with the crosslinking enzyme transglutaminase 2 allowing pathogenic IgA complex formation in situ and mesangial cell activation. A humanized mouse model expressing IgA1 and CD89 develops IgAN in a similar manner as patients. In this model, a food antigen, the gliadin, was shown to be crucial for circulating IgA1 complex formation and deposition, which could be prevented by a gluten-free diet. Identification of these new partners opens new therapeutic prospects for IgAN treatment.

  15. Aberrantly Glycosylated IgA1 as a Factor in the Pathogenesis of IgA Nephropathy

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    Mototsugu Tanaka

    2011-01-01

    Full Text Available Predominant or codominant immunoglobulin (Ig A deposition in the glomerular mesangium characterizes IgA nephropathy (IgAN. Accumulated glomerular IgA is limited to the IgA1 subclass and usually galactose-deficient. This underglycosylated IgA may play an important role in the pathogenesis of IgAN. Recently, antibodies against galactose-deficient IgA1 were found to be well associated with the development of IgAN. Several therapeutic strategies based on corticosteroids or other immunosuppressive agents have been shown to at least partially suppress the progression of IgAN. On the other hand, several case reports of kidney transplantation or acquired IgA deficiency uncovered a remarkable ability of human kidney to remove mesangial IgA deposition, resulting in the long-term stabilization of kidney function. Continuous exposure to circulating immune complexes containing aberrantly glycosylated IgA1 and sequential immune response seems to be essential in the disease progression of IgAN. Removal of mesangial IgA deposition may be a challenging, but fundamental approach in the treatment of IgAN.

  16. Circulating Tumor Necrosis Factor α Receptors Predict the Outcomes of Human IgA Nephropathy: A Prospective Cohort Study.

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    Yun Jung Oh

    Full Text Available The circulating tumor necrosis factor receptors (TNFRs could predict the long-term renal outcome in diabetes, but the role of circulating TNFRs in other chronic kidney disease has not been reported. Here, we investigated the correlation between circulating TNFRs and renal histologic findings on kidney biopsy in IgA nephropathy (IgAN and assessed the notion that the circulating TNFRs could predict the clinical outcome. 347 consecutive biopsy-proven IgAN patients between 2006 and 2012 were prospectively enrolled. Concentrations of circulating TNFRs were measured using serum samples stored at the time of biopsy. The primary clinical endpoint was the decline of estimated glomerular filtration rate (eGFR; ≥ 30% decline compared to baseline. Mean eGFR decreased and proteinuria worsened proportionally as circulating TNFR1 and TNFR2 increased (P < 0.001. Tubulointerstitial lesions such as interstitial fibrosis and tubular atrophy were significantly more severe as concentrations of circulating TNFRs increased, regardless of eGFR levels. The risks of reaching the primary endpoint were significantly higher in the highest quartile of TNFRs compared with other quartiles by the Cox proportional hazards model (TNFR1; hazard ratio 7.48, P < 0.001, TNFR2; hazard ratio 2.51, P = 0.021. In stratified analysis according to initial renal function classified by the eGFR levels of 60 mL/min/1.73 m2, TNFR1 and TNFR2 were significant predictors of renal progression in both subgroups. In conclusion, circulating TNFRs reflect the histology and clinical severity of IgAN. Moreover, elevated concentrations of circulating TNFRs at baseline are early biomarkers for subsequent renal progression in IgAN patients.

  17. New Insights into the Pathogenesis of IgA Nephropathy

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    Novak, Jan; Rizk, Dana; Takahashi, Kazuo; Zhang, XianWen; Bian, Qi; Ueda, Hiroyuki; Ueda, Yoshimi; Reily, Colin; Lai, Ling-Yun; Hao, Chuanming; Novak, Lea; Huang, Zhi-Qiang; Renfrow, Matthew B.; Suzuki, Hitoshi; Julian, Bruce A.

    2015-01-01

    Background IgA nephropathy, a frequent cause of end-stage renal disease, is an autoimmune disease wherein immune complexes consisting of IgA1 with galactose-deficient O-glycans (autoantigen) and anti-glycan autoantibodies deposit in glomeruli and induce renal injury. Multiple genetic loci associated with disease risk have been identified. The prevalence of risk alleles varies geographically: it is the highest in eastern Asia and northern Europe, lower in other parts of Europe and North America, and the lowest in Africa. IgA nephropathy is diagnosed by the pathological assessment of a renal biopsy specimen. Currently, therapy is not disease targeted but rather focused on maintaining control of blood pressure and proteinuria, ideally with suppression of angiotensin II. Possible additional approaches differ between countries. Disease-specific therapy as well as new tools for the diagnosis, prognosis, and assessment of responses to therapy are needed. Summary Glycosylation pathways associated with aberrant O-glycosylation of IgA1 and, thus, production of autoantigen, have been identified. Furthermore, unique characteristics of the autoantibodies in IgA nephropathy have been uncovered. Many of these biochemical features are shared by patients with IgA nephropathy and Henoch-Schönlein purpura nephritis, suggesting that the two diseases may represent opposite ends of a spectrum of a disease process. Understanding the molecular mechanisms involved in the formation of pathogenic IgA1-containing immune complexes will enable the development of disease-specific therapies as well as diagnostic and prognostic biomarkers. Key Message IgA nephropathy is an autoimmune disease caused by the glomerular deposition of nephritogenic circulating immune complexes consisting of galactose-deficient IgA1 (autoantigen) bound by anti-glycan autoantibodies. A better understanding of the multi-step process of the pathogenesis of IgA nephropathy and the genetic and environmental contributing

  18. Diagnosis and treatment of primary glomerular diseases Membranous nephropathy, focal segmental glomerulosclerosis and IgA nephropathy.

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    Deegens, J.K.J.; Wetzels, J.F.M.

    2005-01-01

    Membranous nephropathy, focal segmental glomerulosclerosis (FSGS) and IgA nephropathy are the most frequent and important primary glomerulopathies. Idiopathic membranous nephropathy and primary FSGS usually present with a nephrotic syndrome with or without renal insufficiency, whereas IgA nephropath

  19. Role of complement in IgA nephropathy.

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    Daha, Mohamed R; van Kooten, Cees

    2016-02-01

    Immunoglobulin A nephropathy (IgAN) is characterized by the deposition of IgA in the mesangium of glomeruli. This mesangial IgA has been found to consist mainly of polymeric IgA1 which drives the activation of the mesangial cells and results in excessive production of several inflammatory mediators. The activation of mesangial cells is amplified by the ability of IgA to activate the complement system, originally thought to occur mainly via the alternative pathway of complement. However more recent studies indicate that lectin pathway involvement has a strong association with progression of renal disease. In this review we summarize the contribution of complement to the IgA- mediated inflammatory process.

  20. IgA nephropathy: Causes, prognosis and treatment

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    Francesco Paolo Schena; Diletta Domenica Torres; Giuseppina Cerrullo

    2005-01-01

    @@ IgA nephropathy (IgAN) or Berger's disease is the most common form of primary glomerulonephritis in many renal biopsy registries and it is very frequent in the Eastern regions of the world, such as China (32,1%), Hong Kong (35%), Japan (47,4% )[1,2].

  1. Minimal change disease versus IgA nephropathy.

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    Jabur, Wael Latif

    2009-01-01

    IgA nephropathy is the most common type of the glomerulonephritis all over the world. However, its clinical presentation is variable, as is the underlying histopathological lesion. We report herein a case of an adult with steroid responsive minimal change disease and IgA mesangial deposits. During the first two weeks of therapy with prednisolone, the patient reported dramatic improvement in his clinical condition and remitted his disease. Unfortunately, at the end of the second month of prednisolone therapy, an acute flare of viral hepatitis was diagnosed. Interes-tingly, the acute viral flare was without a concomitant relapse of proteinuria.

  2. Minimal change disease versus IgA nephropathy

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    Jabur Wael

    2009-01-01

    Full Text Available IgA nephropathy is the most common type of the glomerulonephritis all over the world. However, its clinical presentation is variable, as is the underlying histopathological lesion. We report herein a case of an adult with steroid responsive minimal change disease and IgA mesangial deposits. During the first two weeks of therapy with prednisolone, the patient reported dramatic improvement in his clinical condition and remitted his disease. Unfortunately, at the end of the second month of prednisolone therapy, an acute flare of viral hepatitis was diagnosed. Interes-tingly, the acute viral flare was without a concomitant relapse of proteinuria.

  3. Bilateral scleritis and sclerokeratitis associated with IgA nephropathy

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    Garza-Leon, Manuel; Flores, Diana; Alarcón-Galván, Gabriela; Sánchez-Martínez, Concepción

    2012-01-01

    Purpose The purpose of this study is to report a case of bilateral nodular scleritis in a patient with final diagnosis of IgA nephropathy. Methods This is an observational case report. Results A male patient, 42 years old, presented with a bilateral nodular scleritis and OD sclerokeratitis. He had a previous history of acute otitis media and developed posterior renal failure and arterial hypertension. Clinical and systemic findings suggest Wegener's granulomatosis. A kidney biopsy was perform...

  4. Efficacy and safety of mycophenolate mofetil treatment in IgA nephropathy: a systematic review

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    Chen, Youyuan; Li, Yumin; Yang, ShengLin; Li, Yan; Liang, Min

    2014-01-01

    Background IgA nephropathy is the most common primary glomerular disease worldwide and also the most frequent cause of kidney failure. Mycophenolate mofetil (MMF) is a selective immunosuppressant widely used in many autoimmune diseases. However, the benefits and risks of MMF for the treatment of IgA nephropathy remain uncertain. Methods A systematic review and meta-analysis of randomized controlled trials (RCTs) was performed to assess the efficacy and safety of MMF in IgA nephropathy patient...

  5. The association of single nucleotide P-selectin gene polymorphism with IgA nephropathy

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    王朝晖

    2006-01-01

    Objective IgA nephropathy is one of the most com- mon form of primary glomerulonephritis throughout the world and a main renal disease which causes renal failure. P-selectin plays an important role in the pathogenesis and development of IgA nephropathy. The purpose of this study is to find a possible relationship between P-selectin gene polymorphism and IgA nephropathy. Methods In this study,a comprehensive P-selectin gene sur-

  6. Nefropatia por IgA nas espondiloartrites IgA nephropathy in spondyloarthritis

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    Daniela Castelo Azevedo

    2011-02-01

    Full Text Available Pacientes com espondiloartrites poderiam ser mais acometidos pela nefropatia por IgA do que a população geral, havendo, possivelmente, um mecanismo etiopatogênico comum. O seguinte artigo relaciona quatro casos que exemplificam essa possível associaçãoSpondyloarthritis patients can be more frequently affected by IgA nephropathy than the general population, and a common etiopathogenic mechanism can be involved. We report four cases that may exemplify that association

  7. Clinicopathological significance of monoclonal IgA deposition in patients with IgA nephropathy.

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    Nagae, Hiroshi; Tsuchimoto, Akihiro; Tsuruya, Kazuhiko; Kawahara, Shota; Shimomura, Yukiko; Noguchi, Hideko; Masutani, Kosuke; Katafuchi, Ritsuko; Kitazono, Takanari

    2017-04-01

    Clinicopathological significance of monoclonal IgA deposition and its relation to bone marrow abnormalities in IgA nephropathy (IgAN) remains unclear. We retrospectively investigated the prevalence and clinicopathological significance of monoclonal IgA deposition in 65 patients with IgAN. Serum-free light chain ratio, and urinary Bence Jones protein were also measured. Thirty-nine percent of patients were men, median age was 40 and median observation period was 31 months. Five patients (Group M) showed monoclonal IgA lambda deposition and one showed monoclonal IgA kappa deposition. Fifty-nine patients (Group P) showed polyclonal IgA deposition. There were no significant differences in the degree of proteinuria, hematuria and renal function between Group M and Group P. Total protein and albumin were significantly lower in Group M than in Group P. According to the Oxford classification, the percentage of patients with M1 was significantly higher in Group M than in Group P. One patient in Group P showed serum monoclonal IgG lambda. No patient showed abnormal serum-free light chain ratio. Seventy-five percent in Group M and 42 % in Group P were treated with steroid. Three patients in Group P progressed to end-stage renal disease (ESRD). The frequency of disappearance of proteinuria or hematuria and progression to ESRD was not different between the groups. The prevalence of monoclonal IgA deposition was 9.2 %. Although some parameters differed between the groups, renal outcome were similar. Thus, IgAN with monoclonal IgA deposition seems not to be different entity from those with polyclonal IgA deposition.

  8. Critical Role of Kupffer Cell CD89 Expression in Experimental IgA Nephropathy.

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    Xu, Lijun; Li, Bingyu; Huang, Mengwen; Xie, Kun; Li, Dong; Li, You; Gu, Hua; Fang, Jianmin

    2016-01-01

    Although IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide, its etiology remains only partly understood. It is clear that the pathogenesis of IgAN involves the formation of macromolecular IgA1 complexes and increased levels of serum IgA1 and IgA1-immune complexes(IC), due to defective IgA1 clearance. Previous studies suggest that the blood and tissue myeloid cell-expressed IgA Fc receptor (FcαR/CD89) mediates IgA-IC clearance and its dysfunction, via decreased activity or excessive levels of soluble FcαR/sCD89 induces IgAN. Such a mechanism requires robust stimulation of IgAN levels via forced expression of CD89. In the absence of unequivocal evidence supporting such a mechanism to date, we attempted to test the extent of CD89-evoked IgAN by generating a transgenic mouse strain expressing human CD89 under the control of murine CD14 promotor. No deposition of IgA-CD89 complexes or glomerulonephritis was detected, however. Further studies showed that elimination of murine IgA was mediated by Kupffer cells. In patients, however, CD89/IgA complexes were detected, and injection of patient IgA induced IgAN-like features in CD89 Tg mice. In transgenic mice, IgAN pathogenesis involves impaired clearance of abnormal IgA via CD89, primarily by the Kupffer cells. Conditional IgAN progression in CD89 transgenic mice thus reveals important aspects of IgAN pathogenesis.

  9. Diagnosis and treatment of patients with IgA nephropathy in Japan

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    Yasuhiko Tomino

    2016-12-01

    Full Text Available Chronic kidney disease (CKD is a worldwide public health problem that affects millions of people from all racial and ethnic groups. Although CKD is not one specific disease, it is a comprehensive syndrome that includes IgA nephropathy. As reported by the Japanese Society of Nephrology, 13.0 million people have CKD. In Japan, major causes of end-stage kidney disease are type 2 diabetic nephropathy, chronic glomerulonephritis, especially IgA nephropathy, hypertensive nephrosclerosis, and polycystic kidney disease. IgA nephropathy is characterized by polymeric IgA1 with aberrant galactosylation (galactose-deficient IgA1 increased in the blood and deposited in the glomerular mesangial areas, as well as partially in the capillary walls. The tonsils are important as one of the responsible regions in this disease. The clarification of the mechanism of galactose-deficient IgA1 production will pave the way for the development of novel therapies. The results of future research are eagerly awaited. At present, the most important therapeutic goals in patients with IgA nephropathy are the control of hypertension, the decrease of urinary protein excretion, and the inhibition of progression to end-stage kidney disease. Several investigators have reported that renin–angiotensin–aldosterone system inhibitors reduce levels of urinary protein excretion and preserve renal function in patients with IgA nephropathy. In Japan, tonsillectomy and steroid pulse therapy are more effective for patients with IgA nephropathy.

  10. Diagnosis and treatment of patients with IgA nephropathy in Japan.

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    Tomino, Yasuhiko

    2016-12-01

    Chronic kidney disease (CKD) is a worldwide public health problem that affects millions of people from all racial and ethnic groups. Although CKD is not one specific disease, it is a comprehensive syndrome that includes IgA nephropathy. As reported by the Japanese Society of Nephrology, 13.0 million people have CKD. In Japan, major causes of end-stage kidney disease are type 2 diabetic nephropathy, chronic glomerulonephritis, especially IgA nephropathy, hypertensive nephrosclerosis, and polycystic kidney disease. IgA nephropathy is characterized by polymeric IgA1 with aberrant galactosylation (galactose-deficient IgA1) increased in the blood and deposited in the glomerular mesangial areas, as well as partially in the capillary walls. The tonsils are important as one of the responsible regions in this disease. The clarification of the mechanism of galactose-deficient IgA1 production will pave the way for the development of novel therapies. The results of future research are eagerly awaited. At present, the most important therapeutic goals in patients with IgA nephropathy are the control of hypertension, the decrease of urinary protein excretion, and the inhibition of progression to end-stage kidney disease. Several investigators have reported that renin-angiotensin-aldosterone system inhibitors reduce levels of urinary protein excretion and preserve renal function in patients with IgA nephropathy. In Japan, tonsillectomy and steroid pulse therapy are more effective for patients with IgA nephropathy.

  11. An update on pathology of IgA nephropathy.

    Science.gov (United States)

    Soares, Maria Fernanda

    2016-12-01

    IgA Nephropathy (IgAN) is the commonest of the glomerular diseases in the world. Its progression rate of 30-40% of the cases em 20-30 years makes IgAN an important healthcare issue in Nephrology. Diagnosis of IgAN depends on biopsy findings, particularly at immunofluorescence microscopy. The frequence of IgAN diagnosis is variable in different populations and depends on screening and biopsy indication policies. IgAN pathogenesis is considered multifactorial; its primordial defect is the production of galactosis-deficient IgA molecules. This review paper discusses the most uptodate aspects of the pathogenesis, pathological classification and clinical implications of IgAN.

  12. An update on pathology of IgA nephropathy

    Directory of Open Access Journals (Sweden)

    Maria Fernanda Soares

    Full Text Available Abstract IgA Nephropathy (IgAN is the commonest of the glomerular diseases in the world. Its progression rate of 30-40% of the cases em 20-30 years makes IgAN an important healthcare issue in Nephrology. Diagnosis of IgAN depends on biopsy findings, particularly at immunofluorescence microscopy. The frequence of IgAN diagnosis is variable in different populations and depends on screening and biopsy indication policies. IgAN pathogenesis is considered multifactorial; its primordial defect is the production of galactosis-deficient IgA molecules. This review paper discusses the most uptodate aspects of the pathogenesis, pathological classification and clinical implications of IgAN.

  13. Lupus vulgaris with tubercular lymphadenitis and IgA nephropathy.

    Science.gov (United States)

    Khaira, Ambar; Rathi, Om P; Mahajan, Sandeep; Sharma, Alok; Dinda, Amit K; Tiwari, Suresh C

    2008-02-01

    A 14-year-old girl presented with a 10-year history of a large crusted plaque over the right thigh for 10 years and small reddish plaque over the left upper back for 3 months. On routine evaluation, she was found to have hematuria. Skin biopsy from the lesion was suggestive of skin tuberculosis (lupus vulgaris), and kidney biopsy showed features of IgA nephropathy (IgAN). Fine-needle aspiration from the inguinal lymph node was consistent with granulomatous disease. The patient has been on anti-tubercular treatment, and the hematuria has subsided.

  14. Somatic Mutations Modulate Autoantibodies against Galactose-Deficient IgA1 in IgA Nephropathy.

    Science.gov (United States)

    Huang, Zhi Qiang; Raska, Milan; Stewart, Tyler J; Reily, Colin; King, R Glenn; Crossman, David K; Crowley, Michael R; Hargett, Audra; Zhang, Zhixin; Suzuki, Hitoshi; Hall, Stacy; Wyatt, Robert J; Julian, Bruce A; Renfrow, Matthew B; Gharavi, Ali G; Novak, Jan

    2016-11-01

    Autoantibodies against galactose-deficient IgA1 drive formation of pathogenic immune complexes in IgA nephropathy. IgG autoantibodies against galactose-deficient IgA1 in patients with IgA nephropathy have a specific amino-acid sequence, Y1CS3, in the complementarity-determining region 3 of the heavy chain variable region compared with a Y1CA3 sequence in similar isotype-matched IgG from healthy controls. We previously found that the S3 residue is critical for binding galactose-deficient IgA1. To determine whether this difference is due to a rare germline sequence, we amplified and sequenced the corresponding germline variable region genes from peripheral blood mononuclear cells of seven patients with IgA nephropathy and six healthy controls from whom we had cloned single-cell lines secreting monoclonal IgG specific for galactose-deficient IgA1. Sanger DNA sequencing revealed that complementarity-determining region 3 in the variable region of the germline genes encoded the Y1C(A/V)3 amino-acid sequence. Thus, the A/V>S substitution in the complementarity-determining region 3 of anti-galactose-deficient-IgA1 autoantibodies of the patients with IgA nephropathy is not a rare germline gene variant. Modeling analyses indicated that the S3 hydroxyl group spans the complementarity-determining region 3 loop stem, stabilizing the adjacent β-sheet and stem structure, important features for effective binding to galactose-deficient IgA1. Understanding processes leading to production of the autoantibodies may offer new approaches to treat IgA nephropathy. Copyright © 2016 by the American Society of Nephrology.

  15. The origin and activities of IgA1-containing immune complexes in IgA nephropathy

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    Barbora eKnoppova

    2016-04-01

    Full Text Available IgA nephropathy is the most common primary glomerulonephritis, frequently leading to end-stage renal disease, as there is no disease-specific therapy. IgA nephropathy is diagnosed from pathological assessment of a renal biopsy specimen based on predominant or co-dominant IgA-containing immunodeposits, usually with complement C3 co-deposits and with variable presence of IgG and/or IgM. The IgA in these renal deposits is galactose-deficient IgA1, with less than a full complement of galactose residues on the O-glycans in the hinge region of the heavy chains. Research from the past decade led to the definition of IgA nephropathy as an autoimmune disease with a multi-hit pathogenetic process with contributing genetic and environmental components. In this process, circulating galactose-deficient IgA1 (autoantigen is bound by anti-glycan IgG or IgA (autoantibodies to form immune complexes. Some of these circulating complexes deposit in glomeruli, and thereby activate mesangial cells and induce renal injury through cellular proliferation and overproduction of extracellular matrix components and cytokines/chemokines. Glycosylation pathways associated with production of the autoantigen and the unique characteristics of the corresponding autoantibodies in patients with IgA nephropathy have been uncovered. Complement likely plays a significant role in the formation and the nephritogenic activities of these complexes. Complement activation is mediated through the alternative and lectin pathways and probably occurs systemically on IgA1-containing circulating immune complexes as well as locally in glomeruli. Incidence of IgA nephropathy varies greatly by geographical location; the disease is rare in central Africa but accounts for up to 40% of native-kidney biopsies in eastern Asia. Some of this variation may be explained by genetically determined influences on the pathogenesis of the disease. Genome-wide association studies to date have identified 18 risk

  16. Association of liver cirrhosis related IgA nephropathy with portal hypertension

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    A high incidence of IgA nephropathy has been reported in patients with liver cirrhosis, though, clinically evident nephrotic syndrome is very uncommon. Impaired hepatic clearance of circulating IgA immune complexes and subsequent deposition in renal glomeruli has been considered principally in the pathogenesis of liver cirrhosis associated IgA nephropathy. Here we report on a patient with cryptogenic liver cirrhosis and splenic vein thrombosis, who presented with nephrotic syndrome. Renal biopsy showed findings consistent with IgA nephropathy. Lower endoscopy showed features of portal hypertensive colopathy. Following initiation of propranolol and anticoagulant treatment to reduce portal pressure, a gradual decrease of proteinuria and hematuria to normal range was noted. The potential pathogenetic role of portal hypertension in the development of IgA nephropathy in cirrhotic patients is discussed.

  17. Association of liver cirrhosis related IgA nephropathy with portal hypertension.

    Science.gov (United States)

    Kalambokis, Georgios; Christou, Leonidas; Stefanou, Dimitrios; Arkoumani, Evdokia; Tsianos, Epameinondas V

    2007-11-21

    A high incidence of IgA nephropathy has been reported in patients with liver cirrhosis, though, clinically evident nephrotic syndrome is very uncommon. Impaired hepatic clearance of circulating IgA immune complexes and subsequent deposition in renal glomeruli has been considered principally in the pathogenesis of liver cirrhosis associated IgA nephropathy. Here we report on a patient with cryptogenic liver cirrhosis and splenic vein thrombosis, who presented with nephrotic syndrome. Renal biopsy showed findings consistent with IgA nephropathy. Lower endoscopy showed features of portal hypertensive colopathy. Following initiation of propranolol and anticoagulant treatment to reduce portal pressure, a gradual decrease of proteinuria and hematuria to normal range was noted. The potential pathogenetic role of portal hypertension in the development of IgA nephropathy in cirrhotic patients is discussed.

  18. The role of tonsillectomy in IgA nephropathy.

    Science.gov (United States)

    Feriozzi, Sandro; Polci, Rosaria

    2016-02-01

    The IgA nephropathy (IgAN) is a very common glomerulonephritis and can result in end-stage renal disease. From a clinical point of view, IgAN is characterised by repeated events of macrohaematuria associated with infections of the upper airways. In IgAN, the IgA released by the tonsillar lymphatic tissue into blood circulation are defective in glycosylation. These aberrant IgA can reach the glomeruli and deposit into mesangium causing an inflammation with cellular proliferation. The treatment is not yet well defined: steroids and immunosuppressive drugs are suggested in cases with a progressive disease. Tonsillectomy was proposed to reduce the infective events of upper airways and the lymphatic tissue producing undergalactosylated IgA. The experiences in literature coming from Asia report positive effects of tonsillectomy on IgAN. In patients with tonsillectomy, the renal signs improved (less haematuria and proteinuria) and the renal outcome was better (slower progression of renal damage). These were uncontrolled studies and tonsillectomy was associated with steroid and immunosuppressive treatment, so it is not possible to tell the real effect of tonsillectomy. In contrast, the European studies reported that the tonsillectomy was not associated with a better outcome of IgAN. A critical review of the subject reveals that most of the papers with positive results were uncontrolled retrospective experiences, while in a randomised controlled trial paper the advantages of tonsillectomy disappeared. In conclusion, this review, in agreement with the international guidelines, concludes that tonsillectomy does not play any role in the progression of IgAN.

  19. IgA Cutaneous Purpura Post-Renal Transplantation in a Patient With Long-Standing IgA Nephropathy: Case Report and Literature Review.

    Science.gov (United States)

    Sotoodian, Bahman; Robert, Janet; Mahmood, Muhammad N; Yacyshyn, Elaine

    2015-01-01

    IgA vasculitis is a small-vessel vasculitis caused by deposition of IgA antibodies in tissues. IgA nephropathy and IgAV have long been considered related conditions. To assess the prevalence and implications of new-onset Henoch-Schönlein purpura (HSP) after renal transplant in patients with underlying IgA nephropathy. The PubMed database was searched for keywords such as IgAV, IgA vasculitis, Henoch-Schönlein purpura, HSP, IgA nephropathy, and renal transplant. Two cases of new-onset IgA vasculitis post-renal transplant after stopping the prednisone or receiving seasonal influenza vaccine have been reported. We report the case of new-onset IgA cutaneous vasculitis in a renal transplant patient with IgA nephropathy after reduction in his prednisone dosage. The new development of cutaneous IgA vasculitis is unusual in renal transplant patients with IgA nephropathy. Despite these patients' being immunosuppressed, the presence of IgA vasculitis could signal the recurrence of IgA nephropathy. © The Author(s) 2015.

  20. IgA nephropathy and tonsils--an approach from the structure of IgA1 produced by tonsillar lymphocytes.

    Science.gov (United States)

    Hiki, Yoshiyuki; Horie, Akeyo; Yasuda, Yoshinari; Iwase, Hitoo; Sugiyama, Satoshi

    2004-12-01

    Human immunoglobulin A1 (IgA1), which is the predominant subtype to be deposited in glomeruli in IgA nephropathy (IgAN), has a unique mucine-like structure in its hinge region. Namely, it contains O-glycans and proline-rich peptides We previously observed underglycosylation of the hinge region in serum and deposited IgA1 in IgAN. On the other hand, clinical development and exacerbation of IgAN are frequently preceded by episodes of upper respiratory tract infection, and palatine tonsils represent the predominant immunocompetent tissue of the upper respiratory tract. Therefore, we hypothesized that tonsils were one of the origins of glomerular IgA1 in IgAN, and investigated the O-glycan structure of IgA1 produced by tonsillar lymphocytes (tonsillar IgA1). A significant increase in asialo-agalacto type O-glycans was found in the tonsillar IgA1 hinge in IgAN. These results suggest that the tonsils produce underglycosylated IgA1 molecules, which enter the bloodstream and are then deposited in the glomeruli.

  1. Predictors of Progression in IgA Nephropathy in Childhood.

    Science.gov (United States)

    Mizerska-Wasiak, M; Małdyk, J; Turczyn, A; Cichoń-Kawa, K; Rybi-Szumińska, A; Wasilewska, A; Bieniaś, B; Zajączkowska, M; Miklaszewska, M; Pietrzyk, J; Demkow, U; Roszkowska-Blaim, M; Pańczyk-Tomaszewska, M

    2017-01-01

    The aim of this retrospective study was to assess the usefulness of potential predictors of poor prognosis in IgA nephropathy in children. The study population consisted of 55 children aged 11 ± 4 years, diagnosed on the basis of the Oxford classification and MEST score of kidney biopsy findings. Proteinuria, glomerular filtration rate (GFR), and the IgA/C3 serum ratio were assessed in all patients twice: at onset and at follow-up. The patients were treated with steroids, immunosuppressive drugs, and/or angiotensin-converting enzyme inhibitors. Follow-up was at 3.9 ± 2.9 (median 2.7) years. The patients were subdivided into two groups: with GFR IgA/C3 ratio at onset of disease. There was a significant association between GFR reductions at onset and follow-up (AUC = 0.660; p IgA/C3 ratio was higher (p IgA/C3 ratio at onset and reduced GFR (AUC = 0.565; p = 0.46) or proteinuria at follow-up (AUC = 0.263; p = 0.20). We conclude that predictors of poor outcome in childhood IgAN include the following: GFR reduction, nephrotic range proteinuria at onset of disease, and high MEST score in Oxford classification of kidney biopsy. Despite a higher serum IgA/C3 ratio in children with impaired renal function in long-term follow-up, we failed to demonstrate a significant association between this ratio at onset of disease and reduced GFR or persistent proteinuria at follow-up. Thus, IgA/C3 ratio is not a good foreteller of progression of IgA nephropathy in childhood.

  2. Pathogenic role of (S)IgA in IgA nephropathy

    NARCIS (Netherlands)

    Oortwijn, Beatrijs Dorinda

    2007-01-01

    Primary IgA nephropathy (IgAN) is the most common form of primary glomerulonephritis world wide and leads to end stage renal disease in 30-50% of patients. The hallmark of IgAN is the deposition of IgA1 in the mesangial area of the kidney. Since the inflammatory response which leads to progressive

  3. Pathogenic role of (S)IgA in IgA nephropathy

    NARCIS (Netherlands)

    Oortwijn, Beatrijs Dorinda

    2007-01-01

    Primary IgA nephropathy (IgAN) is the most common form of primary glomerulonephritis world wide and leads to end stage renal disease in 30-50% of patients. The hallmark of IgAN is the deposition of IgA1 in the mesangial area of the kidney. Since the inflammatory response which leads to progressive r

  4. A case of rapidly progressive IgA nephropathy in a patient with exacerbation of Crohn’s disease

    OpenAIRE

    Choi Ji-Young; Yu Chung; Jung Hee-Yeon; Jung Min; Kim Yong-Jin; Cho Jang-Hee; Kim Chan-Duck; Kim Yong-Lim; Park Sun-Hee

    2012-01-01

    Abstract Background IgA nephropathy has been reported as a renal involvement in Crohn’s disease. Crescentic IgA nephropathy, which accounts for fewer than 5% of cases of IgA nephropathy, has a poorer prognosis than other forms of crescentic glomerulonephritis. We recently experienced a case of rapidly progressive IgA nephropathy concurrent with exacerbation of Crohn’s disease. Case presentation An 18-year-old male diagnosed with Crohn’s disease underwent a hemicolectomy 2 years prior previous...

  5. Spectrum of IgA nephropathy in a single center

    Directory of Open Access Journals (Sweden)

    Uttara Das

    2015-01-01

    Full Text Available Immunoglobulin A (IgA nephropathy (IgAN is the most common biopsy-proven primary glomerular disease in the world and a major contributor to the worldwide burden of endstage renal failure, with a wide geographical variation. To determine the incidence, clinical profile and histological pattern of IgAN in our institute, we reviewed all the patients who had native kidney biopsies with the diagnosis of primary IgAN during the period from 1998 to 2009 in the context of the clinical features. A total of 116 patients with IgAN were finally analyzed; 85 (73% of the patients were male, the mean age of the patients was 29.2 ± 12.2 (range 10-70 years and the mean duration of disease was 10.4 ± 18.7 months (median: 2 months. Hypertension was present in 74 (63.2% cases. Gross hematuria was rare. The most common clinical presentation was nephrotic syndrome, followed by chronic renal failure. The mean proteinuria level was 2.5 ± 2.3 g/day (median: 1.7 g/day and the mean serum creatinine level was 3.04 ± 3.3 mg/dL (median:1.7 mg/dL. The morphological sub-classification (Haas: Class I was the most common (44.4%, followed by class V (23%. IgA co-deposition with C3 and lambda was the most common finding in the immunofluorescence study. The glomerular filtration rate decreased with advanced histological damage. The incidence of IgAN was 7.5%, which is lower as compared with studies from elsewhere. IgAN in our population had a more severe clinical presentation.

  6. A Randomized, Controlled Trial of Rituximab in IgA Nephropathy with Proteinuria and Renal Dysfunction.

    Science.gov (United States)

    Lafayette, Richard A; Canetta, Pietro A; Rovin, Brad H; Appel, Gerald B; Novak, Jan; Nath, Karl A; Sethi, Sanjeev; Tumlin, James A; Mehta, Kshama; Hogan, Marie; Erickson, Stephen; Julian, Bruce A; Leung, Nelson; Enders, Felicity T; Brown, Rhubell; Knoppova, Barbora; Hall, Stacy; Fervenza, Fernando C

    2017-04-01

    IgA nephropathy frequently leads to progressive CKD. Although interest surrounds use of immunosuppressive agents added to standard therapy, several recent studies have questioned efficacy of these agents. Depleting antibody-producing B cells potentially offers a new therapy. In this open label, multicenter study conducted over 1-year follow-up, we randomized 34 adult patients with biopsy-proven IgA nephropathy and proteinuria >1 g/d, maintained on angiotensin-converting enzyme inhibitors or angiotensin receptor blockers with well controlled BP and eGFRIgA1 or antibodies against galactose-deficient IgA1 did not change. In this trial, rituximab therapy did not significantly improve renal function or proteinuria assessed over 1 year. Although rituximab effectively depleted B cells, it failed to reduce serum levels of galactose-deficient IgA1 and antigalactose-deficient IgA1 antibodies. Lack of efficacy of rituximab, at least at this stage and severity of IgA nephropathy, may reflect a failure of rituximab to reduce levels of specific antibodies assigned salient pathogenetic roles in IgA nephropathy. Copyright © 2017 by the American Society of Nephrology.

  7. Current Understanding of the Role of Complement in IgA Nephropathy

    Science.gov (United States)

    Maillard, Nicolas; Wyatt, Robert J.; Julian, Bruce A.; Kiryluk, Krzysztof; Gharavi, Ali; Fremeaux-Bacchi, Veronique

    2015-01-01

    Complement activation has a role in the pathogenesis of IgA nephropathy, an autoimmune disease mediated by pathogenic immune complexes consisting of galactose-deficient IgA1 bound by antiglycan antibodies. Of three complement-activation pathways, the alternative and lectin pathways are involved in IgA nephropathy. IgA1 can activate both pathways in vitro, and pathway components are present in the mesangial immunodeposits, including properdin and factor H in the alternative pathway and mannan-binding lectin, mannan–binding lectin–associated serine proteases 1 and 2, and C4d in the lectin pathway. Genome–wide association studies identified deletion of complement factor H–related genes 1 and 3 as protective against the disease. Because the corresponding gene products compete with factor H in the regulation of the alternative pathway, it has been hypothesized that the absence of these genes could lead to more potent inhibition of complement by factor H. Complement activation can take place directly on IgA1–containing immune complexes in circulation and/or after their deposition in the mesangium. Notably, complement factors and their fragments may serve as biomarkers of IgA nephropathy in serum, urine, or renal tissue. A better understanding of the role of complement in IgA nephropathy may provide potential targets and rationale for development of complement-targeting therapy of the disease. PMID:25694468

  8. SIGNIFICANCE OF P- SELECTIN EXPRESSION IN IGA NEPHROPATHY

    Institute of Scientific and Technical Information of China (English)

    吴珮; 周同; 李晓; 王伟铭; 陈楠; 董德长

    2000-01-01

    Objective To investigate the role of P-selectin in IgA nephropathy (IgAN). Methods Plasma P-selectin level was measured by ELISA and P-selectin expression in renal tissue was detected by immunohistochemistry and in situ hybridization in 45 patients with IgAN. Results Plasma P-selectin levels in the patients with IgAN were significantly higher than those in the controls. In IgAN, the levels in the patients with nephrotic syndrome or renal function insufficiency were much higher than those in the patients with gross hematuria, abnormal urine analyses or nephritis syndrome. P- selectin was widely expressed within renal tissue in IgAN. Glomerular P- selectin expression was remarkably up - regulated in grade Ⅳ and Ⅴ of IgAN than that in grade Ⅱ and Ⅲ. Moreover, the expression of P- selectin on tubular epithelium or within interstitium was strongly associated with the degree of tubulointerstitial lesions. Conclusion The results suggested that P- selectin might play an important role in IgAN, and the level of P - selectin in plasma and renal tissue might predict the progress of IgAN.

  9. Expression of prorenin receptor in renal biopsies from patients with IgA nephropathy.

    Science.gov (United States)

    Miyazaki, Nagisa; Murata, Ichijiro; Takemura, Genzou; Okada, Hideshi; Kanamori, Hiromitsu; Matsumoto-Miyazaki, Jun; Yoshida, Gakuro; Izumi, Kumiko; Kashi, Hitomi; Niimi, Kaori; Nishiwaki, Ayuko; Miyazaki, Tatsuhiko; Ohno, Michiya; Ohashi, Hiroshige; Suzuki, Fumiaki; Minatoguchi, Shinya

    2014-01-01

    Prorenin receptor (PRR) has been implicated in the onset and progression of various renal diseases, though its possible association with immunoglobulin A (IgA) nephropathy remains unclear. In the present study, we tried to clarify expression and pathophysiological significance of PRR in IgA nephropathy. We immunohistochemically assessed PRR levels in renal biopsy specimens from 48 patients with IgA nephropathy and evaluated its relevance to the clinical and pathological features of the disease. PRR was detected mainly in renal tubular cells, which was confirmed at the subcellular level using immunoelectron microscopy. The PRR-positive area (%PRR area) correlated with daily urinary protein, which is known to reflect disease severity (r=0.286, P=0.049). PRR levels were weaker in tubular cells bordering areas of severe interstitial fibrosis, where α-smooth muscle actin-positive myofibroblasts were present. We also used immunohistochemical detection of microtubule-associated protein-1 light chain 3 (LC3) and electron microscopy to assess autophagy, a cytoprotective mechanism downstream of PRR. We noted an apparent coincidence between autophagy activation in tubular cells and PRR expression in the same cells. Taken together, our findings suggest that renal expression of PRR in IgA nephropathy may be a compensatory response slowing disease progression by preventing tubular cell death and subsequent fibrosis through activation of cytoprotective autophagic machinery. Further studies using different type of kidney diseases could draw conclusion if the present finding is a generalized observation beyond IgA nephropathy.

  10. In silico prediction of specific pathways that regulate mesangial cell proliferation in IgA nephropathy.

    Science.gov (United States)

    Mirfazeli, Elham Sadat; Marashi, Sayed-Amir; Kalantari, Shiva

    2016-12-01

    IgA nephropathy is one of the most common forms of primary glomerulonephritis worldwide leading to end-stage renal disease. Proliferation of mesangial cells, i.e., the multifunctional cells located in the intracapillary region of glomeruli, after IgA- dominant immune deposition is the major histologic feature in IgA nephropathy. In spite of several studies on molecular basis of proliferation in these cells, specific pathways responsible for regulation of proliferation are still to be discovered. In this study, we predicted a specific signaling pathway started from transferrin receptor (TFRC), a specific IgA1 receptor on mesangial cells, toward a set of proliferation-related proteins. The final constructed subnetwork was presented after filtration and evaluation. The results suggest that estrogen receptor (ESR1) as a hub protein in the significant subnetwork has an important role in the mesangial cell proliferation and is a potential target for IgA nephropathy therapy. In conclusion, this study suggests a novel hypothesis for the mechanism of pathogenesis in IgA nephropathy and is a reasonable start point for the future experimental studies on mesangial proliferation process in this disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Proteomic analysis of urinary exosomes from patients of early IgA nephropathy and thin basement membrane nephropathy.

    Science.gov (United States)

    Moon, Pyong-Gon; Lee, Jeong-Eun; You, Sungyong; Kim, Taek-Kyun; Cho, Ji-Hoon; Kim, In-San; Kwon, Tae-Hwan; Kim, Chan-Duck; Park, Sun-Hee; Hwang, Daehee; Kim, Yong-Lim; Baek, Moon-Chang

    2011-06-01

    To identify biomarker candidates associated with early IgA nephropathy (IgAN) and thin basement membrane nephropathy (TBMN), the most common causes presenting isolated hematuria in childhood, a proteomic approach of urinary exosomes from early IgAN and TBMN patients was introduced. The proteomic results from the patients were compared with a normal group to understand the pathophysiological processes associated with these diseases at the protein level. The urinary exosomes, which reflect pathophysiological processes, collected from three groups of young adults (early IgAN, TBMN, and normal) were trypsin-digested using a gel-assisted protocol, and quantified by label-free LC-MS/MS, using an MS(E) mode. A total of 1877 urinary exosome proteins, including cytoplasmic, membrane, and vesicle trafficking proteins, were identified. Among the differentially expressed proteins, four proteins (aminopeptidase N, vasorin precursor, α-1-antitrypsin, and ceruloplasmin) were selected as biomarker candidates to differentiate early IgAN from TBMN. We confirmed the protein levels of the four biomarker candidates by semi-quantitative immunoblot analysis in urinary exosomes independently prepared from other patients, including older adult groups. Further clinical studies are needed to investigate the diagnostic and prognostic value of these urinary markers for early IgAN and TBMN. Taken together, this study showed the possibility of identifying biomarker candidates for human urinary diseases using urinary exosomes and might help to understand the pathophysiology of early IgAN and TBMN at the protein level.

  12. Hyperuricemia is associated with progression of IgA nephropathy.

    Science.gov (United States)

    Bakan, Ali; Oral, Alihan; Elcioglu, Omer Celal; Takir, Mumtaz; Kostek, Osman; Ozkok, Abdullah; Basci, Semih; Sumnu, Abdullah; Ozturk, Savas; Sipahioglu, Murat; Turkmen, Aydın; Voroneanu, Luminita; Covic, Adrian; Kanbay, Mehmet

    2015-04-01

    IgA nephropathy (IgAN) is one of the world's most common glomerular diseases. Hyperuricemia was recently defined as risk factor for chronic kidney disease. We aimed to investigate the impact of baseline serum uric acid levels on progression of IgAN. A total of 93 patients with IgAN were screened. Demographic information and biochemical data were recorded. eGFR (using the CKD-EPI = Chronic Kidney Disease Epidemiology Collaboration formula) was used as renal function marker. Baseline and sixth month eGFR values were calculated. Progression of renal disease was defined as the difference between baseline eGFR and sixth month eGFR (delta eGFR). Mean age of the patients was 40 ± 11 years (60% were males). Baseline mean eGFR was 77.9 ± 30.2 mL/min, and baseline mean serum uric acid was 5.65 ± 1.68 mg/dL. Importantly, baseline serum uric acid levels were found to be associated with the change in eGFR (r = 0.252, p = 0.01). In multivariate analysis (adjusted R(2) = 0.171, p = 0.031), adjusting for age, gender, baseline eGFR, blood pressure, baseline albumin concentration and ACEI and/or ARB use revealed that the baseline serum uric acid levels significantly predicted the change in eGFR. Baseline serum uric acid concentration is directly proportional to the rate of decline in renal functions in patients with IgAN. Uric acid-lowering treatments may be beneficial for the prevention of progression of IgAN. However, randomized controlled studies are needed for this purpose.

  13. Role of glomerular proteoglycans in IgA nephropathy.

    Science.gov (United States)

    Ebefors, Kerstin; Granqvist, Anna; Ingelsten, Madeleine; Mölne, Johan; Haraldsson, Börje; Nyström, Jenny

    2011-04-06

    Mesangial matrix expansion is a prominent feature of the most common form of glomerulonephritis, IgA nephropathy (IgAN). To find molecular markers and improve the understanding of the disease, the gene and protein expression of proteoglycans were investigated in biopsies from IgAN patients and correlated to clinical and morphological data. We collected and microdissected renal biopsies from IgAN patients (n = 19) and from healthy kidney donors (n = 14). Patients were followed for an average time of 4 years and blood pressure was according to target guidelines. Distinct patterns of gene expression were seen in glomerular and tubulo-interstitial cells. Three of the proteoglycans investigated were found to be of special interest and upregulated in glomeruli: perlecan, decorin and biglycan. Perlecan gene expression negatively correlated to albumin excretion and progress of the disease. Abundant decorin protein expression was found in sclerotic glomeruli, but not in unaffected glomeruli from IgAN patients or in controls. Transforming growth factor beta (TGF-β), known to interact with perlecan, decorin and biglycan, were upregulated both on gene and protein level in the glomeruli. This study provides further insight into the molecular mechanisms involved in mesangial matrix expansion in IgAN. We conclude that perlecan is a possible prognostic marker for patients with IgAN. In addition, the up-regulation of biglycan and decorin, as well as TGF-β itself, indicate that regulation of TGF-β, and other profibrotic markers plays a role in IgAN pathology.

  14. Urinary uromodulin excretion predicts progression of chronic kidney disease resulting from IgA nephropathy.

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    Jingjing Zhou

    Full Text Available BACKGROUND: Uromodulin, or Tamm-Horsfall protein, is the most abundant urinary protein in healthy individuals. Recent studies have suggested that uromodulin may play a role in chronic kidney diseases. We examined an IgA nephropathy cohort to determine whether uromodulin plays a role in the progression of IgA nephropathy. METHODS: A total of 344 IgA nephropathy patients were involved in this study. Morphological changes were evaluated with the Oxford classification of IgA nephropathy. Enzyme Linked Immunosorbent Assay (ELISA measured the urinary uromodulin level on the renal biopsy day. Follow up was done regularly on 185 patients. Time-average blood pressure, time-average proteinuria, estimated glomerular filtration rate (eGFR and eGFR decline rate were caculated. Association between the urinary uromodulin level and the eGFR decline rate was analyzed with SPSS 13.0. RESULTS: We found that lower baseline urinary uromodulin levels (P = 0.03 and higher time-average proteinuria (P = 0.04 were risk factors for rapid eGFR decline in a follow-up subgroup of the IgA nephropathy cohort. Urinary uromodulin level was correlated with tubulointerstitial lesions (P = 0.016. Patients that had more tubular atrophy/interstitial fibrosis on the surface had lower urinary uromodulin levels (P = 0.02. CONCLUSIONS: Urinary uromodulin level is associated with interstitial fibrosis/tubular atrophy and contributes to eGFR decline in IgA nephropathy.

  15. Rapamycin ameliorates IgA nephropathy via cell cycle-dependent mechanisms.

    Science.gov (United States)

    Tian, Jihua; Wang, Yanhong; Liu, Xinyan; Zhou, Xiaoshuang; Li, Rongshan

    2015-07-01

    IgA nephropathy is the most frequent type of glomerulonephritis worldwide. The role of cell cycle regulation in the pathogenesis of IgA nephropathy has been studied. The present study was designed to explore whether rapamycin ameliorates IgA nephropathy via cell cycle-dependent mechanisms. After establishing an IgA nephropathy model, rats were randomly divided into four groups. Coomassie Brilliant Blue was used to measure the 24-h urinary protein levels. Renal function was determined using an autoanalyzer. Proliferation was assayed via Proliferating Cell Nuclear Antigen (PCNA) immunohistochemistry. Rat mesangial cells were cultured and divided into the six groups. Methylthiazolyldiphenyl-tetrazolium bromide (MTT) and flow cytometry were used to detect cell proliferation and the cell cycle phase. Western blotting was performed to determine cyclin E, cyclin-dependent kinase 2, p27(Kip1), p70S6K/p-p70S6K, and extracellular signal-regulated kinase 1/2/p- extracellular signal-regulated kinase 1/2 protein expression. A low dose of the mammalian target of rapamycin (mTOR) inhibitor rapamycin prevented an additional increase in proteinuria, protected kidney function, and reduced IgA deposition in a model of IgA nephropathy. Rapamycin inhibited mesangial cell proliferation and arrested the cell cycle in the G1 phase. Rapamycin did not affect the expression of cyclin E and cyclin-dependent kinase 2. However, rapamycin upregulated p27(Kip1) at least in part via AKT (also known as protein kinase B)/mTOR. In conclusion, rapamycin can affect cell cycle regulation to inhibit mesangial cell proliferation, thereby reduce IgA deposition, and slow the progression of IgAN.

  16. Cholestatic jaundice and IgA nephropathy induced by OTC muscle building agent superdrol.

    Science.gov (United States)

    Jasiurkowski, Beata; Raj, Jaya; Wisinger, David; Carlson, Richard; Zou, Lixian; Nadir, Abdul

    2006-11-01

    Over the counter (OTC) medicines are commonly used in the United States despite a lack of scientific evidence for clinical utility and toxicity associated with their use. A case of jaundice and IgA nephropathy as a consequence of use of a muscle enhancing OTC supplement that was advertised as innocuous with no hormonal activity is described. IgA nephropathy has not been described previously in association with the use of testosterone. The case highlights that, besides adulteration, the misrepresentation of chemicals present in OTC medications and supplements can create confusion and a false sense of security with their use.

  17. New developments in the genetics, pathogenesis, and therapy of IgA nephropathy

    Science.gov (United States)

    Magistroni, Riccardo; D’Agati, Vivette D.; Appel, Gerald B.; Kiryluk, Krzysztof

    2015-01-01

    Recent years have brought notable progress in the field of IgA nephropathy. Here, we highlight important new directions and latest developments, including successful discovery of several genetic susceptibility loci, formulation of the multi-hit pathogenesis model that integrates findings from studies of galactose-deficient IgA1, anti-glycan response and immune complex-induced kidney injury, introduction of the Oxford pathology scoring system, and formalization of the Kidney Disease Improving Global Outcomes (KDIGO) consensus treatment guidelines. We focus on the latest genetic findings that confirm a strong contribution of inherited factors and explain some of the geo-ethnic disparities in disease susceptibility. Most IgA nephropathy susceptibility loci discovered to date encode genes involved in the maintenance of the intestinal epithelial barrier and response to mucosal pathogens. The concerted pattern of inter-population allelic differentiation across all Genome Wide Association Studies (GWAS) loci parallels the disease prevalence and correlates with variation in local pathogens, suggesting that multi-locus adaptation might have shaped the present-day landscape of IgA nephropathy. Importantly, the “Intestinal Immune Network for IgA Production” emerged as one of the new targets for potential therapeutic intervention. We place these findings in the context of the multi-hit pathogenesis model and existing knowledge of IgA immunobiology. Lastly, we provide our perspective on the existing treatment options, discuss areas of clinical uncertainty, and outline ongoing clinical trials and translational studies. PMID:26376134

  18. Lack of serologic evidence to link IgA nephropathy with celiac disease or immune reactivity to gluten.

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    Sina Moeller

    Full Text Available IgA nephropathy is the most common form of primary glomerulonephritis worldwide. Mucosal infections and food antigens, including wheat gluten, have been proposed as potential contributing environmental factors. Increased immune reactivity to gluten and/or association with celiac disease, an autoimmune disorder triggered by ingestion of gluten, have been reported in IgA nephropathy. However, studies are inconsistent about this association. We aimed to evaluate the proposed link between IgA nephropathy and celiac disease or immune reactivity to gluten by conducting a comprehensive analysis of associated serologic markers in cohorts of well-characterized patients and controls. Study participants included patients with biopsy-proven IgA nephropathy (n = 99, unaffected controls of similar age, gender, and race (n = 96, and patients with biopsy-proven celiac disease (n = 30. All serum specimens were tested for IgG and IgA antibodies to native gliadin and deamidated gliadin, as well as IgA antibody to transglutaminase 2 (TG2. Anti-TG2 antibody-positive nephropathy patients and unaffected controls were subsequently tested for IgA anti-endomysial antibody and genotyped for celiac disease-associated HLA-DQ2 and -DQ8 alleles. In comparison to unaffected controls, there was not a statistically significant increase in IgA or IgG antibody reactivity to gliadin in individuals with IgA nephropathy. In addition, the levels of celiac disease-specific serologic markers, i.e., antibodies to deamidated gliadin and TG2, did not differ between IgA nephropathy patients and unaffected controls. Results of the additional anti-endomysial antibody testing and HLA genotyping were corroborative. The data from this case-control study do not reveal any evidence to suggest a significant role for celiac disease or immune reactivity to gluten in IgA nephropathy.

  19. The coincidence of IgA nephropathy and Fabry disease

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    Maixnerová Dita

    2013-01-01

    Full Text Available Abstract Background IgA nephropathy (IgAN is the most common glomerulonephritis, which may also coexist with other diseases. We present two patients with an unusual coincidence of IgAN and Fabry disease (FD. Case presentation A 26 year-old man underwent a renal biopsy in February 2001. Histopathology showed very advanced IgAN and vascular changes as a result of hypertension. Because of his progressive renal insufficiency the patient began hemodialysis in August 2001. By means of the blood spot test screening method the diagnosis of FD was suspected. Low activity of alpha-galactosidase A in the patient’s plasma and leukocytes and DNA analysis confirmed the diagnosis of FD. Enzyme replacement therapy started in July 2004. Then the patient underwent kidney transplantation in November 2005. Currently, his actual serum creatinine level is 250 μmol/l. Other organ damages included hypertrophic cardiomyopathy, neuropathic pain and febrile crisis. After enzyme replacement therapy, myocardial hypertrophy has stabilized and other symptoms have disappeared. No further progression of the disease has been noted. The other patient, a 30 year-old woman, suffered from long-term hematuria with a good renal function. Recently, proteinuria (2.6 g/day appeared and a renal biopsy was performed. Histopathology showed IgAN with remarkably enlarged podocytes. A combination of IgAN and a high suspicion of FD was diagnosed. Electron microscopy revealed dense deposits in paramesangial areas typical for IgAN and podocytes with inclusive zebra bodies and myelin figures characteristic of FD. FD was confirmed by the decreased alpha-galactosidase A activity in plasma and leukocytes and by DNA and RNA analysis. Enzyme replacement therapy and family screening were initiated. Conclusions Our results emphasize the role of complexity in the process of diagnostic evaluation of kidney biopsy samples. Electron microscopy represents an integral part of histopathology, and genetic

  20. Corticosteroids in IgA Nephropathy: A Retrospective Analysis from the VALIGA Study

    NARCIS (Netherlands)

    Tesar, V.; Troyanov, S.; Bellur, S.; Verhave, J.C.; Cook, H.T.; Feehally, J.; Roberts, I.S.; Cattran, D.; Coppo, R.

    2015-01-01

    Current guidelines suggest treatment with corticosteroids (CS) in IgA nephropathy (IgAN) when proteinuria is persistently >/=1 g/d despite 3-6 months of supportive care and when eGFR is >50 ml/min per 1.73 m(2). Whether the benefits of this treatment extend to patients with an eGFR

  1. Prevalence and risk factors of hyperuricemia in patients with IgA nephropathy

    Institute of Scientific and Technical Information of China (English)

    梁孟君

    2013-01-01

    Objective To evaluate the prevalence of hyperuricemia in patients with IgA nephropathy and find out the risk factors of hyperuricemia,including clinical and pathological characteristics.Methods A retrospective study enrolled 2566 adult patients,who admitted to the

  2. Combined C4d and CD3 immunostaining predicts immunoglobulin (Ig)A nephropathy progression

    NARCIS (Netherlands)

    Faria, B.; Henriques, C.; Matos, A. C.; Daha, M. R.; Pestana, M.; Seelen, M.

    2015-01-01

    A number of molecules have been shown recently to be involved in the pathogenesis and progression of immunoglobulin (Ig)A nephropathy (IgAN). Among these, we have selected C4d (complement lectin pathway involvement), CD3 (T cell marker, traducing interstitial inflammation), transglutaminase 2 (TGase

  3. [Clinical and pathological features in IgA nephropathy with IgG deposition in the glomerular mesangial area].

    Science.gov (United States)

    Xu, Xiao-Meng; Zhu, Shuang-Shuang; Wang, Xiao-Hong; Shao, Xiao-Fei; Li, Bin; Zhang, Ying; Liu, Qin; Li, Jia-Min; Wang, Hong-Lei; Li, Yong-Qiang; Zou, He-Qun

    2017-03-20

    To investigate the relationship between the clinical and pathological findings in IgA nephropathy with or without IgG deposition in the glomerular mesangial area. The data were collected from 122 patients with a diagnosis of IgA nephropathy by renal biopsy in the Third Affiliated Hospital of Southern Medical University between November, 2009 and February, 2016. All the samples were examined by light microscopy, immunofluorescence and electron microscopy. According to the results of immunofluorescence assay, the patients were divided into IgA group (n=63) and IgA-IgG group (n=59). The pathological classification of IgA nephropathy was analyzed according to Oxford classification and Lee's classification. The clinical and pathological findings were compared between the two groups. Compared with the patients with IgA nephropathy but without IgG deposition, patients with IgA nephropathy with IgG deposition had higher serum creatinine, higher 24-h urine protein, higher blood uric acid, higher triglyceride levels (PIgA nephropathy with IgG deposition in the glomerular mesangial have severer clinical symptoms and more serious pathological changes. Measures should be taken to control IgG deposition in patients with IgA nephropathy to delay the progress of the disease.

  4. Analysis of O-glycan heterogeneity in IgA1 myeloma proteins by Fourier transform ion cyclotron resonance mass spectrometry: implications for IgA nephropathy

    DEFF Research Database (Denmark)

    Renfrow, MB; Mackay, CL; Chalmers, MJ

    2007-01-01

    IgA nephropathy (IgAN) is the most common form of primary glomerulonephritis. In IgAN, IgA1 molecules with incompletely galactosylated O-linked glycans in the hinge region (HR) are present in mesangial immunodeposits and in circulating immune complexes. It is not known whether the galactose defic...

  5. Uncoupling of glomerular IgA deposition and disease progression in alymphoplasia mice with IgA nephropathy.

    Directory of Open Access Journals (Sweden)

    Masashi Aizawa

    Full Text Available Previous clinical and experimental studies have indicated that cells responsible for IgA nephropathy (IgAN, at least in part, are localized in bone marrow (BM. Indeed, we have demonstrated that murine IgAN can be experimentally reconstituted by bone marrow transplantation (BMT from IgAN prone mice in not only normal mice, but also in alymphoplasia mice (aly/aly independent of IgA+ cells homing to mucosa or secondary lymphoid tissues. The objective of the present study was to further assess whether secondary lymph nodes (LN contribute to the progression of this disease. BM cells from the several lines of IgAN prone mice were transplanted into aly/aly and wild-type mice (B6. Although the transplanted aly/aly showed the same degree of mesangial IgA and IgG deposition and the same serum elevation levels of IgA and IgA-IgG immune-complexes (IC as B6, even in extent, the progression of glomerular injury was observed only in B6. This uncoupling in aly/aly was associated with a lack of CD4+ T cells and macrophage infiltration, although phlogogenic capacity to nephritogenic IC of renal resident cells was identical between both recipients. It is suggested that secondary LN may be required for the full progression of IgAN after nephritogenic IgA and IgA/IgG IC deposition.

  6. [Disseminated tuberculosis revealing IgA nephropathy with nephrotic syndrome : A case report].

    Science.gov (United States)

    Morbieu, Caroline; Michel, Pierre-Antoine; Brocheriou, Isabelle; Canestri, Ana; Boffa, Jean-Jacques

    2016-07-01

    A 27-year-old man without any medical history presented concomitantly a pulmonary and urinary tuberculosis and a nephrotic syndrome with hematuria and renal failure. The renal biopsy showed increased mesangial matrix, few focal segmental lesions, and IgA deposits confirming the diagnosis of IgA nephropathy. Nephrotic syndrome remission occurred quickly after antituberculous treatment. The association between tuberculosis and IgA nephropathy has been previously reported in 9 patients. Renal outcome was always favorable with antituberculous treatment. No relapse occurred, with a maximal follow-up of 42 months. Here, we discuss this singular association and previous similar cases. Copyright © 2016 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.

  7. Insulin-like growth factor binding protein-1 levels are increased in patients with IgA nephropathy

    Energy Technology Data Exchange (ETDEWEB)

    Tokunaga, Koki [Department of Digestive and Life-Style Related Disease, Health Research Course, Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8520 (Japan); Uto, Hirofumi, E-mail: hirouto@m2.kufm.kagoshima-u.ac.jp [Department of Digestive and Life-Style Related Disease, Health Research Course, Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8520 (Japan); Takami, Yoichiro; Mera, Kumiko; Nishida, Chika; Yoshimine, Yozo; Fukumoto, Mayumi; Oku, Manei; Sogabe, Atsushi; Nosaki, Tsuyoshi; Moriuchi, Akihiro; Oketani, Makoto; Ido, Akio; Tsubouchi, Hirohito [Department of Digestive and Life-Style Related Disease, Health Research Course, Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8520 (Japan)

    2010-08-20

    Research highlights: {yields} IGFBP-1 mRNA over express in kidneys obtained from mice model of IgA nephropathy. {yields} Serum IGFBP-1 levels are high in patients with IgA nephropathy. {yields} Serum IGFBP-1 levels correlate with renal function and the severity of renal injury. -- Abstract: The mechanisms underlying the pathogenesis of immunoglobulin A (IgA) nephropathy (IgAN) are not well understood. In this study, we examined gene expression profiles in kidneys obtained from mice with high serum IgA levels (HIGA mice), which exhibit features of human IgAN. Female inbred HIGA, established from the ddY line, were used in these experiments. Serum IgA levels, renal IgA deposition, mesangial proliferation, and glomerulosclerosis were increased in 32-week-old HIGA mice in comparison to ddY animals. By microarray analysis, five genes were observed to be increased by more than 2.5-fold in 32-week-old HIGA in comparison to 16-week-old HIGA; these same five genes were decreased more than 2.5-fold in 32-week-old ddY in comparison to 16-week-old ddY mice. Of these five genes, insulin-like growth factor (IGF) binding protein (IGFBP)-1 exhibited differential expression between these mouse lines, as confirmed by quantitative RT-PCR. In addition, serum IGFBP-1 levels were significantly higher in patients with IgAN than in healthy controls. In patients with IgAN, these levels correlated with measures of renal function, such as estimated glomerular filtration rate (eGFR), but not with sex, age, serum IgA, C3 levels, or IGF-1 levels. Pathologically, serum IGFBP-1 levels were significantly associated with the severity of renal injury, as assessed by mesangial cell proliferation and interstitial fibrosis. These results suggest that increased IGFBP-1 levels are associated with the severity of renal pathology in patients with IgAN.

  8. Cellular Signaling and Production of Galactose-Deficient IgA1 in IgA Nephropathy, an Autoimmune Disease

    Directory of Open Access Journals (Sweden)

    Colin Reily

    2014-01-01

    Full Text Available Immunoglobulin A (IgA nephropathy (IgAN, the leading cause of primary glomerulonephritis, is characterized by IgA1-containing immunodeposits in the glomeruli. IgAN is a chronic disease, with up to 40% of patients progressing to end-stage renal disease, with no disease-specific treatment. Multiple studies of the origin of the glomerular immunodeposits have linked elevated circulating levels of aberrantly glycosylated IgA1 (galactose-deficient in some O-glycans; Gd-IgA1 with formation of nephritogenic Gd-IgA1-containing immune complexes. Gd-IgA1 is recognized as an autoantigen in susceptible individuals by anti-glycan autoantibodies, resulting in immune complexes that may ultimately deposit in the kidney and induce glomerular injury. Genetic studies have revealed that an elevated level of Gd-IgA1 in the circulation of IgAN patients is a hereditable trait. Moreover, recent genome-wide association studies have identified several immunity-related loci that associated with IgAN. Production of Gd-IgA1 by IgA1-secreting cells of IgAN patients has been attributed to abnormal expression and activity of several key glycosyltransferases. Substantial evidence is emerging that abnormal signaling in IgA1-producing cells is related to the production of Gd-IgA1. As Gd-IgA1 is the key autoantigen in IgAN, understanding the genetic, biochemical, and environmental aspects of the abnormal signaling in IgA1-producing cells will provide insight into possible targets for future disease-specific therapy.

  9. Clinical and pathological analysis of IgA nephropathy with chronic renal failure.

    Science.gov (United States)

    Liu, Yuyuan; Hu, Qinfeng; Shen, Ping; Tang, Li; Yuan, Gang; Zhou, Yongmei; Chai, Huaqi

    2016-10-01

    To investigative clinical and pathological characteristics of IgA nephropathy with chronic renal failure. Clinical and pathological findings from 65 cases of IgA nephropathy with chronic renal failure were reviewed. Pathological characteristics of all the cases were analyzed according to WHO definition and Oxford Classification. Evaluating the severity of pathological lesions by the Katafuchi R semiquantitative scoring system, and analyzing their relationship with clinical indexes of renal function. Of all 65 cases the male and female ratio was 1.4, and the mean age was 37 ± 13 years old. Levels of systolic pressure, mean arterial pressure (MAP), blood urea nitrogen (BUN), serum creatinine (Scr), uric acid (UA), album (Alb), serum IgG and 24 h urinary protein were related with eGRF level (p IgA deposition was the most common immunopathologic type. Of all the cases, 44.6% accompanied with C3 while 4.6% with C1q. Further analysis revealed there were no relationships between severity of pathological lesion and levels of clinical indexes (Scr and eGRF) (p > 0.05). IgA nephropathy with chronic renal failure usually occurred in young adults, and it had severe clinical condition and pathological changes, while there was no significant relationship between them.

  10. Activation of podocytes by mesangial-derived TNF-alpha: glomerulo-podocytic communication in IgA nephropathy.

    Science.gov (United States)

    Lai, Kar Neng; Leung, Joseph C K; Chan, Loretta Y Y; Saleem, Moin A; Mathieson, Peter W; Lai, Fernand M; Tang, Sydney C W

    2008-04-01

    We have previously documented that human mesangial cell (HMC)-derived TNF-alpha is an important mediator involved in the glomerulo-tubular communication in the development of interstitial damage in IgA nephropathy (IgAN). With the strategic position of podocytes, we further examined the role of mesangial cells in the activation of podocytes in IgAN. There was no binding of IgA from patients with IgAN to podocytes. Podocytes cultured with IgA from patients with IgAN did not induce the release of growth factors or cytokines. Furthermore, podocytes did not express mRNA of known IgA receptors. In contrast, IgA-conditioned medium (IgA-HMC medium) prepared by culturing HMC with IgA from patients with IgAN for 48 h significantly increased the gene expression and protein synthesis of TNF-alpha by podocytes with a 17-fold concentration above that of IgA-HMC medium. The upregulation of TNF-alpha expression by podocyte was only abolished by a neutralizing antibody against TNF-alpha but not by other antibodies. Exogenous TNF-alpha upregulated the synthesis of TNF-alpha by podocytes in an autocrine fashion. IgA-HMC medium prepared with IgA from patients with IgAN also significantly upregulated the expression of both TNF-alpha receptor 1 and 2 in podocytes. Our in vitro finding suggests podocytes may play a contributory role in the development of interstitial damage in IgAN by amplifying the activation of tubular epithelial cells with enhanced TNF-alpha synthesis after inflammatory changes of HMC.

  11. The Origin and Activities of IgA1-Containing Immune Complexes in IgA Nephropathy

    Science.gov (United States)

    Knoppova, Barbora; Reily, Colin; Maillard, Nicolas; Rizk, Dana V.; Moldoveanu, Zina; Mestecky, Jiri; Raska, Milan; Renfrow, Matthew B.; Julian, Bruce A.; Novak, Jan

    2016-01-01

    IgA nephropathy (IgAN) is the most common primary glomerulonephritis, frequently leading to end-stage renal disease, as there is no disease-specific therapy. IgAN is diagnosed from pathological assessment of a renal biopsy specimen based on predominant or codominant IgA-containing immunodeposits, usually with complement C3 co-deposits and with variable presence of IgG and/or IgM. The IgA in these renal deposits is galactose-deficient IgA1, with less than a full complement of galactose residues on the O-glycans in the hinge region of the heavy chains. Research from the past decade led to the definition of IgAN as an autoimmune disease with a multi-hit pathogenetic process with contributing genetic and environmental components. In this process, circulating galactose-deficient IgA1 (autoantigen) is bound by antiglycan IgG or IgA (autoantibodies) to form immune complexes. Some of these circulating complexes deposit in glomeruli, and thereby activate mesangial cells and induce renal injury through cellular proliferation and overproduction of extracellular matrix components and cytokines/chemokines. Glycosylation pathways associated with production of the autoantigen and the unique characteristics of the corresponding autoantibodies in patients with IgAN have been uncovered. Complement likely plays a significant role in the formation and the nephritogenic activities of these complexes. Complement activation is mediated through the alternative and lectin pathways and probably occurs systemically on IgA1-containing circulating immune complexes as well as locally in glomeruli. Incidence of IgAN varies greatly by geographical location; the disease is rare in central Africa but accounts for up to 40% of native-kidney biopsies in eastern Asia. Some of this variation may be explained by genetically determined influences on the pathogenesis of the disease. Genome-wide association studies to date have identified several loci associated with IgAN. Some of these loci are associated

  12. Mesangial cells from patients with IgA nephropathy have increased susceptibility to galactose-deficient IgA1.

    Science.gov (United States)

    Ebefors, Kerstin; Liu, Peidi; Lassén, Emelie; Elvin, Johannes; Candemark, Emma; Levan, Kristina; Haraldsson, Börje; Nyström, Jenny

    2016-04-05

    IgA nephropathy (IgAN) is the most common glomerulonephritis in the world, affecting close to a million people. Circulating galactose-deficient IgA (gd-IgA), present in patients with IgAN, form immune complex deposits in the glomerular mesangium causing local proliferation and matrix expansion. Intriguing though, individuals having gd-IgA deposits in the kidneys do not necessarily have signs of glomerular disease. Recurrence of IgAN only occurs in less than half of transplanted patients with IgAN, indicating that gd-IgA is not the only factor driving the disease. We hypothesize that, in addition to IgA complexes, patients with IgAN possess a subtype of mesangial cells highly susceptible to gd-IgA induced cell proliferation. To test the hypothesis, we designed a technique to culture primary mesangial cells from renal biopsies obtained from IgAN patients and controls. The cell response to gd-IgA treatment was then measured both on gene and protein level and the proliferation rate of the cells in response to PDGF was investigated. When treated with gd-IgA, mesangial cells from patients with IgAN express and release more PDGF compared to controls. In addition, the mesangial cells from patients with IgAN were more responsive to treatment with PDGF resulting in an increased proliferation rate of the cells compared to control. Mesangial cells cultured from patients with IgAN expressed and released more IL-6 than controls and had a higher expression of matrix genes. Both mesangial cells derived from patients with IgAN and controls increased their expressed TGFβ1 and CCL5 when treated with gd-IgA. We conclude that mesangial cells derived from IgAN patients have a mesangioproliferative phenotype with increased reactivity to IgA and that these cellular intrinsic properties may be important for the development of IgA nephropathy.

  13. Potential association of hyperhomocysteinemia with the progression of IgA nephropathy: a retrospective study

    Institute of Scientific and Technical Information of China (English)

    Duan Shuwei; Liu Shuwen; Sun Xuefeng; Zheng Ying; Liu Linchang; Yao Feixiang; Wu Jie

    2014-01-01

    Background The high blood homocysteine (Hcy) levels found in patients with hyperhomocysteinemia (HHcy) have been implicated in an increased risk of cardiovascular disease morbidity and mortality in end-stage renal disease (ESRD).This study investigated the association of HHcy with progression of IgA nephropathy.Methods We analyzed 108 participants newly diagnosed with IgA nephropathy between August 2005 and August 2007 in the Department of Nephrology,Chinese People's Liberation Army General Hospital.The association between clinicopathological factors and the Hcy levels were analyzed by Logistic regression and those with ESRD risk were analyzed by Cox regression.Results Patients were aged (35.71±10.73) years and included 45.71% women and 12.04% patients with HHcy.In multivariate Logistic regression analysis,HHcy was associated with arterial lesions (OR 2.60; 95% CI 1.55-4.34; P<0.001) even when age,body mass index,estimated glomerular filtration rate,mean arterial pressure,and initial proteinuria were taken into account.Mean follow-up was (67.37±16.21) months.HHcy was also associated with worse ESRD-free survival (HR 4.71; 95% CI 1.45 to 15.31; P=0.010).Conclusion HHcy is associated with the risk of intrarenal arterial lesions and may be useful for estimating the prognosis of IgA nephropathy.

  14. A Clinicopathologic Study of Thrombotic Microangiopathy in IgA Nephropathy

    Science.gov (United States)

    Hill, Gary S.; Karras, Alexandre; Jacquot, Christian; Moulonguet, Luc; Kourilsky, Olivier; Frémeaux-Bacchi, Véronique; Delahousse, Michel; Van Huyen, Jean-Paul Duong; Loupy, Alexandre; Bruneval, Patrick; Nochy, Dominique

    2012-01-01

    Thrombotic microangiopathy (TMA) occurs in IgA nephropathy, but its clinical significance is not well described. We retrospectively examined a series of 128 patients diagnosed with IgA nephropathy between 2002 and 2008 who had a mean follow-up of 44±27 months. In our series, 53% presented with lesions of TMA, acute or organized, in arteries and/or arterioles. Among patients with TMA, 4% were normotensive, 25% had controlled hypertension, and 71% had uncontrolled hypertension. Of those with uncontrolled hypertension, 26% had malignant hypertension. Histologically, the group with TMA had a significantly greater percentage of sclerotic glomeruli and worse tubulointerstitial fibrosis than those of the group without TMA. However, a significant minority of patients had near-normal histology, with minimal tubular atrophy (20%) and/or <20% interstitial fibrosis (24%). TMA rarely occurred in the absence of significant proteinuria. During follow-up, a doubling of serum creatinine or ESRD occurred in all patients with laboratory evidence of TMA, in 42% of those with morphologic evidence but no laboratory evidence of TMA, and in 11% of those without TMA. In summary, lesions of TMA are frequent in IgA nephropathy and may occur in normotensive patients with near-normal renal histology. Although the pathophysiologic mechanisms involved remain undetermined, the current study rules out severe hypertension or advanced renal disease as sole causes. PMID:22052055

  15. Early pre-eclampsia unmasks underlying IgA nephropathy

    OpenAIRE

    Mona Singh; Akhenaton Pappoe; Don, Burl R.

    2010-01-01

    Mona Singh, Akhenaton Pappoe, Burl R DonDivision of Nephrology, University of California Davis Medical Center, Sacramento, CA, USAAbstract: Pre-eclampsia is the most ominous complication of pregnancy, and primary glomerular diseases can mimic pre-eclampsia in presentation. A patient presented at 21 weeks gestation with signs and symptoms of both pre-eclampsia and primary glomerular nephropathy. A critical clinical decision whether to continue or terminate the pregnancy was dependent on result...

  16. [Extracapillary IgA nephropathy associated with infection with hepatitis C virus and hepatic cirrhosis].

    Science.gov (United States)

    Cabezuelo, J B; Enríquez, R; Andrada, E; Amorós, F; Sirvent, A E; Reyes, A

    2000-01-01

    We describe a 36 year old man who was admitted to the hospital with dyspnea, edema of the lower limbs, arterial hypertension and oliguric renal failure. He had microhematuria and nephrotic range proteinuria, immunological tests were normal or negative. Renal biopsy revealed global (55%) or segmental glomeruloesclerosis, remaining glomeruli showed extracapillary proliferation (25%). Immunofluorescence study disclosed IgA mesangial deposits. He was also diagnosed as having liver cirrhosis with positive serology against hepatitis C virus. He was treated with dialysis, antihypertensive drugs and steroids with improvement of the renal function. However, ten months later maintenance hemodialysis became necessary. We emphasize two points: first IgA glomerulonephritis is rarely associated with hepatitis C infection, and second crescentic IgA nephropathy has been infrequently reported in liver cirrhosis.

  17. A simultaneous liver-kidney transplant recipient with IgA nephropathy limited to native kidneys and BK virus nephropathy limited to the transplant kidney.

    Science.gov (United States)

    Ujire, Manasa P; Curry, Michael P; Stillman, Isaac E; Hanto, Douglas W; Mandelbrot, Didier A

    2013-08-01

    Immunoglobulin A (IgA) deposition in the native kidneys of patients with liver disease is well described. Secondary IgA nephropathy usually is thought to be benign, but hematuria, proteinuria, and loss of kidney function have been reported in this context. BK virus nephropathy is an important cause of kidney transplant loss; however, BK virus nephropathy is rare in the native kidneys of patients who underwent transplantation of other organs. We report the case of a patient with alcohol-related end-stage liver disease and chronic kidney disease with hematuria who underwent simultaneous liver-kidney transplantation. His kidney function decreased over the course of several weeks posttransplantation. Biopsy of the transplant kidney showed BK virus nephropathy, but no IgA deposits. In contrast, biopsy of the native kidneys showed IgA deposits, but no BK virus nephropathy. To our knowledge, this is the first reported case of a simultaneous liver-kidney transplantation wherein both the native and transplant kidneys were biopsied posttransplantation and showed exclusively different pathologies. These findings confirm the predilection of BK virus nephropathy for transplant rather than native kidneys.

  18. β1,4-galactosyltransferase 1 is a novel receptor for IgA in human mesangial cells.

    Science.gov (United States)

    Molyneux, Karen; Wimbury, David; Pawluczyk, Izabella; Muto, Masahiro; Bhachu, Jasraj; Mertens, Peter R; Feehally, John; Barratt, Jonathan

    2017-07-24

    IgA nephropathy is characterized by mesangial deposition of IgA, mesangial cell proliferation, and extracellular matrix production. Mesangial cells bind IgA, but the identity of all potential receptors involved remains incomplete. The transferrin receptor (CD71) acts as a mesangial cell IgA receptor and its expression is upregulated in many forms of glomerulonephritis, including IgA nephropathy. CD71 is not expressed in healthy glomeruli and blocking CD71 does not completely abrogate mesangial cell IgA binding. Previously we showed that mesangial cells express a receptor that binds the Fc portion of IgA and now report that this receptor is an isoform of β-1,4-galactosyltransferase. A human mesangial cell cDNA library was screened for IgA binding proteins and β-1,4-galactosyltransferase identified. Cell surface expression of the long isoform of β-1,4-galactosyltransferase was shown by flow cytometry and confocal microscopy and confirmed by immunoblotting. Glomerular β-1,4-galactosyltransferase expression was increased in IgA nephropathy. IgA binding and IgA-induced mesangial cell phosphorylation of spleen tyrosine kinase and IL-6 synthesis were inhibited by a panel of β-1,4-galactosyltransferase-specific antibodies, suggesting IgA binds to the catalytic domain of β-1,4-galactosyltransferase. Thus, β-1,4-galactosyltransferase is a constitutively expressed mesangial cell IgA receptor with an important role in both mesangial IgA clearance and the initial response to IgA deposition. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  19. Aberrant O-glycosylation and anti-glycan antibodies in an autoimmune disease IgA nephropathy and breast adenocarcinoma

    DEFF Research Database (Denmark)

    Stuchlová Horynová, Milada; Raška, Milan; Clausen, Henrik

    2013-01-01

    Glycosylation abnormalities have been observed in autoimmune diseases and cancer. Here, we compare mechanisms of aberrant O-glycosylation, i.e., formation of Tn and sialyl-Tn structures, on MUC1 in breast cancer, and on IgA1 in an autoimmune disease, IgA nephropathy. The pathways of aberrant O......-glycosylation, although different for MUC1 and IgA1, include dysregulation in glycosyltransferase expression, stability, and/or intracellular localization. Moreover, these aberrant glycoproteins are recognized by antibodies, although with different consequences. In breast cancer, elevated levels of antibodies recognizing...... aberrant MUC1 are associated with better outcome, whereas in IgA nephropathy, the antibodies recognizing aberrant IgA1 are part of the pathogenetic process....

  20. 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.

  1. The efficacy and influencing factors of combination of prednisone and MTX in patients with IgA nephropathy

    Institute of Scientific and Technical Information of China (English)

    Xuan Cao; Jian Chen; Ya-Lin Hu

    2016-01-01

    Objective:To evaluate the efficacy and factors of prednisone combined with cyclophosphamide (CTX) treatment of primary immunoglobulin A (IgA).Methods:Ninty six cases of IgA nephropathy patients were treated with prednisone combined CTX from January 2013 to December 2014. Renal function before and after treatment was measured and the effects of prednisone combined CTX in patients with IgA nephropathy were analyzed.Results:Thirty eight cases were cured in 96 cases of IgA nephropathy patients (39.58%), 42 cases were effective (43.75%), 16 cases were ineffective (16.67%), totally, and 80 were was ffective (83.33%). After treatment, blood urea nitrogen (BUN), serum creatinine (blood Scr), 24 h urine protein (24 h Uab) were lower than before treatment, and endogenous creatinine clearance (Ccr) were significantly higher than before treatment (P<0.05). After logistic regression, 24 h urine protein levels, Ccr before treatment, LEE kidney tissue classification, hypertension were risk factors of prednisone combined with CTX treatment on prognosis of patients with IgA nephropathy.Conclusions:Prednisone combined CTX is effective in the treatment of IgA nephropathy, but clinical and pathological features of patients should be considered in the choice of the program.

  2. Serum Galactose-Deficient IgA1 Level Is Not Associated with Proteinuria in Children with IgA Nephropathy

    Directory of Open Access Journals (Sweden)

    M. Colleen Hastings

    2012-01-01

    Full Text Available Introduction. Percentage of galactose-deficient IgA1 (Gd-IgA1 relative to total IgA in serum was recently reported to correlate with proteinuria at time of sampling and during follow-up for pediatric and adult patients with IgA nephropathy. We sought to determine whether this association exists in another cohort of pediatric patients with IgA nephropathy. Methods. Subjects were younger than 18 years at entry. Blood samples were collected on one or more occasions for determination of serum total IgA and Gd-IgA1. Gd-IgA1 was expressed as serum level and percent of total IgA. Urinary protein/creatinine ratio was calculated for random specimens. Spearman’s correlation coefficients assessed the relationship between study variables. Results. The cohort had 29 Caucasians and 11 African-Americans with a male : female ratio of 1.9 : 1. Mean age at diagnosis was 11.7 ± 3.7 years. No statistically significant correlation was identified between serum total IgA, Gd-IgA1, or percent Gd-IgA1 versus urinary protein/creatinine ratio determined contemporaneously with biopsy or between average serum Gd-IgA1 or average percent Gd-IgA1 and time-average urinary protein/creatinine ratio. Conclusion. The magnitude of proteinuria in this cohort of pediatric patients with IgA nephropathy was influenced by factors other than Gd-IgA1 level, consistent with the proposed multi-hit pathogenetic pathways for this renal disease.

  3. IgA nephropathy in systemic lupus erythematosus patients: case report and literature review.

    Science.gov (United States)

    da Silva, Leonardo Sales; Almeida, Bruna Laiza Fontes; de Melo, Ana Karla Guedes; de Brito, Danielle Christine Soares Egypto; Braz, Alessandra Sousa; Freire, Eutília Andrade Medeiros

    2016-01-01

    Systemic erythematosus lupus (SLE) is a multisystemic autoimmune disease which has nephritis as one of the most striking manifestations. Although it can coexist with other autoimmune diseases, and determine the predisposition to various infectious complications, SLE is rarely described in association with non-lupus nephropathies etiologies. We report the rare association of SLE and primary IgA nephropathy (IgAN), the most frequent primary glomerulopathy in the world population. The patient was diagnosed with SLE due to the occurrence of malar rash, alopecia, pleural effusion, proteinuria, ANA 1: 1280, nuclear fine speckled pattern, and anticardiolipin IgM and 280U/mL. Renal biopsy revealed mesangial hypercellularity with isolated IgA deposits, consistent with primary IgAN. It was treated with antimalarial drug, prednisone and inhibitor of angiotensin converting enzyme, showing good progress. Since they are relatively common diseases, the coexistence of SLE and IgAN may in fact be an uncommon finding for unknown reasons or an underdiagnosed condition. This report focus on the importance of the distinction between the activity of renal disease in SLE and non-SLE nephropathy, especially IgAN, a definition that has important implications on renal prognosis and therapeutic regimens to be adopted in both the short and long terms.

  4. IgA nephropathy in systemic lupus erythematosus patients: case report and literature review

    Directory of Open Access Journals (Sweden)

    Leonardo Sales da Silva

    2016-06-01

    Full Text Available Abstract Systemic erythematosus lupus (SLE is a multisystemic autoimmune disease which has nephritis as one of the most striking manifestations. Although it can coexist with other autoimmune diseases, and determine the predisposition to various infectious complications, SLE is rarely described in association with non‐lupus nephropathies etiologies. We report the rare association of SLE and primary IgA nephropathy (IgAN, the most frequent primary glomerulopathy in the world population. The patient was diagnosed with SLE due to the occurrence of malar rash, alopecia, pleural effusion, proteinuria, ANA 1: 1,280, nuclear fine speckled pattern, and anticardiolipin IgM and 280 U/mL. Renal biopsy revealed mesangial hypercellularity with isolated IgA deposits, consistent with primary IgAN. It was treated with antimalarial drug, prednisone and inhibitor of angiotensin converting enzyme, showing good progress. Since they are relatively common diseases, the coexistence of SLE and IgAN may in fact be an uncommon finding for unknown reasons or an underdiagnosed condition. This report focus on the importance of the distinction between the activity of renal disease in SLE and non‐SLE nephropathy, especially IgAN, a definition that has important implications on renal prognosis and therapeutic regimens to be adopted in the short and long term.

  5. Childhood Henoch-Sch(o)nlein Purpura Nephritis and IgA Nephropathy:One Disease Entity?--A Clinico-pathologically Comparative Study

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    In order to characterize their relationship through clinicopathological comparison between IgA nephropathy and Henoch-Schonlein purpura nephritis (HSPN), 31 children with IgA nephropathy aged between 3 to 15 years and 120 children with HSPN aged between 4 to 15 years were compared with each other in clinical manifestation, blood biochemistry, serum immunology and followup study. Renal pathological findings under light microscope, immunofluorescence and electronic microscope were analyzed and also compared between 31 children with IgA nephropathy and 32 biopsied children with HSPN. The results showed that the onset age was over 12 years in 25.8 %children with IgA nephropathy, but only 10 % in HSPN (P<0.05). The clinical patterns of IgA nephropathy and HSPN were similar, but extra-renal manifestations were more often in HSPN, all of them had skin purpura, 59 % had gastrointestinal symptoms and 47 % suffered from arthralgia,compared with only abdominal pain in 3.2 % children with IgA nephropathy. The renal pathological investigation showed global sclerosis in 35.5 % of IgA nephropathy and 3.1% of HSPN, mesangial sclerosis in 41.9 % of IgA nephropathy and 6.3 % of HSPN, but endothelial proliferation in 65.6% of HSPN and 29 % of IgA nephropathy (all P<0.01). Thin basement membrane nephropathy was only found in 6.5 % children with IgA nephropathy, no in HSPN. The electronic dense deposits in HSPN were sparse, loose and wildly spread in glomerular mesangium, subendothelial area and even intra basement membrane, but it was dense, lumpy and mostly limited in mesangium and paramesangium in IgA nephropathy. Predominant IgA deposits were found in 81.2 %of HSPN, and overwhelming IgG deposits in 12.5 % of HSPN with relatively weak IgA deposits,moreover 6.3 % of HSPN showed linear IgG deposits in glomerular capillary. Totally 71.9 % of HSPN had IgG deposits in glomeruli and only 19.4 % of IgA nephropathy showed glomerular IgG deposits (P<0.01). No IgG deposit was observed

  6. Retrospective study of mycophenolate mofetil treatment in IgA nephropathy with proliferative pathological phenotype

    Institute of Scientific and Technical Information of China (English)

    Liang Yan; Zhang Junjun; Liu Dongwei; Quan Songxia; Xing Guolan; Liu Zhangsuo

    2014-01-01

    Background Mycophenolate mofetil (MMF) and cyclophosphamide (CTX) are widely used in treating various kidney diseases.However,whether they are effective and which one is better for treating IgA nephropathy patients with proliferative pathological phenotype in renal diseases,such as endocapillary proliferation,cellular crescents,and/or capillary loops fibrinoid necrosis is still unknown.We,therefore,initiated a study to compare the effects of MMF and CTX in treating IgA nephropathy with the above pathological lesions.Methods One hundred and nineteen patients with IgA nephropathy who had at least one of the three aforementioned lesions were enrolled.All patients were treated with prednisone; 48 patients received prednisone only (Pred group),40 received MMF and prednisone (MMF + Pred group),and 31 were treated with CTX and prednisone (CTX + Pred group).The median time of follow-up was 30 months (maximum:96 months).The primary endpoint was defined as renal survival.The incidence of remission of proteinuria was the secondary endpoint.Results Serum creatinine in all groups declined significantly at different follow-up times (P=0.002),and the differences among the three groups were significant (P<0.001).At 24 months of follow-up,the decline rates were 12.35%,32.95%,and 24.14% in the Pred,MMF + Pred,and CTX + Pred groups respectively.For urine protein excretion,the decline rates were 49.12% (Pred),73.67% (MMF + Pred),and 63.53% (CTX + Pred) respectively at 24 months of follow-up.The differences among the three groups were not significant (P=0.714).Renal survival (the primary endpoint) was significantly different (P=0.027); however,the sencondary endpoint was similar for all the three groups (P=0.100).Conclusions For IgA nephropathy patients with endocapillary proliferation,cellular crescents,and/or fibrinoid necrosis of capillary loops,prednisone combined with MMF was more effective in lowering the serum creatinine than with CTX.Combined MMF and orednisone

  7. Cleavage of a Recombinant Human Immunoglobulin A2 (IgA2)-IgA1 Hybrid Antibody by Certain Bacterial IgA1 Proteases

    OpenAIRE

    Senior, Bernard W.; Dunlop, James I.; Batten, Margaret R.; Kilian, Mogens; Woof, Jenny M.

    2000-01-01

    To understand more about the factors influencing the cleavage of immunoglobulin A1 (IgA1) by microbial IgA1 proteases, a recombinant human IgA2/IgA1 hybrid molecule was generated. In the hybrid, termed IgA2/A1 half hinge, a seven-amino-acid sequence corresponding to one half of the duplicated sequence making up the IgA1 hinge was incorporated into the equivalent site in IgA2. Insertion of the IgA1 half hinge into IgA2 did not affect antigen binding capacity or the functional activity of the h...

  8. Correlation of proteinuria with podocyte foot process effacement in IgA nephropathy: an ultrastructural study.

    Science.gov (United States)

    Tewari, Rohit; Nada, Ritambhra; Rayat, Charan Singh; Boruah, Dibyajyoti; Dudeja, Puja; Joshi, Kusum; Sakhuja, Vinay

    2015-04-01

    Proteinuria is an uncommon clinical manifestation of IgA nephropathy and is usually seen in cases with severe lesions like endocapillary proliferation. However, it is occasionally seen even with cases with mild glomerular manifestations and may even be of nephrotic range. Podocyte foot process effacement. Severity of proteinuria. Podocyte foot process effacement was measured. Morphometric analysis was performed on transmission electron microscope images using a computerized digital photomicrograph system (BioWizard 4.2 Image analysis software, New Delhi, India). Proteinuria was measured quantitatively assigned into five grades. It was found that as the extent of proteinuria increased, the effacement ratio also increased, and this was most significant between "no" proteinuria and the rest of the categories. Nephrotic presentation in IgA nephropathy is a known phenomenon and in certain cases may show near normal glomerular morphology with severe foot process effacement on EM being the only significant finding to explain the proteinuria. Proteinuria in these cases shows a significant correlation with degree of foot process effacement. Renal biopsy is important in these cases because they are known to have a better prognosis and are usually steroid responsive.

  9. The incidence of biopsy-proven IgA nephropathy is associated with multiple socioeconomic deprivation.

    Science.gov (United States)

    McQuarrie, Emily P; Mackinnon, Bruce; McNeice, Valerie; Fox, Jonathan G; Geddes, Colin C

    2014-01-01

    Chronic kidney disease is more common in areas of socioeconomic deprivation, but the relationship with the incidence and diagnosis of biopsy-proven renal disease is unknown. In order to study this, all consecutive adult patients undergoing renal biopsy in West and Central Scotland over an 11-year period were prospectively analyzed for demographics, indication, and histologic diagnosis. Using the Scottish Index of Multiple Deprivation, 1555 eligible patients were separated into quintiles of socioeconomic deprivation according to postcode. Patients in the most deprived quintile were significantly more likely to undergo biopsy compared with patients from less deprived areas (109.5 compared to 95.9 per million population/year). Biopsy indications were significantly more likely to be nephrotic syndrome, or significant proteinuria without renal impairment. Patients in the most deprived quintile were significantly more likely to have glomerulonephritis. There was a significant twofold increase in the diagnosis of IgA nephropathy in the patients residing in the most compared with the least deprived postcodes not explained by the demographics of the underlying population. Thus, patients from areas of socioeconomic deprivation in West and Central Scotland are significantly more likely to undergo native renal biopsy and have a higher prevalence of IgA nephropathy.

  10. IgA nephropathy: A clinicopathologic study from two centers in Saudi Arabia

    Directory of Open Access Journals (Sweden)

    Khawajah Azhar

    2010-01-01

    Full Text Available A total of 42 patients, who were diagnosed to have primary Immunoglobulin A neph-ropathy (IgAN at the King Abdul Aziz University Hospital and King Faisal Hospital, Jeddah over the last seven years, were studied. The objective was to analyze their clinical and pathological fea-tures and to classify them according to Hass Classification by using light, immunofluorescence and electron microscopy. Majority of the study cases were males in the second, third and fourth decades of life. Hematuria was the most common clinical complaint followed by proteinuria. There were varying degrees of mesangial proliferation. Majority of the cases presented with class-2 followed by class-3. Immunofluorescence demonstrated diffuse granular deposition of IgA in the glomerular mesangium in majority of the cases. Ultrastructural analysis showed electron dense deposits within the matrix of the mesangium and paramesangium in majority of the cases. Sub-endothelial deposits and mesangial interposition were demonstrated in few cases. Extensive effacement with fusion of the visceral epithelial foot processes was detected in only few patients while focal effacement was demonstrated in many cases. Irregularities of the glomerular basement membrane were seen in some cases. We conclude that IgA nephropathy is an immune-complex glomerular disease, which occurs at all ages and with higher frequency in males and presents mostly with hematuria and proteinuria. Public health awareness is seriously needed to perform the investigations at an early stage.

  11. Identification of distinct glycoforms of IgA1 in plasma from patients with IgA nephropathy and healthy individuals

    DEFF Research Database (Denmark)

    Lehoux, Sylvain; Mi, Rongjuan; Aryal, Rajindra P

    2014-01-01

    Immunoglobulin A nephropathy (IgAN) is the most common form of glomerulonephritis worldwide and is histologically characterized by the deposition of IgA1 and consequent inflammation in the glomerular mesangium. Prior studies suggested that serum IgA1 from IgAN patients contains aberrant...... there are different glycoforms of IgA1 in plasma from patients with IgAN and healthy individuals. While total plasma IgA in IgAN patients was elevated ~1.6-fold compared to that in healthy donors, IgA1 in all samples was unexpectedly separable into two distinct glycoforms: one with core 1 based O......-glycans, and the other exclusively containing Tn/STn structures. Importantly, Tn antigen present on IgA1 from IgAN patients and controls was convertible into the core 1 structure in vitro by recombinant T-synthase. Our results demonstrate that undergalactosylation of O-glycans in IgA1 is not restricted to Ig...

  12. Analysis of O-glycan heterogeneity in IgA1 myeloma proteins by Fourier transform ion cyclotron resonance mass spectrometry: implications for IgA nephropathy

    DEFF Research Database (Denmark)

    Renfrow, MB; Mackay, CL; Chalmers, MJ

    2007-01-01

    IgA nephropathy (IgAN) is the most common form of primary glomerulonephritis. In IgAN, IgA1 molecules with incompletely galactosylated O-linked glycans in the hinge region (HR) are present in mesangial immunodeposits and in circulating immune complexes. It is not known whether the galactose...... deficiency in IgA1 proteins occurs randomly or preferentially at specific sites. We have previously demonstrated the first direct localization of multiple O-glycosylation sites on a single IgA1 myeloma protein by use of activated ion-electron capture dissociation (AI-ECD) Fourier transform ion cyclotron...... resonance (FT-ICR) tandem mass spectrometry. Here, we report the analysis of IgA1 O-glycan heterogeneity by use of FT-ICR MS and liquid chromatography FT-ICR MS to obtain unbiased accurate mass profiles of IgA1 HR glycopeptides from three different IgA1 myeloma proteins. Additionally, we report the first AI...

  13. NLRP3 inflammasome: Pathogenic role and potential therapeutic target for IgA nephropathy

    Science.gov (United States)

    Tsai, Yu-Ling; Hua, Kuo-Feng; Chen, Ann; Wei, Chyou-Wei; Chen, Wen-Shiang; Wu, Cheng-Yeu; Chu, Ching-Liang; Yu, Yung-Luen; Lo, Chia-Wen; Ka, Shuk-Man

    2017-01-01

    We have previously showed that IL-1β is involved in the pathogenesis of both spontaneously occurring and passively induced IgA nephropathy (IgAN) models. However, the exact causal-relationship between NLRP3 inflammasome and the pathogenesis of IgAN remains unknown. In the present study, we showed that [1] IgA immune complexes (ICs) activated NLRP3 inflammasome in macrophages involving disruption of mitochondrial integrity and induction of mitochondrial ROS, bone marrow-derived dendritic cells (BMDCs) and renal intrinsic cells; [2] knockout of NLRP3 inhibited IgA ICs-mediated activation of BMDCs and T cells; and [3] knockout of NLRP3 or a kidney-targeting delivery of shRNA of NLRP3 improved renal function and renal injury in a mouse IgAN model. These results strongly suggest that NLRP3 inflammasome serves as a key player in the pathogenesis of IgAN partly through activation of T cells and mitochondrial ROS production and that a local, kidney-targeting suppression of NLRP3 be a therapeutic strategy for IgAN. PMID:28117341

  14. Functional networks of aging markers in the glomeruli of IgA nephropathy: a new therapeutic opportunity

    Science.gov (United States)

    Jiang, Hong; Liang, Ludan; Qin, Jing; Lu, Yingying; Li, Bingjue; Wang, Yucheng; Lin, Chuan; Zhou, Qin; Feng, Shi; Yip, Shun H.; Xu, Feng; Lai, EnYin; Wang, Junwen; Chen, Jianghua

    2016-01-01

    IgA nephropathy(IgAN) is the most common primary glomerular disease in China. Primary infections always occur before IgAN. However, the pathology of IgAN is still unclear. Previously we found that LL37, a protein secreted by senescent cells, was specific for the progression of IgAN, and also played a role in the neutrophil function. So we hypothesized that the infiltration of neutrophils, inflammation factors, and aging markers, which were modulated by functional networks, induced the immune response and renal injury. RNA-Sequencing (RNA-seq) can be used to study the whole transcriptome and detect splicing variants that are expressed in a specific cell type or tissue. We separate glomerulus from the renal biopsy tissues. After RNA extraction, the sequences were analyzed with Illumina HiSeq 2000/2500. 381 genes with differential expression between the IgAN patients and the healthy controls were identified. Only PLAU, JUN, and FOS were related to DNA damage, telomere dysfunction-induced aging markers, neutrophil function and IgA nephropathy. The networks showed the possibility of these genes being connected. We conclude that DNA damage and telomere dysfunction could play important roles in IgA nephropathy. In addition, neutrophils are also important factors in this disease. The networks of these markers showed the mechanism pathways that are involved in the duration of the occurrence and progression of IgA nephropathy and might be a new therapeutic opportunity for disease treatment. PMID:27127888

  15. Comparison of different normalization strategies for the analysis of glomerular microRNAs in IgA nephropathy.

    Science.gov (United States)

    Bockmeyer, Clemens L; Säuberlich, Karen; Wittig, Juliane; Eßer, Marc; Roeder, Sebastian S; Vester, Udo; Hoyer, Peter F; Agustian, Putri A; Zeuschner, Philip; Amann, Kerstin; Daniel, Christoph; Becker, Jan U

    2016-08-24

    Small nucleolar RNAs (snoRNAs) have been used for normalization in glomerular microRNA (miRNA) quantification without confirmation of validity. Our aim was to identify glomerular reference miRNAs in IgA nephropathy. We compared miRNAs in human paraffin-embedded renal biopsies from patients with cellular-crescentic IgA-GN (n = 5; crescentic IgA-GN) and non-crescentic IgA-GN (n = 5; IgA-GN) to mild interstitial nephritis without glomerular abnormalities (controls, n = 5). Laser-microdissected glomeruli were used for expression profiling of 762 miRNAs by low-density TaqMan arrays (cards A and B). The comparison of different normalization methods (GeNormPlus, NormFinder, global mean and snoRNAs) in crescentic IgA-GN, IgA-GN and controls yielded similar results. However, levels of significance and the range of relative expression differed. In median, two normalization methods demonstrated similar results. GeNormPlus and NormFinder gave different top ranked reference miRNAs. Stability ranking for snoRNAs varied between cards A and B. In conclusion, we suggest the geometric mean of the most stable reference miRNAs found in GeNormPlus (miR-26b-5p), NormFinder (miR-28-5p) and snoRNAs (RNU44) as reference. It should be considered that significant differences could be missed using one particular normalization method. As a starting point for glomerular miRNA studies in IgA nephropathy we provide a library of miRNAs.

  16. Oxidative damages in tubular epithelial cells in IgA nephropathy: role of crosstalk between angiotensin II and aldosterone

    Directory of Open Access Journals (Sweden)

    Lim Ai-Ing

    2011-10-01

    Full Text Available Abstract Background Inhibition of the renin-angiotensin-aldosterone system (RAAS slows down the progression of chronic renal diseases (CKD including IgA nephropathy (IgAN. Herein, we studied the pathogenetic roles of aldosterone (Aldo in IgAN. Methods Human mesangial cells (HMC was activated with polymeric IgA (pIgA from IgAN patients and the effects on the expression of RAAS components and TGF-β synthesis examined. To study the roles of RAAS in the glomerulotubular communication, proximal tubular epithelial cells (PTEC was cultured with conditioned medium from pIgA-activated HMC with eplerenone or PD123319, the associated apoptotic event was measured by the generation of nicotinamide adenine dinucleotide phosphate (NADPH oxidase and reactive oxygen species (ROS. Results Polymeric IgA up-regulated the Aldo synthesis and aldosterone synthase expression by HMC. The release of TGF-β by HMC was up-regulated synergistically by AngII and Aldo and this was inhibited by incubation of HMC with losartan plus eplerenone. Cultured PTEC express the mineralocorticoid receptor, but not synthesizing aldosterone. Apoptosis, demonstrated by cleaved PARP expression and caspase 3 activity, was induced in PTEC activated by conditioned medium prepared from HMC cultured with pIgA from IgAN patients. This apoptotic event was associated with increased generation of NADPH oxidase and ROS. Pre-incubation of PTEC with PD123319 and eplerenone achieved complete inhibition of PTEC apoptosis. Conclusions Our data suggest that AngII and Aldo, released by pIgA activated HMC, served as mediators for inducing apoptosis of PTEC in glomerulo-tubular communications. Crosstalk between AngII and Aldo could participate in determining the tubular pathology of IgAN.

  17. 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...... exposes N-acetylgalactosamine-containing neoepitopes recognized by naturally occurring IgG or IgA1 antibodies resulting in formation of immune complexes. IgA1 contains up to six O-glycosylation sites per heavy chain; it is not known whether the glycosylation defect occurs randomly or preferentially...... at specific sites. We sought to define the aberrant glycosylation of a galactose-deficient IgA1 myeloma protein and analyze the formation of the immune complexes and their biological activities. Supplementation of serum or cord-blood serum with this IgA1 protein resulted in formation of new IgA1 complexes...

  18. IgA 肾病患者 IgA1糖基化异常及其致病机制%The pathopoiesis mechanism of abnormal IgA1 glycosylation in IgA nephropathy patients

    Institute of Scientific and Technical Information of China (English)

    林淑芃

    2015-01-01

    IgA 肾病(IgAN)是导致终末期肾病最常见的原发性肾小球疾病。其病理特点为 IgA1在肾小球系膜区沉积,IgA1分子的异常糖基化是导致 IgAN 发病的关键因素。多种与 IgAN 相关的基因位点已经被发现。这些基因编码的细胞因子参与了 IgA1糖基化异常的发病机制。此外糖基化酶缺乏、分子伴侣甲基化异常都可能导致 IgA1异常糖基化。异常糖基化的 IgA1可通过自我聚集或形成免疫复合物沉积于系膜区,进而刺激系膜细胞增殖、分泌系膜基质、细胞因子、趋化因子、生长因子等,导致肾小球损伤。对 IgA1异常糖基化的深入研究有助于了解 IgA 肾病的发病机制并提供新的诊断与治疗措施。%IgA nephropathy (IgAN)is the most common primary glomerular disease that can result in end-stage renal disease,and is histologically characterized by the deposition of IgA1 in the glomerular mesangium.The abnormal IgA1 glycosylation is the key factor in the pathogenesis of IgAN.Multiple genetic loci associated with IgAN have been identified,and the cytokines coded by them are involved in the pathopoiesis mechanism of abnormal IgA1 glycosylation.In addition,the lack of glycosylase and abnormal methylation of molecular chaperone may also be involved in the aberrant glycosylation of IgA1.Abnormally glycosylated IgA1 can deposit in the mesangium through their own assembly together or formation of immunocomplex,which can subsequently stimulate mesangial cell proliferation and secretion of extracellular matrix,cytokines,chemokines,and growth factors,etc,leading to glomerular injury.In-depth research on IgA1 abnormal glycosylation will help to understand the pathogenesis of IgAN and provide new diagnosis and treatment methods.

  19. Optimal Proteinuria Target for Renoprotection in Patients with IgA Nephropathy

    Science.gov (United States)

    Nam, Ki Heon; Kie, Jeong Hae; Lee, Mi Jung; Chang, Tae-Ik; Kang, Ea Wha; Kim, Dong Wook; Lim, Beom Jin; Park, Jung Tak; Kwon, Young Eun; Kim, Yung Ly; Park, Kyoung Sook; An, Seong Yeong; Oh, Hyung Jung; Yoo, Tae-Hyun; Kang, Shin-Wook; Choi, Kyu Hun; Jeong, Hyeon Joo; Han, Dae-Suk; Han, Seung Hyeok

    2014-01-01

    Background Proteinuria is a target for renoprotection in kidney diseases. However, optimal level of proteinuria reduction in IgA nephropathy (IgAN) is unknown. Methods We conducted a retrospective observational study in 500 patients with biopsy-proven IgAN. Time-averaged proteinuria (TA-P) was calculated as the mean of every 6 month period of measurements of spot urine protein-to-creatinine ratio. The study endpoints were a 50% decline in estimated glomerular filtration rate (eGFR), onset of end-stage renal disease (ESRD), and slope of eGFR. Results During a median follow-up duration of 65 (12–154) months, a 50% decline in eGFR occurred in 1 (0.8%) patient with TA-P of proteinuria reduction can be lowered in the management of IgAN. PMID:25003873

  20. Controlled prospective trial of prednisolone and cytotoxics in progressive IgA nephropathy.

    Science.gov (United States)

    Ballardie, Francis W; Roberts, Ian S D

    2002-01-01

    In a single-center, multiple-referral source study, 38 patients with progressive IgA nephropathy and controlled hypertension were randomized to treatment with prednisolone and cytotoxic agents, to therapy with low-dose cyclophosphamide then azathioprine, and to control groups. The follow-up period lasted 2 to 6 yr. Renal survival, as assessed by Kaplan-Meier analysis annually to 5 yr, showed significant preservation of function from 3 yr in the treatment group and 82, 82, 72, and 72% for 2, 3, 4, and 5 yr, respectively, compared with 68, 47, 26, and 6% in controls. Rate of loss of renal function, evaluated objectively by least-squares analyses of reciprocal serum creatinine, was reduced-and in one-third of the patients, arrested-during immunosuppressive treatment. Proteinuria, present in all patients at the time of entry into the trial, was reduced by treatment from 12 mo, compared with pretreatment levels or controls; erythrocyturia was reduced from 6 mo. Histologic activity and chronicity indexes were determined in renal biopsies performed at trial entry. Multivariate analysis demonstrated that mesangial cell proliferation and matrix scores were highest in those patients with more rapidly progressive disease. No morphologic variable or residual renal function predicted response to immunosuppressive therapy at entry. Mean arterial pressures did not differ significantly between treatment and control groups. There was thus no explanation other than treatment for the improved outcome in patients who received immunosuppressive therapy. Morbidity attributable to treatment or to renal failure occurred in both groups; an audit showed that benefits of therapy outweighed expected or minor side effects of drugs in this population at risk of end-stage renal failure. Patients selected for moderately progressive IgA nephropathy benefit from treatment with prednisolone and cytotoxic agents; results are consistent with modulation of systemic immune response or nephritic injury

  1. Study of the variables associated with local complement activation in IgA nephropathy.

    Science.gov (United States)

    Segarra-Medrano, Alfons; Carnicer-Caceres, Clara; Valtierra-Carmeno, Naiara; Agraz-Pamplona, Irene; Ramos-Terrades, Natalia; Jatem Escalante, Elías; Ostos-Roldan, Elena

    1. To identify the variables that are associated with urinary levels of properdin, MBL, C4d, and C5b-9 in patients with idiopathic IgA nephropathy. 2. To analyse whether urinary levels of MBL and/or C4d are useful for identifying the presence of mesangial deposits of C4d/MBL. A total of 96 patients with IgA nephropathy were studied. Demographic, clinical and biochemical variables were recorded at the time of diagnosis. Renal lesions were quantified using the Oxford classification. Immunohistochemical staining for MBL, MASP-2, properdin, C4d, and C5b-9 was performed in kidney biopsies, and in urine, the levels of properdin, MBL, C4d and C5b-9 were determined. In multivariate analysis, the independent predictors of C4d and MBL levels in urine were the mesangial deposits of each protein and, to a lesser extent, the urinary protein excretion. The independent predictors of urinary levels of C5b-9 were MBL properdin and proteinuria. Urinary excretion of C4d had a sensitivity of 90% (95% CI: 58,7 to 99) and a specificity of 73% (95% CI: 54-87) for detecting mesangial C4d deposits, and the level of MBL had a sensitivity of 83.9% (95% CI: 62-95) and a specificity of 81.6% (95% CI: 65-92) for identifying mesangial deposits of MBL. The main predictor of urinary concentration of C4d and MBL was the presence of their respective mesangial deposits. Urine MBL may contribute to complement activation in the tubular luz through the lectin pathway. Urinary levels of MBL and C4d could be sensitive and specific biomarkers for the identification of patients with mesangial deposits of MBL and C4d. Copyright © 2017. Published by Elsevier España, S.L.U.

  2. Efficient generation of human IgA monoclonal antibodies.

    Science.gov (United States)

    Lorin, Valérie; Mouquet, Hugo

    2015-07-01

    Immunoglobulin A (IgA) is the most abundant antibody isotype produced in humans. IgA antibodies primarily ensure immune protection of mucosal surfaces against invading pathogens, but also circulate and are present in large quantities in blood. IgAs are heterogeneous at a molecular level, with two IgA subtypes and the capacity to form multimers by interacting with the joining (J) chain. Here, we have developed an efficient strategy to rapidly generate human IgA1 and IgA2 monoclonal antibodies in their monomeric and dimeric forms. Recombinant monomeric and dimeric IgA1/IgA2 counterparts of a prototypical IgG1 monoclonal antibody, 10-1074, targeting the HIV-1 envelope protein, were produced in large amounts after expression cloning and transient transfection of 293-F cells. 10-1074 IgAs were FPLC-purified using a novel affinity-based resin engrafted with anti-IgA chimeric Fabs, followed by a monomers/multimers separation using size exclusion-based FPLC. ELISA binding experiments confirmed that the artificial IgA class switching of 10-1074 did not alter its antigen recognition. In summary, our technical approach allows the very efficient production of various forms of purified recombinant human IgA molecules, which are precious tools in dissecting IgA B-cell responses in physiological and pathophysiological conditions, and studying the biology, function and therapeutic potential of IgAs.

  3. Extracapillary proliferation in IgA nephropathy; recent findings and new ideas.

    Science.gov (United States)

    Nasri, Hamid; Mubarak, Muhammed

    2015-01-01

    IgA nephropathy (IgAN) is an autoimmune disorder and is the most common form of primary glomerulonephritis (GN) worldwide. Directory of Open Access Journals (DOAJ), Google Scholar, PubMed (NLM), LISTA (EBSCO) and Web of Science have been searched. It is a slowly progressing disorder that leads to end-stage renal disease (ESRD) in up to 50% of the patients within 25 years of the onset of the disease. IgAN is defined by predominant IgA deposition in the mesangial area on immunofluorescence (IF) microscopy. Its histology varies from mild focal segmental proliferation of mesangial cells to severe diffuse global proliferation with extracapillary proliferation (crescent formation). The Oxford classification, designed in 2009, is a new classification for the evaluation of morphologic lesions of IgAN. This classification, containing four pathology variables, was found to have prognostic implications. The variables included are mesangial hypercellularity (M), endocapillary proliferation (E), segmental glomerulosclerosis (S) and the proportion of interstitial fibrosis and tubular atrophy (T). However, crescents were not included in the Oxford classification. In this mini-review, we describe the recent publications about the significance of extracapillary proliferation in IgAN and we conclude that, there is much controversy about the role of extracapillary proliferation as a significant prognostic factor in IgAN. Hence, it is important to re-consider crescents in IgAN patients. Therefore, we suggest further investigations on this aspect of IgAN disease.

  4. Determination of optimal blood pressure for patients with IgA nephropathy based on renal histology.

    Science.gov (United States)

    Osawa, Y; Narita, I; Imai, N; Iino, N; Iguchi, S; Ueno, M; Shimada, H; Nishi, S; Arakawa, M; Gejyo, F

    2001-03-01

    To evaluate the optimal BP control for patients with IgA nephropathy (IgAN) based on the histologic severity of the nephropathy and the degree of renal dysfunction. We analyzed 332 consecutive renal biopsy specimens and clinical data from patients with IgAN. Patients were divided into three groups based on their BP at the time of biopsy: an optimal BP (SBP or = 140 mmHg and/or DBP > or = 90 mmHg), and an intermediate BP group. Each biopsy specimen was evaluated for mesangial proliferation, degree of sclerosis and/or hyalinosis of the arterioles and the interlobular artery using a semiquantitative method. Creatinine clearance and the percentage of sclerosed glomeruli were also determined. Both the degree of renal dysfunction and the histologic changes correlated significantly with BP, even in patients with a BP <140/90 mmHg. The patients with an optimal BP at the time of biopsy had significantly less histologic damage with respect to mesangial proliferation and vessel changes than those with an intermediate or hypertensive BP. In the patients with a hypertensive BP, the percentage of sclerotic glomeruli was significantly higher and the creatinine clearance was significantly lower. The optimal BP proposed by the WHO in 1999 prevents histologic evidence of renal damage for patients with IgAN.

  5. A panel of serum biomarkers differentiates IgA nephropathy from other renal diseases.

    Directory of Open Access Journals (Sweden)

    Hiroyuki Yanagawa

    Full Text Available BACKGROUND AND OBJECTIVES: There is increasing evidence that galactose-deficient IgA1 (Gd-IgA1 and Gd-IgA1-containing immune complexes are important for the pathogenesis of IgA nephropathy (IgAN. In the present study, we assessed a novel noninvasive multi-biomarker approach in the diagnostic test for IgAN. MATERIALS AND METHODS: We compared serum levels of IgA, IgG, Gd-IgA1, Gd-IgA1-specific IgG and Gd-IgA1-specific IgA in 135 IgAN patients, 79 patients with non-IgAN chronic kidney disease (CKD controls and 106 healthy controls. Serum was collected at the time of kidney biopsy from all IgAN and CKD patients. RESULTS: Each serum marker was significantly elevated in IgAN patients compared to CKD (P<0.001 and healthy controls (P<0.001. While 41% of IgAN patients had elevated serum Gd-IgA1 levels, 91% of these patients exhibited Gd-IgA1-specific IgG levels above the 90th percentile for healthy controls (sensitivity 89%, specificity 92%. Although up to 25% of CKD controls, particularly those with immune-mediated glomerular diseases including lupus nephritis, also had elevated serum levels of Gd-IgA1-specific IgG, most IgAN patients had elevated levels of Gd-IgA1-specific antibody of both isotypes. Serum levels of Gd-IgA1-specific IgG were associated with renal histological grading. Furthermore, there was a trend toward higher serum levels of Gd-IgA1-specific IgG in IgAN patients with at least moderate proteinuria (≥1.0 g/g, compared to patients with less proteinuria. CONCLUSIONS: Serum levels of Gd-IgA1-specific antibodies are elevated in most IgAN patients, and their assessment, together with serum levels of Gd-IgA1, improves the specificity of the assays. Our observations suggest that a panel of serum biomarkers may be helpful in differentiating IgAN from other glomerular diseases.

  6. Losartan and Dexamethasone may inhibit chemotaxis to reduce the infiltration of Th22 cells in IgA nephropathy.

    Science.gov (United States)

    Xiao, Chenggen; Zhou, Qiaoling; Li, Xiaozhao; Li, Hui; Zhong, Yong; Meng, Ting; Zhu, Mengyuan; Sun, Hong; Liu, Shuang; Tang, Rong; Pu, Jiaxi; Xu, Yan; Xiao, Ping

    2017-01-01

    Angiotensin II is considered a major profibrotic factor that is involved in tissue remodeling processes, as the inhibition of Angiotensin II can halt renal inflammatory processes. Dexamethasone, an important anti-inflammatory and immunosuppressive agent, has been widely used to treat renal disease for decades. In this study, we explored the frequency of Th22 cells in a mouse model of IgA nephropathy and compared the possible effects of Losartan and Dexamethasone on Th22 cells. The experiments were performed using 6-week-old BALB/c female mice in an established IgA nephropathy model. The mice were randomly separated into 4 groups, which were administered Losartan (30mg/kg/d) or Dexamethasone (10mg/kg/d) and subjected to IgA nephropathy or the normal control treatment for 1month. The frequency of Th22 cells was measured via flow cytometry, and the relative pathological changes in renal morphology were measured with different pathological staining methods. Immunohistochemistry was performed to verify the expression of CCR10 and CCL27, which is specialized receptor on Th22 cells and its corresponding chemokine, respectively. The concentrations of CCL27 and IL-22 in renal tissue homogenates and sera were detected using ELISAs. Losartan and Dexamethasone differentially decreased the frequency of Th22 cells after 1month, and mesangial cell proliferation was also improved. Moreover, the expression of CCR10, CCL27 and IL-22 was reduced by treatment with either drug. However, significant differences between Losartan and Dexamethasone were not observed. Based on these findings, Losartan and Dexamethasone may suppress inflammatory responses by inhibiting the chemotaxis of Th22 cells in IgA nephropathy.

  7. Circulating CD89-IgA complex does not predict deterioration of kidney function in Korean patients with IgA nephropathy.

    Science.gov (United States)

    Jhee, Jong Hyun; Kang, Hye-Young; Wu, Meiyan; Nam, Bo Young; Chang, Tae-Ik; Jung, Su-Young; Park, Seohyun; Kim, Hyoungnae; Yun, Hae-Ryong; Kee, Youn Kyung; Yoon, Chang-Yun; Park, Jung Tak; Yoo, Tae-Hyun; Kang, Shin-Wook; Han, Seung Hyeok

    2017-06-16

    Soluble CD89 (sCD89)-IgA complex plays a key role in the pathogenesis of IgA nephropathy (IgAN). However, there is a lack of evidence supporting this complex as a good biomarker for disease progression. This study aimed to evaluate the usefulness of sCD89-IgA complex for risk stratification of IgAN. A total of 326 patients with biopsy-proven IgAN were included. sCD89-IgA complex was measured by sandwich-enzyme-linked immunosorbent assay. The study endpoints were a 30% decline in estimated glomerular filtration rate (eGFR). sCD89-IgA complex levels were inversely and weakly associated with eGFR at the time of biopsy (r=-0.12, p=0.03). However, the significance between the two factors was lost in the multivariate linear regression after adjustment of clinical factors (β=0.35, p=0.75). In a multivariate Cox model, the highest (hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.35-1.61; p=0.45) and middle (HR, 0.93; 95% CI, 0.46-1.89; p=0.84) tertiles of sCD89-IgA complex levels were not associated with an increased risk of developing a 30% decrease in eGFR. Furthermore, the decline rates in eGFR did not differ between groups and C-statistics revealed that the sCD89-IgA complex were not superior to clinical factors in predicting disease progression. This study found no association between sCD89-IgA complex levels and disease progression in IgAN. Although sCD89 can contribute to the formation of immune complexes, our findings suggest that the sCD89-IgA level is not a good predictor of adverse outcomes and has limited clinical utility as a biomarker for risk stratification in IgAN.

  8. Significance of urinary full-length megalin in patients with IgA nephropathy.

    Directory of Open Access Journals (Sweden)

    Takuto Seki

    Full Text Available BACKGROUND AND OBJECTIVES: Megalin is highly expressed at the apical membranes of proximal tubular epithelial cells. A urinary full-length megalin (C-megalin assay is linked to the severity of diabetic nephropathy in type 2 diabetes. This study examined the relationship between levels of urinary C-megalin and histological findings in adult patients with IgA nephropathy (IgAN. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Urine samples voided in the morning on the day of renal biopsy were obtained from 73 patients with IgAN (29 men and 44 women; mean age, 33 years and 5 patients with membranous nephropathy (MN. Renal pathologic variables were analyzed using the Oxford classification of IgAN, the Shigematsu classification and the Clinical Guidelines of IgAN in Japan. The levels of urinary C-megalin were measured by sandwich ELISA. RESULTS: Histological analysis based on the Oxford classification revealed that the levels of urinary C-megalin were correlated with mesangial hypercellularity in IgAN patients (OR = 1.76, 95% CI: 1.04-3.27, P<0.05. There was a significant correlation between the levels of urinary C-megalin and the severity of chronic extracapillary abnormalities according to the Shigematsu classification in IgAN patients (β = 0.33, P = 0.008. The levels of urinary C-megalin were significantly higher in all risk levels of IgAN patients requiring dialysis using the Clinical Guidelines of IgAN in Japan than in the control group. The levels of urinary C-megalin were significantly higher in the high risk and very high risk grades than in the low risk grade (P<0.05. The levels of urinary C-megalin were significantly higher in MN patients compared to the control group. CONCLUSIONS: The levels of urinary C-megalin are associated with histological abnormalities in adult IgAN patients. There is a possibility that urinary C-megalin is an independent predictor of disease progression of IgAN. In addition, our results suggest that

  9. Intermedin ameliorates IgA nephropathy by inhibition of oxidative stress and inflammation.

    Science.gov (United States)

    Wang, Yanhong; Tian, Jihua; Guo, Haixiu; Mi, Yang; Zhang, Ruijing; Li, Rongshan

    2016-05-01

    IgA nephropathy (IgAN) is the most frequent form of glomerulonephritis worldwide. The role of oxidative stress and inflammation in the pathogenesis of IgAN has been reported. Intermedin (IMD) is a newly discovered peptide that is closely related to adrenomedullin. We have recently reported that IMD can significantly reduce renal ischemia/reperfusion injury by diminishing oxidative stress and suppressing inflammation. The present study was designed to explore whether IMD ameliorates IgAN via oxidative stress- and inflammation-dependent mechanisms. Our results showed that IMD administration resulted in the prevention of albuminuria and ameliorated renal pathomorphological changes. These findings were associated with (1) decreased renal TGF-β1 and collagen IV expression, (2) an increased SOD level and reduced MDA level, (3) the inhibition of the renal activation of NF-κB p65 and (4) the downregulation of the expression of inflammatory factors (TNF-α, MCP-1 and MMP-9) in the kidney. These results indicate that IMD in the kidney protects against IgAN by reducing oxidative stress and suppressing inflammation.

  10. IgA Nephropathy: A Twenty Year Retrospective Single Center Experience

    Directory of Open Access Journals (Sweden)

    Jacob Rube

    2009-01-01

    Full Text Available IgA nephropathy (IgAN is a common glomerular disease whose etiology is unknown. Previous studies have described the clinical and laboratory features but none have specifically compared patients during different time periods. This 20 year retrospective study was performed to assess trends in the severity of IgAN from 1989–2008. We reviewed 57 patient charts that contained a confirmed biopsy diagnosis of IgAN and recorded data at the time of diagnosis and the final follow-up appointment. Clinical data included physical examination, urine, and blood tests. Patients were separated into two cohorts, Cohort 1 1989–1998 and Cohort 2 1999–2008. An increase in severity was noted in Cohort 2 based on a significantly higher Up/c and lower serum albumin level. Other prognostic indicators including GFRe, hematocrit, and glomerular injury score also demonstrated a trend towards more severe disease over the past 20 years. The patients in both Cohorts received similar treatments and had comparable renal function at the last follow-up visit. Based on our findings, we suggest that although a kidney biopsy is required to diagnose IgAN, the procedure may not be necessary in patients clinically suspected of having the disease but who have normal kidney function and minimal urine abnormalities.

  11. Comparison of a Bayesian Network with a Logistic Regression Model to Forecast IgA Nephropathy

    Directory of Open Access Journals (Sweden)

    Michel Ducher

    2013-01-01

    Full Text Available Models are increasingly used in clinical practice to improve the accuracy of diagnosis. The aim of our work was to compare a Bayesian network to logistic regression to forecast IgA nephropathy (IgAN from simple clinical and biological criteria. Retrospectively, we pooled the results of all biopsies (n=155 performed by nephrologists in a specialist clinical facility between 2002 and 2009. Two groups were constituted at random. The first subgroup was used to determine the parameters of the models adjusted to data by logistic regression or Bayesian network, and the second was used to compare the performances of the models using receiver operating characteristics (ROC curves. IgAN was found (on pathology in 44 patients. Areas under the ROC curves provided by both methods were highly significant but not different from each other. Based on the highest Youden indices, sensitivity reached (100% versus 67% and specificity (73% versus 95% using the Bayesian network and logistic regression, respectively. A Bayesian network is at least as efficient as logistic regression to estimate the probability of a patient suffering IgAN, using simple clinical and biological data obtained during consultation.

  12. Comparison of a Bayesian network with a logistic regression model to forecast IgA nephropathy.

    Science.gov (United States)

    Ducher, Michel; Kalbacher, Emilie; Combarnous, François; Finaz de Vilaine, Jérome; McGregor, Brigitte; Fouque, Denis; Fauvel, Jean Pierre

    2013-01-01

    Models are increasingly used in clinical practice to improve the accuracy of diagnosis. The aim of our work was to compare a Bayesian network to logistic regression to forecast IgA nephropathy (IgAN) from simple clinical and biological criteria. Retrospectively, we pooled the results of all biopsies (n = 155) performed by nephrologists in a specialist clinical facility between 2002 and 2009. Two groups were constituted at random. The first subgroup was used to determine the parameters of the models adjusted to data by logistic regression or Bayesian network, and the second was used to compare the performances of the models using receiver operating characteristics (ROC) curves. IgAN was found (on pathology) in 44 patients. Areas under the ROC curves provided by both methods were highly significant but not different from each other. Based on the highest Youden indices, sensitivity reached (100% versus 67%) and specificity (73% versus 95%) using the Bayesian network and logistic regression, respectively. A Bayesian network is at least as efficient as logistic regression to estimate the probability of a patient suffering IgAN, using simple clinical and biological data obtained during consultation.

  13. Significance of tonsillectomy combined with steroid pulse therapy for IgA nephropathy with mild proteinuria.

    Science.gov (United States)

    Komatsu, Hiroyuki; Sato, Yuji; Miyamoto, Tetsu; Tamura, Masahito; Nakata, Takeshi; Tomo, Tadashi; Nishino, Tomoya; Miyazaki, Masanobu; Fujimoto, Shouichi

    2016-02-01

    Medical intervention for patients with IgA nephropathy and mild proteinuria (proteinuria (0.4-1.0 g/day) at diagnosis were eligible to participate in this study. We compared the clinicopathological findings at diagnosis, a decline in renal function defined as a 50 or 100% increase in serum creatinine (sCr) and clinical remission (CR) defined as the disappearance of hematuria and proteinuria (proteinuria, and histological severity did not significantly differ among the groups. Only two patients each in the TSP (4.3%) and non-ST (8.3%) groups achieved a 50% increase in sCr during a mean follow-up period of 4.7 years. At the final observation, 71.7, 44.4, and 41.7% of patients in the TSP, ST, and non-ST groups, respectively, achieved CR (p = 0.032). Cox proportional hazards models revealed that TSP led to CR more effectively than non-TSP by a factor of about threefold (hazard ratio, 2.74; p = 0.008). TSP therapy has potential for inducing CR in patients with IgAN and mild proteinuria (<1.0 g/day).

  14. Presence of Streptococcus mutans strains harbouring the cnm gene correlates with dental caries status and IgA nephropathy conditions

    Science.gov (United States)

    Misaki, Taro; Naka, Shuhei; Hatakeyama, Rina; Fukunaga, Akiko; Nomura, Ryota; Isozaki, Taisuke; Nakano, Kazuhiko

    2016-01-01

    Streptococcus mutans is a major pathogen of human dental caries. Strains harbouring the cnm gene, which encodes Cnm, a collagen-binding protein, contribute to the development of several systemic diseases. In this study, we analysed S. mutans strains isolated from the oral cavity of immunoglobulin (Ig)A nephropathy (IgAN) patients to determine potential relationships between cnm and caries status as well as IgAN conditions. Saliva specimens were collected from 109 IgAN patients and the cnm status of isolated S. mutans strains was determined using PCR. In addition, the dental caries status (decayed, missing or filled teeth [DMFT] index) in patients who agreed to dental consultation (n = 49) was evaluated. The DMFT index and urinary protein levels in the cnm-positive group were significantly higher than those in the cnm-negative group (p S. mutans strains from the oral cavity may be associated with urinary protein levels in IgAN patients, especially those with a high dental caries status. PMID:27811984

  15. Cleavage of a recombinant human immunoglobulin A2 (IgA2)-IgA1 hybrid antibody by certain bacterial IgA1 proteases

    DEFF Research Database (Denmark)

    Senior, B; Dunlop, JI; Batten, MR

    2000-01-01

    To understand more about the factors influencing the cleavage of immunoglobulin A1 (IgA1) by microbial IgA1 proteases, a recombinant human IgA2/IgA1 hybrid molecule was generated. In the hybrid, termed IgA2/A1 half hinge, a seven-amino-acid sequence corresponding to one half of the duplicated...... sequence making up the IgA1 hinge was incorporated into the equivalent site in IgA2. Insertion of the IgA1 half hinge into IgA2 did not affect antigen binding capacity or the functional activity of the hybrid molecule, as judged by its ability to bind to IgA Fcalpha receptors and trigger respiratory bursts...... in neutrophils. Although the IgA2/A1 hybrid contained only half of the IgA1 hinge, it was found to be cleaved by a variety of different bacterial IgA1 proteases, including representatives of those that cleave IgA1 in the different duplicated halves of the hinge, namely, those of Prevotella melaninogenica...

  16. In Acute IgA Nephropathy, Proteinuria and Creatinine Are in the Spot, but Podocyturia Operates in Silence: Any Place for Amiloride?

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    H. Trimarchi

    2017-01-01

    Full Text Available IgA nephropathy is the most frequent cause of primary glomerulonephritis, portends erratic patterns of clinical presentation, and lacks specific treatment. In general, it slowly progresses to end-stage renal disease. The clinical course and the response to therapy are usually assessed with proteinuria and serum creatinine. Validated biomarkers have not been identified yet. In this report, we present a case of acute renal injury with proteinuria and microscopic hematuria in a young male. A kidney biopsy disclosed IgA nephropathy. Podocyturia was significantly elevated compared to normal subjects. Proteinuria, renal function, and podocyturia improved promptly after steroids and these variables remained normal after one year of follow-up, when steroids had already been discontinued and patient continued on valsartan and amiloride. Our report demonstrates that podocyturia is critically elevated during an acute episode of IgA nephropathy, and its occurrence may explain the grim long-term prognosis of this entity. Whether podocyturia could be employed in IgA nephropathy as a trustable biomarker for treatment assessment or even for early diagnosis of IgA nephropathy relapses should be further investigated.

  17. Clinicopathological features, diagnosis, and treatment of IgA nephropathy with minimal change disease related to exposure to mercury-containing cosmetics: a case report
.

    Science.gov (United States)

    Niu, Hong-Xin; Li, Shen-Heng; Li, Hong-Ying; Chen, Yi-Hua; Liu, Wei-Wei; Li, Pei-Lin; Long, Hai-Bo

    2017-04-01

    Membranous nephropathy and minimal change disease (MCD) have been involved in mercury-induced nephrotic syndrome. IgA nephropathy is not known to be a common pathological type. In the present article, we report a case of IgA nephropathy with MCD following exposure to mercury-containing skin lightening cream. The patient was a 39-year-old woman who presented with nephrotic syndrome. She had a 6-month history of using as many as 8 kinds of skin-lightening creams, and urinary mercury excretion was high. Renal biopsy revealed IgA nephropathy with MCD. The use of cosmetics was stopped and chelation therapy was given. After 4 courses (1 month) of chelation therapy, there was a complete remission of proteinuria and hematuria, and urine tests remained normal during the 5-year follow-up period. The unique clinical and pathological features of IgA nephropathy with MCD had raised the controversial question of whether MCD and IgA deposition are separate entities or a common pathophysiology. Repeated renal biopsy and similar cases were helpful and should be carried out as far as possible.
.

  18. Race/ethnicity and disease severity in IgA nephropathy

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    Chertow Glenn M

    2004-09-01

    Full Text Available Abstract Background Relatively few U.S.-based studies in chronic kidney disease have focused on Asian/Pacific Islanders. Clinical reports suggest that Asian/Pacific Islanders are more likely to be affected by IgA nephropathy (IgAN, and that the severity of disease is increased in these populations. Methods To explore whether these observations are borne out in a multi-ethnic, tertiary care renal pathology practice, we examined clinical and pathologic data on 298 patients with primary glomerular lesions (IgAN, focal segmental glomerulosclerosis, membranous nephropathy and minimal change disease at the University of California San Francisco Medical Center from November 1994 through May 2001. Pathologic assessment of native kidney biopsies with IgAN was conducted using Haas' classification system. Results Among individuals with IgAN (N = 149, 89 (60% were male, 57 (38% white, 53 (36% Asian/Pacific Islander, 29 (19% Hispanic, 4 (3% African American and 6 (4% were of other or unknown ethnicity. The mean age was 37 ± 14 years and median serum creatinine 1.7 mg/dL. Sixty-six patients (44% exhibited nephrotic range proteinuria at the time of kidney biopsy. The distributions of age, gender, mean serum creatinine, and presence or absence of nephrotic proteinuria and/or hypertension at the time of kidney biopsy were not significantly different among white, Hispanic, and Asian/Pacific Islander groups. Of the 124 native kidney biopsies with IgAN, 10 (8% cases were classified into Haas subclass I, 12 (10% subclass II, 23 (18% subclass III, 30 (25% subclass IV, and 49 (40% subclass V. The distribution of Haas subclass did not differ significantly by race/ethnicity. In comparison, among the random sample of patients with non-IgAN glomerular lesions (N = 149, 77 (52% patients were male, 51 (34% white, 42 (28% Asian/Pacific Islander, 25 (17% Hispanic, and 30 (20% were African American. Conclusions With the caveats of referral and biopsy biases, the race

  19. Association of Megsin Gene Variants With IgA Nephropathy in Northwest Chinese Population

    Science.gov (United States)

    Wei, Lin-Ting; Fu, Rong-Guo; Gao, Jie; Yu, Qiao-Ling; Dong, Feng-Ming; Wang, Zhe; Wang, Meng; Liu, Xing-Han; Dai, Zhi-Jun

    2016-01-01

    Abstract Megsin is a mesangial cell-predominant gene that encodes a serpin family protein which is expressed in the renal mesangium. Overexpression of megsin has been observed in the glomeruli of patients with IgA nephropathy (IgAN). The aim of this study was to evaluate the association of megsin polymorphisms (rs1055901 and rs1055902) with IgAN in a Chinese population. We examined 351 patients with histologically proven IgAN and compared them with 310 age, sex, and ethnicity-matched healthy subjects. Two single nucleotide polymorphisms (SNPs) in megsin were genotyped by Sequenom MassARRAY. SPSS 18.0 was used for statistical analyses, and SNP Stats to test for associations between these polymorphisms and IgAN risk. Odds ratios with 95% confidence intervals were used to assess the relationships. We found that rs1055901 and rs1055902 SNPs were not correlated with susceptibility to IgAN in Northwest Chinese population. Analyses of the relationship between genotypes and clinical variables indicated that in patients with IgAN, rs1055901 was associated with 24-hour proteinuria, an increase in blood pressure, and Lee's grade (P = 0.04, 0.02, and 0.04, respectively), and rs1055902 was associated with 24-hour proteinuria and Lee's grade (P = 0.03 and 0.01, respectively). However, the results showed no association between these gene variants and sex of the patients. These results indicate that megsin gene variants may play a role in the severity, development, and/or progression of IgAN in Northwest Chinese population. PMID:26871801

  20. Long-Term Survival of Patients with IgA Nephropathy After Dialysis Therapy

    Directory of Open Access Journals (Sweden)

    Hiroyuki Komatsu

    2013-12-01

    Full Text Available Background/Aims: How dialysis affects the survival of patients with biopsy-proven IgA nephropathy (IgAN is not fully understood. The present long-term cohort study quantifies the survival rates and incidence of cardio-cerebrovascular diseases (CCVDs among such patients in Japan. Methods: Fifty-two of 433 patients with IgAN who had reached end-stage kidney disease underwent renal replacement therapy (RRT between 1981 and 2010. The overall survival rate and incidence of CCVDs in these patients were evaluated during follow-up for 11.3 ± 6.4 years. Results: The mean age at starting RRT was 42.8 ± 13.3 years. Only seven patients died during follow-up (mortality rate, 1.2/100 person-years and Kaplan-Meier analysis revealed favorable survival rates of 93.3% and 65.1% at 10 and 20 years, respectively, compared with that of patients with glomerulonephritis in the registry of the Japanese Society for Dialysis Therapy who required RRT. Malignancy and CCVDs were causes of death at 13.6 ± 4.8 and 3.9 ± 1.3 years, respectively, after starting RRT. Fatal and non-fatal CCVDs developed in 15 (incidence, 2.7/100 person-years patients and acute coronary syndrome and cerebral hemorrhage developed relatively soon after starting RRT. Cox proportional hazards models revealed that age at the time of starting RRT was a significant factor affecting the onset of CCVDs. Meanwhile, a history of having had corticosteroid as an initial treatment did not affect the onset of events. Conclusion: Although the survival of patients with IgAN is favorable after dialysis, the onset of CCVDs during the early phase of dialysis should be carefully monitored.

  1. Corticosteroid Treatment Influences TA-Proteinuria and Renal Survival in IgA Nephropathy.

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    Cristina Sarcina

    Full Text Available The clinical course of IgA nephropathy (IgAN and its outcome are extremely variable. Proteinuria at baseline has been considered one of the most important risk factors. More recently, mean proteinuria of follow-up (time-average proteinuria: TAp was described as a stronger marker of renal survival, suggesting to consider it as a marker of disease activity and response to treatment. We evaluated predictors of renal survival in IgAN patients with different degrees of renal dysfunction and histological lesions, focusing on the role of the therapy in influencing TAp. We performed a retrospective analysis of three prospective, randomized, clinical trials enrolling 325 IgAN patients from 1989 to 2005. Patients were divided into 5 categories according to TAp. The primary endpoint of the 100% increase of serum creatinine occurred in 54 patients (16.6% and renal survival was much better in groups having lower TAp. The median follow up was 66.6 months (range 12 to 144. The primary endpoint of the 100% increase of serum creatinine occurred in 54 patients (16,6% and renal survival was much better in groups having lower TA proteinuria. At univariate analysis plasma creatinine and 24h proteinuria, systolic (SBP and diastolic (DBP blood pressure during follow-up and treatment with either steroid (CS or steroid plus azathioprine (CS+A were the main factors associated with lower TAp and renal survival. At multivariate analysis, female gender, treatment with S or S+A, lower baseline proteinuria and SBP during follow-up remained as the only variables independently influencing TAp. In conclusion, TA-proteinuria is confirmed as one of the best outcome indicators, also in patients with a severe renal insufficiency. A 6-month course of corticosteroids seems the most effective therapy to reduce TAp.

  2. Identification of new susceptibility loci for IgA nephropathy in Han Chinese.

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    Li, Ming; Foo, Jia-Nee; Wang, Jin-Quan; Low, Hui-Qi; Tang, Xue-Qing; Toh, Kai-Yee; Yin, Pei-Ran; Khor, Chiea-Chuen; Goh, Yu-Fen; Irwan, Ishak D; Xu, Ri-Cong; Andiappan, Anand K; Bei, Jin-Xin; Rotzschke, Olaf; Chen, Meng-Hua; Cheng, Ching-Yu; Sun, Liang-Dan; Jiang, Geng-Ru; Wong, Tien-Yin; Lin, Hong-Li; Aung, Tin; Liao, Yun-Hua; Saw, Seang-Mei; Ye, Kun; Ebstein, Richard P; Chen, Qin-Kai; Shi, Wei; Chew, Soo-Hong; Chen, Jian; Zhang, Fu-Ren; Li, Sheng-Ping; Xu, Gang; Tai, E Shyong; Wang, Li; Chen, Nan; Zhang, Xue-Jun; Zeng, Yi-Xin; Zhang, Hong; Liu, Zhi-Hong; Yu, Xue-Qing; Liu, Jian-Jun

    2015-06-01

    IgA nephropathy (IgAN) is one of the most common primary glomerulonephritis. Previously identified genome-wide association study (GWAS) loci explain only a fraction of disease risk. To identify novel susceptibility loci in Han Chinese, we conduct a four-stage GWAS comprising 8,313 cases and 19,680 controls. Here, we show novel associations at ST6GAL1 on 3q27.3 (rs7634389, odds ratio (OR)=1.13, P=7.27 × 10(-10)), ACCS on 11p11.2 (rs2074038, OR=1.14, P=3.93 × 10(-9)) and ODF1-KLF10 on 8q22.3 (rs2033562, OR=1.13, P=1.41 × 10(-9)), validate a recently reported association at ITGAX-ITGAM on 16p11.2 (rs7190997, OR=1.22, P=2.26 × 10(-19)), and identify three independent signals within the DEFA locus (rs2738058, P=1.15 × 10(-19); rs12716641, P=9.53 × 10(-9); rs9314614, P=4.25 × 10(-9), multivariate association). The risk variants on 3q27.3 and 11p11.2 show strong association with mRNA expression levels in blood cells while allele frequencies of the risk variants within ST6GAL1, ACCS and DEFA correlate with geographical variation in IgAN prevalence. Our findings expand our understanding on IgAN genetic susceptibility and provide novel biological insights into molecular mechanisms underlying IgAN.

  3. Clinicopathologic features of IgA nephropathy patients with different levels of proteinuria.

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    Ai, Zhen; Xu, Ricong; Liu, Wenting; Zhou, Qian; Li, Bin; Huang, Fengxian; Yu, Xueqing; Yang, Qiongqiong

    2016-07-01

    To investigate the clinicopathologic features of IgA nephropathy (IgAN) patients with different levels of proteinuria and its clinical significance. This was a single-center retrospective cohort study. Patients with biopsy-proven primary IgAN were enrolled from January 2006 to December 2011 in The First Affiliated Hospital of Sun Yat-sen University, divided into six groups based on proteinuria at biopsy (≤ 0.30 g/d, 0.31 - 0.50 g/d, 0.51 - 1.00 g/d, 1.01 - 2.00 g/d, 2.01 - 3.00 g/d, and > 3.00 g/d). Demographic and clinicopathologic data were collected and analyzed. 1,413 patients were enrolled in this study, with the median proteinuria being 0.61 g/d (interquartile range 0.30 - 1.29). Patients with proteinuria > 0.50 g/d showed significant differences in their clinicopathologic characteristics with higher prevalence of hypertension, hypoalbuminemia, hyperuricemia, hypercholesterolemia and hypertriglyceridemia, worse renal function, higher proportions of segmental glomerulosclerosis, tubular atrophy/interstitial fibrosis, and interstitial inflammation. Even the patients with proteinuria 0.31 - 0.50 g/d exhibited higher uric acid, lower total serum protein and albumin, higher proportions of crescents, and global glomerulosclerosis. Furthermore, multiple risk factors linear regression analysis has shown that there were significant associations between proteinuria and serum albumin, uric acid, total cholesterol, triglyceride, systolic blood pressure, degrees of segmental glomerulosclerosis, proportions of crescents, and global glomerulosclerosis. Clinicopathologic features were significantly worse in IgAN patients with increasing of proteinuria.

  4. Corticosteroid Treatment Influences TA-Proteinuria and Renal Survival in IgA Nephropathy.

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    Sarcina, Cristina; Tinelli, Carmine; Ferrario, Francesca; Visciano, Bianca; Pani, Antonello; De Silvestri, Annalisa; De Simone, Ilaria; Del Vecchio, Lucia; Terraneo, Veronica; Furiani, Silvia; Santagostino, Gaia; Corghi, Enzo; Pozzi, Claudio

    2016-01-01

    The clinical course of IgA nephropathy (IgAN) and its outcome are extremely variable. Proteinuria at baseline has been considered one of the most important risk factors. More recently, mean proteinuria of follow-up (time-average proteinuria: TAp) was described as a stronger marker of renal survival, suggesting to consider it as a marker of disease activity and response to treatment. We evaluated predictors of renal survival in IgAN patients with different degrees of renal dysfunction and histological lesions, focusing on the role of the therapy in influencing TAp. We performed a retrospective analysis of three prospective, randomized, clinical trials enrolling 325 IgAN patients from 1989 to 2005. Patients were divided into 5 categories according to TAp. The primary endpoint of the 100% increase of serum creatinine occurred in 54 patients (16.6%) and renal survival was much better in groups having lower TAp. The median follow up was 66.6 months (range 12 to 144). The primary endpoint of the 100% increase of serum creatinine occurred in 54 patients (16,6%) and renal survival was much better in groups having lower TA proteinuria. At univariate analysis plasma creatinine and 24h proteinuria, systolic (SBP) and diastolic (DBP) blood pressure during follow-up and treatment with either steroid (CS) or steroid plus azathioprine (CS+A) were the main factors associated with lower TAp and renal survival. At multivariate analysis, female gender, treatment with S or S+A, lower baseline proteinuria and SBP during follow-up remained as the only variables independently influencing TAp. In conclusion, TA-proteinuria is confirmed as one of the best outcome indicators, also in patients with a severe renal insufficiency. A 6-month course of corticosteroids seems the most effective therapy to reduce TAp.

  5. Association between polymorphisms in Interleukin-17 receptor A gene and childhood IgA nephropathy

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    Seung-Ah Baek

    2010-02-01

    Full Text Available Purpose : Interleukin-17 (IL-17 is produced by activated CD4+T cells and exhibits pleiotropic biological activity on various cell types. IL-17 was reported to be involved in the immunoregulatory response in IgA nephropathy (IgAN. Our aim was to investigate the association between single-nucleotide polymorphisms (SNPs in IL-17 receptor A (IL-17RA gene and childhood IgAN. Methods : We analyzed the SNPs in the IL-17RA in 156 children with biopsy-proven IgAN and 245 healthy controls. We divided the IgAN patients into 2 groups and compared them with respect to proteinuria (?#180; and &gt;4 mg/m2/h, ?#180;0 and &gt;40 mg/m2/h, respectively and the presence of pathological levels of biomarkers of diseases such as interstitial fibrosis, tubular atrophy, or global sclerosis. Results : No difference was observed between the SNP genotypes rs2895332, rs1468488, and rs4819553 between IgAN patients and control subjects. In addition, no significant difference was observed between allele frequency of SNPs rs2895 332, rs1468488, and rs4819553 between patients in the early and advanced stage of the disease. However, significant difference was observed between the genotype of SNP rs2895332 between patients with proteinuria (&gt;4 mg/m2/h and those without proteinuria (codominant model OR 0.36, 95% CI 0.19&#8211;0.66, P&lt;0.001; dominant model OR 0.35, 95% CI 0.17&#8211;0.69 P=0.002; recessive model OR 0.12, 95% CI 0.01&#8211;1.06 P=0.025. Conclusion : Our results indicate that the SNP in IL-17RA (rs2895332 may be related to the development of proteinuria in IgAN patients.

  6. Proteinuria during Follow-Up Period and Long-Term Renal Survival of Childhood IgA Nephropathy.

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    Kamei, Koichi; Harada, Ryoko; Hamada, Riku; Sakai, Tomoyuki; Hamasaki, Yuko; Hataya, Hiroshi; Ito, Shuichi; Ishikura, Kenji; Honda, Masataka

    2016-01-01

    Proteinuria is the most important risk factor for IgA nephropathy progression. The purpose of this study is to evaluate the long-term outcome and risk factors for poor prognosis in childhood IgA nephropathy. Patients who were diagnosed with IgA nephropathy between 1972 and 1992 at the Tokyo Metropolitan Kiyose Children's Hospital were included. We analyzed risk factors for progression to end-stage kidney disease (ESKD) and chronic renal insufficiency (CRI) using Kaplan-Meier method and multivariate analyses of Cox proportional hazard model. One hundred patients were included and the median observation period was 11.8 years. Twelve and 17 patients progressed to ESKD and CRI, respectively. The survival probabilities were 90.0% at 10 years and 79.8% at 20 years for ESKD, and 86.1% at 10 years and 72.3% at 20 years for CRI. Notably, patients with heavy proteinuria with hypoalbuminemia during follow-up period showed extremely poor prognosis. In this group, the survival rate at 10 years from ESKD and CRI was 40.6% and 20.8%, respectively. By multivariate analysis, proteinuria at diagnosis and proteinuria during follow-up period were risk factors for ESKD, whereas glomeruli showing mesangial proliferation ≥50% and proteinuria during follow-up period were risk factors for CRI. Patients without heavy proteinuria during follow-up period did not develop CRI and 63% of patients with mild proteinuria during follow-up period showed no proteinuria at the last observation. The degree of proteinuria during follow-up period is the strongest risk factor for ESKD and CRI.

  7. Glomerular basement membrane injuries in IgA nephropathy evaluated by double immunostaining for α5(IV) and α2(IV) chains of type IV collagen and low-vacuum scanning electron microscopy.

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    Masuda, Yukinari; Yamanaka, Nobuaki; Ishikawa, Arimi; Kataoka, Mitue; Arai, Takashi; Wakamatsu, Kyoko; Kuwahara, Naomi; Nagahama, Kiyotaka; Ichikawa, Kaori; Shimizu, Akira

    2015-06-01

    The glomerulus contains well-developed capillaries, which are at risk of injury due to high hydrostatic pressure, hyperfiltration, hypertension and inflammation. However, the pathological alterations of the injured glomerular basement membrane (GBM), the main component of the glomerular filtration barrier, are still uncertain in cases of glomerulonephritis. We examined the alterations of the GBM in 50 renal biopsy cases with IgA nephropathy (31.8 ± 17.6 years old) using double immunostaining for the α2(IV) and α5(IV) chains of type IV collagen, and examining the ultrastructural alterations by transmission electron microscopy (TEM) and low-vacuum scanning electron microscopy (LV-SEM). The GBM of IgA nephropathy cases showed various morphological and qualitative alterations. In the TEM findings, thinning, gaps, rupture, thickening with a lamellar and reticular structure and double contours were detected in the GBM. Double immunostaining for α5(IV) and α2(IV) showed thickening of the GBM with reduced α5(IV) and increased α2(IV), or mosaic images of α5(IV) and α2(IV), and holes, fractures, spiny projections and rupture of α5(IV) in the GBM. In addition, LV-SEM showed an etched image and multiple holes in a widening and wavy GBM. These findings might be associated with the development of a brittle GBM in IgA nephropathy. Glomerular basement membrane alterations were frequently noted in IgA nephropathy, and were easily evaluated by double immunostaining for α2(IV) and α5(IV) of type IV collagen and LV-SEM. The application of these analyses to human renal biopsy specimens may enhance our understanding of the alterations of the GBM that occur in human glomerular diseases.

  8. Effect of Immunosuppressive Drugs on the Changes of Serum Galactose-Deficient IgA1 in Patients with IgA Nephropathy.

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    Kim, Min Jeong; Schaub, Stefan; Molyneux, Karen; Koller, Michael T; Stampf, Susanne; Barratt, Jonathan

    2016-01-01

    Galactose-deficient IgA1 (Gd-IgA1) and IgA-IgG complexes are known to play an important role in the pathogenesis of IgA nephropathy (IgAN). We aimed therefore to determine the impact of immunosuppression on the serum levels of Gd-IgA1, total IgA1 and IgA-IgG complexes in IgAN patients. In a retrospective study, serum samples from IgAN patients collected before transplantation (t0) and at 3- and 6-month posttransplant (t3 & t6) were used to measure the levels of Gd-IgA1, total IgA1 and IgA-IgG complexes. The area under the curves (AUC) of immunosuppressants was calculated by the plot of plasma trough level or dosage of each immunosuppressant versus time and was interpreted as the extent of drug exposure. Thirty-six out of 64 IgAN patients, who underwent kidney transplantation between 2005 and 2012, were enrolled. From t0 to t3, serum Gd-IgA1 and total IgA1 decreased significantly (24.7 AU (18.6-36.1) to 17.2 (13.1-29.5) (pIgA-IgG complexes remained similar. From t3 to t6, Gd-IgA1 and IgA-IgG complexes significantly increased (17.2 AU (13.1-29.5) to 23.9 (16.8-32.0) (p = 0.0143); OD 0.16 (0.06-0.31) to 0.26 (0.14-0.35) (p = 0.0242)), while total IgA1 remained similar. According to median regression analysis, AUC of prednisone t0-6 was significantly associated with the decrease of Gd-IgA1 t0-6 (P = 0.01) and IgA1 t0-6 (p = 0.002), whereas AUC of tacrolimus t0-6 was associated with the decrease of IgA1 t0-6 (p = 0.02). AUC of prednisone t0-3 was associated with the decrease of IgA-IgG complexes t0-3 (p = 0.0036). The association of AUC prednisone t0-6 with Gd-IgA1 t0-6 remained highly significant after adjustment for other immunosuppressants (p = 0.0036). Serum levels of Gd-IgA1, total IgA1 and IgA-IgG in patients with IgAN vary according to the changing degrees of immunosuppression. The exposure to prednisone most clearly influenced the serum levels of Gd-IgA1.

  9. Clinicopathological Features and Outcomes of IgA Nephropathy with Hematuria and/or Minimal Proteinuria

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    Min Tan

    2015-04-01

    Full Text Available Background/Aims: Information regarding the clinical and histological prognostic factors of IgA nephropathy (IgAN is mostly derived from patients in whom diagnostic renal biopsies were performed because their proteinuria levels were higher than 1-2 g/d. The clinicopathological features and outcomes of IgAN patients presenting with normal blood pressure, normal renal function, hematuria and minimal or no proteinuria are not well described. We therefore conducted a study of the clinicopathological features and outcomes in IgAN patients with these characteristics. Methods: The clinical, laboratory, and pathological manifestations and long-term outcomes of all IgAN patients with the above-mentioned characteristics were collected. The relationships between renal pathology, injury, long-term outcomes and clinical factors were studied, and the risk factors of IgAN were analyzed using multivariate logistic regression. Results: Of all of the renal biopsy cases, IgAN with the above features accounted for 8.9%. Among these patients, 67.2% (253 showed simultaneous hematuria and proteinuria, 23.1% (87 showed only hematuria, and 9.7% (36 showed only proteinuria. Additionally, 33.8% (127 patients showed macroscopic hematuria and 65.1% (245 had a prodromal infection. Regarding renal pathological changes, 45.5% (171 of the patients were unexpectedly classified as Grade II to IV (Hass classification. Proteinuria at the time of renal biopsy was an independent predictor of more severe renal pathological injury. After a median follow-up of 75 months, 61 (16.2% patients experienced adverse events. Among these patients, 28 (7.45% exhibited hypertension, 22 (5.85% presented proteinuria levels >1 g/24 h, and 11 (2.9% developed impaired renal function. Conclusions: Severe renal histological injury may be observed in some IgAN patients with benign clinical characteristics. Proteinuria is an independent predictor of severe renal pathological injury in IgAN patients with

  10. Mortality of IgA nephropathy patients: a single center experience over 30 years.

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    Hajeong Lee

    Full Text Available Research on the prognosis of IgA nephropathy (IgAN has focused on renal survival, with little information being available on patient survival. Hence, this investigation aimed to explore long-term patient outcome in IgAN patients. Clinical and pathological characteristics at the time of renal biopsy were reviewed in 1,364 IgAN patients from 1979 to 2008. The outcomes were patient death and end stage renal disease (ESRD progression. Overall, 71 deaths (5.3% and 277 cases of ESRD (20.6% occurred during 13,916 person-years. Ten-, 20-, and 30-year patient survival rates were 96.3%, 91.8%, and 82.7%, respectively. More than 50% patient deaths occurred without ESRD progression. Overall mortality was elevated by 43% from an age/sex-matched general population (GP (standardized mortality ratio [SMR], 1.43; 95% confidence interval [CI], 1.04-1.92. Men had comparable mortality to GP (SMR, 1.22; 95% CI, 0.82-1.75, but, in women, the mortality rate was double (SMR, 2.17; 95% CI, 1.21-3.57. Patients with renal risk factors such as initial renal dysfunction (estimated glomerular filgration rate <60 ml/min per 1.73 m(2; SMR, 1.70; 95% CI, 1.13-2.46, systolic blood pressure ≥ 140 mmHg (SMR, 1.88; 95% CI, 1.19-2.82 or proteinuria ≥ 1 g/day (SMR, 1.66; 95% CI, 1.16-2.29 had an elevated mortality rate. Patients with preserved renal function, normotension, and proteinuria <1 g/day, however, had a similar mortality rate to GP. When risk stratification was performed by counting the number of major risk factors present at diagnosis, low-risk IgAN patients had a mortality rate equal to that of GP, whereas high-risk patients had a mortality rate higher than that of GP. This investigation demonstrated that overall mortality in IgAN patients was higher than that of GP. Women and patients with renal risk factors had a higher mortality than that of GP, Therefore, strategies optimized to alleviate major renal risk factors are warranted to reduce patient mortality.

  11. The Unexplored Roles of Human Serum IgA

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    Leong, Ka Wai

    2014-01-01

    The roles of human serum IgA, in contrast to that of mucosal IgA, are relatively unexplored. Previous studies have shown that IgA mediates either pro- or anti-inflammatory effects in innate immune cells. Serum IgA has been shown to interact with many proteins and glycoproteins of which the functions and mechanisms are not fully characterized. Here, we present fresh perspectives into the roles of serum IgA, describing novel IgA–protein interactions, the importance of its glycosylation status in normal functions, and the plausible role of IgA as a driver and regulator of autoimmune diseases/immune overactivation. Other potential roles, including the regulation of cytokines, effector cell function, and homeostasis, are considered in view of the maintenance of immune function. We anticipate future research to uncover new anti-inflammatory or pro-inflammatory roles of human serum IgA in immune functions and dysfunctions, with implications on systemic lupus erythematosus (SLE). PMID:25188736

  12. [A clinicopathological study of IgA nephropathy after tonsillectomy--with emphasis on renal histology and the timing of tonsillectomy].

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    Koichi, K; Yamaji, S; Kimura, T; Yosizawa, T; Tujie, H

    1993-08-01

    We studied the effects and the timing of tonsillectomy on IgA nephropathy by urinalysis, serum Cr, IgA, ASLO and renal histology. The renal histology was classified into three groups according to its progression. Tonsillectomy was carried out in 31 patients (12 males and 19 females) with IgA nephropathies diagnosed by renal biopsy. The average age at tonsillectomy was 30.4 years old. The effects of tonsillectomy were followed up from more than 1 year (average 36.9 months) after operation. An improvement in urinary findings was observed in 77% and in 22 cases (71%) the tonsillectomy was evaluated as having been effective based on urinary findings and renal function. The difference between the effective group and the ineffective group, in terms of the tonsillectomy, was significant for serum Cr but not for urinary findings, serum IgA or ASLO. The effective rate in groups I and II, based on renal histological classification, was 96%. In group III (advanced stage), no case was considered to show an effective response. We conclude that tonsillectomy in IgA nephropathies should be carried out at an early stage, while renal function is normal and before renal histology has progressed to that of group III.

  13. Co-expression of MMP-9/IgA and TIMP-1/IgA in renal tissue of IgA nephropathy and its significance%MMP-9/IgA和TIMP-1/IgA在IgA肾病患者肾组织中的共表达及意义

    Institute of Scientific and Technical Information of China (English)

    师锁柱; 张雪光; 陈香美

    2011-01-01

    目的 观察基质金属蛋白酶-9(MMP-9)及其组织抑制因子-1(TIMP-1)和免疫球蛋白A(IgA)在IgA肾病不同病变肾小球内共表达情况,探讨IgA沉积在IgA肾病进展中的作用.方法 采用石蜡切片免疫荧光双标记技术,对56例不同病理分级IgA肾病(Lee氏分级Ⅰ-Ⅴ级)患者肾组织中MMP-9/IgA、TIMP-1/IgA共表达变化进行检测.结果 在Lee氏分级Ⅰ-Ⅱ级肾小球中TIMP-1/IgA有少量表达,MMP-9/IgA表达最多.Lee氏分级Ⅲ级肾小球中TIMP-1/IgA表达增多,MMP-9/IgA表达减少,在Lee氏分级Ⅳ-Ⅴ级重度系膜病变肾小球内TIMP-1/IgA表达最多,MMP-9/IgA有少量表达,而在硬化肾小球内两者表达最少.结论 在IgA肾病进展过程中随着肾小球内IgA沉积增多,肾小球内TIMP-1表达逐渐增高,MMP-9表达逐渐减少,提示IgA沉积引起的MMP-9/TIMP-1失衡参与了IgA肾病肾小球硬化过程.%Objective To study the role of immunoglobulin A(IgA) deposition in the progress of IgA nephropathy by observing the co-expression of matrix metalloproteinase-9(MMP-9), its tissue inhibitor-l(TIMP-l) and IgA in IgA nephropathy patients with variant glomerular lesions. Methods Co-expression of MMP-9/IgA and TTMP-l/IgA in renal tissues from 56 patients with IgA nephropathy(Lee levels I-V) was detected with immunofluorescence double-staining. Results The TIMP-1/IgA was lowly expressed while the MMP-9/IgA was highly expressed in glomeruli of patients with IgA nephropathy(Lee levels I-II). The expression level of TIMP-1/IgA was higher while that of MMP-9/IgA was lower in glomeruli of patients with IgA neprhropathy(Lee level HI). The expression level of TIMP-1/IgA was the highest while that of MMP-9/IgA was lower in glomeruli of patients with IgA nephropathy(Lee level IV-V) and the lowest in sclerotic glomeruli of patients with IgA nephropathy. Conclusion The IgA deposition and TTMP-1 expression are increased while the MMP-9 expression is decreased during the progress of IgA

  14. Collapsing glomerulopathy following anabolic steroid use in a 16-year-old boy with IgA nephropathy

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    S M Matthai

    2015-01-01

    Full Text Available Collapsing glomerulopathy (CG is a proliferative podocytopathy, increasingly recognized in a variety of disease conditions. We report a case of CG in a 16-year-old boy with IgA nephropathy (IgAN who presented with acute kidney injury, marked proteinuria and hypertension following a short period of anabolic steroid use. Although CG has been associated with long-term anabolic steroid use among body builders, there is no data on the effect of anabolic steroid use in persons with underlying renal disease like IgAN. We postulate that development of CG in our patient could be temporally linked to intake of body-building steroids along with a predisposing background renal disease of IgAN.

  15. Periodontal disease bacteria specific to tonsil in IgA nephropathy patients predicts the remission by the treatment.

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    Yasuyuki Nagasawa

    Full Text Available BACKGROUND: Immunoglobulin (IgA nephropathy (IgAN is the most common form of primary glomerulonephritis in the world. Some bacteria were reported to be the candidate of the antigen or the pathogenesis of IgAN, but systematic analysis of bacterial flora in tonsil with IgAN has not been reported. Moreover, these bacteria specific to IgAN might be candidate for the indicator which can predict the remission of IgAN treated by the combination of tonsillectomy and steroid pulse. METHODS AND FINDINGS: We made a comprehensive analysis of tonsil flora in 68 IgAN patients and 28 control patients using Denaturing gradient gel electrophoresis methods. We also analyzed the relationship between several bacteria specific to the IgAN and the prognosis of the IgAN. Treponema sp. were identified in 24% IgAN patients, while in 7% control patients (P = 0.062. Haemophilus segnis were detected in 53% IgAN patients, while in 25% control patients (P = 0.012. Campylobacter rectus were identified in 49% IgAN patients, while in 14% control patients (P = 0.002. Multiple Cox proportional-hazards model revealed that Treponema sp. or Campylobactor rectus are significant for the remission of proteinuria (Hazard ratio 2.35, p = 0.019. There was significant difference in remission rates between IgAN patients with Treponema sp. and those without the bacterium (p = 0.046, and in remission rates between IgAN patients with Campylobacter rectus and those without the bacterium (p = 0.037 by Kaplan-Meier analysis. Those bacteria are well known to be related with the periodontal disease. Periodontal bacteria has known to cause immune reaction and many diseases, and also might cause IgA nephropathy. CONCLUSION: This insight into IgAN might be useful for diagnosis of the IgAN patients and the decision of treatment of IgAN.

  16. Clinical Experience of Professor Zhai Wen-sheng Treatment of Primary IgA Nephropathy%翟文生教授治疗免疫球蛋白A沉积性肾病(IgA nephropathy)的经验

    Institute of Scientific and Technical Information of China (English)

    赵小静

    2011-01-01

    目的:总结翟文生教授治疗原发性免疫球蛋白A沉积性肾病(IgA nephropathy)临床经验.方法:探讨该病的病因病机,提出热、瘀、虚是IgA肾病病机、辨证论治的关键;重视清热解毒利咽、活血化瘀、扶正补虚在治疗中的作用.结果与结论:翟文生教授治疗Isa肾病的经验对临床有重要的指导意义.%Objective:To summarize the clinical experience of professor ZhaiWenSheng treatment of primary IgA nephropathy. Methods:To explore the causes and pathogenesis f the disease,proposed heat, blood stasis, virtual is pathogenesis of IgA nephropathy, syndrome differentiation and treatment key, Attention clearing heat and the pharynx, promoting blood circulation to remove blood stasis, centralizer fill in the treatment of virtual function. Results and Conclusion: Professor ZhaiWenSheng treatment experience of clinical IgA nephropathy have important significance and deserves further study.

  17. Obesity-Related Nephropathy Associated with IgA Nephropathy:a Clinicopathological Analysis of Two Cases%肥胖相关性肾病伴IgA肾病2例临床病理分析

    Institute of Scientific and Technical Information of China (English)

    陈霓; 郝丽; 梁兴澜; 郑智勇; 余英豪

    2011-01-01

    Objective : To study the histomorphological characteristics, diagnosis and differential diagnosis of obesity - related glomerulopathy ( ORG ) associated with IgA nephropathy.Methods : Two cases of ORG associated with IgA nephropathy were reported and the literatures were reviewed.Results:The two cases occurred in 1 woman and 1 man, median age 35.5 years, the main symptoms of urinary abnormalities, overweight, BMI surpassed the normal value.Microscopic showed that ORG associated with IgA nephropathy included : diffuse glomeruli hypertrophy, mesangial and paramesangial deposition and a certain number of glomerular sclerosis.Immunohistochemistry showed that the IgA deposits in the mesangial area deposition.Ultrastructurally showed that mesangial deposits with a small amount of fusion of foot processes and microvilli degeneration.Conclusion: ORG associated with IgA Nephropathy is extremely rare.Its diagnosis is mainly relying on its clinical manifestation, pathology, phenotype, patients with obesity and overweight BMI.Differential diagnosis between IgA deposition associated nephropathy and glomerular sclerosis associated nephropathy is necessary.Treatments are diverse, while the prognosis is difficult to predict.%目的:探讨肥胖相关性肾病(ORG)伴IgA肾病的组织形态学特征、诊断、鉴别诊断、治疗及预后.方法:回顾性分析2例ORG伴IgA肾病的临床病理资料,并结合文献进行复习.结果:2例均为成年人,男女各1例,中位年龄35.5岁;以尿检异常为主要症状,体型肥胖,BMI均超正常值.光镜示:肾小球显著肥大,系膜区及系膜旁区沉积物伴一定数量的肾小球硬化.免疫组化显示以IgA沉积为主的系膜区沉积.电镜显示系膜区少量沉积物伴足突融合及微绒毛变性.结论:ORG伴IgA肾病非常罕见,依赖病理形态学和免疫表型,结合患者有肥胖及BMI超标即可确诊.病理学上需与IgA沉积及肾小球硬化相关肾病加以鉴别.ORG伴IgA肾病治疗方法多种,其预后较难预测.

  18. Prognostic Value of Serum Biomarkers of Autoimmunity for Recurrence of IgA Nephropathy after Kidney Transplantation.

    Science.gov (United States)

    Berthoux, Francois; Suzuki, Hitoshi; Mohey, Hesham; Maillard, Nicolas; Mariat, Christophe; Novak, Jan; Julian, Bruce A

    2017-06-01

    A prognostic biomarker for IgA nephropathy (IgAN) recurrence after renal transplant is lacking. We followed 96 consecutive first renal transplant recipients with native kidney IgAN (79 men; 92 deceased donors; mean age =48.1 years) on calcineurin inhibitor-based immunosuppression over 10 years for death, allograft failure, and clinicopathologic recurrence (CPR; clinically evident and biopsy-proven). Using time-dependent Cox regression analysis and receiver operating characteristic curves, we assessed prognostic significance of levels of galactose-deficient IgA1 (Gd-IgA1; autoantigen) and Gd-IgA1-specific IgG and IgA autoantibodies in serum obtained at time of transplant or native-kidney IgAN diagnosis (30 patients only). Overall, 13 patients died, 34 kidneys failed (17 due to CPR), and 34 patients developed CPR after a mean interval of 5.8 years. Compared with healthy controls (n=30), patients had significantly elevated serum Gd-IgA1 levels at diagnosis and transplant, but levels did not associate with any outcome. Patients also had significantly elevated levels of normalized (but not total) serum Gd-IgA1-specific IgG autoantibodies at diagnosis and transplant, and the level at transplant associated with higher risk of CPR (relative risk, 2.68; 95% confidence interval, 1.26 to 5.71; P=0.01; area under the receiver operating characteristic curve, 0.62; 95% confidence interval, 0.51 to 0.74; P=0.05). Normalized Gd-IgA1-specific IgG autoantibody level remained an independent risk factor for CPR in multivariate analysis. Serum Gd-IgA1-specific IgA autoantibody level did not change between diagnosis and transplant or predict outcome. This study emphasizes post-transplant prognostic value of normalized serum IgG antiglycan autoantibody level in patients with IgAN. Copyright © 2017 by the American Society of Nephrology.

  19. MiR-100-3p and miR-877-3p regulate overproduction of IL-8 and IL-1β in mesangial cells activated by secretory IgA from IgA nephropathy patients.

    Science.gov (United States)

    Liang, Yan; Zhao, Guoqiang; Tang, Lin; Zhang, Junjun; Li, Tianfang; Liu, Zhangsuo

    2016-10-01

    IgA nephropathy (IgAN) is the most common type of primary glomerulonephritis, characterized by mesangial deposition of pathogenic IgA and the injury to mesangial cells. Our previous studies indicate that secretory IgA (SIgA) plays an important role in the pathogenesis of IgAN, and miR-16 is involved in destructive process in mesangial cells mediated by the SIgA from IgAN patients. Our current study aimed to study the role of miRNAs in the effect of SIgA from IgAN patients on mesangial cells. MicroRNA microarray and cytokines assay were performed to obtain the differential microRNAs expression profile in human renal mesangial cells stimulated by SIgA from IgAN patients (P-SIgA) with the cells treated by SIgA from healthy subjects (N-SgA) as control. The microRNAs with the most significant differences in microarray analysis were validated by quantitative RT-PCR. Among them, miR-100-3p and miR-877-3p were selected to predict target gene related to cytokines detecting in this study. Fifty-six differentially expressed microRNAs were chosen and 17 microRNAs with the most prominent changes were validated. Compared with N-SIgA, P-SIgA increased the production of interleukin (IL)-1β, IL-8, monocyte chemotactic protein-1 and transforming growth factor-β1. In addition, we for the first time demonstrated that over-production of IL-8 induced by the SIgA was regulated by down-expression of miR-100-3p in mesangial cells. Similarly, IL-1β over-production was regulated by down-expression of miR-877-3p. Our findings represent a pathogenic microRNAs expression profiling in human mesangial cells activated by P-SIgA. Furthermore, we provide a new explanation characterizing the molecular mechanism responsible for the regulation of IL-1β and IL-8 production in P-SIgA-triggered mesangial cells. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Bacterial IgA protease-mediated degradation of agIgA1 and agIgA1 immune complexes as a potential therapy for IgA Nephropathy

    Science.gov (United States)

    Wang, Li; Li, Xueying; Shen, Hongchun; Mao, Nan; Wang, Honglian; Cui, Luke; Cheng, Yuan; Fan, Junming

    2016-01-01

    Mesangial deposition of aberrantly glycosylated IgA1 (agIgA1) and its immune complexes is a key pathogenic mechanism of IgA nephropathy (IgAN). However, treatment of IgAN remains ineffective. We report here that bacteria-derived IgA proteases are capable of degrading these pathogenic agIgA1 and derived immune complexes in vitro and in vivo. By screening 14 different bacterial strains (6 species), we found that 4 bacterial IgA proteases from H. influenzae, N. gonorrhoeae and N. meningitidis exhibited high cleaving activities on serum agIgA1 and artificial galactose-depleted IgA1 in vitro and the deposited agIgA1-containing immune complexes in the mesangium of renal biopsy from IgAN patients and in a passive mouse model of IgAN in vitro. In the modified mouse model of passive IgAN with abundant in situ mesangial deposition of the agIgA-IgG immune complexes, a single intravenous delivery of IgA protease from H. influenzae was able to effectively degrade the deposited agIgA-IgG immune complexes within the glomerulus, demonstrating a therapeutic potential for IgAN. In conclusion, the bacteria-derived IgA proteases are biologically active enzymes capable of cleaving the circulating agIgA and the deposited agIgA-IgG immune complexes within the kidney of IgAN. Thus, the use of such IgA proteases may represent a novel therapy for IgAN. PMID:27485391

  1. Anti-Glomerular Basement Membrane Disease Combined with IgA Nephropathy Complicated with Reversible Posterior Leukoencephalopathy Syndrome: An Unusual Case

    Science.gov (United States)

    Ge, Ya-ting; Liao, Jin-lan; Liang, Wei; Xiong, Zu-ying

    2015-01-01

    Patient: Male, 24 Final Diagnosis: Crescentic glomerulonephritis (type I) with IgA nephropathy Symptoms: Headache • gross hematuria • nocturia • seizures Medication: Cyclophosphamide Clinical Procedure: Dignosis to treatment Specialty: Nephrology Objective: Rare co-existance of disease or pathology Background: Anti-glomerular basement membrane disease (anti-GBM disease) is an autoimmune glomerulonephritis disease that is characterized by IgG linear deposition along the non-collagen domain of α3 chains of type IV collagen on the GBM. Although anti-GBM disease accompanied with IgA linear deposition along GBMs was discussed previously in some papers, anti-GBM disease combined with IgA granular deposition in the mesangial area, especially complicated with reversible posterior leukoencephalopathy syndrome (RPLS), was rarely reported. RPLS is usually caused by hypertensive encephalopathy, renal decompensation, fluid retention, and adverse effects of immunosuppressive drugs. Case Report: A male patient with the chief complaints of headache, gross hematuria, and nocturia was referred to our hospital. Based on renal biopsy, the diagnosis was finally confirmed as anti-GBM disease combined with IgA nephropathy and, the patient received comprehensive treatment, including cyclophosphamide (CTX), which led to symptom improvement. Two days after the third impulse CTX was given, he suddenly experienced headache and dizziness, which eventually developed into a tonic-clonic seizure. RPLS was identified by cranial magnetic resonance imaging (MRI) with reversible neuroimaging. After diazepam and antihypertension management, seizures were controlled. RPLS, a neurological complication, was found in anti-GBM disease with IgA nephropathy during our immunosuppressants therapy for the first time. Conclusions: It is worth paying more attention to patients with rapidly progressive glomerulonephritis (RPGN), as they might be complicated with RPLS during intravenous administration of CTX

  2. The Clinical Significance of Uric Acid and Complement Activation in the Progression of IgA Nephropathy

    Directory of Open Access Journals (Sweden)

    Yasar Caliskan

    2016-02-01

    Full Text Available Background/Aims: The aim of this study is to investigate the utility of clinical [age, gender, mean arterial pressure (MAP] and laboratory parameters [eGFR, hemoglobin (Hgb, serum levels of creatinine, uric acid, albumin, proteinuria, hematuria] and also histopathological lesions (Oxford classification parameters, crescents, intensity and pattern of staining for C3, C1Q, IgA, IgG, IgM as progression markers in patients with IgA Nephropathy (IgAN. Methods: A total of 111 IgAN patients with a follow-up period >1 year or who reached kidney failure [GFR category G5 chronic kidney disease (CKD] Results: Mean follow-up period was 33±29 months. Thirty-seven (33.3% patients progressed to kidney failure and 4 (3.6% patients developed eGFR decline ≥50% from the baseline after a median of 23 and 65 months, respectively. In multivariate Cox regression analysis, baseline levels of Hgb (HR:0.782, 95% CI 0.559-0.973, p=0.037, serum uric acid (HR:1.293, 95% CI 1.023-1.621, p=0.046, eGFR (HR:0.966, 95% CI 0.947-0.984, p=0.004 and intensity of C3 staining (HR:1.550, 95% CI 1.198-1.976, p=0.049 predicted primary endpoint. Serum uric acid level was associated independently with T score (β=0.303, p=0.005 in patients with eGFR>30 ml/min/m2. Conclusions: Hyperuricemia and the deposition of C3 are independent risk factors for IgAN progression.

  3. Reactivities of N-acetylgalactosamine-specific lectins with human IgA1 proteins

    DEFF Research Database (Denmark)

    Moore, J.S.; Kulhavy, R.; Tomana, M.

    2007-01-01

    Lectins are proteins with specificity of binding to certain monosaccharides or oligosaccharides. They can detect abnormal glycosylation patterns on immunoglobulins in patients with various chronic inflammatory diseases, including rheumatoid arthritis and IgA nephropathy (IgAN). However, lectins...... exhibit binding heterogeneity, depending on their source and methods of isolation. To characterize potential differences in recognition of terminal N-acetylgalactosamine (GalNAc) on IgA1, we evaluated the binding characteristics of several commercial preparations of GalNAc-specific lectins using a panel...... of IgA1 and, as controls, IgA2 and IgG myeloma proteins. These lectins originated from snails Helix aspersa (HAA) and Helix pomatia (HPA), and the plant Vicia villosa (VV). Only HAA and HPA bound exclusively to IgA1, with its O-linked glycans composed of GalNAc, galactose, and sialic acid. In contrast...

  4. Discovery of new risk loci for IgA nephropathy implicates genes involved in immunity against intestinal pathogens

    Science.gov (United States)

    Kiryluk, Krzysztof; Li, Yifu; Scolari, Francesco; Sanna-Cherchi, Simone; Choi, Murim; Verbitsky, Miguel; Fasel, David; Lata, Sneh; Prakash, Sindhuri; Shapiro, Samantha; Fischman, Clara; Snyder, Holly J.; Appel, Gerald; Izzi, Claudia; Viola, Battista Fabio; Dallera, Nadia; Vecchio, Lucia Del; Barlassina, Cristina; Salvi, Erika; Bertinetto, Francesca Eleonora; Amoroso, Antonio; Savoldi, Silvana; Rocchietti, Marcella; Amore, Alessandro; Peruzzi, Licia; Coppo, Rosanna; Salvadori, Maurizio; Ravani, Pietro; Magistroni, Riccardo; Ghiggeri, Gian Marco; Caridi, Gianluca; Bodria, Monica; Lugani, Francesca; Allegri, Landino; Delsante, Marco; Maiorana, Mariarosa; Magnano, Andrea; Frasca, Giovanni; Boer, Emanuela; Boscutti, Giuliano; Ponticelli, Claudio; Mignani, Renzo; Marcantoni, Carmelita; Di Landro, Domenico; Santoro, Domenico; Pani, Antonello; Polci, Rosaria; Feriozzi, Sandro; Chicca, Silvana; Galliani, Marco; Gigante, Maddalena; Gesualdo, Loreto; Zamboli, Pasquale; Maixnerová, Dita; Tesar, Vladimir; Eitner, Frank; Rauen, Thomas; Floege, Jürgen; Kovacs, Tibor; Nagy, Judit; Mucha, Krzysztof; Pączek, Leszek; Zaniew, Marcin; Mizerska-Wasiak, Małgorzata; Roszkowska-Blaim, Maria; Pawlaczyk, Krzysztof; Gale, Daniel; Barratt, Jonathan; Thibaudin, Lise; Berthoux, Francois; Canaud, Guillaume; Boland, Anne; Metzger, Marie; Panzer, Ulf; Suzuki, Hitoshi; Goto, Shin; Narita, Ichiei; Caliskan, Yasar; Xie, Jingyuan; Hou, Ping; Chen, Nan; Zhang, Hong; Wyatt, Robert J.; Novak, Jan; Julian, Bruce A.; Feehally, John; Stengel, Benedicte; Cusi, Daniele; Lifton, Richard P.; Gharavi, Ali G.

    2014-01-01

    We performed a genome-wide association study (GWAS) of IgA nephropathy (IgAN), the most common form of glomerulonephritis, with discovery and follow-up in 20,612 individuals of European and East Asian ancestry. We identified six novel genome-wide significant associations, four in ITGAM-ITGAX, VAV3 and CARD9 and two new independent signals at HLA-DQB1 and DEFA. We replicated the nine previously reported signals, including known SNPs in the HLA-DQB1 and DEFA loci. The cumulative burden of risk alleles is strongly associated with age at disease onset. Most loci are either directly associated with risk of inflammatory bowel disease (IBD) or maintenance of the intestinal epithelial barrier and response to mucosal pathogens. The geo-spatial distribution of risk alleles is highly suggestive of multi-locus adaptation and the genetic risk correlates strongly with variation in local pathogens, particularly helminth diversity, suggesting a possible role for host-intestinal pathogen interactions in shaping the genetic landscape of IgAN. PMID:25305756

  5. Periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome and IgA nephropathy.

    Science.gov (United States)

    Sugimoto, Keisuke; Fujita, Shinsuke; Miyazawa, Tomoki; Okada, Mitsuru; Takemura, Tsukasa

    2013-01-01

    A syndrome of periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA), as well as immunoglobulin A nephropathy (IgAN), may be caused by autoimmune reactivity nephropathy. A 10-year-old boy presented with periodic fever, exudative tonsillitis, oral aphthous ulcer, and cervical lymph node inflammation. These conditions had occurred at intervals of about 2-6 weeks since the age of 3 years. Microscopic hematuria, first detected at age 8 years, worsened during episodes of PFAPA-related fever; since 10 years of age, the hematuria was accompanied by sustained proteinuria. Examination of a kidney biopsy specimen led to a diagnosis of IgAN. In the kidney specimen, fractalkine immunoreactivity and heavy macrophage infiltration were prominent. Multi-drug cocktail therapy improved the urinalysis findings, and subsequent tonsillectomy succeeded in controlling recurrences of PFAPA and IgAN. In a post-treatment renal biopsy specimen, mesangial proliferation was decreased, and fractalkine immunoreactivity was absent. Immunologic reactions against certain antigens in local mucosa, including tonsils, may be impaired in PFAPA and IgAN, as evidenced by the suppression of both diseases in our patient by tonsillectomy. Accordingly, the concurrence of PFAPA and IgAN in our patient appeared to be a consequence of shared autoimmune mechanisms and systemic and local increases in cytokine concentrations, rather than coincidence.

  6. Corticotherapy response in primary IgA nephropathy Resposta à corticoterapia na nefropatia da IgA primária

    Directory of Open Access Journals (Sweden)

    Natália Novaretti

    2013-03-01

    Full Text Available INTRODUCTION: Some beneficial effects from long-term use of corticosteroids have been reported in patients with IgA nephropathy. OBJECTIVE: This retrospective study aimed to evaluate the outcome of proteinuria and renal function according to a protocol based on a 6-month course of steroid treatment. METHOD: Twelve patients were treated with 1 g/day intravenous methylprednisolone for 3 consecutive days at the beginning of months 1, 3, and 5 plus 0.5 mg/kg oral prednisone on alternate days for 6 months (treated group. The control group included 9 untreated patients. RESULTS: Proteinuria (median and 25th and 75th percentiles at baseline in the treated group was 1861 mg/24h (1518; 2417 mg/24h and was 703 mg/24h (245; 983 and 684 mg/24h (266; 1023 at the 6th (p INTRODUÇÃO: Tem sido sugerido que tratamento mais prolongado com corticosteroides pode ser benéfico em pacientes com nefropatia da IgA primária. OBJETIVO: Neste estudo retrospectivo avaliamos os efeitos na proteinúria e na função renal após 12 meses do protocolo baseado no uso por 6 meses de corticosteroides. MÉTODO: Doze pacientes receberam pulsos de 1 g/dia de metilprednisolona intravenosa por 3 dias consecutivos no início dos meses 1, 3 e 5, seguidos por prednisona (0,5 mg/kg por via oral em dias alternados após cada pulso durante 6 meses (grupo tratado. O grupo controle foi composto por nove pacientes não tratados. RESULTADOS: A proteinúria (mg/24h; mediana; 25º; 75º percentis no período basal no grupo tratado foi de 1861 (1518; 2417 e de 703 (245; 983 e de 684 (266; 1023 nos 6º (p < 0,05 vs. basal e 12º (p < 0,05 vs. basal meses, respectivamente. No grupo controle, a proteinúria foi de 1900 (1620; 3197 no período basal e de 2290 (1500; 2975 e de 1600 (1180; 2395 nos 6º e 12º meses, respectivamente (não significantes vs. basal. Comparado com o grupo controle, o grupo tratado teve menor proteinúria (p < 0,05 e número maior de pacientes em remissão (p < 0,05 nos 6º

  7. IgA Structure Variations Associate with Immune Stimulations and IgA Mesangial Deposition.

    Science.gov (United States)

    Oruc, Zeliha; Oblet, Christelle; Boumediene, Ahmed; Druilhe, Anne; Pascal, Virginie; Le Rumeur, Elisabeth; Cuvillier, Armelle; El Hamel, Chahrazed; Lecardeur, Sandrine; Leanderson, Tomas; Morelle, Willy; Demengeot, Jocelyne; Aldigier, Jean-Claude; Cogné, Michel

    2016-09-01

    IgA1 mesangial deposition is the hallmark of IgA nephropathy and Henoch-Schönlein purpura, the onset of which often follows infections. Deposited IgA has been reported as polymeric, J chain associated, and often, hypogalactosylated but with no information concerning the influence of the IgA repertoire or the link between immune stimuli and IgA structure. We explored these issues in the α1KI mouse model, which produces polyclonal human IgA1 prone to mesangial deposition. Compared with mice challenged by a conventional environment, mice in a specific pathogen-free environment had less IgA deposition. However, serum IgA of specific pathogen-free mice showed more galactosylation and much lower polymerization. Notably, wild-type, α1KI, and even J chain-deficient mice showed increased polymeric serum IgA on exposure to pathogens. Strict germfree conditions delayed but did not completely prevent deposition; mice housed in these conditions had very low serum IgA levels and produced essentially monomeric IgA. Finally, comparing monoclonal IgA1 that had different variable regions and mesangial deposition patterns indicated that, independently of glycosylation and polymerization, deposition might also depend on IgA carrying specific variable domains. Together with IgA quantities and constant region post-translational modifications, repertoire changes during immune responses might, thus, modulate IgA propensity to deposition. These IgA features are not associated with circulating immune complexes and C3 deposition and are more pertinent to an initial IgA deposition step preceding overt clinical symptoms in patients.

  8. IgA Enhances IGF-1 Mitogenic Activity Via Receptor Modulation in Glomerular Mesangial Cells: Implications for IgA-Induced Nephropathy.

    Science.gov (United States)

    Al-Eisa, Amal; Dhaunsi, Gursev S

    2017-06-27

    Glomerulonephritis due to mesangial proliferation is responsible for renal dysfunction in IgA nephropathy (IgAN), however molecular mechanisms of pathogenesis are not well known. We examined the effect of IgA on Insulin-like Growth Factor-1 (IGF-1) activity, a potent mitogen with vital role in growth and development of children, and IGF-1 receptor (IGF-1R) in cultures of glomerular mesangial cells (GMC). GMC were isolated from rat kidneys using sieving and enzymatic digestion of tissue homogenates, and cultured in RPMI 1640 medium. GMC cultures were treated with IgA (0-10 µg/ml) in the presence or absence of IGF-1 and fetal bovine serum (FBS), and BrdU incorporation was measured. IGF-1 levels were assayed along with real-time PCR quantification of IGF-1R mRNA. Treatment of GMC with IgA (5 -10 µg/ml) significantly (p IgA-mediated effects were more pronounced in IGF-1 treated cells that were significantly (p IgA significantly increased the levels of IGF-1 in culture supernatants and GMC homogenates. IGF-1R mRNA was significantly (p IgA treated cells particularly by co-treatment with IGF-1. These findings show that IgA enhances the IGF-1 activity in GMC via stimulation of IGF-1R gene transcription and suggest a role for IGF-1 in pathogenesis of IgAN. © 2017 The Author(s). Published by S. Karger AG, Basel.

  9. The Akt/mTOR/p70S6K pathway is activated in IgA nephropathy and rapamycin may represent a viable treatment option.

    Science.gov (United States)

    Tian, Jihua; Wang, Yanhong; Guo, Haixiu; Li, Rongshan

    2015-12-01

    IgA nephropathy (IgAN) is one of the most frequent forms of glomerulonephritis, and 20 to 40% of patients progress to end-stage renal disease (ESRD) within 20 years of disease onset. However, little is known about the molecular pathways involved in the altered physiology of mesangial cells during IgAN progression. This study was designed to explore the role of mTOR signaling and the potential of targeted rapamycin therapy in a rat model of IgAN. After establishing an IgA nephropathy model, the rats were randomly divided into four groups: control, control+rapamycin, IgAN and IgA+rapamycin. Western blotting and immunohistochemistry were performed to determine phospho-Akt, p70S6K and S6 protein levels. Coomassie Brilliant Blue was utilized to measure 24-h urinary protein levels. The biochemical parameters of the rats were analyzed with an autoanalyzer. To evaluate IgA deposition in the glomeruli, FITC-conjugated goat anti-rat IgA antibody was used for direct immunofluorescence. Cellular proliferation and the mesangial matrix in glomeruli were assayed via histological and morphometric procedures. Our results showed that p70S6K, S6 and Akt phosphorylation were significantly upregulated in IgAN rats, and rapamycin effectively inhibited p70S6K and S6 phosphorylation. A low dose of the mTOR inhibitor rapamycin reduced proteinuria, inhibited IgA deposition, and protected kidney function in an IgAN rat model. Low-dose rapamycin treatment corresponded to significantly lower cellular proliferation rates and a decreased mesangial matrix in the glomeruli. In conclusion, the Akt/mTOR/p70S6K pathway was activated in IgAN, and our findings suggested that rapamycin may represent a viable option for the treatment of IgAN.

  10. Research progress of microRNA in IgA nephropathy%microRNA在IgA肾病发病机制中的研究进展

    Institute of Scientific and Technical Information of China (English)

    孙嫱; 沈颖

    2014-01-01

    IgA肾病发病机制复杂,病因不明,一些microRNA可能参与其致病过程,并且可能与其关键酶——核心β1、3半乳糖基转移酶相关.现介绍表观遗传学的定义,microRNA的概念、基本结构和功能.结合文献总结、概述目前在IgA肾病患者中已经发现的异常表达的microRNA,以及其可能的作用方式.%IgA nephropathy is a complex disease with unclear mechanism,microRNAs may involve in the disease,and some of them may be associated with the key enzyme of IgA nephropathy-core β1 3-galactosyl-transferase.The concept of epigenetics and the structures and functions of microRNA were introduced.Through reviewing the related researches,several microRNAs expressing abnormally in IgA nephropathy was found.

  11. A case of sporadic medullary cystic kidney disease type 1 (MCKD1) with kidney enlargement complicated by IgA nephropathy.

    Science.gov (United States)

    Suzuki, Taihei; Iyoda, Masayuki; Yamaguchi, Yutaka; Shibata, Takanori

    2015-07-01

    Medullary cystic kidney disease (MCKD) is a progressive tubulointerstitial nephropathy, and it leads to end-stage kidney disease (ESKD). It is an autosomal dominant inherited disease, and is categorized into two types according to the localizing chromosome and timing of ESKD onset. Its pathogenesis has not been revealed clearly, thus accumulation of the cases is very valuable. We report here the first reported case of MCKD with kidney enlargement complicated by IgA nephropathy. A 70-year-old male was admitted to our hospital because of renal dysfunction and bilateral kidney enlargement. He was diagnosed as having MCKD complicated by IgA nephropathy (IgA-N) by renal biopsy. We speculated that he had MCKD type 1 on the basis of the late onset of renal failure and no significant evidence of mutation in the UMOD gene that is associated with MCKD type 2. Thereafter, his kidney function decreased progressively and he started to receive hemodialysis. This is an interesting case of MCKD1 in terms of its sporadic nature, kidney enlargement, and complication of IgA-N.

  12. IgA肾病遗传学的研究进展%Research Progress of IgA Nephropathy Genetics

    Institute of Scientific and Technical Information of China (English)

    齐尔

    2012-01-01

    IgA nephropathy( IgAN ) is the most common form of primary glomerulonephritis worldwide. It is a polygenic, multifactorial and complex diseases. The discovery of familial IgAJN and diverse prevalence between different populations indicate a genetic mechanism in the development of IgAJN. By linkage analysis and candidate-gene association studies to find IgAJN susceptibility gene mapping and clear disease-causing mutation has been a hotspot of genetic studies recently. Defects in IgA, glycosylation lead to formation of immune complexes which constitute a heritable risk factor for IgAJN. Continuous improvement of genomics( including genome-wide association studies )offers promising tools for elucidating the genetic basis of IgAN. In the past few years, animal models of IgAJN have made a lot of advances and have reflected the pathogenesis of IgAJN from different aspects.%IgA肾病(IgAN)是世界范围内最常见的原发性肾小球肾炎,是一种多基因、多因素决定的复杂性疾病.家族聚集起病及发病率的人种差异均提示遗传因素为重要致病机制之一.通过连锁分析和候选基因关联研究的方法找到IgAN致病易患基因图谱和明确致病突变基因已成为当前研究的热点.血清IgA1糖基化的缺陷导致免疫复合物的形成,构成了遗传性IgAN的危险因素.不断完善的基因组学方法(包括全基因组关联研究)为阐明IgAN的遗传基础提供了有力的工具.近年来IgAN动物模型研究有了许多新的进展,从不同侧面反映了IgAN的发病机制.

  13. Cyclosporine A combined with medium/low dose prednisone in progressive IgA nephropathy.

    Science.gov (United States)

    Xu, Lin; Liu, Zhong-Cheng; Guan, Guang-Ju; Lv, Xue-Ai; Luo, Qing

    2014-08-01

    The aim of the present study was to evaluate the efficacy of cyclosporine A (CsA) combined with medium/low dose prednisone in the treatment of progressive immunoglobulin A nephropathy (IgAN). Ninety-six patients who satisfied the inclusion criteria were enrolled in a prospective controlled clinical study. They were assigned into two groups and initially given either 0.6-0.8 mg/kg/day prednisone (maximum 40 mg/day) plus 3 mg/kg/day CsA (CsA group), or 1 mg/kg/day prednisone (maximum 60 mg/day) alone (steroid group). During therapy, the dose of prednisone was reduced in both groups and the dose of CsA was gradually tailed off over the first 3 months and maintained at 2 mg/kg/day in the CsA group. Urinary protein excretion, serum biochemical indexes, clinical efficacy and side effects of CsA were assayed. A significant decline in mean 24-hour urinary protein excretion (p prednisone and CsA (p 0.05). CsA at a dose of 2-3 mg/kg/day in combination with medium/low dose prednisone was effective in inducing remission of IgAN, especially for patients with Lee's Grade III IgAN, and is a safe and effective choice for short-term treatment of patients with progressive IgAN.

  14. Glomerulo-tubular junction stenosis as a factor contributing to glomerular obsolescence in IgA nephropathy.

    Science.gov (United States)

    Sato, Mitsuhiro; Hotta, Osamu; Taguma, Yoshio

    2002-05-01

    Periglomerular fibrosis (PF) is an interstitial injury observed in various renal diseases. It is speculated that this lesion, by occluding the glomerulo-tubular junction (GTJ) and causing atubular glomeruli, may result functionally in a reduction of the glomerular filtration rate (GFR) and may be a factor contributing to the progression of renal disease. In the present study, 340 renal biopsy specimens were analysed to determine whether or not there was nephron injury derived from such a mechanism, as well as direct glomerular injury, in IgA nephropathy (IgAN). The patients were divided into five groups according to the degree of glomerular sclerosis. The average age was lower in groups with milder sclerosis and serum creatinine (Cr) was elevated in groups with more severe sclerosis. Because the GTJ was assumed to disappear when an atubular glomerulus was formed, the ratio of the number of glomeruli with discernible GTJ to the total number of glomeruli was evaluated. As glomerular sclerosis progressed, discernible GTJ reduced significantly (p <0.001) and the degree of PF increased significantly (p <0.05). By serial section study in cases with pronounced PF, transitions between the stages of stenosis of the GTJ and atubular glomeruli were observed. It is speculated that the occlusion of the GTJ eventually hyalinizes the glomerulus; in such cases, glomerular obsolescence of the collapse type might be formed. On the other hand, obsolescence of the mesangial proliferative type might be formed in the hyalinization derived from direct glomerular injury. In this context, glomerular obsolescence of the collapse type was observed more frequently and was accompanied by more increased PF than obsolescence of the mesangial proliferative type (p <0.001). These results suggest that in addition to direct glomerular injury, nephron injury derived from interstitial damage of this type plays an important contributory role in the progression of IgAN.

  15. Circulating TNF receptors 1 and 2 are associated with the severity of renal interstitial fibrosis in IgA nephropathy.

    Directory of Open Access Journals (Sweden)

    Yuji Sonoda

    Full Text Available The current study aimed to examine whether the levels of TNF receptors 1 and 2 (TNFR1 and TNFR2 in serum and urine were associated with other markers of kidney injury and renal histological findings, including TNFR expression, in IgA nephropathy (IgAN. The levels of the parameters of interest were measured by immunoassay in 106 biopsy-proven IgAN patients using samples obtained immediately before renal biopsy and in 34 healthy subjects. Renal histological findings were evaluated using immunohistochemistry. The levels of serum TNFRs were higher in IgAN patients than in healthy subjects. The levels of both TNFRs in serum or urine were strongly correlated with each other (r > 0.9. Serum TNFR levels were positively correlated with the urinary protein to creatinine ratio (UPCR and four markers of tubular damage of interest (N-acetyl-β-D-glucosaminidase [NAG], β2 microglobulin [β2m], liver-type fatty acid-binding protein [L-FABP], and kidney injury molecule-1 [KIM-1] and negatively correlated with estimated glomerular filtration rate (eGFR. Patients in the highest tertile of serum TNFR levels showed more severe renal interstitial fibrosis than did those in the lowest or second tertiles. The tubulointerstitial TNFR2-, but not TNFR1-, positive area was significantly correlated with the serum levels of TNFRs and eGFR. Stepwise multiple regression analysis revealed that elevated serum TNFR1 or TNFR2 levels were a significant determinant of renal interstitial fibrosis after adjusting for eGFR, UPCR, and other markers of tubular damage. In conclusion, elevated serum TNFR levels were significantly associated with the severity of renal interstitial fibrosis in IgAN patients. However, the source of TNFRs in serum and urine remains unclear.

  16. Clinical-pathologic significance of CD163 positive macrophage in IgA nephropathy patients with crescents.

    Science.gov (United States)

    Li, Jun; Liu, Chang-Hua; Gao, Bo; Xu, Dao-Liang

    2015-01-01

    CD163, a marker of M2 macrophages, express anti-inflammatory properties. This study aims to investigate the difference of CD163 positive macrophages expression between IgA nephropathy patients with and without crescents. Renal tissues from IgAN patients (n = 24), including IgAN with crescents (n = 10), IgAN without crescents (n = 14), minimal change disease (MCD, as disease control, n = 8) and normal control kidneys (negative control, n = 3), were included in this study. Expressions of CD163 and CD68 in renal tissues were detected by immunohistochemistry or immunofluorescence. Compared with IgAN without crescent, IgAN patients with crescents have lower serum albumin and poor renal function. CD163 was mainly expressed in acute tubulointerstitial lesions. CD163 positive cells accumulate in areas around tubules with RBC casts. CD163 positive cells can also be seen in tubular lumen. CD163 positive cells can be seen in glomerular lesions, including endocapillary hypercellularity, cellular crescent and fibrous-cellular crescent. There were more CD163 positive cells in tubulointerstitial and glomerular lesions in IgAN patients with crescents. CD163 positive cells number in tubulointerstitial tissue was positive correlated with percentage of crescents, proteinuria, and negative correlated with serum albumin, eGFR. CD163 positive cells number in glomeruli was positive correlated with percentage of crescents, and was negative correlated with eGFR. Percentage of crescents was negative correlated with serum albumin, eGFR, and positive correlated with proteinuria. Dual staining showed that CD163 positive cells also expressed CD68. CD163 positive macrophages were involved in active crescent disease, acute tubular injury and glomerular lesions of IgAN with crescents.

  17. Calcitriol in the treatment of IgA nephropathy with non-nephrotic range proteinuria: a meta-analysis of randomized controlled trials
.

    Science.gov (United States)

    Deng, Jin; Zheng, Xin; Xie, Hongping; Chen, Lu

    2017-01-01

    The aim of the present study was to investigate the efficacy and safety of calcitriol for treating Chinese patients with IgA nephropathy presenting as non-nephrotic range proteinuria, and a comprehensive meta-analysis was conducted using the related randomized controlled trials (RCTs). We searched for RCTs of calcitriol for the treatment of IgA nephropathy in the CNKI, CBM, Cochrane Central Register of Controlled Trials, PUBMED, and EMBASE databases. The studies included in our meta-analysis were strictly determined according to the inclusion and exclusion criteria. We evaluated the quality of the included studies using the Jadad score sheet and performed the meta-analysis using RevMan software (version 5.30). Our meta-analysis, which included 7 RCTs involving 310 Chinese participants, showed that calcitriol contributed to a decrease in proteinuria standard mean difference (SMD) -1.49, 95% CI (-2.37, -0.62); p = 0.0008). No significant differences were observed in serum creatinine (SMD -0.13, 95% CI (-0.53, 0.27); p = 0.52), serum calcium (SMD 0.28, 95% CI (-0.08, 0.65); p = 0.13), or serum phosphorus (SMD 0.03, 95% CI (-0.07, 0.14); p = 0.57) levels. All of the adverse reactions mentioned in these studies were mild. These data indicated that calcitriol is a promising treatment to reduce proteinuria in Chinese patients with IgA nephropathy presenting as non-nephrotic range proteinuria, and it has only mild side effects.
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  18. Altered urinary excretion of aquaporin 2 in IgA nephropathy.

    Science.gov (United States)

    Rocchetti, Maria Teresa; Tamma, Grazia; Lasorsa, Domenica; Suriano, Ida Valentina; D'Apollo, Annamaria; Papale, Massimo; Mastrofrancesco, Lisa; Grandaliano, Giuseppe; Svelto, Maria; Valenti, Giovanna; Gesualdo, Loreto; Di Paolo, Salvatore

    2011-10-01

    The intrarenal renin-angiotensin system (RAS) activation plays a pivotal role in immunoglobulin A nephropathy (IgAN) pathogenesis, which is still largely undefined. Recently, vasopressin (AVP) has been advocated to contribute to the genesis and progression of chronic kidney diseases (CKD) directly, and indirectly, via RAS activation. Our aim is to explore the intrarenal activity of AVP, its relationship with RAS activity, as well as its modulation by therapies in IgAN. In this observational study, we measured plasma copeptin, a surrogate marker of AVP, the urine excretion of aquaporin 2 (AQP2), a protein reflecting renal AVP action, and angiotensinogen (AGT), a parameter of renal RAS activation, and their relationship with renal function in 44 IgAN patients at the time of renal biopsy, without any drug therapy, and after 6-month treatment with ACEi or steroid+ACEi. Twenty-one patients with other CKD and 40 healthy subjects were recruited as controls. ELISAs were used to measure all variables of interest. At baseline, IgAN patients showed higher urinary levels of AQP2, compared with controls and patients with other CKD. Urinary AQP2 and AGT levels strongly correlated with the presence of arterial hypertension. Steroids+ACEi caused the decrease of all the variables examined. The fall of urinary AQP2 and AGT following drug treatments was associated with the decrease of daily proteinuria. Our findings would support the involvement of AVP-AQP2 axis, interacting with the RAS, in the progression of IgAN and candidate AQP2 as a possible novel marker of the disease.

  19. Outcome results in children with IgA nephropathy: a single center experience

    Science.gov (United States)

    Bulut, Ipek Kaplan; Mir, Sevgi; Sozeri, Betul; Bulut, Mustafa Orhan; Sen, Sait; Dincel, Nida

    2012-01-01

    Background Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis. Patients manifest variable clinical symptoms (eg, microhematuria) with preserved or progressive deterioration of renal function resulting in end-stage renal disease. The aim of this study was to evaluate patients from a single center to describe the clinical features, treatments, and follow-up results of those with the disease. Methods This is a retrospective data study of all children with IgAN. Patients who had a histopathologically proven diagnosis of IgAN and were followed up for at least 5 years were included in the study. Renal biopsy, graded as Hass classification, was performed on all patients. A total of 39 patients were included in the study. Results The mean follow-up time (± standard deviation) was 10.4 ± 3.51 (range 5–16) years. Twenty-nine patients (74.4%) were male and ten (25.6%) were female. Nineteen (48.7%) patients presented with recurrent macroscopic hematuria, ten (25.6%) with microscopic hematuria ± proteinuria, six (15.4%) with nephritic syndrome, and four (10.3%) with nephrotic syndrome. All patients underwent a renal biopsy, which was graded according to the Hass classification. At the end of follow-up time, 18 (46.1%) patients were normal, 15 (38.5%) had minor urinary abnormalities, three (7.7%) had active renal disease, and three (7.7%) developed renal failure. Conclusion The results of the present study are better than those from most other series. The majority of children with IgAN in this study were admitted with recurrent macroscopic hematuria and found to have a good prognosis. We suggest that children with IgAN have a good prognosis in the first 5-year follow-up period. PMID:22334797

  20. IgA nephropathy and psoriatic arthritis that improved with steroid pulse therapy and mizoribine in combination with treatment for chronic tonsillitis and epipharyngitis.

    Science.gov (United States)

    Kaneko, Tomohiro; Mii, Akiko; Fukui, Megumi; Nagahama, Kiyotaka; Shimizu, Akira; Tsuruoka, Shuichi

    2015-01-01

    A 65-year-old man was admitted to our hospital with edema and renal dysfunction. He had received a diagnosis of psoriatic arthritis at 50 years of age. As a renal biopsy showed IgA nephropathy (IgAN), bilateral tonsillectomy was performed, and one course of steroid pulse therapy with an oral steroid and mizoribine were subsequently administered. The patient's proteinuria gradually reduced in association with an improvement in the renal function. In addition, the rash and arthralgia were ameliorated. In this case, adding treatment for chronic epipharyngitis accelerated the curative effects, and focal infection therapy consisting of immunosuppressive drugs was effective for both IgAN and psoriatic arthritis.

  1. Pregnancy in patients with IgA nephropathy%IgA 肾病与妊娠相关的研究进展

    Institute of Scientific and Technical Information of China (English)

    史亚男; 叶文玲

    2016-01-01

    IgA nephropathy ,as one of the most common types of glomerulonephritis ,often occurs in women of child‐bearing age .The mutual influence between IgA nephropathy and pregnancy ,and the appropriate timing of pregnancy in patients with IgA nephropathy were summarized in this review .Most studies showed that pregnancy in IgA nephropathy patients with CKD 1‐2 was not associated with increased risk of kidney disease progression .Howev‐er ,higher frequencies of caesarean delivery ,increased preterm delivery rate and lower average birth weight of new‐borns were observed in those patients .Renal insufficiency ,proteinuria and high blood pressure during pregnancy were risk factors for the adverse outcomes of pregnancy .We therefore suggest that pregnancy should be considered only for patients with blood pressure maintained within the normal range ,proteinuria being less than 1 .0 g/24 h and normal renal function or mild renal dysfunction .%Ig A肾病是最常见的原发性肾小球肾炎之一,好发于育龄期,本文主要概述了Ig A肾病与妊娠的相互影响及IgA肾病患者妊娠的时机选择和妊娠前准备。研究表明,慢性肾脏病(CKD)1~2期的IgA肾病患者妊娠不增加肾功能下降的风险,但Ig A肾病患者的剖腹产比例、早产发生率及低体质量儿发生率均高于正常人群。肾功能不全、蛋白尿、高血压是不良妊娠的危险因素。建议Ig A肾病患者具备血压维持正常、尿蛋白排泄率<1.0 g/24 h、肾功能正常或仅轻度损伤等条件时开始妊娠。

  2. Separation of Two Distinct O-Glycoforms of Human IgA1 by Serial Lectin Chromatography Followed by Mass Spectrometry O-Glycan Analysis.

    Science.gov (United States)

    Lehoux, S; Ju, T

    2017-01-01

    Human immunoglobulin A1 (IgA1), which carries four to six mucin-type O-glycans (O-glycans) on its hinge region (HR), is the most abundant O-glycoprotein in plasma or serum. While normal O-glycans from hematopoietic-originated cells are core 1-based complex structures, many reports showed that the IgA1 from patients with IgA nephropathy (IgAN) carries undergalactosylated or truncated O-glycans such as the Tn antigen and its sialylated version the SialylTn (STn) antigen on the HR. Yet, there is still a debate whether Tn/STn on the HR of IgA1 is specific to the IgA1 from patients with IgAN since these antigens have also been seen in serum IgA1 of healthy individuals. An additional question is whether the O-glycans at all sites on the two HRs of one IgA1 molecule are homogeneous (either all normal or all Tn/STn) or heterogeneous (both normal and Tn/STn O-glycans). To address these questions, we conducted a systematic study on the O-glycans of plasma IgA1 from both IgAN patients and healthy controls using serial HPA and PNA lectin chromatography followed by western blotting and further analysis of O-glycans from HPA-bound and PNA-bound IgA1 fractions by mass spectrometry. Unexpectedly, we found that a variable minor fraction of IgA1 from both IgAN patients and healthy controls had Tn/STn antigens, and that the O-glycoprotein IgA1 molecules from most samples had only two distinct O-glycoforms: one major glycoform with homogeneous normal core 1-based O-glycans and one minor glycoform with homogeneous Tn/STn antigens. These results raised a serious question about the role of Tn/STn antigens on IgA1 in pathogenesis of IgAN, and there is a demand for a practical methodology that any laboratory can utilize to analyze the O-glycans of IgA1. Herein, we describe the methodology we developed in more detail. The method could also be applied to the analysis of any other O-glycosylated proteins.

  3. Recent Research Progress of Pathogenesis of IgA Nephropathy%IgA肾病发病机制的新进展

    Institute of Scientific and Technical Information of China (English)

    郭燕

    2012-01-01

    Deposition of IgA in the glomeruli,the hallmark of IgA nephropathy,is a quite common phenomenon. Aberrant O-linked galactosylation of IgA subclass ( IgA1 ) appears to play a central role in the process and auto-immunity to a conformational epitope related to glycans at the hinge region of IgA1 is apparently required. Both circulating immune complex and in-situ immune complex mechanism have been proven to exist. Mediator systems, such as complement activation and engagement of innate immune system, also play prominent roles in determining the clinical onset and severity of disease. Progress in understanding the details of the pathogenesis of IgA nephropathy will lead to diagnosis improvement,more accurate individualized prognosis and personalized treatment regimens for this globally distributed and very common primary disease.%免疫球蛋白A(IgA)沉积于肾小球是IgA肾病的特点,是非常普遍的现象.IgA亚类(IgA1)的异常O-联半乳糖基化在这个过程中起到主要作用,针对IgA1铰链区聚多糖相关表位的自身免疫是必要的发病条件.已证明既存在循环免疫复合物也存在原位免疫复合物.先天免疫素质及中介系统,如补体系统也在临床发病及病情演变中起重要作用.对于IgA肾病详细机制的理解有助于改善诊断方法,也有助于对这一常见的原发性全球分布疾病做出更加精确的个性化预后预测及个性化治疗方法 的改进.

  4. BMP-7 PROTEIN EXPRESSION IS DOWNREGULATED IN HUMAN DIABETIC NEPHROPATHY.

    Science.gov (United States)

    Ivanac-Janković, Renata; Ćorić, Marijana; Furić-Čunko, Vesna; Lovičić, Vesna; Bašić-Jukić, Nikolina; Kes, Petar

    2015-06-01

    Bone morphogenetic protein-7 (BMP-7) is expressed in all parts of the normal kidney parenchyma, being highest in the epithelium of proximal tubules. It protects kidney against acute and chronic injury, inflammation and fibrosis. Diabetic nephropathy is the leading cause of chronic kidney disease, and is characterized by decreased expression of BMP-7. The aim of our study was to analyze whether the expression of BMP-7 is significantly changed in advanced stages of human diabetic nephropathy. Immunohistochemical analysis of the expression of BMP-7 was performed on archival material of 30 patients that underwent renal biopsy and had confirmed diagnosis of diabetic nephropathy. Results showed that BMP-7 was differently expressed in the cytoplasm of epithelial cells of proximal tubules and podocytes among all stages of diabetic nephropathy. At early stages of diabetic nephropathy, BMP-7 was strongly positive in proximal tubules and podocytes, while low expression was recorded in the majority of samples at advanced stages. In conclusion, increased expression of BMP-7 at initial stages of diabetic nephropathy with subsequent decrease at advanced stage highlights the role of BMP-7 in the protection of kidney structure and function. Further investigations should be focused on disturbances of BMP-7 receptors and signaling pathways in patients with diabetic nephropathy.

  5. The IgA nephropathy Biobank. An important starting point for the genetic dissection of a complex trait

    Directory of Open Access Journals (Sweden)

    Alexopoulos Efstathios

    2005-12-01

    Full Text Available Abstract Background IgA nephropathy (IgAN or Berger's disease, is the most common glomerulonephritis in the world diagnosed in renal biopsied patients. The involvement of genetic factors in the pathogenesis of the IgAN is evidenced by ethnic and geographic variations in prevalence, familial clustering in isolated populations, familial aggregation and by the identification of a genetic linkage to locus IGAN1 mapped on 6q22–23. This study seems to imply a single major locus, but the hypothesis of multiple interacting loci or genetic heterogeneity cannot be ruled out. The organization of a multi-centre Biobank for the collection of biological samples and clinical data from IgAN patients and relatives is an important starting point for the identification of the disease susceptibility genes. Description The IgAN Consortium organized a Biobank, recruiting IgAN patients and relatives following a common protocol. A website was constructed to allow scientific information to be shared between partners and to divulge obtained data (URL: http://www.igan.net. The electronic database, the core of the website includes data concerning the subjects enrolled. A search page gives open access to the database and allows groups of patients to be selected according to their clinical characteristics. DNA samples of IgAN patients and relatives belonging to 72 multiplex extended pedigrees were collected. Moreover, 159 trios (sons/daughters affected and healthy parents, 1068 patients with biopsy-proven IgAN and 1040 healthy subjects were included in the IgAN Consortium Biobank. Some valuable and statistically productive genetic studies have been launched within the 5th Framework Programme 1998–2002 of the European project No. QLG1-2000-00464 and preliminary data have been published in "Technology Marketplace" website: http://www.cordis.lu/marketplace. Conclusion The first world IgAN Biobank with a readily accessible database has been constituted. The knowledge gained

  6. Geographic differences in genetic susceptibility to IgA nephropathy: GWAS replication study and geospatial risk analysis.

    Directory of Open Access Journals (Sweden)

    Krzysztof Kiryluk

    Full Text Available IgA nephropathy (IgAN, major cause of kidney failure worldwide, is common in Asians, moderately prevalent in Europeans, and rare in Africans. It is not known if these differences represent variation in genes, environment, or ascertainment. In a recent GWAS, we localized five IgAN susceptibility loci on Chr.6p21 (HLA-DQB1/DRB1, PSMB9/TAP1, and DPA1/DPB2 loci, Chr.1q32 (CFHR3/R1 locus, and Chr.22q12 (HORMAD2 locus. These IgAN loci are associated with risk of other immune-mediated disorders such as type I diabetes, multiple sclerosis, or inflammatory bowel disease. We tested association of these loci in eight new independent cohorts of Asian, European, and African-American ancestry (N = 4,789, followed by meta-analysis with risk-score modeling in 12 cohorts (N = 10,755 and geospatial analysis in 85 world populations. Four susceptibility loci robustly replicated and all five loci were genome-wide significant in the combined cohort (P = 5×10⁻³²-3×10⁻¹⁰, with heterogeneity detected only at the PSMB9/TAP1 locus (I² = 0.60. Conditional analyses identified two new independent risk alleles within the HLA-DQB1/DRB1 locus, defining multiple risk and protective haplotypes within this interval. We also detected a significant genetic interaction, whereby the odds ratio for the HORMAD2 protective allele was reversed in homozygotes for a CFHR3/R1 deletion (P = 2.5×10⁻⁴. A seven-SNP genetic risk score, which explained 4.7% of overall IgAN risk, increased sharply with Eastward and Northward distance from Africa (r = 0.30, P = 3×10⁻¹²⁸. This model paralleled the known East-West gradient in disease risk. Moreover, the prediction of a South-North axis was confirmed by registry data showing that the prevalence of IgAN-attributable kidney failure is increased in Northern Europe, similar to multiple sclerosis and type I diabetes. Variation at IgAN susceptibility loci correlates with differences in disease prevalence

  7. 277例IgA肾病患者病理分型与临床特点分析%Pathological classiifcation and clinical manifestations of 277 patients with IgA nephropathy

    Institute of Scientific and Technical Information of China (English)

    王建; 李庆士; 李龙海; 胡冬梅; 董葆

    2015-01-01

    ObjectiveTo summarize different pathologic classiifcation and clinical manifestations of IgA nephropathy.MethodA retrospective analysis of 277 patients with IgA nephropathy in our hospital from January 2010 to July 2014, all of these patients had taken kidney pathologic examination, the pathologic classification and the relationship among various clinical indexes were analyzed.ResultMild mesangial proliferative IgA nephropathy, moderate mesangial proliferative IgA nephropathy, focal proliferative IgA nephropathy with ischemic renal injury, focal hyperplasia sclerosing IgA nephropathy with partial crescent formation, focal proliferative IgA nephropathy with acute renal tubular injury, focal proliferative IgA nephropathy with partial glomerular sclerosis, focal proliferative IgA nephropathy respectively accounted for 11.91%, 0.36%, 3.61%, 0.72%, 3.61%, 4.33%, 63.54%; the serum creatinine levels of the last five classiifcations was signiifcantly higher than that of the ifrst two and the difference of 24h urinary protein level was not statistically signiifcant among different pathological classiifcation.ConclusionClinical differences among different pathologic classiifcation of IgA nephropathy are obvious. Getting renopuncture biopsy in time has an important guiding signiifcance in the early treatment and deserve to be expanded clinically.%目的:总结分析不同IgA肾病病理分型及临床表现。方法回顾性分析2010年1月至2014年7月本院收治的277例IgA肾病患者的临床资料,均接受肾脏病理检查,分析病理分型与各临床指标间的关系。结果轻度系膜增生性IgA肾病、中度系膜增生性IgA肾病、局灶增生性IgA肾病伴缺血性肾损伤、局灶增生硬化性IgA肾病伴部分新月体形成、局灶增生性IgA肾病伴急性肾小管损伤、局灶增生性IgA肾病伴部分肾小球硬化、局灶增生性IgA肾病分别占11.91%、0.36%、3.61%、0.72%、3.61%、4.33%、63.54%,后五种分型IgA肾

  8. The urine albumin-to-creatinine ratio is a reliable indicator for evaluating complications of chronic kidney disease and progression in IgA nephropathy in China

    Directory of Open Access Journals (Sweden)

    Lu Huan

    2016-05-01

    Full Text Available OBJECTIVE: This study investigated the correlation between the albumin-to-creatinine ratio in the urine and 24-hour urine proteinuria and whether the ratio can predict chronic kidney disease progression even more reliably than 24-hour proteinuria can, particularly in primary IgA nephropathy. METHODS: A total of 182 patients with primary IgA nephropathy were evaluated. Their mean urine albumin-to-creatinine ratio and 24-hour proteinuria were determined during hospitalization. Blood samples were also analyzed. Follow-up data were recorded for 44 patients. A cross-sectional study was then conducted to test the correlation between these parameters and their associations with chronic kidney disease complications. Subsequently, a canonical correlation analysis was employed to assess the correlation between baseline proteinuria and parameters of the Oxford classification. Finally, a prospective observational study was performed to evaluate the association between proteinuria and clinical outcomes. Our study is registered in the Chinese Clinical Trial Registry, and the registration number is ChiCTR-OCH-14005137. RESULTS: A strong correlation (r=0.81, p<0.001 was found between the ratio and 24-hour proteinuria except in chronic kidney disease stage 5. First-morning urine albumin-to-creatinine ratios of ≥125.15, 154.44 and 760.31 mg/g reliably predicted equivalent 24-hour proteinuria ‘thresholds’ of ≥0.15, 0.3 and 1.0 g/24 h, respectively. In continuous analyses, the albumin-to-creatinine ratio was significantly associated with anemia, acidosis, hypoalbuminemia, hyperphosphatemia, hyperkalemia, hypercholesterolemia and higher serum cystatin C. However, higher 24-hour proteinuria was only associated with hypoalbuminemia and hypercholesterolemia. Higher tubular atrophy and interstitial fibrosis scores were also associated with a greater albumin-to-creatinine ratio, as observed in the canonical correlation analysis. Finally, the albumin

  9. Scarcity of autoreactive human blood IgA(+) memory B cells.

    Science.gov (United States)

    Prigent, Julie; Lorin, Valérie; Kök, Ayrin; Hieu, Thierry; Bourgeau, Salomé; Mouquet, Hugo

    2016-10-01

    Class-switched memory B cells are key components of the "reactive" humoral immunity, which ensures a fast and massive secretion of high-affinity antigen-specific antibodies upon antigenic challenge. In humans, IgA class-switched (IgA(+) ) memory B cells and IgA antibodies are abundant in the blood. Although circulating IgA(+) memory B cells and their corresponding secreted immunoglobulins likely possess major protective and/or regulatory immune roles, little is known about their specificity and function. Here, we show that IgA(+) and IgG(+) memory B-cell antibodies cloned from the same healthy humans share common immunoglobulin gene features. IgA and IgG memory antibodies have comparable lack of reactivity to vaccines, common mucosa-tropic viruses and commensal bacteria. However, the IgA(+) memory B-cell compartment contains fewer polyreactive clones and importantly, only rare self-reactive clones compared to IgG(+) memory B cells. Self-reactivity of IgAs is acquired following B-cell affinity maturation but not antibody class switching. Together, our data suggest the existence of different regulatory mechanisms for removing autoreactive clones from the IgG(+) and IgA(+) memory B-cell repertoires, and/or different maturation pathways potentially reflecting the distinct nature and localization of the cognate antigens recognized by individual B-cell populations.

  10. Amino acid sequence requirements in the human IgA1 hinge for cleavage by streptococcal IgA1 proteases

    DEFF Research Database (Denmark)

    Senior, BW; Batten, MR; Kilian, Mogens

    2002-01-01

    All the IgA1 proteases of the different pathogenic species of Streptococcus cleave the hinge of the alpha chain of human IgA1 only at one proline-threonine peptide bond. In order to study the importance of these amino acids for cleavage, several hinge mutant recombinant IgA1 antibodies were...... constructed. The mutations were found to be without major effect upon the structure or functional abilities of the antibodies. However, they had a major effect upon their sensitivity to cleavage by some of the IgA1 proteases....

  11. Amino acid sequence requirements in the hinge of human immunoglobulin A1 (IgA1) for cleavage by streptococcal IgA1 proteases

    DEFF Research Database (Denmark)

    Batten, MR; Senior, BW; Kilian, Mogens

    2003-01-01

    The amino acid sequence requirements in the hinge of human immunoglobulin A1 (IgA1) for cleavage by IgA1 proteases of different species of Streptococcus were investigated. Recombinant IgA1 antibodies were generated with point mutations at proline 227 and threonine 228, the residues lying on either...... side of the peptide bond at which all streptococcal IgA1 proteases cleave wild-type human IgA1. The amino acid substitutions produced no major effect upon the structure of the mutant IgA1 antibodies or their functional ability to bind to Fcalpha receptors. However, the substitutions had a substantial...... effect upon sensitivity to cleavage with some streptococcal IgA1 proteases, with, in some cases, a single point mutation rendering the antibody resistant to a particular IgA1 protease. This effect was least marked with the IgA1 protease from Streptococcus pneumoniae, which showed no absolute requirement...

  12. Human Cell Line-Derived Monoclonal IgA Antibodies for Cancer Immunotherapy

    Science.gov (United States)

    Hart, Felix; Danielczyk, Antje; Goletz, Steffen

    2017-01-01

    IgA antibodies have great potential to improve the functional diversity of current IgG antibody-based cancer immunotherapy options. However, IgA production and purification is not well established, which can at least in part be attributed to the more complex glycosylation as compared to IgG antibodies. IgA antibodies possess up to five N-glycosylation sites within their constant region of the heavy chain as compared to one site for IgG antibodies. The human GlycoExpress expression system was developed to produce biotherapeutics with optimized glycosylation and used here to generate a panel of IgA isotype antibodies directed against targets for solid (TA-mucin 1, Her2, EGFR, Thomsen–Friedenreich) and hematological (CD20) cancer indications. The feasibility of good manufacturing practice was shown by the production of 11 g IgA within 35 days in a one liter perfusion bioreactor, and IgA antibodies in high purity were obtained after purification. The monoclonal IgA antibodies possessed a high sialylation degree, and no non-human glycan structures were detected. Kinetic analysis revealed increased avidity antigen binding for IgA dimers as compared to monomeric antibodies. The IgA antibodies exhibited potent Fab- and Fc-mediated functionalities against cancer cell lines, whereby especially granulocytes are recruited. Therefore, for patients who do not sufficiently benefit from therapeutic IgG antibodies, IgA antibodies may complement current regiment options and represent a promising strategy for cancer immunotherapy. In conclusion, a panel of novel biofunctional IgA antibodies with human glycosylation was successfully generated.

  13. Human Cell Line-Derived Monoclonal IgA Antibodies for Cancer Immunotherapy

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    Felix Hart

    2017-05-01

    Full Text Available IgA antibodies have great potential to improve the functional diversity of current IgG antibody-based cancer immunotherapy options. However, IgA production and purification is not well established, which can at least in part be attributed to the more complex glycosylation as compared to IgG antibodies. IgA antibodies possess up to five N-glycosylation sites within their constant region of the heavy chain as compared to one site for IgG antibodies. The human GlycoExpress expression system was developed to produce biotherapeutics with optimized glycosylation and used here to generate a panel of IgA isotype antibodies directed against targets for solid (TA-mucin 1, Her2, EGFR, Thomsen–Friedenreich and hematological (CD20 cancer indications. The feasibility of good manufacturing practice was shown by the production of 11 g IgA within 35 days in a one liter perfusion bioreactor, and IgA antibodies in high purity were obtained after purification. The monoclonal IgA antibodies possessed a high sialylation degree, and no non-human glycan structures were detected. Kinetic analysis revealed increased avidity antigen binding for IgA dimers as compared to monomeric antibodies. The IgA antibodies exhibited potent Fab- and Fc-mediated functionalities against cancer cell lines, whereby especially granulocytes are recruited. Therefore, for patients who do not sufficiently benefit from therapeutic IgG antibodies, IgA antibodies may complement current regiment options and represent a promising strategy for cancer immunotherapy. In conclusion, a panel of novel biofunctional IgA antibodies with human glycosylation was successfully generated.

  14. Evaluation of monoclonal antibodies with specificity for human IgA, IgA subclasses and allotypes and secretory component. Results of an IUIS/WHO collaborative study

    NARCIS (Netherlands)

    Mestecky, J.; Hamilton, R.G.; Magnusson, C.G.M.; Jefferis, R.; Vaerman, J.P.; Goodall, M.; Lange, G.G. de; Moro, I.; Aucouturier, P.; Radl, J.; Cambiaso, C.; Silvain, C.; Preud'homme, J.L.; Kusama, K.; Carlone, G.M.; Biewenga, J.; Kobayashi, K.; Skvaril, F.; Reimer, C.B.

    1996-01-01

    51 monoclonal antibodies (McAb) with putative specificity for human IgA, the IgA subclasses, Am allotypes or secretory component (SC) were evaluated for immunoreactivity and specificity by nine laboratories employing immunodiffusion, agglutination, immunohistological assays, immunoblotting and

  15. Evaluation of monoclonal antibodies with specificity for human IgA, IgA subclasses and allotypes and secretory component. Results of an IUIS/WHO collaborative study

    NARCIS (Netherlands)

    Mestecky, J.; Hamilton, R.G.; Magnusson, C.G.M.; Jefferis, R.; Vaerman, J.P.; Goodall, M.; Lange, G.G. de; Moro, I.; Aucouturier, P.; Radl, J.; Cambiaso, C.; Silvain, C.; Preud'homme, J.L.; Kusama, K.; Carlone, G.M.; Biewenga, J.; Kobayashi, K.; Skvaril, F.; Reimer, C.B.

    1996-01-01

    51 monoclonal antibodies (McAb) with putative specificity for human IgA, the IgA subclasses, Am allotypes or secretory component (SC) were evaluated for immunoreactivity and specificity by nine laboratories employing immunodiffusion, agglutination, immunohistological assays, immunoblotting and direc

  16. Human mucosal IgA in health and disease

    NARCIS (Netherlands)

    Yuvaraj, Saravanan

    2007-01-01

    Het eiwit immunoglobuline A (IgA) is een antistof die het binnendringen van bacteriën en andere ziekmakende stoffen in ons lichaam voorkomt. Daarmee zorgt het voor de eerstelijns afweer tegen infecties. UMCG-promovendus Saravanan Yuvaraj onderzocht de mogelijkheden genetisch gemoduleerde IgA

  17. Validation study of Oxford Classification of IgA Nephropathy: the significance of extracapillary hypercellularity and mesangial IgG immunostaining.

    Science.gov (United States)

    Ştefan, Gabriel; Ismail, Gener; Stancu, Simona; Zugravu, Adrian; Andronesi, Andreea; Mandache, Eugen; Mircescu, Gabriel

    2016-08-01

    The Oxford classification (OC) of IgA Nephropathy (IgAN) identified mesangial hypercellularity (M), endocapillary hypercellularity (E), segmental glomerulosclerosis (S), and tubular atrophy/interstitial fibrosis (T) as predictors of outcome. We aimed to validate the OC and to investigate the clinical significance of extracapillary hypercellularity and IgG immunostaining. We examined the renal outcome at December 31, 2014, of 121 adult patients with biopsy proven primary IgAN between 2003 and 2013. The primary endpoint was doubling of serum creatinine or renal replacement therapy initiation. The mean observation period was 59.7 months. Thirty-one percent of the patients presented with a grade of extracapillary hypercellularity. In comparison with the group with no crescents, they had higher grade of inflammation, lower eGFR and increased proteinuria. There were no differences between the IgA and IgA&IgG immunostaining groups regarding the disease progression risk factors. Mean kidney survival time for the entire cohort was 10.6 (9.1, 12.0) years. In the Cox regression model, the independent predictors of decreased renal survival were eGFR at time of biopsy, S1 and the presence of crescents. Our study showed that extracapillary proliferation and S1 had the greatest importance in establishing the renal prognosis of patients with IgAN.

  18. Light chain immunofluorescence in various nephropathies

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    Megha S Uppin

    2011-01-01

    Full Text Available Context: Light chain immunofluoresence (IF in renal biopsy is routinely used in the diagnosis of light chain deposition disease (LCDD, amyloidosis and cast nephropathy. Light chain predominance has also been reported in certain glomerulopathies like IgA nephropathy. However, pathogenesis of this pattern of deposition in various glomerulopathies is uncertain. Aim: To discuss the pathogenesis and utility of light chain IF in nephropathies. Setting and Design: Retrospective study. Materials and Methods: The pattern of light chain IF and light microscopic diagnosis in 306 cases of various nephropathies was reviewed. Direct IF was done in all these cases with commercial fluorescence (Fluoresciene Isothiocynate conjugated polyclonal rabbit anti-human antisera against IgM, IgG, IgA, C3, C1q, kappa and lambda light chains. Results: Light chain deposits were seen in 240 (78.43% cases. In IgA nephropathy, lupus nephritis and post-infectious glomerulonephritis (PIGN, lambda positivity was more as compared to kappa. Light chain deposits in LCDD and membranous nephropathy were more kappa type. The IF pattern in amyloidosis was not consistent. Conclusion: The pathogenesis of light chain predominance in glomerulopathies is not clear and it depends on isoelectric point and size of the immune complex. Light chain IF should be performed routinely in all the renal biopsies.

  19. Transferrin receptor and Fc α/μ receptor may not be the major IgA1 receptor on human mesangial cells

    Institute of Scientific and Technical Information of China (English)

    HU Rui-hai; ZHANG Ying; ZHAO Ming-hui

    2005-01-01

    @@ IgA nephropathy (IgAN) is the most common form of primary glomerulonephritis.1 The histopathology of IgAN is characterized by abundance of mesangial matrix and proliferation of mesangial cells. IgA1 deposition in the mesangium plays an important role in the inflammatory process in this disease.

  20. Expression and clinical significance of NF-κB, CTGF and OPN in mononuclear cells in peripheral blood as well as renal tissues in patients with IgA nephropathy

    Institute of Scientific and Technical Information of China (English)

    Cheng-Luo Hao; Chang-Bin Liao

    2016-01-01

    Objective:To study the expression and clinical significance of NF-κB, CTGF and OPN in mononuclear cells in peripheral blood as well as renal tissues in patients with IgA nephropathy. Methods:A total of 25 nephropathy patients diagnosed with IgA nephropathy and 25 patients receiving nephrectomy due to trauma or tumor in our hospital were studied. Peripheral blood and kidney tissues were collected to test NF-κB, CTGF, OPN, T-bet, GATA-3, RORγT and Foxp3 expressions.Results:CTGF and OPN percentages in peripheral blood mononuclear cells and kidney tissues of nephropathy patients were higher than those of the control group. NF-κB, CTGF and OPN expressions were significantly higher in M1, E1, S1 group patients’ peripheral blood mononuclear cells and renal tissues than those in M0, E1 and S1 group. T-bet, GATA-3 and RORγT expressions in nephropathy patients’ peripheral blood were significantly higher than those in the control group, and were positively correlated with NF-κB, CTGF and OPN expressions. The expression of Foxp3 was significantly lower than that of control group, and was negatively correlated with NF-κB, CTGF and OPN expressions.Conclusions: The expression of NF-κB, CTGF and OPN in peripheral blood mononuclear cells and renal tissue in patients with IgA nephropathy is abnormally high and can evaluate the prognosis of the disease and the differentiation of CD4+T cells.

  1. IgA肾病湿热证的血清蛋白质组学研究%Serum proteomics study on IgA nephropathy with Shire syndrome

    Institute of Scientific and Technical Information of China (English)

    刘垠浩; 王丽萍

    2014-01-01

    目的:应用表面加强激光解析电离-飞行时间-质谱(SELDI-TOF-MS)技术,对IgA肾病(IgAN)湿热证患者进行血清蛋白质指纹图谱检测,分析探讨该人群中所表达的特异蛋白,试图从蛋白质组层面寻找与IgA肾病湿热证相关的血清标志物。方法:采集IgA肾病患者的血清样本共29例(湿热证14例,非湿热证15例),同时选择非IgA肾病的湿热证肾病患者血清样本10例和健康人血清样本15例。采用表面增强激光解析离子化蛋白质芯片分析仪实现各组血清蛋白质表达谱的检测,后运用Biomarker WizardTM和Biomarker PatternsTM软件进行数据分析,最终识别IgA肾病湿热证特异表达的蛋白质,并建立证候决策树模型。结果:IgA肾病湿热证组与非湿热证组之间共检出有7个蛋白峰具有显著差异(P<0.05);IgA肾病湿热证组与非IgA肾病湿热证组之间共检出有4个蛋白峰具有显著差异(P<0.05);IgA肾病湿热证组与健康对照组之间共检出有5个蛋白峰具有显著差异(P<0.05);综合以上各组对比结果,并结合统计学分析证实,M/Z(质荷比)为4987.92所代表的“Beta-defensin 33蛋白”可能是IgA肾病湿热证的特异血清蛋白标志物。经筛选以M/Z为1092.71等11个蛋白峰组成的证候决策模型能很好地将IgA肾病湿热证区分出来,该模型的敏感性为92.86%,特异性为87.50%。进一步对此决策模型进行盲法验证,结果其敏感性为90.00%,特异性为86.67%。结论:IgA肾病湿热证的发生发展,可能是以M/Z为4987.92所代表的“Beta-defensin 33蛋白”的差异表达为物质基础的,同时建立了分子生物学证候决策树模型。%Objective: By applying the technology of SELDI-TOF-MS to detect the serum protein fingerprints of IgA nephropathy(IgAN) patients, analyze the serum specific proteins expressed by the IgA nephropathy patients who are diagnosed with

  2. Human IgA inhibits adherence of Acanthamoeba polyphaga to epithelial cells and contact lenses.

    Science.gov (United States)

    Campos-Rodríguez, Rafael; Oliver-Aguillón, Gabriela; Vega-Pérez, Luz M; Jarillo-Luna, Adriana; Hernández-Martínez, Dolores; Rojas-Hernández, Saúl; Rodríguez-Monroy, Marco A; Rivera-Aguilar, Víctor; González-Robles, Arturo

    2004-09-01

    Specific anti-Acanthamoeba IgA antibodies have been detected in the serum and tears of patients and healthy individuals. However, the role of human secretory IgA antibodies in inhibiting the adherence of Acanthamoeba had not been previously investigated. Therefore, the purpose of this study was to purify secretory IgA from human colostrum and analyze its effect on the adherence of Acanthamoeba trophozoites to contact lenses and Madin-Darby canine kidney (MDCK) cells. IgA antibodies to Acanthamoeba polyphaga in colostrum of healthy women as well as in saliva and serum of healthy subjects were analyzed by ELISA and Western blot analysis. In serum, saliva, and colostrum, we detected IgA antibodies that recognized several antigens of A. polyphaga. In addition, colostrum and IgA antibodies purified from it inhibited adherence of A. polyphaga trophozoites to contact lenses and MDCK cells. These results suggest that IgA antibodies may participate in the resistance to the amoebic infection, probably by inhibiting the adherence of the trophozoites to contact lenses and corneal epithelial cells.

  3. The tetraspanin CD37 protects against glomerular IgA deposition and renal pathology.

    Science.gov (United States)

    Rops, Angelique L; Figdor, Carl G; van der Schaaf, Alie; Tamboer, Wim P; Bakker, Marinka A; Berden, Jo H; Dijkman, Henry B P M; Steenbergen, Eric J; van der Vlag, Johan; van Spriel, Annemiek B

    2010-05-01

    The tetraspanin protein CD37 is a leukocyte-specific transmembrane protein that is highly expressed on B cells. CD37-deficient (CD37(-/-)) mice exhibit a 15-fold increased level of immunoglobulin A (IgA) in serum and elevated numbers of IgA+ plasma cells in lymphoid organs. Here, we report that CD37(-/-) mice spontaneously develop renal pathology with characteristics of human IgA nephropathy. In young naïve CD37(-/-) mice, mild IgA deposition in glomeruli was observed. However, CD37(-/-) mice developed high titers of IgA immune complexes in serum during aging, which was associated with increased glomerular IgA deposition. Severe mesangial proliferation, fibrosis, and hyalinosis were apparent in aged CD37(-/-) mice, whereas albuminuria was mild. To further evaluate the role of CD37 in glomerular disease, we induced anti-glomerular basement membrane (GBM) nephritis in mice. CD37(-/-) mice developed higher IgA serum levels and glomerular deposits of anti-GBM IgA compared with wild-type mice. Importantly, glomerular macrophage and neutrophil influx was significantly higher in CD37(-/-) mice during both the heterologous and autologous phase of anti-GBM nephritis. Taken together, tetraspanin CD37 controls the formation of IgA-containing immune complexes and glomerular IgA deposition, which induces influx of inflammatory myeloid cells. Therefore, CD37 may protect against the development of IgA nephropathy.

  4. Complete remission of nephrotic syndrome and acute kidney injury in crescentic IgA nephropathy: Role of mycophenolate sodium

    Directory of Open Access Journals (Sweden)

    D Bhandari

    2016-01-01

    Full Text Available Optimal therapy and prognosis of crescentic-IgA nephropathy (C-IgAN are not known. Reported treatment options for C-IgAN include combination of corticosteroids and cyclophosphamide for 6 months. The role of mycophenolate sodium in C-IgAN is unknown. We report a case of C-IgAN that was successfully treated with combination immunosuppressive therapy.

  5. Mesangial C3 deposition and decreased serum C3 levels in patients with IgA nephropathy

    Institute of Scientific and Technical Information of China (English)

    章晓炎

    2014-01-01

    Objective To explore the clinical significance of complement activation in Ig A nephropathy(IgAN)patients and provide new potential therapy targets.Methods Biopsy-proven IgAN patients admitted in our renal center were retrospectively recruited.Demographic,baseline clinical and pathological data were recorded as well as the follow-up results.Patients were divided into three groups,negative,weak positive and strong positive

  6. O-Linked Glycosylation Determines the Nephritogenic Potential of IgA Rheumatoid Factor

    Science.gov (United States)

    Kihara, Masao; Ito, Kiyoaki; Nakata, Junichiro; Otani, Masako; Tran, Ngoc Lan; Morito, Naoki; Takahashi, Satoru; Wada, Yoshinao

    2014-01-01

    Deficient glycosylation of O-linked glycans in the IgA1 hinge region is associated with IgA nephropathy in humans, but the pathogenic contribution of the underlying structural aberrations remains incompletely understood. We previously showed that mice implanted with cells secreting the class-switch variant 6-19 IgA anti-IgG2a rheumatoid factor, but not 46-42 IgA anti-IgG2a rheumatoid factor, develop glomerular lesions resembling IgA nephropathy. Because the levels of O-linked glycosylation in the hinge region and the structures of N-linked glycans in the CH1 domain differ in 6-19 IgA and 46-42 IgA, we determined the respective contributions of O- and N-linked glycans to the nephritogenic potential of the 6-19 IgA rheumatoid factor in mice. Wild-type 6-19 IgA secreted by implanted cells induced significant formation of glomerular lesions, whereas poorly O-glycosylated 6-19 IgA glycovariants or a 6-19 IgA hinge mutant lacking O-linked glycans did not. However, we observed no apparent heterogeneity in the structure of N-linked glycans attached to three different sites of the Fc regions of nephritogenic and non-nephritogenic 6-19 IgAs. Collectively, our data suggest a critical role of O-linked glycans attached to the hinge region in the development of IgA nephropathy–like GN induced by 6-19 IgA rheumatoid factor in mice. PMID:24511137

  7. Aberrant Blood Vessel Formation Connecting the Glomerular Capillary Tuft and the Interstitium Is a Characteristic Feature of Focal Segmental Glomerulosclerosis-like IgA Nephropathy

    Directory of Open Access Journals (Sweden)

    Beom Jin Lim

    2016-05-01

    Full Text Available Background: Segmental glomerulosclerosis without significant mesangial or endocapillary proliferation is rarely seen in IgA nephropathy (IgAN, which simulates idiopathic focal segmental glomerulosclerosis (FSGS. We recently recognized aberrant blood vessels running through the adhesion sites of sclerosed tufts and Bowman’s capsule in IgAN cases with mild glomerular histologic change. Methods: To characterize aberrant blood vessels in relation to segmental sclerosis, we retrospectively reviewed the clinical and histologic features of 51 cases of FSGS-like IgAN and compared them with 51 age and gender-matched idiopathic FSGS cases. Results: In FSGS-like IgAN, aberrant blood vessel formation was observed in 15.7% of cases, 1.0% of the total glomeruli, and 7.3% of the segmentally sclerosed glomeruli, significantly more frequently than in the idiopathic FSGS cases (p = .009. Aberrant blood vessels occasionally accompanied mild cellular proliferation surrounding penetrating neovessels. Clinically, all FSGS-like IgAN cases had hematuria; however, nephrotic range proteinuria was significantly less frequent than idiopathic FSGS. Conclusions: Aberrant blood vessels in IgAN are related to glomerular capillary injury and may indicate abnormal repair processes in IgAN.

  8. Improvement of the method of obtaining human IgA Fc-fragments

    Directory of Open Access Journals (Sweden)

    O. Y. Galkin

    2015-02-01

    Full Text Available To address a number of fundamental and applied problems in immunology, molecular and cellular biology and biotechnology it is necessary to obtain Fc-fragments of immunoglobulins. Fc-fragments may be used for studying of the effector functions of antibodies which are mediated by these areas. They are often used as an immunogen to produce anti-specie (based on so-called secondary antibody conjugate in the development of serological tests for diagnostics (predominantly such conjugate based on monoclonal antibodies. The work is aimed to develop improved methods of obtaining and allocation of Fc-fragments of human IgA. To achieve this objective, optimization of hydrolysis of IgA with subsequent purification of Fс-fragments have been carried out. Improved method of obtaining Fc-fragments of IgA provides: papain hydrolysis of immunoglobulin in the environment of nitrogen for 4 h, allowing to achieve maximum output of Fc-fragments without their further degradation: isolation and purification of Fc-fragments of human IgA by one-stage gel filtration on sephadex G-100; control of purity of the target product by electrophoresis in polyacrylamide gel with sodium dodecyl sulfate and Ouchterlony immunodiffusion. Enzymatic hydrolysis was carried out at the optimal temperature of papain (37 °C. As the oxygen in the air may have inhibitory effect on enzymatic hydrolysis reaction, the reaction mixture was incubated in the nitrogen atmosphere to prevent inactivation of papain. To reduce the incident degradation of immunoglobulin molecules, papain hydrolysis was carried out without using an enzyme activator (cysteine. Usage of the proposed scheme allows obtaining Fc-fragments of human IgA of high purity. Outcome of Fc-fragments after all stages of purification was about 18% of the initial amount of IgA in the preparation. Molecular weight from Fc-fragments of human IgA was equal to approximately 70 kDa.

  9. The Relationship between the Serum IgA, C3 Levels, IgA/C3 Ratio and Pathologicalgrading of IgA Nephropathy%血清IgA、C3及IgA/C3在IgA肾病病理分级评估中的意义

    Institute of Scientific and Technical Information of China (English)

    许慧丽; 何永成; 陈洪滔; 李彤

    2014-01-01

    Objective Observe the correlation between the serum IgA,C3 levels, IgA/ C3 ratio and Lee’s grading system,explore the relationship between the serum IgA, C3 Levels,IgA/ C3 Ratio and Pathological grading of IgA Nephropathy.Methods 320 patients with primary IgA nephropathy were diagnosised by renal biopsy in the second people hospital of ShenZhen,the levels of serum IgA,C3 were detected with turbidimetric method and the Pathological grading was evaluated according to the standard of Lee grading.Result The serum IgA levels of patients with Lee’sⅠ and Ⅱgrade was not higher than the patients with Lee’s Ⅲ,Ⅳ,Ⅴ grade[(2.75±1.10 VS 2.85±1.26) g/L,P>0.05];but the serum C3 levels of patients with Lee’sⅠ and Ⅱgrade was lower than the patients with Lee’s Ⅲ,Ⅳ,Ⅴ grade[(1.18±0.33 VS 1.04±0.29) ,P0.05)】;血清C3水平分别为【(1.18±0.33)vs(1.04±0.29) g/L,(P<0.05)】;血清IgA/C3率分别为【(2.71±1.19)vs(3.24±1.69)g/L,(P<0.05)】。结论 IgA/ C3比值在评估IgA肾病病理分级有重要参考意义。

  10. The role of Chlamydia Trachomatis in renal tissue in the pathogenesis IGA-nephropathy related to age

    Directory of Open Access Journals (Sweden)

    I. A. Rakityanskaya

    2012-01-01

    Full Text Available IgA-nephropathy is the most common form of primary glomerulonephritis in the world and therefore the mechanisms of this isease are actively explored. In our study, an analysis of renal biopsy issue from 117 patients IgA-nephropathy in the presence of Chlamydia trachomatis antigen related to age (before and after 60 years. It was shown that the presence of C. trachomatis in the glomerular zone influence on the severity of segmental sclerosis (p <0.05, and its presence in the interstitium affect on the size of the glomeruli (p <0.02 and severity of degeneration of epithelial tubules (p <0.02 regardless of patient age. It was shown the effect of C. trachomatis on the expression of local immune response of kidney tissue. In patients under 60 years: C. trachomatis in the glomeruli affects the number of cells of the phenotype CD25 (p = 0,04 and CD19 / κ (p = 0,034 in the glomerular infiltration and the presence of antigen in the interstitium affect the expression of CD95 (APO-1/Fas (p = 0,038 by mononuclear cells infiltration and formation of deposits S5b-C9 (p = 0,042 in the interstitial space. In patients older than 60 years of presence C. trachomatis in the glomerular zone impacts on the expression of TNF-α (p = 0,039 in the glomeruli, the presence of antigen in interstitium affect the number of cells CD71 (p = 0,025 in the interstitial infiltrate. Based on these results, we concluded that the presence of Chlamydia trachomatis antigen has an impact on the development and course of the disease and is the etiologic agent in patients with IgA-nephropathy, regardless of age.

  11. Urinary C3dg and C5b-9 indicate active immune disease in human membranous nephropathy.

    Science.gov (United States)

    Brenchley, P E; Coupes, B; Short, C D; O'Donoghue, D J; Ballardie, F W; Mallick, N P

    1992-04-01

    We have measured complement activation markers, C3dg and C5b-9 in plasma and urine from patients with idiopathic membranous nephropathy and IgA nephropathy. There was no significant difference in levels of plasma C5b-9 between the patient groups. However, high plasma concentrations of C3dg were associated significantly with IgA nephropathy with 45% of patients having levels over 25 U/ml (P less than 0.001). High concentrations of urinary C3dg and C5b-9 were associated significantly with membranous nephropathy (43% and 43% of the patient group, respectively) compared to patients with IgA nephropathy (10% and 0%, respectively, P less than 0.001). In a retrospective analysis of 31 patients with membranous nephropathy, 66% of patients with high initial urinary C5b-9 showed an unstable clinical course compared to 18% of patients with initially absent or low C5b-9 (P less than 0.001). We suggest that high urinary C5b-9 identifies those patients with a membranous lesion which retains an active immunological component contributing to the pathology of progressive glomerular damage.

  12. Association between the AGTR1 A1166C polymorphism and risk of IgA nephropathy: a meta-analysis.

    Science.gov (United States)

    Xu, J M; Song, X; Gao, F; Wang, R

    2015-12-29

    Numerous studies have evaluated the association between the A1166C polymorphism in the angiotensin II type 1 receptor (AGTR1) gene and immunoglobulin A nephropathy (IgAN) risk. However, this relationship remains controversial. Our aim was to evaluate the relationship between this polymorphism and IgAN susceptibility by performing a meta-analysis. Articles were identified in the PubMed, Google Scholar, and China National Knowledge Infrastructure databases, and after selection, five eligible studies were included. Statistical analyses were carried out using Stata 12.0, combining data from all the relevant studies. The pooled odds ratios (ORs) regarding the association between the AGTR1 A1166C polymorphism and IgAN risk were not statistically significant [A vs C: OR = 0.64, 95% confidence interval (CI) = 0.24-1.68; AA vs AC+CC: OR = 1.02, 95%CI = 0.74-1.39; CC vs AC+AA: OR = 1.20, 95%CI = 0.48-2.98; AC vs AA+CC: OR = 0.96, 95%CI = 0.70-1.31]. In conclusion, the AGTR1 gene A1166C polymorphism may not be correlated with IgAN susceptibility. However, further studies should be performed to confirm this finding.

  13. Individuals of Pacific Asian origin with IgA nephropathy have an increased risk of progression to end-stage renal disease.

    Science.gov (United States)

    Barbour, Sean J; Cattran, Daniel C; Kim, S Joseph; Levin, Adeera; Wald, Ron; Hladunewich, Michelle A; Reich, Heather N

    2013-11-01

    IgA nephropathy (IgAN) accounts for a far higher proportion of end-stage renal disease (ESRD) in Asia compared with North America. It is not known whether this is entirely because of differences in disease prevalence or a higher risk of disease progression. The lack of a racially diverse population cohort followed longitudinally has previously precluded the ability to address this question. To determine whether Asians in North America with IgAN are at higher risk for ESRD, we analyzed a cohort of 202 patients of self-reported Pacific Asian origin and 467 of other origin from the Toronto GN Registry followed up for a median of 46.4 months. The primary outcome of ESRD (dialysis, transplantation, or eGFR below 15) was analyzed using Cox regression analysis. Baseline eGFR was 59.6 ml/min/1.73 m(2), and median proteinuria was 1.8 g/day. ESRD occurred in 213 patients. By univariable analysis, the risk of ESRD was similar between the two groups (hazard ratio 0.98, 95% CI 0.73, 1.31); however, after adjusting for age, gender, eGFR, medication use, blood pressure, and proteinuria, the risk of ESRD was significantly higher in Pacific Asian individuals (hazard ratio 1.56, 95% CI 1.10, 2.22). This was supported by a significant 1.62 ml/min/1.73 m(2)/year faster rate of eGFR decline (95% CI -3.19, -0.5) and an increased risk of a reduction in eGFR by half (hazard ratio 1.81, 95% CI 1.25, 2.62). Thus, in a large multiracial cohort of patients with IgAN, individuals of Pacific Asian origin have a higher risk of progression to ESRD.

  14. Decreased Serum C3 Levels in Immunoglobulin A (IgA) Nephropathy with Chronic Kidney Disease: A Propensity Score Matching Study

    Science.gov (United States)

    Yang, Xi; Wei, Ri-bao; Wang, Yang; Su, Ting-Yu; Li, Qing-Ping; Yang, Ting; Huang, Meng-Jie; Li, Kun-Ying; Chen, Xiang-Mei

    2017-01-01

    Background The effects of low serum C3 levels and the activation of the complement system on the development and the prognosis of IgAN are unclear. The present study aimed to determine whether decreased levels of complement C3 influence the prognosis of IgAN patients with chronic kidney disease. Material/Methods We enrolled a total of 1564 patients with primary IgAN diagnosed by renal biopsy at the Chinese PLA General Hospital from January 2011 to March 2015. The endpoint was end-stage renal disease (ESRD) or a doubling of the baseline serum creatinine (D-SCr) level. All patients were using 1: 1 propensity score matching (PSM), and the baseline values were not significantly different between these 2 groups (P>0.05). Results During a follow-up period, 14 patients in the group with decreased C3 levels reached the endpoint, with 12 patients with normal C3 levels. There was no significant difference between the 2 groups in achieving D-SCr or ESRD (P=0.676). In multivariate Cox analysis, adjusted for demographic and laboratory examination, the risk of reaching the endpoint was comparable in the 2 groups (HR, 0.70; 95% CI, 0.27–1.78; P=0.449;). Furthermore, the risk of reaching ESRD (HR, 0.83; 95% CI, 0.25–2.75; P=0.757) and D-SCr (HR, 1.45; 95% CI, 0.20–10.60; P=0.718) did not differ between the 2 groups. Conclusions Decreased serum C3 levels in IgA nephropathy with chronic kidney disease did not play a decisive role in renal progression. PMID:28166191

  15. Osthole mitigates progressive IgA nephropathy by inhibiting reactive oxygen species generation and NF-κB/NLRP3 pathway.

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    Kuo-Feng Hua

    Full Text Available Renal reactive oxygen species (ROS and mononuclear leukocyte infiltration are involved in the progressive stage (exacerbation of IgA nephropathy (IgAN, which is characterized by glomerular proliferation and renal inflammation. The identification of the mechanism responsible for this critical stage of IgAN and the development of a therapeutic strategy remain a challenge. Osthole is a pure compound isolated from Cnidiummonnieri (L. Cusson seeds, which are used as a traditional Chinese medicine, and is anti-inflammatory, anti-apoptotic, and anti-fibrotic both in vitro and in vivo. Recently, we showed that osthole acts as an anti-inflammatory agent by reducing nuclear factor-kappa B (NF-κB activation in and ROS release by activated macrophages. In this study, we examined whether osthole could prevent the progression of IgAN using a progressive IgAN (Prg-IgAN model in mice. Our results showed that osthole administration resulted in prevention of albuminuria, improved renal function, and blocking of renal progressive lesions, including glomerular proliferation, glomerular sclerosis, and periglomerular mononuclear leukocyte infiltration. These findings were associated with (1 reduced renal superoxide anion levels and increased Nrf2 nuclear translocation, (2 inhibited renal activation of NF-κB and the NLRP3 inflammasome, (3 decreased renal MCP-1 expression and mononuclear leukocyte infiltration, (4 inhibited ROS production and NLRP3 inflammasome activation in cultured, activated macrophages, and (5 inhibited ROS production and MCP-1 protein levels in cultured, activated mesangial cells. The results suggest that osthole exerts its reno-protective effects on the progression of IgAN by inhibiting ROS production and activation of NF-κB and the NLRP3 inflammasome in the kidney. Our data also confirm that ROS generation and activation of NF-κB and the NLRP3 inflammasome are crucial mechanistic events involved in the progression of the renal disorder.

  16. Baseline proteinuria, urinary osmotic pressure, and renal function as positive predictors of corticosteroids plus cyclophosphamide treatment efficacy in IgA nephropathy

    Institute of Scientific and Technical Information of China (English)

    Fang Jing; Li Wenge; Li Duo; Tan Zhao

    2014-01-01

    Background Very limited data are available on factors predictive of corticosteroids plus cyclophosphamide treatment efficacy on IgA nephropathy (IgAN).The aim of the study was to research the clinical factors predictive of treatment efficacy in IgAN.Methods One hundred and fifty-nine patients with IgAN (proteinuria ≥2 g/d and estimated glomerular filtration rate 30-89 ml·min-1·1.73 m-2) were treated with corticosteroids/cyclophosphamide followed by a 12-month follow-up.According to their response,these patients were divided into remission group (proteinuria <0.5 g/d) and non-remission group (proteinuria ≥0.5 g/d),and their clinical data collected.Results In the present study,72.96% of the individuals underwent a complete remission,and their response was related to baseline proteinuria,urinary osmotic pressure,and renal function (P <0.05).Patients with baseline proteinuria more than 3 g/d,urinary osmotic pressure greater than 600 mOsm/L,and eGFR 60-89 ml·min-1·1.73 m-2 responded well to the combination of corticosteroids and cyclophosphamide (86.90% vs.57.33%,P=0.000; 81.48% vs.64.10%,P=0.014; 83.17% vs.55.17%,P=0.000).Conclusion The response to the combination of corticosteroids and cyclophosphamide might be well associated with baseline proteinuria,urinary osmotic pressure,and renal function in patients with IgAN.

  17. Genetic polymorphisms of the renin-angiotensin-aldosterone system in Chinese patients with end-stage renal disease secondary to IgA nephropathy

    Institute of Scientific and Technical Information of China (English)

    HUANG Hai-dong; LIN Fu-jun; LI Xin-juan; WANG Li-rui; JIANG Geng-ru

    2010-01-01

    Background Genetic variability in the renin-angiotensin-aldosterone system may modify renal responses to injury and disease progression. The angiotensin l-converting enzyme (ACE) gene insertion/deletion (l/D), the angiotensinogen (AGT) gene, M235T, the aldosterone synthase (CYP11B2) gene, C-344T, and the angiotensin Ⅱ type 1 receptor (AT1 R)gene, A1166C, have been shown to be associated with IgA nephropathy (IgAN) and its progression. We determined the presence of these polymorphisms in 130 Chinese patients with IgAN, including 47 patients with end-stage renal disease (ESRD) and 120 healthy Chinese subjects, to assess their impact on the susceptibility to disease and the liability of progression to ESRD.Methods Genotyping was performed with DNA isolated from peripheral leucocytes using polymerase chain reaction amplification of the polymorphic sequence, restriction enzyme digestion, and separation and identification of DNA fragments. Clinical data from renal biopsies were collected.Results ACE, AGT, CYP and AT1R genotype distributions were similar in patients with lgAN and in controls. Comparing patients with ESRD (IgAN-ESRD) and those without ESRD (IgAN-non ESRD), there was a significant increase only in the ACE DD genotype (P <0.05) among the four gene polymorphisms. There was significant dominance of the male (P <0.05), more marked hypertension (P <0.01), proteinuria (P <0.01) and increased serum creatinine during renal biopsy (P <0.01) in the IgAN-ESRD group.Conclusion Among the ACE, AGT, AT1R and CYP gene polymorphisms, only the DD genotype may predispose the individual to increased risk of progression to ESRD in the Chinese population.

  18. Association Between IFN-γ Gene Polymorphisms and IgA Nephropathy in a Chinese Han Population

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    Jie Gao

    2017-04-01

    Full Text Available Background/Aims: IFN-γ was reported to be involved in the development and progression of Immunoglobulin A nephropathy (IgAN, however, few studies have investigated the association between IFN-γ polymorphisms and IgAN. Therefore, we performed a case-control study to assess the association between IFN-γ polymorphisms and the risk of IgAN. Methods: Sequenom MassARRAY was used to genotype two SNPs (rs1861494 and rs2430561 in 351 patients with IgAN and 310 healthy controls. Associations were evaluated as odd ratios (OR with 95% confidence intervals (CI. Results: No association was found between IFN-γ rs1861494 and IgAN risk or clinical parameters. For rs2430561, the AA genotype was more common in patients with IgAN, compared with controls (AT vs. AA: OR = 0.57, P = 0.035. IFN-γ-rs2430561 T allele may be a protective factor for IgAN susceptibility (T vs. A: OR = 0.59, P = 0.04. Subgroup analysis based on clinical features revealed no significant association between rs2430561 polymorphism and clinical data such as gender, 24-h urine protein, blood pressure, Oxford classifcation and estimated glomerular fltration rate. IgAN patients had a higher IFN-γ serum level than healthy controls and patients with rs1861494 AA genotype had a higher IFN-γ serum level compared with those with AG/GG genotypes. Conclusions: IFN-γ polymorphisms may be involved in the development and progression of IgAN.

  19. The size of palatine tonsils cannot be used to decide the indication of tonsillectomy for IgA nephropathy

    Science.gov (United States)

    Adachi, Mika; Kosukegawa, Hideyuki; Nomura, Yuri; Watanabe, Kenichi; Sato, Toshinobu; Taguma, Yoshio

    2017-01-01

    Abstract Background. Tonsillectomy is one of the treatment strategies for immunoglobulin A nephropathy (IgAN). The relationship between the indication of tonsillectomy and the size of palatine tonsils (PTs) in patients with IgAN remains controversial. Methods. This retrospective cohort study investigated 57 patients with IgAN who underwent tonsillectomy combined with steroid pulse therapy (SPT). They were classified into two groups, the hypertrophy group and the nonhypertrophy group, according to the weight of their excised PTs. The effects of tonsillectomy combined with SPT on clinical remission (CR) and the histopathological findings of PTs were compared between the two groups. Results. During the mean follow-up period of 45.5 (range 6–133) months, 78.9% of the patients achieved CR (79.3 versus 78.6%, P = 0.945) and the baseline serum creatinine doubled only in one patient in the nonhypertrophy group (0 versus 3.6%, P = 0.491). No significant difference was observed in the incidence of CR between the two groups by the Kaplan–Meier method (P = 0.839). The predictor for CR, identified in Cox proportional hazards models, was baseline proteinuria [hazard ratio 0.14 (95% CI 0.032–0.621) P = 0.010]. Although macroscopic pus plugs were observed on the surface of PTs in almost 60% of patients in each group, microscopic pus plugs in the crypt and the enlarged interfollicular area were observed in all patients. Conclusions. The treatment effect of tonsillectomy combined with SPT and the pathological features of PTs in IgAN were equal, regardless of the size of the PTs. Therefore, the size of PTs should not be included as a factor when deciding the indication of tonsillectomy for IgAN. PMID:28396738

  20. Clinicopathological study of IgA nephropathy patients with microalbuminuria%微量白蛋白尿对于IgA肾病患者的临床、病理研究

    Institute of Scientific and Technical Information of China (English)

    郭宗运; 吴玉梅

    2014-01-01

    目的:总结表现为微量白蛋白尿的IgA肾病( IgAN)患者的临床及病理的特点,探讨微量白蛋白尿对于IgAN的病理改变及预后的影响。方法对90例微量白蛋白尿IgAN患者的临床和病理资料进行回顾性分析,探讨其相关性。结果90例临床表现为微量白蛋白尿的IgAN患者中,14例(15.6%)存在肾功能异常,18.4%的肾功能正常的患者中存在LeeⅢ级以上的病理损害,多因素logistic回归分析显示微量白蛋白尿是IgAN病理损伤的独立危险因素。结论微量白蛋白尿是IgAN病理损伤的独立危险因素,临床表现为微量白蛋白尿的IgAN患者的病理损伤亦可能较重,微量白蛋白尿可影响IgAN患者的预后。%Objective:To Summarize the clinicopathological features of IgA nephrology( IgAN)patients with microalbu-minuria and investigate the influence of microalbuminuria to IgA nephropathy pathological changes and prognosis. Methods:The clinical and pathological data of all IgAN patients with microalbuminuria was retrospectively analyzed,to discuss the correlation. Results:14 cases(15. 6%)of IgA nephrology(IgAN)patients with clinical manifestations included microalbu-minuria existed abnormal renal function,18. 4% of patients with normal renal function existed pathological damage accord-ing with Lee’s grade Ⅲ or more severe. Multifactor logistic regression analysis revealed that microalbuminuria was inde-pendent risk factors for renal pathological lesions of IgA nephropathy. Conclusions:Microalbuminuria is independent risk factors for renal pathological lesions of IgA nephropathy,severe renal histological injury may be seen in some IgAN patients with microalbuminuria,and microalbuminuria effects the prognosis of these patients.

  1. Recombinant human immunoglobulin (Ig)A1 and IgA2 anti-D used for detection of IgA deficiency and anti-IgA

    DEFF Research Database (Denmark)

    Nielsen, Leif K; Dziegiel, Morten Hanefeld

    2008-01-01

    To avoid anaphylactic reactions, immunoglobulin (Ig)A-deficient patients with anti-IgA should be transfused with IgA-deficient blood components. There is a need for fast and robust assays for demonstration of IgA deficiency and for detection of anti-IgA.......To avoid anaphylactic reactions, immunoglobulin (Ig)A-deficient patients with anti-IgA should be transfused with IgA-deficient blood components. There is a need for fast and robust assays for demonstration of IgA deficiency and for detection of anti-IgA....

  2. Research progress of galactose - deficient IgA1 antibodies in diagnosis and treatment of IgA nephropathy%异常糖基化IgA1抗体在IgA肾病诊治中的作用研究进展

    Institute of Scientific and Technical Information of China (English)

    张红; 周楠; 沈颖

    2016-01-01

    研究发现,异常糖基化 IgA1抗体是导致 IgA 肾病(IgAN)发病的重要机制之一。该抗体水平与IgAN 患者蛋白尿水平及肾脏病变程度有显著相关性,检测该抗体对 IgAN 的诊断具有指导价值,其敏感性和特异性可分别达到88%~89%及92%~95%。该抗体对评估临床预后具有指导意义,现对其在 IgAN 诊治的作用进行综述,为治疗 IgAN 提供新方向。%In recent years,studies have shown that galactose - deficient IgA1(Gd - IgA1)antibodies are im-portant in the pathogenesis of IgA nephropathy(IgAN). Serum levels of Gd - IgA1 antibodies are associated with levels of proteinuria and renal histological grading. Measuring the antibodies has guidance value in the diagnosis of IgAN,for its sensitivity and specificity can be up to 88% - 89% and 89% - 92% respectively. In addition,the antibodies play an important role in clinical prognosis,and it may provide a new direction for treatment in IgAN. Now,its role in prognosis of IgAN was reviewed.

  3. 免疫球蛋白A肾病中免疫球蛋白A与乙型肝炎病毒抗原关系的研究%Correlation between immunoglobulin A and HBVAg in IgA nephropathy

    Institute of Scientific and Technical Information of China (English)

    姚舒蕾; 王晨; 高丽芳; 张晓琴; 卫建平

    2016-01-01

    Objective To investigate the correlation between imumnoglobulin A (IgA) of IgA nephropathy (I-gAN) in kidney tissues and hepatitis B virus antigens (HBVAg), and serum IgA, respectively. Methods The IgA pre-cipitation in glomerular of 66 different types of IgAN was determined by immunofluorescence double staining and laser confocal microscopy. The status of HBsAg and HBcAg were determined by two-step immunohistochemistry in 66 cases of IgAN tissues. The correlation between IgA precipitation and HBVAg infection and serum IgA was examined and compared, respectively. Results Immunofluorescence double staining showed that IgA was mainly in the glomerular mesangial area. A small amount of IgA granular deposition was found in the capillary loop. The precipita-tion of IgA in positive HBVAg kidney tissues was significantly higher than that in the negative HBVAg group ( P<0.05) and control group (P<0.05), which was correlated with the degree of renal lesions. There was no statistically significant difference between IgA precipitation and serum IgA in IgAN tissues. Conclusion The development of IgAN may be correlated with IgA precipitation in positive HBVAg kidney tissues with IgAN. The concentration of serum IgA may not be the decisive factor in the occurrence of IgAN.%目的:观察免疫球蛋白A肾病(IgAN)肾组织中的IgA与乙型肝炎病毒(HBV)抗原(HBVAg)及血清IgA之间的关系。方法用免疫荧光双套染技术配合激光共聚焦显微镜观察IgA在66例不同类型IgAN肾小球中的沉积量;免疫组织化学二步法检测66例IgAN肾组织HBV表面抗原(HBsAg)、HBV核心抗原(HBcAg),对比研究IgA沉积量与HBVAg感染及血清IgA的关系。结果免疫荧光双套染法显示IgA主要在肾小球系膜区、少量在毛细血管袢呈颗粒状沉积;HBVAg阳性的肾组织IgA沉积量明显高于HBVAg阴性组(P<0.05)与对照组(P<0.05),且与肾脏病变程度有关。 IgA肾病肾组织中IgA沉积

  4. Urinary peptidomics provides a noninvasive humanized readout of diabetic nephropathy in mice.

    Science.gov (United States)

    Klein, Julie; Ramirez-Torres, Adela; Ericsson, Anette; Huang, Yufeng; Breuil, Benjamin; Siwy, Justyna; Mischak, Harald; Peng, Xiao-Rong; Bascands, Jean-Loup; Schanstra, Joost P

    2016-11-01

    Nephropathy is among the most frequent complications of diabetes and the leading cause of end-stage renal disease. Despite the success of novel drugs in animal models, the majority of the subsequent clinical trials employing those drugs targeting diabetic nephropathy failed. This lack of translational value may in part be due to an inadequate comparability of human disease and animal models that often capture only a few aspects of disease. Here we overcome this limitation by developing a multimolecular noninvasive humanized readout of diabetic nephropathy based on urinary peptidomics. The disease-modified urinary peptides of 2 type 2 diabetic nephropathy mouse models were identified and compared with previously validated urinary peptide markers of diabetic nephropathy in humans to generate a classifier composed of 21 ortholog peptides. This classifier predicted the response to disease and treatment with inhibitors of the renin-angiotensin system in mice. The humanized classifier was significantly correlated with glomerular lesions. Using a human type 2 diabetic validation cohort of 207 patients, the classifier also distinguished between patients with and without diabetic nephropathy, and their response to renin-angiotensin system inhibition. Thus, a combination of multiple molecular features common to both human and murine disease could provide a significant change in translational drug discovery research in type 2 diabetic nephropathy.

  5. 37例儿童IgA肾病临床与病理分析%Clinical and pathological features of 37 children with IgA nephropathy

    Institute of Scientific and Technical Information of China (English)

    周纬; 陈难

    2001-01-01

    为了探讨IgA肾病的临床与病理改变的关系,对37例IgA肾病进行临床分型并与肾小球、肾小管间质改变及免疫病理特点的关系进行比较。结果:临床分型中单纯血尿(血尿)18例占49%,肾病综合征(肾病)14例占38%,血尿和蛋白尿3例占8%,肾炎综合征(肾炎)2例占5%。肾小球病理损害以III级为主占54%,临床各型与肾小球病理损害无相关性。肾小管间质改变24例,血尿组7例占39%,其中I级为43%,II级为57%。肾病组均有改变,其中II级11例占78%,III级3例占22%。血尿和蛋白尿组2例占66%,肾炎组1例占50%。免疫病理改变为IgA 16例,IgAG 6例,IgAM 10例,IgAGM 5例。血尿组以单纯IgA沉积为主占66%,肾病组则以IgAM型为主占50%。提示IgA肾病临床以单纯血尿为主,其次为肾病综合征;肾小球病理损害程度与临床分型无相关性,但肾病组肾小管间质均有改变且程度也较血尿组为重。免疫病理血尿组以单纯IgA为主,而肾病组以IgAM为主。%To explore the relationship between clinical findings and pathological changes of IgA nephropathy (IgAN), 37 children with IgAN were undertaken clinical classification and renal-pathological comparison including glomerulus change, renal tubule-interstitial change and immunopathology. The results showed that there were 18 (49%) cases with hematuria, 14 (38%) cases with nephrotic syndrome, 3(8%) cases with both of hematuria and proteineuria, and 2 (5%) cases with nephritic syndrome in the clinical classification. 54% of cases with glomerulus changes was as class III. No significant relationship was found between clinical classification and glomerulus changes. There were 24 cases with renal-tubule interstitial changes and 7 cases with hematuria. 43% of them were classified as class I and 57% as class II.All cases with nephrotic syn-drome developed renal tubule-interstitial change. 78% (11 cases) of them were as class II and 22

  6. Low Birth Weight and Risk of Progression to End Stage Renal Disease in IgA Nephropathy-A Retrospective Registry-Based Cohort Study.

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    Paschal Ruggajo

    Full Text Available Low Birth Weight (LBW is a surrogate for fetal undernutrition and is associated with impaired nephron development in utero. In this study, we investigate whether having been born LBW and/or small for gestational age (SGA predict progression to ESRD in IgA nephropathy (IgAN patients.Retrospective registry-based cohort study.The Medical Birth Registry has recorded all births since 1967 and the Norwegian Renal Registry has recorded all patients with ESRD since 1980. Based on data from the Norwegian Kidney Biopsy Registry we included all patients diagnosed with IgAN in Norway from 1988-2013. These registries were linked and we analysed risk of progression to ESRD associated with LBW (defined as birth weight less than the 10th percentile and/or SGA (defined as birth weight less than the 10th percentile for gestational week by Cox regression statistics.We included 471 patients, of whom 74 developed ESRD. As compared to patients without LBW, patients with LBW had a hazard ratio (HR of 2.0 (95% confidence interval 1.1-3.7 for the total cohort, 2.2 (1.1-4.4 for males and 1.3 (0.30-5.8 for females. Corresponding HRs for SGA were 2.2 (1.1-4.2, 2.7 (1.4-5.5 and 0.8 (0.10-5.9. Further analyses showed that as compared to patients with neither LBW nor SGA, patients with either SGA or LBW did not have significantly increased risks (HRs of 1.3-1.4 but patients who were both LBW and SGA had an increased risk (HR 3.2 (1.5-6.8.Mean duration of follow-up only 10 years and maximum age only 46 years.Among IgAN patients, LBW and/or SGA was associated with increased risk for progression to ESRD, the association was stronger in males.

  7. In IgA Nephropathy, Glomerulosclerosis Is Associated with Increased Urinary CD80 Excretion and Urokinase-Type Plasminogen Activator Receptor-Positive Podocyturia

    Directory of Open Access Journals (Sweden)

    Hernán Trimarchi

    2017-05-01

    Full Text Available Background: Podocyturia may determine the evolution to podocytopenia, glomerulosclerosis, and renal failure. According to the Oxford classification of IgA nephropathy (IgAN, the S1 lesion describes glomerulosclerosis. Urokinase-type plasminogen activator receptor (uPAR participates in podocyte attachment, while CD80 increases in glomerulosclerosis. We measured uPAR-positive urinary podocytes and urinary CD80 (uCD80 in controls and in IgAN subjects with M1E0S0T0 and M1E0S1T0 Oxford scores to assess a potential association between podocyturia, inflammation, and glomerulosclerosis. Methods: The groups were as follows: controls (G1, n = 20 and IgAN group (G2, n = 39, subdivided into M1E0S0T0 (G2A, n = 21 and M1E0S1T0 (G2B, n = 18. Among the included variables, we determined uPAR-positive podocytes/gram of urinary creatinine (gUrCr and uCD80 ng/gUrCr. Biopsies with interstitial fibrosis and tubular atrophy <10% were included. Results: Groups were not different in age and gender; urinary protein-creatinine (uP/C ratio, Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI equation, uPAR-positive podocytes/gUrCr, and uCD80 were significantly increased in G2 versus G1. G2A and G2B were not different in age, gender, hypertension, and follow-up. G2B displayed significantly higher uP/C, uPAR-positive podocytes, uCD80, and lower CKD-EPI versus G2A. Strong significant correlations were encountered between uCD80 and podocyturia in G2A and G2B. However, when G1 was compared to G2A and G2B separately, the differences with respect to uP/C, uPAR-positive podocytes, and podocyturia were significantly stronger versus G2B than versus G2A. Conclusions: IgAN presents elevated uCD80 excretion and uPAR-positive podocyturia, while CD80 correlates with podocyturia. Glomerulosclerosis (S1 at the time of biopsy is associated with higher uP/C, lower renal function, increased uPAR-positive podocyturia, and CD80 excretion, and is independent of M1. In IgAN, uPAR may

  8. Levels and complexity of IgA antibody against oral bacteria in samples of human colostrum.

    Science.gov (United States)

    Petrechen, L N; Zago, F H; Sesso, M L T; Bertoldo, B B; Silva, C B; Azevedo, K P; de Lima Pereira, S A; Geraldo-Martins, V R; Ferriani, V P L; Nogueira, R D

    2015-01-01

    Streptococcus mutans (SM) have three main virulence antigens: glucan binding protein B (gbpB), glucosyltransferase (Gtf) and antigens I/II (Ag I/II) envolved in the capacity of those bacteria to adhere and accumulate in the dental biofilm. Also, the glycosyltransferases 153 kDa of Streptococcus gordonii (SGO) and 170kDa of Streptococcus sanguinis (SSA) were important antigens associated with the accumulation of those bacterias. Streptococcus mitis (SMI) present IgA1 protease of 202 kDa. We investigated the specificity and levels IgA against those antigens of virulence in samples of human colostrum. This study involved 77 samples of colostrum that were analyzed for levels of immunoglobulian A, M and G by Elisa. The specificity of IgA against extracts of SM and initials colonizators (SSA, SMI, SGO) were analyzed by the Western blot. The mean concentration of IgA was 2850.2 (±2567.2) mg/100 mL followed by IgM and IgG (respectively 321.8±90.3 and 88.3±51.5), statistically different (pbacteria antigens and theirs virulence antigens. To SM, the GbpB was significantly lower detected than others antigens of SM (p0.4). So, the breast milk from first hours after birth presented significant levels of IgA specific against important virulence of antigens those oral streptococci, which can disrupt the installation and accumulation process of these microorganisms in the oral cavity. Copyright © 2014 Elsevier GmbH. All rights reserved.

  9. Relationship of the quaternary structure of human secretory IgA to neutralization of influenza virus

    Science.gov (United States)

    Suzuki, Tadaki; Kawaguchi, Akira; Ainai, Akira; Tamura, Shin-ichi; Ito, Ryo; Multihartina, Pretty; Setiawaty, Vivi; Pangesti, Krisna Nur Andriana; Odagiri, Takato; Tashiro, Masato; Hasegawa, Hideki

    2015-01-01

    Secretory IgA (S-IgA) antibodies, the major contributors to humoral mucosal immunity to influenza virus infection, are polymeric Igs present in many external secretions. In the present study, the quaternary structures of human S-IgA induced in nasal mucosa after administration of intranasal inactivated influenza vaccines were characterized in relation to neutralization potency against influenza A viruses. Human nasal IgA antibodies have been shown to contain at least five quaternary structures. Direct and real-time visualization of S-IgA using high-speed atomic force microscopy (AFM) demonstrated that trimeric and tetrameric S-IgA had six and eight antigen-binding sites, respectively, and that these structures exhibited large-scale asynchronous conformational changes while capturing influenza HA antigens in solution. Furthermore, trimeric, tetrameric, and larger polymeric structures, which are minor fractions in human nasal IgA, displayed increased neutralizing potency against influenza A viruses compared with dimeric S-IgA, suggesting that the larger polymeric than dimeric forms of S-IgA play some important roles in protection against influenza A virus infection in the human upper respiratory tract. PMID:26056267

  10. Relationship of the quaternary structure of human secretory IgA to neutralization of influenza virus.

    Science.gov (United States)

    Suzuki, Tadaki; Kawaguchi, Akira; Ainai, Akira; Tamura, Shin-ichi; Ito, Ryo; Multihartina, Pretty; Setiawaty, Vivi; Pangesti, Krisna Nur Andriana; Odagiri, Takato; Tashiro, Masato; Hasegawa, Hideki

    2015-06-23

    Secretory IgA (S-IgA) antibodies, the major contributors to humoral mucosal immunity to influenza virus infection, are polymeric Igs present in many external secretions. In the present study, the quaternary structures of human S-IgA induced in nasal mucosa after administration of intranasal inactivated influenza vaccines were characterized in relation to neutralization potency against influenza A viruses. Human nasal IgA antibodies have been shown to contain at least five quaternary structures. Direct and real-time visualization of S-IgA using high-speed atomic force microscopy (AFM) demonstrated that trimeric and tetrameric S-IgA had six and eight antigen-binding sites, respectively, and that these structures exhibited large-scale asynchronous conformational changes while capturing influenza HA antigens in solution. Furthermore, trimeric, tetrameric, and larger polymeric structures, which are minor fractions in human nasal IgA, displayed increased neutralizing potency against influenza A viruses compared with dimeric S-IgA, suggesting that the larger polymeric than dimeric forms of S-IgA play some important roles in protection against influenza A virus infection in the human upper respiratory tract.

  11. Detection of IL-6 in human milk and its involvement in IgA production.

    Science.gov (United States)

    Saito, S; Maruyama, M; Kato, Y; Moriyama, I; Ichijo, M

    1991-09-01

    A large amount of interleukin-6 (IL-6) was found to be contained in human whey. The concentration of IL-6 in colostrum was significantly higher than that in serum or in milk taken 1 month after parturition. Colostrum contained many more mononuclear cells than late milk. In terms of the proportion of monocytes, T cells and B cells, however, there is no difference between colostrum and late milk. There is a significantly positive correlation between the concentration of IL-6 and the number of mononuclear cells in milk. This demonstrates that IL-6 in whey is derived in part from mononuclear cells. Stimulation of human milk mononuclear cells by Staphylococcus aureus Cowan I in the presence of anti-IL-6 antibody markedly decreased the production of IgA. This suggests that IL-6 contained in milk is closely associated with the local production of IgA in the breast.

  12. Inhibition of Entamoeba histolytica proteolytic activity by human salivary IgA antibodies.

    Science.gov (United States)

    Guerrero-Manríquez, G G; Sánchez-Ibarra, F; Avila, E E

    1998-11-01

    Entamoeba histolytica is a protozoan parasite that causes amoebiasis in humans; as the infection occurs mainly in the intestinal epithelium, the secretory immune response of the host could have an influence on the outcome. Secretory IgA antibodies against E. histolytica have been detected in asymptomatic and symptomatic patients, but little is known about their protective role. E. histolytica cysteine proteases seem to be involved in the pathogenesis of amoebiasis; therefore, it is important to evaluate the human IgA response against these proteases and its effect on their enzymatic activity. When human saliva samples with and without antibodies against E. histolytica were tested by Western blot against one purified 70 kDa amoebic cysteine protease, 84% of anti-amoeba-positive samples recognized it. The secretory IgA purified from a pool of anti-protease-positive samples had a strong in vitro inhibitory effect on the E. histolytica proteolytic activity. These results suggest that this effect, if it occurs in vivo, could be an important protective factor against this parasite.

  13. IgA antibodies to Toxoplasma gondii in human tears

    NARCIS (Netherlands)

    Meek, B.; Klaren, V.N.A.; Haeringen, van N.J.; Kijlstra, A.; Peek, R.

    2000-01-01

    PURPOSE. To investigate whether mucosal immune responses directed against the ubiquitous parasite Toxoplasma gondii can be detected in tears of healthy humans. METHODS. Nonstimulated tears and blood were obtained from 62 healthy humans (mean age, 35 ± 10 [SD] years). Serum anti-T. gondii immunoglobu

  14. Human renal medullary interstitial cells and analgesic nephropathy.

    Science.gov (United States)

    Whiting, P H; Tisocki, K; Hawksworth, G M

    1999-01-01

    The aim of this study was to investigate the effects of known papillotoxins using cultures of human renal interstital medullary cells (hRMIC). The culture of hMIC was based on the primary culture of human renal medullary explants, selective detachment of interstitial cells and selective overgrowth of these cells in a serum-rich medium after dilution cloning. The homogeneous population of cells obtained exhibited the characteristic morphological and functional characteristics of Type I interstitial cells, viz. stellate-shaped cells demonstrating numerous lipid droplets, abundant endoplasmic reticulum and mitochondria, fine filaments underlying the cell membrane and the production of extracellular matrix. Cytotoxicity studies using hMIC and known papillotoxins clearly demonstrated a reduction in cell viability that varied with bath exposure time and type of agent tested. While only phenylbutazone and mefenamic acid produced significant cytotoxicity after a 24 h incubation period, cell viability assessed using the MTT assay was only profoundly reduced by aspirin and paracetamol following sub-chronic exposure for 7 days. The rank order of cytotoxicity observed in hMIC was phenylbutazone > mefenamic acid > aspirin > paracetamol. The results demonstrate the potential of hMIC for investigating and defining the early cellular events in the pathogenesis of analgesic nephropathy.

  15. Interstitial nephritis and interstitial nephropathy

    Institute of Scientific and Technical Information of China (English)

    1992-01-01

    920710 A study of the cytomegalovirus-DNA in serum and renal tissue of patients-with IgA nephropathy. LIU Zhihong(刘志红),et al. Dept Nephrol, Jinling Hosp,Nanjing,210002. Nail Med J China 1992; 72(4): 198-200. Cytomegalovirus (CMV) has been suspectedto be involved in the pathogenesis of IgA nep-

  16. Tubule-interstitial lesions in children with IgA nephropathy%肾小管间质损害在儿童IgA肾病中的临床意义

    Institute of Scientific and Technical Information of China (English)

    李艳红; 汪清

    2013-01-01

    目的 探讨肾小管间质损害在儿童IgA肾病中的临床意义.方法 分析住院的IgA肾病患儿的临床与病理资料,探讨IgA肾病患儿的肾小管间质损害与临床、实验室指标及其他病理参数的关系.结果 98例符合IgA肾病诊断标准的患儿中,23例未见肾小管间质损害,56例患儿存在肾小管间质轻度损害,19例存在重度损害.与无肾小管间质损害的患儿比较,肾小管间质损害患儿的病情加重,表现为血清白蛋白水平下降和血肌酐及尿素氮水平增高(P<0.05).病理可见随着肾小管间质损害程度的加重,肾小球损害程度亦加重,表现为肾小球硬化发生率逐渐增多,以及评价肾小球总体损害的积分逐渐增高(P<0.05).结论 IgA肾病患儿的肾小管间质损害与肾小球病变程度相平行,随着肾小管间质损害程度的加重,IgA肾病患儿的病情亦逐渐加重,提示肾小管间质损害与肾小球病变直接相关,肾小管间质损害可能是影响儿童IgA肾病预后不良的因素之一.%Objective To explore the clinical significance of tubule-interstitial lesions (TIL) in children with IgA nephropathy. Methods 98 children with biopsy-proven IgA nephropathy were enrolled in this study, 56 with mild TIL, 19 with severe, and 23 without TIL. Data regarding clinical and laboratory features were obtained. Semi-quantitative scores for glomerular and tubulointerstitial damage were used to evaluate renal histological lesions. Results There was a significant decrease in serum creatinine and urea nitrogen, but an increase in serum albumin, in patients with TIL compared with patients without TIL. TIL was significantly associated with increased severity of glomerular damage. Conclusion TIL correlates well with clinical and histological features in children with IgA nephropathy, which suggests TIL may be one of the factors that predispose children with IgA nephropathy to develop into end-stage renal failure.

  17. 伴有肉眼血尿的IgA肾病患者临床特点分析%Study on clinical features of idiopathic IgA nephropathy with gross hematuria

    Institute of Scientific and Technical Information of China (English)

    刘玺; 沈明静; 缪蕙

    2012-01-01

    Objective To study the clinical features of idiopathic IgA nephropathy with gross hematuria. Methods Seventy six patients with IgA nephropathy diagnosed by renal biopsy were divided into study group and control group according to whether with gross hematuria or not. Twenty two patients with gross hematuria were allocated in study group; and 54 patients without gross hematuria were allocated in control group. Katafuchi semi - quantitative analysis had been applied for determination of the severity of renal lesions in patients, and it combined with clinical features had been applied to analyze the characteristics of pathological changes and clinical characteristics of patients. Results ①Patients in study group were significantly higher in precursory infection rate, incidence of hypertension was lower than that of control group, serum level of creatinine was lower than that of control group, and mean duration of disease was shorter than that of control group ( P 0. 05 ). ② Scores of renal pathology, vascular scores, and scores of glomerular sclerosis and thickening of vessel wall were lower than those of control group ( P 0.05).②研究组患者肾脏病理积分、血管积分、球硬化积分及血管壁增厚积分低于对照组(P<0.05).结论 伴有肉眼血尿的IgA肾病患者发病期多伴有前驱感染,病程中高血压发生率、血肌酐水平较不伴有肉眼血尿的IgA肾病患者低.病理改变较不伴有肉眼血尿的IgA肾病轻,预后相对较好.

  18. 他克莫司在难治性IgA肾病中的疗效观察%Tacrolimus in treatment of refractory IgA nephropathy:a clinical observation

    Institute of Scientific and Technical Information of China (English)

    廖丹; 肖欢; 姜丹; 张林

    2013-01-01

    Object:To observe the efficacy and safety of the combined application of Tacrolimus and moderate dose glucocorticoid in the treatment of refractory IgA nephropathy.Method:Forty-three patients with refractory IgA nephropathy were randomized to the single Glucocorticoids group(Prednisone 30 mg•d-1) and drug combination group(combined medication of Prednisone 30 mg•d-1 and Tacrolimus 1 mg•d-1). The blood trough concentration of tacrolimus was maintained at 3-7ng•dl-1. Before and after treatment of 4 weeks, 12 weeks and 24 weeks, the detection result including 24-hour urinary protein excretion, Urinary red blood cellcount, Urine specific gravity, CCr, BUN, Cr, TP, ALB, AST, ALT, GLU and the Adverse Reaction, were recorded and analyzed.Result:To the contrast, in BUN、Cr、TP、AST、ALT and GLU, there were no difference between the groups (P >0.05). Compared with the single Glucocorticoids group, 24-hour urinary protein excretion, Urinary red blood cellcount, Onset time, Complete remission rate and ALB were significantly bet er in drug combination group (P0.05)。联合治疗组24小时尿蛋白定量、尿红细胞计数、起效时间、完全缓解率、ALB和单纯激素组比较具有统计学意义(P<0.01)。结论:采用他克莫司联合中等剂量糖皮质激素治疗难治性IgA肾病的治疗效果更为显著,无明显不良反应发生,为难治性IgA肾病的治疗提供了新的方向。

  19. Immunology of membranous nephropathy: from animal models to humans.

    Science.gov (United States)

    Sinico, R A; Mezzina, N; Trezzi, B; Ghiggeri, G M; Radice, A

    2016-02-01

    Membranous nephropathy (MN), the leading cause of nephrotic syndrome in adults, is characterized by the deposition of subepithelial immune deposits that consist mainly of immunoglobulin (Ig)G and complement. Most of the cases are primary or idiopathic (iMN), while only approximately 25% of the cases are secondary to some known disease such as systemic lupus erythematosus, hepatitis B, drugs and malignancies. Most of our knowledge on the pathogenesis of iMN has relied upon old experimental models (i.e. Heymann nephritis) that have shown that immune deposits are formed in situ by the reaction of autoantibodies against the respective podocyte antigen. Recent findings indicate that podocyte proteins also act as an autoantigen in human iMN. The M-type phospholipase A2 receptor (PLA2R) has been identified as the main target antigen, as it can be found in approximately 70% of iMN patients but only rarely in other glomerulonephritides. Podocytes damage in the experimental model of Heymann nephritis is complement-mediated. In humans, the presence of complement within the subepithelial deposits is well established, but IgG4, which does not activate complement by classical or alternative pathways, represents the predominant subclass of IgG anti-PLA2R. Some evidence suggests that IgG4 anti-PLA2R autoantibodies can bind mannan-binding lectin (MBL) and activate the lectin complement pathway. A genetic background for iMN has been demonstrated by genome-wide association studies that have shown highly significant associations of the PLA2R1 and the human leucocyte antigen (HLA)-DQA1 loci with iMN. In addition to their diagnostic value, anti-PLA2R antibodies may be useful to monitor disease activity and predict response to treatment.

  20. Preliminary application of virtual touch tissue quantification imaging in diagnosis of IgA nephropathy%声触诊组织定量技术在系膜增生型IgA肾病诊断中的应用

    Institute of Scientific and Technical Information of China (English)

    梁晓宁; 郭瑞君; 李硕; 张颖; 张岩; 孙宏

    2015-01-01

    目的:探讨声触诊组织定量技术(VTQ)对系膜增生型IgA肾病的诊断价值。方法收集2013年12月至2014年7月在首都医科大学附属北京朝阳医院肾内科住院,被诊断为IgA肾病的患者85例,排除病情危重者、无法配合检查者、病理类型为非系膜细胞增生性IgA肾病者,最终入组54例系膜细胞增生型IgA肾病患者,108个肾脏。选取体检的健康志愿者54例,共计108个肾脏,作为健康对照组。使用VTQ技术分别测量健康对照组与系膜细胞增生型IgA肾病患者双肾中部肾实质及集合系统VTQ的SWV值,并进行比较。结果健康对照组双肾中部肾实质与集合系统的SWV值分别为(2.13±0.13)m/s、(1.15±0.02) m/s;IgA肾病组双肾中部肾实质与集合系统的SWV值分别为(3.07±0.62) m/s、(1.12±0.29) m/s。健康对照组肾实质与IgA肾病组肾实质SWV值比较,差异有统计学意义(t=-14.481,P0.05);健康对照组肾实质与集合系统SWV值比较,差异有统计学意义(t=-54.01,P<0.01);IgA肾病组肾实质与集合系统SWV值比较,差异有统计学意义(t=26.09,P<0.01)。伴随肾功能不全的加重,慢性肾病患者肾实质SWV值呈递增趋势(F=798.70, P<0.001)。叶间动脉阻力指数随慢性肾病1、2、3、4期逐渐增大。结论 VTQ技术对评价IgA肾病肾功能损害程度有一定诊断价值,为早期提示肾功能减低及判断其临床分期提供一个新的观察指标。%Objective To evaluate the value of virtual touch quantization (VTQ) imaging in diagnosis of IgA nephropathy. Methods The clinical data of 85 patients with IgA nephropathy were analyzed, who were treated in Capital Medical University Affiliate Beijing Chaoyang Hospital from December 2013 to July 2014. The patients who was with critical condition, unable to cooperate and with other pathological types were excluded. Finally 108 kidneys of IgA nephropathy with

  1. Expression of monocyte chemoattractant protein-1 in IgA nephropathy and its significance%IgA 肾病患者肾脏 MCP-1的表达及意义

    Institute of Scientific and Technical Information of China (English)

    钱白音; 吴锡信; 麦美芳; 张桦; 李中和; 崔彤霞

    2014-01-01

    Objective To evaluate the role of monocyte chemoattractant protein-1(MCP-1) in the mechanism of pro-gression of IgA nephropathy.Methods A total of 34 patients with biopsy proven IgA nephropathy were studied.The ex-pression of MCP-1 in renal tissues were detected by immunohistochemical staining method; the levels of serum creatinine ( Scr) were examined by sarcosine oxidase method;MCP-1 expression in renal tissue in patients with different degree of tu-bulointerstitial lesions and different levels of Scr were compared.Molecular weight of urinary protein were detected by sodi-um dodecyl sulfate-polyacrylamide gel electrophoresis( SDS-PAGE) , and were further typed;MCP-1 expression in renal tis-sue in patients with different molecular weight of urinary protein were compared.And the relationship between the MCP-1 expression and the twenty-four-hour urine protein quantitation in patients with IgA nephropathy was analyzed by pearson cor-relation analysis.Results MCP-1 expression was mainly in renal tubular epithelial cells of IgA nephropathy patients, and was in positive correlation to twenty-four-hour urine protein quantitation (r=0.34,P140μmol/L group than Scr≤140μmol/L group (P<0.05), and was significantly higher in 10 kD proteinuria group than 23 kD proteinuria group (P<0.05).Conclusion MCP-1 may play an important role in the progression of IgA nephropathy.Low molecular weight urinary protein such as 10 kD protein may have close relationship with the expression of MCP-1 in renal tissue of IgA nephropathy.%目的:观察IgA肾病患者肾脏单核细胞趋化蛋白-1(MCP-1)表达变化,并探讨其作用。方法用免疫组织化学染色法检测34例同步行肾活检诊断明确的IgA肾病患者肾脏MCP-1表达,用肌氨酸氧化酶法检测血清肌酐( Scr),比较不同程度肾小管间质病变及不同血清肌酐水平患者MCP-1的差异。用SDS-PAGE法检测尿蛋白分子量,并进一步分型,对不同

  2. Immunoglobulins in nasal secretions of healthy humans: structural integrity of secretory immunoglobulin A1 (IgA1) and occurrence of neutralizing antibodies to IgA1 proteases of nasal bacteria

    DEFF Research Database (Denmark)

    Kirkeby, L; Rasmussen, TT; Reinholdt, Jesper

    2000-01-01

    Certain bacteria, including overt pathogens as well as commensals, produce immunoglobulin A1 (IgA1) proteases. By cleaving IgA1, including secretory IgA1, in the hinge region, these enzymes may interfere with the barrier functions of mucosal IgA antibodies, as indicated by experiments in vitro....... Previous studies have suggested that cleavage of IgA1 in nasal secretions may be associated with the development and perpetuation of atopic disease. To clarify the potential effect of IgA1 protease-producing bacteria in the nasal cavity, we have analyzed immunoglobulin isotypes in nasal secretions of 11...... healthy humans, with a focus on IgA, and at the same time have characterized and quantified IgA1 protease-producing bacteria in the nasal flora of the subjects. Samples in the form of nasal wash were collected by using a washing liquid that contained lithium as an internal reference. Dilution factors and...

  3. Lectin-based analysis of fucose and sialic acid expressions on human amniotic IgA during normal pregnancy.

    Science.gov (United States)

    Orczyk-Pawiłowicz, Magdalena; Augustyniak, Daria; Hirnle, Lidia; Kątnik-Prastowska, Iwona

    2013-08-01

    The sugar moiety of IgA is known to provide a link between the innate and adaptive immune systems. Terminally located glycotopes on IgA are potential ligands engaged in the interactions which may modulate the biological activities of IgA. In the present work the expressions of Maackia amurensis (MAA), Sambucus nigra (SNA), Lens culinaris (LCA), Tetragonolobus purpureus (LTA), and Ulex europaeus (UEA) reactive glycotopes on maternal plasma and amniotic IgA were evaluated in relation to the progression of a normal human pregnancy, from the 2nd trimester, throughout the 3rd trimester, perinatal period, post-date pregnancy and delivery, by lectin-IgA-ELISA, using specific biotinylated lectins. The amniotic and maternal plasma IgA concentrations and a degree of SNA and LCA reactivity of maternal plasma IgA were almost unaltered during the normal pregnancy. The amniotic IgA from the 2nd trimester was decorated by MAA-, SNA-reactive and LCA-, LTA-, and UEA-reactive glycotopes. At the turn of the 2nd and 3rd trimesters the expression of MAA-, SNA-, LTA-, and UEA-reactive glycotopes, except for LCA-reactive, increased and remained almost at unaltered levels throughout the perinatal period and delivery. However, in the post-date pregnancy the expression of LCA-, LTA-, and UEA-reactive and SNA-reactive glycotopes were significantly higher. The unique fucosylated and sialylated glycovariants of amniotic IgA associated with the progression of the normal pregnancy may illustrate a general importance of carbohydrate-lectin receptor interactions in the control and modulation of biological events to ensuring homeostasis during pregnancy, protection and well-being of fetus.

  4. A study of the association of human secretory component with IgA and IgM proteins.

    Science.gov (United States)

    Weicker, J; Underdown, B J

    1975-04-01

    Human secretory component (SC) was isolated from colostral whey, and the binding of 125I-SC to purified IgA and IgM monoclonal proteins was studied using two methods to separate free from immunoglobulin-bound 125I-SC: a) gel filtration on Sephadex G-200, and b) precipitation of 125I-SC-Ig complexes with anti-Ig antibody. Both IgA dimeric proteins and IgM pentamers bound 125I-SC with approximately one SC-binding site per mole of polymer and similar affinity. Assuming a reversible equilibrium, an apparent association constant congruent to 10-8 M-1 was calculated to govern the binding of 125I-SC to immunoglobulin polymers. The assignment of a single association constant may be an oversimplication, particularly for the case of IgA polymers, since evidence was obtained that disulfide bonds were formed in the 125I-SC-IgA complex. Despite the complexity of the reaction, binding of 125I-SC to both IgA and IgM polymers could be analyzed by standard methods of saturation analysis, and both were shown to have a similar affinity for 125I-SC. No differences were noted in the affinity of 125I-SC binding to the IgA1 and IgA2 subclasses. Binding of monomeric IgA and IgM proteins could not be measured and was at least 100-fold lower than that found for IgA and IgM polymers. Complexes of 125I-SC with IgA dimers were presumed to involve covalent bond formation, since these complexes did not dissociate in guanidine-HCl. One IgA2 trimer did not form a covalent bond since it was completely dissociated in guanidine. In contrast, 125I-SC-IgM complexes were dissociated in denaturing solvent, indicating that such complexes were held together primarily by non-covalent bonds. Experiments with (Fc)5 mu isolated by high temperature tryptic digestion of IgM showed that binding of 125I-SC was to the Fc region of IgM proteins. It was suggested that the binding of SC with similar affinity to both IgA and IgM polymers may be important in the biologic function of both these immunoglobulin classes.

  5. 试论IgA肾病临床表现与肾脏病理的关系%the Relationship between IgA Nephropathy Clinical Manifestationand Renal Pathology

    Institute of Scientific and Technical Information of China (English)

    何东; 廖静

    2013-01-01

    目的临床分析IgA肾病患者的临床表现及肾脏病理关系。方法选取我院2011年8月至2012年8月收治的200例肾穿刺活检患者,给予B超肾活检、免疫检查、光镜检查,分析确诊的IgA临床特点与病理。结果经过检查后得知,有70例患者确诊为IgA肾病,其中15例肾病综合征、2例肾小球肾炎、9例血尿、17例隐匿性肾小球肾炎、25例慢性肾小球肾炎、1例肾功能不全、1例妊娠伴随慢性肾炎。病理类型:12例轻微病变、15例系膜增殖型、25例局灶节段性硬化、9例FSGS型、5例增生硬化型。结论针对IgA肾病患者,其临床表现和病理表现之间的严重程度不完全相符,实施肾活检,可有有效判断肾脏疾病病理类型,有利于确定治疗方案,改善预后。%Objective Clinical analysis of the relationship between theclinical manifestation and renal pathology in patients with IgA nephropathy. Methods In our hospital from 2011 August to 2012August were treated 200 cases of renal biopsy in patients with B-mode ultrasonography, renal biopsy, immunological examination, light microscopy, IgA analysis of clinical characteristics andpathologic diagnosis. Results After examination after that, of 70 patients diagnosed as IgA nephropathy, of which 15 cases of nephrotic syndrome, 2 cases of glomerulonephritis, 9 cases of hematuria, 17 cases of Latent Glomerulonephritis, 25 cases of chronic glomerulonephritis, 1 cases of renal insufifciency, 1 cases of pregnancy with chronic nephritis. Pathological types:12 cases ofmild lesion, 15 cases of mesangial proliferative type, 25 cases of focal segmental sclerosis, 9 cases of type FSGS, 5 cases ofproliferative sclerosing. Conclusion Patients with IgA nephropathy, the severity of the clinical manifestations andpathological findings between the not entirely consistent, implementation of renal biopsy, can effectively judge thepathological type of kidney disease, to determine the

  6. Human IgA-binding peptides selected from random peptide libraries: affinity maturation and application in IgA purification.

    Science.gov (United States)

    Hatanaka, Takaaki; Ohzono, Shinji; Park, Mirae; Sakamoto, Kotaro; Tsukamoto, Shogo; Sugita, Ryohei; Ishitobi, Hiroyuki; Mori, Toshiyuki; Ito, Osamu; Sorajo, Koichi; Sugimura, Kazuhisa; Ham, Sihyun; Ito, Yuji

    2012-12-14

    Phage display system is a powerful tool to design specific ligands for target molecules. Here, we used disulfide-constrained random peptide libraries constructed with the T7 phage display system to isolate peptides specific to human IgA. The binding clones (A1-A4) isolated by biopanning exhibited clear specificity to human IgA, but the synthetic peptide derived from the A2 clone exhibited a low specificity/affinity (K(d) = 1.3 μm). Therefore, we tried to improve the peptide using a partial randomized phage display library and mutational studies on the synthetic peptides. The designed Opt-1 peptide exhibited a 39-fold higher affinity (K(d) = 33 nm) than the A2 peptide. An Opt-1 peptide-conjugated column was used to purify IgA from human plasma. However, the recovered IgA fraction was contaminated with other proteins, indicating nonspecific binding. To design a peptide with increased binding specificity, we examined the structural features of Opt-1 and the Opt-1-IgA complex using all-atom molecular dynamics simulations with explicit water. The simulation results revealed that the Opt-1 peptide displayed partial helicity in the N-terminal region and possessed a hydrophobic cluster that played a significant role in tight binding with IgA-Fc. However, these hydrophobic residues of Opt-1 may contribute to nonspecific binding with other proteins. To increase binding specificity, we introduced several mutations in the hydrophobic residues of Opt-1. The resultant Opt-3 peptide exhibited high specificity and high binding affinity for IgA, leading to successful isolation of IgA without contamination.

  7. The Expression of Soluble and Active Recombinant Haemophilus influenzae IgA1 Protease in E. coli

    Directory of Open Access Journals (Sweden)

    Shinong Long

    2010-01-01

    Full Text Available Immunoglobulin A1 (IgA1 proteases from Haemophilus influenzae are extracellular proteases that specifically cleave the hinge region of human IgA1, the predominant class of immunoglobulin present on mucosal membranes. The IgA1 proteases may have the potential to cleave IgA1 complexes in the kidney and be a therapeutic agent for IgA1 nephropathy (IgAN, a disease characterized by deposition of the IgA1 antibody in the glomerulus. We have screened for the expression of recombinant H. influenzae IgA1 protease by combining various expression plasmids, IgA1 protease constructs, and E. coli strains under multiple conditions. Using the method we have developed, approximately 20–40 mg/L of soluble and active H. influenzae IgA1 protease can be produced from E. coli strain C41(DE3, a significant increase in yield compared to the yield upon expression in H. influenzae or other related bacteria.

  8. Potent neutralizing serum immunoglobulin A (IgA) in human immunodeficiency virus type 2-exposed IgG-seronegative individuals

    DEFF Research Database (Denmark)

    Lizeng, Q; Nilsson, C; Sourial, S

    2004-01-01

    Links Potent neutralizing serum immunoglobulin A (IgA) in human immunodeficiency virus type 2-exposed IgG-seronegative individuals.Lizeng Q, Nilsson C, Sourial S, Andersson S, Larsen O, Aaby P, Ehnlund M, Bjorling E. Research Center, South Hospital, Stockholm, Sweden. The mechanisms behind...... the resistance to human immunodeficiency virus type 2 (HIV-2) infection are still not fully understood. In the present study, we explored the HIV-2-specific humoral serum immunoglobulin A (IgA) immune response in HIV-2-exposed IgG-seronegative (EGSN) individuals. Serum samples from heterosexual EGSN individuals...... and their known HIV-2-infected partners, as well as controls originating from Guinea-Bissau in Africa, were studied. Antibody reactivity to native and recombinant envelope glycoproteins was investigated, and the capacity of purified serum IgA to neutralize HIV-2(SBL6669) was tested. Our results showed that 16...

  9. Mice overexpressing BAFF develop a commensal flora–dependent, IgA-associated nephropathy

    Science.gov (United States)

    McCarthy, Douglas D.; Kujawa, Julie; Wilson, Cheryl; Papandile, Adrian; Poreci, Urjana; Porfilio, Elisa A.; Ward, Lesley; Lawson, Melissa A.E.; Macpherson, Andrew J.; McCoy, Kathy D.; Pei, York; Novak, Lea; Lee, Jeannette Y.; Julian, Bruce A.; Novak, Jan; Ranger, Ann; Gommerman, Jennifer L.; Browning, Jeffrey L.

    2011-01-01

    B cell activation factor of the TNF family (BAFF) is a potent B cell survival factor. BAFF overexpressing transgenic mice (BAFF-Tg mice) exhibit features of autoimmune disease, including B cell hyperplasia and hypergammaglobulinemia, and develop fatal nephritis with age. However, basal serum IgA levels are also elevated, suggesting that the pathology in these mice may be more complex than initially appreciated. Consistent with this, we demonstrate here that BAFF-Tg mice have mesangial deposits of IgA along with high circulating levels of polymeric IgA that is aberrantly glycosylated. Renal disease in BAFF-Tg mice was associated with IgA, because serum IgA was highly elevated in nephritic mice and BAFF-Tg mice with genetic deletion of IgA exhibited less renal pathology. The presence of commensal flora was essential for the elevated serum IgA phenotype, and, unexpectedly, commensal bacteria–reactive IgA antibodies were found in the blood. These data illustrate how excess B cell survival signaling perturbs the normal balance with the microbiota, leading to a breach in the normal mucosal-peripheral compartmentalization. Such breaches may predispose the nonmucosal system to certain immune diseases. Indeed, we found that a subset of patients with IgA nephropathy had elevated serum levels of a proliferation inducing ligand (APRIL), a cytokine related to BAFF. These parallels between BAFF-Tg mice and human IgA nephropathy may provide a new framework to explore connections between mucosal environments and renal pathology. PMID:21881212

  10. Pulmonary Limited MPO-ANCA Microscopic Polyangiitis and Idiopathic Lung Fibrosis in a Patient with a Diagnosis of IgA Nephropathy

    Directory of Open Access Journals (Sweden)

    Alwin Tilanus

    2015-01-01

    Full Text Available We present a case of a male patient with chronic renal insufficiency, due to crescentic glomerulonephritis with IgA deposits, who successively developed (idiopathic thrombocytopenic purpura (ITP and MPO-ANCA microscopic polyangiitis (MPA with pulmonary fibrosis. The patient presented with cough, weight loss, and dyspnea on exertion. CT imaging and pulmonary function tests were compatible with interstitial pneumonitis with pulmonary fibrosis. Laboratory results showed high MPO-ANCA titers; the urinary sediment was bland. The patient was treated successfully with cyclophosphamide and methyl-prednisolone. This unique case illustrates the diagnostic and therapeutic challenges of an unusual presentation of microscopic polyangiitis presenting first as isolated kidney disease with recurrence in the form of pneumonitis without renal involvement, in association with renal IgA deposits and ITP as coexisting autoimmune conditions.

  11. Internalization and trafficking of nontypeable Haemophilus influenzae in human respiratory epithelial cells and roles of IgA1 proteases for optimal invasion and persistence.

    Science.gov (United States)

    Clementi, Cara F; Håkansson, Anders P; Murphy, Timothy F

    2014-01-01

    Nontypeable Haemophilus influenzae (NTHI) is a leading cause of opportunistic infections of the respiratory tract in children and adults. Although considered an extracellular pathogen, NTHI has been observed repeatedly within and between cells of the human respiratory tract, and these observations have been correlated to symptomatic infection. These findings are intriguing in light of the knowledge that NTHI persists in the respiratory tract despite antibiotic therapy and the development of bactericidal antibodies. We hypothesized that intracellular NTHI avoids, escapes, or neutralizes the endolysosomal pathway and persists within human respiratory epithelial cells and that human IgA1 proteases are required for optimal internalization and persistence of NTHI. Virtually all strains encode a human IgA1 protease gene, igaA, and we previously characterized a novel human IgA1 protease gene, igaB, that is associated with disease-causing strains and is homologous to the IgA1 protease that is unique to pathogenic Neisseria spp. Here, we show that NTHI invades human bronchial epithelial cells in vitro in a lipid raft-independent manner, is subsequently trafficked via the endolysosomal pathway, and is killed in lysosomes after variable durations of persistence. IgaA is required for optimal invasion. IgaB appears to play little or no role in adherence or invasion but is required for optimal intracellular persistence of NTHI. IgaB cleaves lysosome-associated membrane protein 1 (LAMP1) at pHs characteristic of the plasma membrane, early endosome, late endosome, and lysosome. However, neither IgA1 protease inhibits acidification of intracellular vesicles containing NTHI. NTHI IgA1 proteases play important but different roles in NTHI invasion and trafficking in respiratory epithelial cells.

  12. 来氟米特联合雷公藤多苷治疗IgA肾病的临床研究%Clnical study of Leflunomide combined with Tripterygium Wilfordii in treatment of IgA nephropathy

    Institute of Scientific and Technical Information of China (English)

    隋剑颖

    2011-01-01

    Objective: To observe the clinical efficacy of Leflunomide combined with Tripterygium Wilfordii on IgA nephropathy. Methods: 80 patients were randomly divided into treatment group and control group, each group contained 40 cases. The treatment group was given Leflunomide combined with Tripterygium Wilfordii, and the control group with given Enalapril, and both group continued for therapeutical period of 12 months. Results: Total effective rate of treatment group with 87.5% was obviously higher than the control group's 62.5%, and there was statistical difference (x2=12.56, P< 0.05). After treatment, urine protein of treatment group was (0.63±0.21) g/24h, and serum albumin was (41.32±13.42) g/L, both compared with those of control group has statistical difference (all P<0.05). Conclusion: Leflunomide combined with Tripterygium Wilfordii could difinitely reduce urine protein and raise serum albumin of IgA nephropathy, with less side effect.%目的:观察来氟米特联合雷公藤多苷治疗IgA肾病的临床效果.方法:将IgA肾病患者80例随机分为治疗组和对照组,各40例.治疗组给予来氟米特联合雷公藤多苷,对照组给予依那普利,疗程均为12个月.结果:治疗组总有效率为87.5%(35/40),对照组为62.5%(25/40),差异有统计学意义(X2=12.56,P<0.05).治疗组治疗后尿蛋白为(0.63±0.21)g/24 h,血清白蛋白为(41.32±13.42)g/L,均较治疗前及与对照组治疗后差异有统计学意义(均P<0.05).结论:两药联用治疗IgA肾病患者能提高患者的血清白蛋白,显著降低患者的尿蛋白,副作用少.

  13. Progress of Toll-like receptors and the pathogenesis of IgA nephropathy%Toll样受体与IgA肾病发病机制的研究进展

    Institute of Scientific and Technical Information of China (English)

    王云

    2014-01-01

    IgA肾病是儿童和青少年时期最常见的原发性肾小球肾炎,是引起终末期肾功能衰竭的重要原因之一,其病理特征是以IgA或IgA为主的免疫复合物在肾小球系膜区沉积.近年来免疫因素异常成为其研究热点,但具体发病机制尚未被完全阐明.Toll样受体是进化中比较保守的一个受体家族,它能特异地识别病原相关的分子模式,不仅在激活天然免疫中发挥重要作用,而且还调节获得性免疫,是连接天然免疫和获得性免疫的桥梁.研究显示Toll样受体在IgA肾病发生、发展过程中起着重要作用.该文就其生物学特征及IgA肾病发病机制进行综述.%Immunoglobulin A nephropathy (IgAN),characterized pathologically by deposition of IgA complexes in the glomerular mesangium,is the most common form of primary glomerulo-nephritis in children and adolescents and is considered to be one of the important cause of end-stage renal failure.Abnormal immune factors become the research hotspot in recent years,but the specific pathogenesis has not yet been fully elucidated.Toll-like receptors are a family of receptors,which have been evolutionarily conserved to recognize pathogen-associated molecular patterns.Toll-like receptors do not only play an important role in activation of innate immune,but also regulate acquired immune,which is a bridge connecting the natural immune and acquired immune.Studies have shown that Toll-like receptors plays an important role in the process of occurrence and development of IgAN.This paper reviews its biological characteristics and the pathogenesis of IgA nephropathy.

  14. 查表型饮食疗法在IgA肾病患者饮食管理中的应用%The application of chart diet therapy on nutrition management in patients with IgA nephropathy

    Institute of Scientific and Technical Information of China (English)

    孙莉莉; 娄小平; 王荟苹; 张军军

    2016-01-01

    目的:评价查表型饮食疗法在IgA肾病患者饮食管理中的应用效果。方法:将72例IgA肾病患者随机分为实验组与对照组,实验组采用查表型饮食疗法制定食谱,只需要查表即可找到符合患者特点的每天食谱,对照组采用传统细算法,随访6个月,评价住院第1天、随访3个月、随访6个月饮食达标情况、SGA评分、血清白蛋白、肾小球滤过率等生理指标。结果:实验组与对照组比较,饮食达标较高,SGA评分较低,血清白蛋白、血红蛋白、24小时尿蛋白定量、BMI等生理指标得到改善。结论:查表型饮食疗法操作简便,可提高患者饮食治疗的依从性,改善患者营养状况。%Objective: To evaluate the effect of chart diet therapy on nutrition management in patients with IgA nephropathy. Methods: Totally 72 IgA nephropathy patients were randomly divided into experimental group and control group. The experimental group used the chart diet therapy to create meal plans, while the control group used the traditonal calories calculation method following up in 6 month and evaluating the nutrition status, SGA, Alb, TG, CHOLand other physiological indexes at three different times, first day of admission, 3 month follow up and 6 month follow up. Result: Compared with control group, the nutrition statu, SGA, Alb, Hb, 24-UP, BMI of experimental group were better. Conclusion: The chart diet therapy was easy to operate, and could improve the compliance and nutrition status.

  15. IgA1 dominant subclass of latent IgA mesangial deposition in donated kidney.

    Science.gov (United States)

    Oka, Kazumasa; Nishimura, Kenji; Kishikawa, Hidefumi; Ichikawa, Yasuji

    2016-01-01

    In the pathogenesis of immunoglobulin A nephropathy (IgAN), the IgA1 subclass is more important than the IgA2 subclass. In healthy men, the prevalence of mesangial IgA deposition has been previously investigated. However, it remains unknown whether the presence of urinary abnormalities depends on the subclass of IgA deposition. We researched the subclasses of IgA (IgA1 and IgA2) by the direct immunofluorescence (IF) staining method using specimens in which we identified the deposition of IgA through zero-hour renal transplant biopsies from donors without urinary abnormalities. The samples of the zero-hour biopsies were collected from 46 cases of living renal transplant patients at Nishinomiya Hospital, Hyogo Prefecture, from January 2011 to December 2013. In seven of the 46 cases (15%), IgA deposition and C3 in mesangium were confirmed. All seven cases showed IgA1 predominant mesangial deposition on IF. The results of the histological evaluations for all seven cases were Oxford Classification M0.S0.E0.T0. This study showed similar patterns of latent mesangial IgA deposition according to IgA subclass and frequency of C3 deposition as IgAN. Latent mesangial IgA deposition may require some, as yet undefined factors, to become clinically apparent as IgAN.

  16. Chromatographic separation and purification of secretory IgA from human milk.

    Science.gov (United States)

    Khayam-Bashi, H; Blanken, R M; Schwartz, C L

    1977-01-01

    Defatted and decaseinated human milk was concentrated and was fractionated on a preparative DEAE cellulose column. Elution with various concentrations of sodium chloride in Tris-HCl buffer (pH 8.0, 0.01 M) resulted in fractions that were rich in either secretory immunoglobulin A (SIgA) (0.1 M NaCl) or free secretory component (SC) (0.05 M NaCl). The fractions, which were eluted with 0.10 M NaCl from the preparative column, were further fractionated on a G-200 Sephadex column. Repeated fractionation on this column resulted in a single purified fraction, which contained very high SIgA activity and showed immunological cross-reaction with both SC and serum IgA. Additional studies indicated that this fraction was homogeneous as shown by immunoprecipitin and disc gel electrophoresis. Injection of this purified SIgA into rabbits resulted in the production of monospecific antisera.

  17. The generation and evaluation of recombinant human IgA specific for Plasmodium falciparum merozoite surface protein 1-19 (PfMSP119

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    Corran Patrick H

    2011-07-01

    Full Text Available Abstract Background Human immunoglobulin G (IgG plays an important role in mediating protective immune responses to malaria. Although human serum immunoglobulin A (IgA is the second most abundant class of antibody in the circulation, its contribution, if any, to protective responses against malaria is not clear. Results To explore the mechanism(s by which IgA may mediate a protective effect, we generated fully human IgA specific for the C-terminal 19-kDa region of Plasmodium falciparum merozoite surface protein 1 (PfMSP119, a major target of protective immune responses. This novel human IgA bound antigen with an affinity comparable to that seen for an epitope-matched protective human IgG1. Furthermore, the human IgA induced significantly higher NADPH-mediated oxidative bursts and degranulation from human neutrophils than the epitope-matched human IgG1 from which it was derived. Despite showing efficacy in in vitro functional assays, the human IgA failed to protect against parasite challenge in vivo in mice transgenic for the human Fcα receptor (FcαRI/CD89. A minority of the animals treated with IgA, irrespective of FcαRI expression, showed elevated serum TNF-α levels and concomitant mouse anti-human antibody (MAHA responses. Conclusions The lack of protection afforded by MSP119-specific IgA against parasite challenge in mice transgenic for human FcαRI suggests that this antibody class does not play a major role in control of infection. However, we cannot exclude the possibility that protective capacity may have been compromised in this model due to rapid clearance and inappropriate bio-distribution of IgA, and differences in FcαRI expression profile between humans and transgenic mice.

  18. A new mouse model resembling human diabetic nephropathy: uncoupling of VEGF with eNOS as a novel pathogenic mechanism.

    Science.gov (United States)

    Nakagawa, T

    2009-02-01

    Diabetics develop a variety of histological abnormalities in the kidney. Early features include glomerular hypertrophy, glomerular basement membrane thickening, and mesangial expansion, whereas mesangiolysis, glomerular capillary aneurysm and nodular lesions develop in late phase. The goal of preventing diabetic nephropathy is important, but its achievement has been difficult due in part to a lack of an animal model for human diabetic nephropathy. Most animal models develop mild lesions in early phase diabetes, but not advanced lesions in late phase. Vascular endothelial growth factor (VEGF) mediates diabetic nephropathy, but its precise role remains to be determined. A complexity of VEGF function is that it is protective in nondiabetic renal diseases but is deleterious in diabetic nephropathy. Because diabetes is associated with endothelial dysfunction, we hypothesized that VEGF is deleterious in the setting of endothelial dysfunction. To test this hypothesis, we recently developed a new model of diabetic nephropathy in mice deficient in endothelial nitric oxide synthase (eNOS). Importantly, these mice developed the advanced lesions of diabetic nephropathy resembling to those in human diabetic nephropathy. In addition, these models also exhibit an uncoupling condition of VEGF with NO. In this review, we discuss our hypothesis which is that uncoupling of VEGF with NO causes advanced diabetic nephropathy.

  19. Dual renin-angiotensin system blockade plus oral methylprednisone for the treatment of proteinuria in IgA nephropathy Doble bloqueo del sistema renina-angiotensina más metilprednisona oral para el tratamiento de la proteinuria en la nefropatía por IgA

    Directory of Open Access Journals (Sweden)

    Hernán Trimarchi

    2007-10-01

    Full Text Available Renin-angiotensin system inhibition is a widely accepted approach to initially deal with proteinuria in IgA nephropathy, while the role of immunosuppressants remains controversial in many instances. A prospective, uncontrolled, open-label trial was undertaken in patients with biopsy-proven IgA nephropathy with proteinuria > 0.5 g/day and normal renal function to assess the efficacy of a combination treatment of angiotensin converting enzyme inhibitors plus angiotensin receptor blockers enalapril valsartan coupled with methylprednisone to decrease proteinuria to levels below 0.5 g/day. Twenty patients were included: Age 37.45 ± 13.26 years (50% male; 7 patients (35% were hypertensive; proteinuria 2.2 ± 1.86 g/day; serum creatinine 1.07 ± 0.29 mg/dl; mean follow-up 60.10 ± 31.47 months. IgA nephropathy was subclassified according to Haas criteria. Twelve patients (60% were class II; seven (35% were class III and one (5% class V. All patients received dual reninangiotensin system blockade as tolerated. Oral methylprednisone was started at 0.5 mg/kg/day for the initial 8 weeks and subsequently tapered bi-weekly until the maintenance dose of 4 mg was reached. Oral steroids were discontinued after 24 weeks (6 months of therapy but renin-angiotensin inhibition remained unchanged. At 10 weeks of therapy proteinuria decreased to 0.15 ± 0.07 g/day (P El doble bloqueo del sistema renina-angiotensina con inhibidores de la enzima convertidora de angiotensina junto a bloqueadores del receptor tipo I de angiotensina II es aceptado como tratamiento en la proteinuria de la nefropatía por IgA, ya que el rol de los inmunosupresores continúa siendo controvertido. Estudio prospectivo, no controlado, abierto para pacientes con nefropatía por IgA con proteinurias >0.5 g/día y creatininas séricas <1.4 mg/dl, para evaluar la eficacia de tratamiento de enalapril más valsartán asociado a metilprednisona vía oral para disminuir las proteinurias a <0.5 g

  20. Nasal IgA Provides Protection against Human Influenza Challenge in Volunteers with Low Serum Influenza Antibody Titre.

    Science.gov (United States)

    Gould, Victoria M W; Francis, James N; Anderson, Katie J; Georges, Bertrand; Cope, Alethea V; Tregoning, John S

    2017-01-01

    In spite of there being a number of vaccines, influenza remains a significant global cause of morbidity and mortality. Understanding more about natural and vaccine induced immune protection against influenza infection would help to develop better vaccines. Virus specific IgG is a known correlate of protection, but other factors may help to reduce viral load or disease severity, for example IgA. In the current study we measured influenza specific responses in a controlled human infection model using influenza A/California/2009 (H1N1) as the challenge agent. Volunteers were pre-selected with low haemagglutination inhibition (HAI) titres in order to ensure a higher proportion of infection; this allowed us to explore the role of other immune correlates. In spite of HAI being uniformly low, there were variable levels of H1N1 specific IgG and IgA prior to infection. There was also a range of disease severity in volunteers allowing us to compare whether differences in systemic and local H1N1 specific IgG and IgA prior to infection affected disease outcome. H1N1 specific IgG level before challenge did not correlate with protection, probably due to the pre-screening for individuals with low HAI. However, the length of time infectious virus was recovered from the nose was reduced in patients with higher pre-existing H1N1 influenza specific nasal IgA or serum IgA. Therefore, IgA contributes to protection against influenza and should be targeted in vaccines.

  1. Evidence for local expansion of IgA plasma cell precursors in human ileum

    NARCIS (Netherlands)

    Yuvaraj, S.; Dijkstra, G.; Burgerhof, J.G.M.; Dammers, P.M.; Stoel, M.; Visser, Annie; Kroese, F.G.M.; Bos, N.A.

    2009-01-01

    IgA plays a crucial role in establishment and maintenance of mucosal homeostasis between host cells and commensal bacteria. To this end, numerous IgA plasma cells are located in the intestinal lamina propria. Whether the (immediate) precursor cells for these plasma cells can expand locally is not

  2. Nefropatia por IgA em portadores de espondiloartrites acompanhados no Serviço de Reumatologia do Hospital das Clínicas da UFMG IgA nephropathy in patients with spondyloarthritis followed-up at the Rheumatology Service of Hospital das Clínicas/UFMG

    Directory of Open Access Journals (Sweden)

    Daniela Castelo Azevedo

    2011-10-01

    -B27 positivity, creatinine and urea serum levels, major comorbidities, hematuria and proteinuria. Patients with hematuria were subsequently assessed for the presence of dysmorphic red blood cells in urine, and those with proteinuria underwent 24-hour urine protein measurement. Renal biopsy was performed in patients with glomerular hematuria and/or proteinuria over 3.5 g/24-hour. RESULTS: Seventy-six patients were assessed. Microscopic hematuria was the most frequently found abnormality in urinalysis (44.7%, usually intermittent and in spot urine samples during patients' follow-up. In eight patients (10.5%, glomerular hematuria was suspected. Renal biopsy was performed in fi ve of them, showing IgA nephropathy in four (5.3% and thin membrane disease in one patient. CONCLUSIONS: A high frequency of urinalysis alterations was observed in that subgroup of patients, as well as a high prevalence of IgA nephropathy. Although further studies on this subject are needed to better clarify these results, periodic urinalysis of patients with spondyloarthritis should be recommended.

  3. Univariate and multiple linear regression analyses for 23 single nucleotide polymorphisms in 14 genes predisposing to chronic glomerular diseases and IgA nephropathy in Han Chinese

    Directory of Open Access Journals (Sweden)

    Hui Wang

    2014-01-01

    Full Text Available Immunoglobulin A nephropathy (IgAN is a complex trait regulated by the inter-action among multiple physiologic regulatory systems and probably involving numerous genes, which leads to inconsistent findings in genetic studies. One possibility of failure to replicate some single-locus results is that the underlying genetics of IgAN nephropathy is based on multiple genes with minor effects. To learn the association between 23 single nucleotide polymorphisms (SNPs in 14 genes predisposing to chronic glomerular diseases and IgAN in Han males, the 23 SNPs genotypes of 21 Han males were detected and analyzed with a BaiO gene chip, and their asso-ciations were analyzed with univariate analysis and multiple linear regression analysis. Analysis showed that CTLA4 rs231726 and CR2 rs1048971 revealed a significant association with IgAN. These findings support the multi-gene nature of the etiology of IgAN and propose a potential gene-gene interactive model for future studies.

  4. The role of activation of the lectin pathway of complement in pathogenesy of IgA nephropathy%补体活化的凝集素途径在IgA肾病发病中的作用

    Institute of Scientific and Technical Information of China (English)

    张伟; 王墨; 李秋

    2011-01-01

    To investigate the mechanism of activation the lectin pathway of complement in IgA nephropathy,enzyme-linked immunosorbent assay was performed to detect mining level of serumal mannose-binding lectin (MBL); immunohistochemical method was performed to detect expression of MBL、MASP-1、C3、Clq、IgA and C5b-9 on renal specimens. Patients of IgAN were characterized into MBL-positive cases and MBL-negative cases by glomerular co-deposition of MBL and MASP, and were analyzed distinction of couch expressionition retrospectively. Glomerular deposition of MBL was observed in 22 of 53 cases (41.5%) with IgAN and showed a mesangial pattern. All MBL-positive cases, but none of the MBL-negative cases showed glomerular co-deposition of MBLassociated serine proteases, C3 and C5b-9. Among patients of IgAN, serum level of MBL did not show significant difference than unimpaired patients. Patients of IgAN with glomerular MBL deposition, pathology classification was not correlation with intension of MBL deposition. Intension of MBL deposition was positive correlation with IgA in patients of IgAN. MBL-positive cases have significantly more proteinuria and more attacking macroscopic hematuria as MBL-negative cases, which shows activation of the mero-lectin pathway of complement is significant in IgA nephropathy.%目的 探讨补体活化的凝集素途径在IgA1肾病发病中的作用.方法 用ELISA方法 检测20例IgAN患儿和正常儿童血清的MBL水平,免疫组化检测53例IgA肾病、23例非IgA沉积肾小球疾病患儿1肾组织甘露聚糖结合凝集素(MBL)、MBL相关的丝氨酸蛋白酶(MASP-1)、C3、C1q、IgA和C5b-9的表达,了解有无MBL-MASP-1途径补体活化参与IgAN发病;回顾性分析MBL-MASP-1沉积阳性组和MBL-MASP-1沉积阴性组患儿不同临床表现的差异;分析IgAN的MBL沉积强度与病理分级的相关性,了解不同程度补体活化与IgAN病理损害的关系.结果 22例IgAN患儿肾小球有MBL、MASP-1、C3和C5b-9

  5. leflunomide对IgA肾病大鼠肾脏保护作用的机制研究%Study on protective effects and its mechanism of leflunomide on renal tissue in rat IgA nephropathy model

    Institute of Scientific and Technical Information of China (English)

    汤颖; 娄探奇; 王成; 彭晖; 刘迅; 唐骅

    2008-01-01

    目的 观察leflunomide对实验性IgA肾病(IgAN)大鼠肾脏病理及肾组织转化生长因子-β1(TGF-β1)、单核细胞趋化因子-1(MCP-1)表达的影响.方法 建立IgAN大鼠模型,随机分成模型组、泼尼松组、leflunomide组,同时设立正常对照组.用免疫荧光和光镜观察免疫复合物在肾脏的沉积及系膜区基质增生程度;用免疫组化和逆转录-聚合酶链反应(RT-PCR)方法分别检测肾组织TGF-β1、MCP-1的蛋白和基因表达水平.结果 与模型组比较,leflunomide组免疫复合物在肾脏的沉积明显减少,系膜区基质增生程度显著减轻(P均<0.01);leflunomide在基因和蛋白水平均能够有效抑制TGF-β1和MCP-1在肾组织中的表达(P<0.05或P<0.01).结论 leflunomide能减少免疫复合物在肾脏的沉积,并且下调TGF-β1、MCP-1在肾脏的表达,减少局部炎症反应,减轻系膜区基质增生,延缓肾脏纤维化的进程,保护肾脏.%Objective To observe the effects of leflunomide on renal pathology and expression of transforming growth factor-β1 (TGF-β1), monocyte chemotaxis peptidel (MCP-1) in renal tissue of experimental IgA nephropathy in rat. Methods IgA nephropathy model was reproduced in rats. They were randomly divided into leflunomide group, prednisone group, nephropathy control group, and normal control group. The deposition of immunocomplex in renal tissue and degree of mesangial matrix hyperplasia in mesangial region were detected by immunofluorescence and light microscope;the level of expression of gene and protein of TGF-β1 and MCP-1 in renal tissue were determined by immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR) methods. Results Compared with model group,leflunomide lessened the deposit of immunocomplex in renal tissue, alleviated the hyperplasia of mesangial matrix (all P<0. 01). Leflunomide could also inhibit the expression of TGF-β1, MCP-1 at the level of gene and protein in renal tissue (P<0

  6. Complex Etiology, Prophylaxis and Hygiene Control in Mycotoxic Nephropathies in Farm Animals and Humans

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    Stoycho D. Stoev

    2008-04-01

    Full Text Available Various etiological factors contributing to the development of mycotoxic nephropathy in farm animals and humans are reviewed. The possible synergistic effect between ochratoxin A (OTA and other mycotoxins, as penicillic acid (PA and fumonisin B1 (FB1, contributing to this nephropathy is also considered and discussed. The most convenient ways of prophylaxis and various preventive measures against OTA contamination of feeds or foods are reviewed. A reference is made concerning the most successful methods of veterinary hygiene control in the slaughterhouses in order to prevent the entering of OTA in commercial channels with a view to human health. The economic efficacy of these prophylactic procedures is also considered. An evaluation of human exposure to OTA is made.

  7. O-Glycosylated IgA Rheumatoid Factor Induces IgA Deposits and Glomerulonephritis

    Science.gov (United States)

    Otani, Masako; Nakata, Junichiro; Kihara, Masao; Leroy, Valérie; Moll, Solange; Wada, Yoshinao

    2012-01-01

    Structural aberrations of O-linked glycans present in the IgA1 hinge region are associated with IgA nephropathy, but their contribution to its pathogenesis remains incompletely understood. In this study, mice implanted with hybridoma secreting 6-19 IgA anti-IgG2a rheumatoid factor, but not 46-42 IgA rheumatoid factor bearing the same IgA allotype, developed mesangial deposits consisting of IgA, IgG2a, and C3. Studies in immunoglobulin- and C3-deficient mice revealed that the development of these glomerular lesions required the formation of IgA-IgG2a immune complexes and subsequent activation of complement. The proportion of polymeric and monomeric forms, the IgG2a-binding affinity, and the serum levels of IgA-IgG2a immune complexes were similar between 6-19 IgA– and 46-42 IgA–injected mice. In contrast, the analysis of oligosaccharide structures revealed highly galactosylated O-linked glycans in the hinge region of 6-19 IgA and poorly O-glycosylated in the hinge region of 46-42 IgA. Furthermore, the structure of N-linked glycans in the CH1 domain was the complex type in 6-19 IgA and the hybrid type in 46-42 IgA. In summary, this study demonstrates the presence of O-linked glycans in the hinge region of mouse IgA and suggests that 6-19 IgA rheumatoid factor–induced GN could serve as an experimental model for IgA nephropathy. PMID:22193386

  8. Value of urine NGAL and N - acetyl - β - D - glucosaminidase in early diagnosis of IgA nephropathy%尿NGAL和N-乙酰-β-D-氨基葡萄糖苷酶对IgA肾病早期诊断的价值研究

    Institute of Scientific and Technical Information of China (English)

    王寅; 童俊容; 何凤; 罗正茂; 张虹

    2011-01-01

    Objective:To explore the value of urine NGAL and N - acetyl - p - D - glucosaminidase in diagnosing early injury of IgA nephropathy. Methods: 85 patients with lgA nephropathy were categorized into two groups ( Hass I - II group and Hass III~ V group). 30 healthy subjects were recruited as controls. Ungal and Unag were detected by commercial available ELISA kit according to the manufacturer's instructions. And the ratio of Ungal/Cr and Unag/Cr were calculated. Receiver operating characteristic (ROC) curve analysis was used to evaluat the two on the sensitivity and specificity of diagnosis on IgA nephropathy. The area under the ROC curve and the best diagnostic cut -off value were calculated. Results: The levels of Ungal,Unag,Un-GAL/Cr and Unag/Cr are significantly higher in IgAN patients than in control group. The area under ROC curve of Ungal/Cr and Unag/Cr were 0.941 and 0.846 respectively. The best diagnostic cut - off value were 3.50 g /mmol Cr and 1.20 U /mmol Cr. Taking the boundary value to diagnose IgA nephropathy, the sensitivity and specificity for Ungal/Cr and Unag/Cr were 91.2% , 93.7% and 83.3% , 84.9% respectively. Conclusion: Ungal is an objective indicator of early renal damage in IgA nephropathy. Ungal/Cr has higher sensitivity and specificity for the diagnosis of IgA nephropathy than Unag /Cr,and it is expected to be diagnostic indicator for IgA nephropathy.%目的:探讨尿中性粒细胞明胶酶相关脂蛋白(neutrophil gelatinase associated lipocalin,NGAL)和N-乙酰-β-D-氨基葡萄糖苷酶(N - acetyl -β-D - glucosaminidase,NAG)对IgA肾病早期诊断价值.方法:选择IgA肾病患者85例,根据Hass分级Hass Ⅰ~Ⅱ(A组)40例、Hass Ⅲ~V(B组)45例;正常对照组30例.应用ELISA法检测尿液NGAL(uNGAL)和uNAG的浓度,并计算uNGAL/Cr比值和uNAG/Cr比值,进而对uNGAL/Cr和uNAG/Cr进行受试者工作特征(ROC)曲线分析,计算ROC曲线下面积和最佳诊断界值.结果:IgA肾病患者的uNGAL、uNAG、uNGAL/Cr

  9. New Experimental Models of Diabetic Nephropathy in Mice Models of Type 2 Diabetes: Efforts to Replicate Human Nephropathy

    Directory of Open Access Journals (Sweden)

    María José Soler

    2012-01-01

    Full Text Available Diabetic nephropathy (DN is the leading cause of end-stage renal disease. The use of experimental models of DN has provided valuable information regarding many aspects of DN, including pathophysiology, progression, implicated genes, and new therapeutic strategies. A large number of mouse models of diabetes have been identified and their kidney disease was characterized to various degrees. Most experimental models of type 2 DN are helpful in studying early stages of DN, but these models have not been able to reproduce the characteristic features of more advanced DN in humans such as nodules in the glomerular tuft or glomerulosclerosis. The generation of new experimental models of DN created by crossing, knockdown, or knockin of genes continues to provide improved tools for studying DN. These models provide an opportunity to search for new mechanisms involving the development of DN, but their shortcomings should be recognized as well. Moreover, it is important to recognize that the genetic background has a substantial effect on the susceptibility to diabetes and kidney disease development in the various models of diabetes.

  10. Association of DDT and heptachlor epoxide in human blood with diabetic nephropathy.

    Science.gov (United States)

    Everett, Charles J; Thompson, Olivia M

    2015-01-01

    Six organochlorine pesticides and pesticide metabolites in human blood were tested to determine their relationships with diabetic nephropathy. The data were derived from the National Health and Nutrition Examination Survey (NHANES) 1999-2004 (unweighted, n=2992, population estimate=133,088,752). The six chemicals were p,p'-DDT (dichlorodiphenyltrichloroethane), p,p'-DDE (dichlorodiphenyltrichloroethylene), beta-hexachlorocyclohexane, oxychlordane, trans-nonachlor and heptachlor epoxide. In this research, total diabetes included diagnosed and undiagnosed diabetes (glycohemoglobin, A1c ≥6.5%), and nephropathy was defined as a urinary albumin to creatinine ratio >30 mg/g, representing microalbuminuria and macroalbuminuria. The pesticide p,p'-DDT and pesticide metabolite heptachlor epoxide were significantly associated with total diabetes with nephropathy, with odds ratios of 2.08 (95% CI 1.06-4.11) and 1.75 (95% CI 1.05-2.93), respectively. Organochlorine pesticides are thought to act through the constitutive androstane receptor/pregnane X receptor disease pathway, but this is not well established. When p,p'-DDT and heptachlor epoxide were both elevated, the odds ratio for diabetic nephropathy was 2.76 (95% CI 1.31-5.81), and when six of six organochlorine pesticides and pesticide metabolites, were elevated, the odds ratio for diabetic nephropathy was 3.00 (95% CI 1.08-8.36). The differences in the odds ratios for these groups appear to be due to differences in the mean heptachlor epoxide concentration of each category. Organochlorine pesticides and pesticide metabolites are known to have estrogenic, antiestrogenic or antiandrogenic activity. The constitutive androstane receptor/pregnane X receptor pathway is thought to interact with the aryl hydrocarbon receptor pathway, and the associations noted may be due to that interaction.

  11. Ochratoxin A levels in human serum and foods from nephropathy patients in Tunisia: where are you now?

    Science.gov (United States)

    Hmaissia Khlifa, K; Ghali, R; Mazigh, C; Aouni, Z; Machgoul, S; Hedhili, A

    2012-07-01

    Ochratoxin A is a natural mycotoxin with nephrotoxic properties that can contaminate food products. It has been detected in high amount in human serum collected from nephropathy patients, especially those categorized as having a chronic interstitial nephropathy of unknown etiology. In the present study, ochratoxin A levels were measured in commonly consumed food items and in serum samples from nephropathy and healthy subjects in Tunisia. To assess ochratoxin A, a high performance liquid chromatography method was optimized. The ochratoxin A assay showed very different scales of ochratoxin A serum and food contamination from 0.12 to 1.5 ng/mL and 0.11 to 6.1 ng/g respectively, and in healthy subjects and 0.11 to 33.8 ng/g for food and 0.12 to 3.8 ng/mL for serum in nephropathy patients suffering from chronic interstitial nephropathy of unknown etiology. The disease seems related to ochratoxin A serum levels and food contaminations, since the healthy group was significantly different from the nephropathy group (Pochratoxin A contamination. Those results combined with data published already, emphasize the likely endemic aspect of ochratoxin A-related nephropathy occurring in Tunisia.

  12. Lessons From the KK-Ay Mouse, a Spontaneous Animal Model for the Treatment of Human Type 2 Diabetic Nephropathy

    OpenAIRE

    Tomino, Yasuhiko

    2012-01-01

    Abstract Diabetic nephropathy is a major cause of end-stage kidney disease (ESKD) in patients with type 1 and type 2 diabetes throughout the world. In human glomeruli, expansion of diffuse mesangial matrices, exudative lesions and/or segmental nodular sclerosis are pathological features of diabetic nephropathy. There have been many reports on the pathogenesis and treatment of type 2 diabetes using various animal models. It appears that KK-Ay mice, especially in terms of their immunohistologic...

  13. Secretory component as the mucosal transport receptor: separation of physicochemically analogous human IgA fractions with different receptor-binding capacities.

    Science.gov (United States)

    Schiff, J M; Fisher, M M; Underdown, B J

    1986-01-01

    This paper describes the separation and characterization of several IgA fractions from the same human monoclonal source, based on their ability to bind secretory component (SC). The study was undertaken to elucidate features of the immunoglobulin-binding site for SC, and to examine the dependence of mucosal transport on IgA-SC interaction. Enrichment or depletion of SC-binding activity was accomplished on an affinity adsorbant made with SC from human colostral whey. The affinity-purified human IgA fractions contained IgA polymers and were 77% active in rebinding to the adsorbant; this activity was diminished significantly by direct radioiodination. The non-adherent IgA fractions contained both polymer and monomer, and were only 8% active in rebinding to the adsorbant. When the polymer and monomer components were separated from each other, the non-adherent polymer was found to resemble the affinity-purified fraction by all criteria examined including J-chain content, except that the SC-binding capacity was greater than five-fold lower. These findings have two implications for the SC-binding site on human IgA: first, the presence of J-chain is insufficient to bestow IgA with SC-binding activity; second, a critical tyrosine participates in maintaining the SC-binding region, possibly on the IgA heavy chain. The relationship between SC binding and mucosal transport was tested in the rat hepatobiliary model. All radiolabeled human IgA fractions were captured rapidly from blood by the rat liver, but only the SC-binding fractions underwent substantial intact transport to bile (greater than 70% of the injected dose). Even though a nominal proportion of the SC-non-adherent IgA appeared in bile (4-15% of the dose), most IgA in these fractions was rapidly degraded within the liver. Thus, only a small amount of monomeric and polymeric IgA can use alternative receptors to get to bile by diversion from the degradative pathway. Polymeric IgA can undergo efficient transport across

  14. Selective expansion of T cell receptor (TCR) V beta 6 in tonsillar and peripheral blood T cells and its induction by in vitro stimulation with Haemophilus parainfluenzae in patients with IgA nephropathy

    Science.gov (United States)

    Nozawa, H; Takahara, M; Yoshizaki, T; Goto, T; Bandoh, N; Harabuchi, Y

    2008-01-01

    IgA nephropathy (IgAN), the most common form of primary glomerulonephritis, is recognized as a disease that often becomes worse during acute tonsillitis. Although many reports have shown that tonsillectomy is an effective treatment for IgAN patients, the immunological evidence has not yet been investigated fully. In this study, we compared the expression of T cell receptor (TCR) V beta families in tonsillar T cells of IgAN patients to those of non-IgAN patients. The reverse transcription–polymerase chain reaction (RT–PCR) and flow cytometric analyses showed that the TCR V beta 6 was used more frequently in tonsillar T cells of IgAN patients than in those of non-IgAN patients (P < 0·01 each). Similarly, the proportions of TCR V beta 6-positive cells in peripheral blood T cells were significantly higher in IgAN patients than in non-IgAN patients (P < 0·05). After tonsillectomy, the proportions decreased in IgAN patients (P < 0·05), but did not in non-IgAN patients. Furthermore, in vitro stimulation with Haemophilus parainfluenzae antigen, which is reported to deposit in the glomerular mesangium of IgAN, enhanced expression of TCR V beta 6 in tonsillar T cells from both IgAN and non-IgAN patients. These results suggest that TCR V beta 6-positive tonsillar T cells might be activated by H. parainfluenzae, move into the kidney through blood circulation and induce glomerulonephritis. PMID:17983447

  15. 浅析活性维生素D联合血管紧张素受体拮抗剂治疗IGA肾病有效性%Analysis of the Effectiveness of Active Vitamin D Combined With Angiotensin Receptor Antagonist in the Treatment of IGA Nephropathy

    Institute of Scientific and Technical Information of China (English)

    郭陆晋

    2015-01-01

    目的:分析活性维生素D联合血管紧张素受体拮抗剂治疗IGA肾病有效性。方法随机抽取2010年4月~2014年11月诊治的80例IgA肾病患者,分为研究组和对比组。对比组服用厄贝沙坦进行治疗。而研究组在对比组的基础上增加骨化三醇胶丸进行治疗,分析两组治疗效果。结果在治疗结束之后,两组患者的尿蛋白的数值低于治疗(P 0.05)。结论活性维生素D联合血管紧张素受体拮抗剂治疗IGA肾病效果显著,其安全性高。%Objective To analyze the effectiveness of active vitamin D combined with angiotensin receptor antagonist in the treatment of IGA nephropathy. Methods 80 patients with IgA nephropathy in April 2010~November 2014 were randomly divided into study group and control group. Contrast group took irbesartan treatment. The research group on the basis of the comparison group increased Calcitriol Soft Capsules treatment, analysis of the treatment effect of the two groups.ResultsAfter the treatment, the urine protein of the two groups was significantly lower than that of the treatment (P 0.05). Conclusion Active vitamin D combined with angiotensin receptor antagonist in the treatment of IGA nephropathy is remarkable, and its safety is high, it is worthy of clinical application.

  16. Using Two Kinds of BSA Dose Establish IgA Nephropathy Rats Model Bservation%运用两种BSA剂量建立IgA肾病大鼠模型观察

    Institute of Scientific and Technical Information of China (English)

    张静; 李静; 桑晓红; 刘健; 王丽娜; 苗娜

    2013-01-01

    目的:目前IgA肾病(IgAN)动物模型并无经典造模方法,本实验选择国内较常用方法建立大鼠IgAN模型,分两个时间点观察不同剂量牛血清白蛋白(bovine serum albumin,BSA)灌胃联合注射脂多糖(lipopolysaccharide,LPS)+四氯化碳(carbon terachloride,CCL4)方法建立IgA肾病模型效果.方法:将SPF级健康雄性SD大鼠60只(平均体重200~240 g)随机分为3组,每组20只.低剂量组(A组):BSA400 mg/kg(100 g/L)隔天灌胃,持续12周;皮下注射蓖麻油0.3 ml+CCL4 0.10 ml,每周1次持续12周,第8周LPS 0.05 mg尾静脉注射.高剂量组(B组):BSA增加至600 mg/kg(100 g/L),余干预同低剂量组.对照组(C组)生理盐水4 ml/kg灌胃,0.4 ml皮下注射.建模后第8周、12周每组各处死10只大鼠,留取血、尿、肾组织标本检测.观察指标:一般情况、蛋白尿、血尿、肝肾功能、肾组织病理.结果:模型组大鼠血肌酐、尿素氮及尿蛋白均明显增高(P<0.05),高剂量组显著高于低剂量组(P<0.05),且肾组织病理8周后均出现轻中度系膜细胞及系膜基质的增生,12周末显著伴肾间质轻度纤维化,高剂量组病变较重;12周末均有荧光出现,均强于第8周,低剂量组荧光表达不典型,高剂量组表达强于低剂量组(P<0.05).电镜报告与病理表现一致.结论:运用BSA+LPS+CCL4联合造模方法在12周左右可建立快速IgA肾病动物模型,而且高剂量BSA(600 mg/kg)组肾组织病变更显著,模型更典型.此模型的建立及运用可以为IgA肾病临床及基础研究提供良好动物模型基础.%Objective:At present there is no classic method to construct IgAN model in SD rats. To observe IgA nephropa-thy model effect, the experiment divided into two time points at different concentrations bovine serum albumin lavage combined injection lipopolysaccharide + carbon tetrachloride method to establish IgA nephropathy model effect. Methods: Sixty health male SD rats weighing 200 ~ 240 g were randomized

  17. Correlation of the clinical features and the Oxford pathological type of primary IgA nephropathy%原发性IgA肾病临床与IgA肾病牛津分类的相关性

    Institute of Scientific and Technical Information of China (English)

    周宏伟; 苏震; 朱慧萍; 林海霞; 许菲菲; 吕吟秋; 陈波

    2013-01-01

    目的:探讨IgA肾病牛津分类与临床指标之间的相关性,为进一步指导治疗、判断预后提供依据.方法:选取2010年7月至2012年6月在温州医科大学附属第一医院经肾活检确诊的原发性IgA肾病患者205例,结合其临床和病理资料,按不同条件分组,进行临床病理分析.结果:按IgA肾病牛津分类对患者的病理资料进行评价,病理损伤以局灶节段性肾小球硬化(S1)多见,病理类型以系膜细胞增多(M0型)节段性肾小球硬化(S1型)毛细血管内细胞增多(E0型)肾小管萎缩/间质纤维化(T0型)即M0S1E0T0多见.患者临床表现与病理之间的相关性分析:①系膜细胞增多(M)、毛细血管内细胞增多(E)、肾小管萎缩/间质纤维化(T)与肾活检时蛋白尿高度相关(P<0.05);②毛细血管内细胞增多(E)、肾小管萎缩/间质纤维化(T)、肾微小动脉病变与肾活检时平均动脉压(MAP)升高相关(P< 0.05);③系膜细胞增多(M)、肾小管萎缩/间质纤维化(T)与肾活检时血肌酐升高相关(P< 0.01).结论:原发性IgA肾病临床表现多样,病理类型以M0S1E0T0多见.原发性IgA肾病临床表现与IgA肾病牛津分类之间具有相关性,IgA肾病牛津分类与临床特点有关,可以有效地指导临床.%Objective:To study the correlation between clinical features and the Oxford pathological classification in IgA nephropathy (IgAN).Methods:Two hundred and five IgAN patients from the First Affiliated Hospital of Wenzhou Medical College which had been diagnosed by renal biopsy from July 2010 to June 2012 were reviewed.All of the pathological and clinical data were analyzed with SPSS 16.0.Results:Segmental glomerulosclerosis was the main pathological damage and M0S1E0T0 was the major type in renal histology.During the patient biopsy,the correlation was presence as follows:(① The proteinuria was related to renal pathological findings (including the mesangial proliferation,endocapillary proliferation

  18. Impact of the -675 4G/5G polymorphism of the plasminogen activator inhibitor-1 gene on childhood IgA nephropathy.

    Science.gov (United States)

    Han, Su-Ryun; Kim, Cheon-Jong; Lee, Byung-Cheol

    2012-04-01

    Plasminogen activator inhibitor-1 (PAI-1) is an important regulator of the fibrinolytic pathway and extracellular matrix (ECM) turnover. The -675 4G/5G polymorphism in the PAI-1 promoter is associated with altered PAI-1 transcription, suggesting that this polymorphism may be a candidate risk factor for diseases characterized by ECM accumulation, such as immunoglobulin A nephropathy (IgAN) and mesangial proliferative glomerulonephritis (MesPGN). We genotyped childhood patients with biopsy-confirmed IgAN (n=111) and MesPGN (n=47), and healthy control subjects (n=230) for the -675 4G/5G PAI-1 polymorphism by polymerase chain reaction-restriction fragment length polymorphism methods. The distribution of the 4G/4G (27.9%), 4G/5G (45.1%) and 5G/5G (27.0%) genotypes in IgAN patients was significantly different from the healthy controls (32.2, 54.3 and 13.5%, respectively) (p=0.0092). There was no significant difference in the genotype distributions of the 4G/5G polymorphism between MesPGN patients and the healthy controls. Regarding the impact of the polymorphism on IgAN, the 4G/4G genotype was markedly increased in patients with proteinuria (≥1,000 mg/day) and/or hypertension when compared to patients without proteinuria and hypertension (OR=5.23, 95% CI 1.34-20.38, P=0.0183). These findings indicate that the PAI-1 gene polymorphism may affect the susceptibility of childhood IgAN.

  19. Concurrent Drug-Induced Linear Immunoglobulin A Dermatosis and Immunoglobulin A Nephropathy

    OpenAIRE

    Kim, Ji Seok; Choi, Misoo; Nam, Chan Hee; Kim, Jee Young; Park, Byung Cheol; Kim, Myung Hwa; Hong, Seung Phil

    2015-01-01

    Diseases associated with immunoglobulin A (IgA) antibody include linear IgA dermatosis, IgA nephropathy, Celiac disease, Henoch-Schönlein purpura, etc. Although usually idiopathic, IgA antibody is occasionally induced by drugs (e.g., vancomycin, carbamazepine, ceftriaxone, and cyclosporine), malignancies, infections, and other causes. So far, only a few cases of IgA bullous dermatosis coexisting with IgA nephropathy have been reported. A 64-year-old female receiving intravenous ceftriaxone an...

  20. Phagocytosis of IgA Immune Complexes by Human U937 Cells

    Institute of Scientific and Technical Information of China (English)

    郭彩云; 崔薇; 张伟

    2003-01-01

    In order to study FcαR Ⅰ mediated phagocytosis ot lgA immune complexes by U937 cells, antigen 8.9NIP/BSA was labeled with FITC and reacted with anti-NIP IgA or anti-NIP IgG antibody to form immune complexes (ICs). They were then incubated with phorbol 12-myristate B-acetate (PMA) stimulated U937 cells. The phagocytosed ICs were quantified by flow cytometry. The results was that the expression of FcαR Ⅰ on U937 cells was higher than that of FcγR Ⅰ , FcyR Ⅱ and FcγR Ⅲ. After stimulation by PMA, expression of FcαR Ⅰ on U937 cells was markedly upregulated and the phagocytosis of IgA ICs was enhanced. FcαR Ⅰ mediated specific IgA phagocytosis was stronger than FcγR Ⅰ and FcγR Ⅱ mediated IgG phagocytosis. Complement receptors, CR1 and CR3, enhanced U937 cell phagocytosis of IgA ICs. It concludes that FcγR Ⅰ mediated strong phagocytosis of IgA ICs.

  1. Effects and safety of low doses of leflunomide combined with the adefovir dipivoxilin in the treatment of patients with IgA nephropathy and hepatitis B virus%小剂量来氟米特联合阿德福韦酯治疗合并慢性乙肝的IgA肾炎临床观察

    Institute of Scientific and Technical Information of China (English)

    郭永兵

    2011-01-01

    目的 观察小剂量(10mg)来氟米特联合阿德福韦酯治疗合并慢性乙肝的IgA肾炎的临床疗效和安全性.方法 22例伴乙肝的IgA肾炎和24例不伴乙肝的IgA肾炎分成两组,分别给予小剂量和全剂量(20 mg)的来氟米特进行为期6个月的临床观察.结果 两组蛋白尿均明显减轻(P<0.01)),两组总有效率差异无统计学意义(P>0.05);血清白蛋白均明显提高(P<0.01);血脂紊乱改善且两组均没有严重的不良反应.结论 小剂量的来氟米特治疗伴乙肝的IgA肾炎疗效肯定,无严重的不良反应.%Objective To investigate the effects and safety of low doses of leflunomide (10 mg/d) combined with the adefovir dipivoxil in the treatment of patients with IgA nephropathy and hepatitis B virus.Methods Twenty -two patients with IgA nephropathy and hepatitis B virus were treated with low doses of leflunomide combined with the adefovir dipivoxil.Another 24 cases of patients with IgA nephropathy no hepatitis B virus were treated with normal doses of leflunomide(20 mg/d) combined with the adefovir dipivoxil.Their therapeutic effects and safety were recorded and analysed through six months clinical observations respectively.Results Urinary protein of two group patients were both decreased obviously (P < 0.01 ) ).Serum albumin of two group patients were both obviously improved (P < 0.01 ).The total effectiveness of the two groups were not statistically significant (P >0.05 ).Only mild tolerable adverse effects were observed.Conclusions Low doses of leflunomide combined with adefovir dipivoxil therapy can be one of the safe and effective choices for treatment of patients with IgA nephropathy and hepatitis B virus.

  2. Detection and specificity of anti-Staphylococcus intermedius secretory IgA in human tears.

    Science.gov (United States)

    Lan, J; Willcox, M D; Jackson, G D

    1997-05-01

    Secretory IgA (sIgA) is the predominant immunoglobulin present in tears that protects the ocular surface against various antigens. Staphylococcus intermedius is a member of the normal ocular microbiota. The presence and the specificity of immunoglobulin A to S. intermedius was determined by fluorescent assay, ELISA and western blots. Three immunodominant antigens of S. intermedius were detected of 145, 127 and 61 kDa. Staphylococcus intermedius-specific IgA cross reacted with Staphylococcus aureus but not with Gram negative bacteria. This indicates that specific IgA may play an important role in the protection of the eye by limiting the levels of Gram positive normal microbiota and defending against the more pathogenic S. aureus.

  3. IgG and IgA with Potential Microbial-Binding Activity Are Expressed by Normal Human Skin Epidermal Cells

    Directory of Open Access Journals (Sweden)

    Dongyang Jiang

    2015-01-01

    Full Text Available The innate immune system of the skin is thought to depend largely on a multi-layered mechanical barrier supplemented by epidermis-derived antimicrobial peptides. To date, there are no reports of antimicrobial antibody secretion by the epidermis. In this study, we report the expression of functional immunoglobulin G (IgG and immunoglobulin A (IgA, previously thought to be only produced by B cells, in normal human epidermal cells and the human keratinocyte line HaCaT. While B cells express a fully diverse Ig, epidermal cell-expressed IgG or IgA showed one or two conservative VHDJH rearrangements in each individual. These unique VDJ rearrangements in epidermal cells were found neither in the B cell-derived Ig VDJ databases published by others nor in our positive controls. IgG and IgA from epidermal cells of the same individual had different VDJ rearrangement patterns. IgG was found primarily in prickle cells, and IgA was mainly detected in basal cells. Both epidermal cell-derived IgG and IgA showed potential antibody activity by binding pathogens like Staphylococcus aureus, the most common pathogenic skin bacteria, but the microbial-binding profile was different. Our data indicates that normal human epidermal cells spontaneously express IgG and IgA, and we speculate that these Igs participate in skin innate immunity.

  4. Concurrent Drug-Induced Linear Immunoglobulin A Dermatosis and Immunoglobulin A Nephropathy.

    Science.gov (United States)

    Kim, Ji Seok; Choi, Misoo; Nam, Chan Hee; Kim, Jee Young; Park, Byung Cheol; Kim, Myung Hwa; Hong, Seung Phil

    2015-06-01

    Diseases associated with immunoglobulin A (IgA) antibody include linear IgA dermatosis, IgA nephropathy, Celiac disease, Henoch-Schönlein purpura, etc. Although usually idiopathic, IgA antibody is occasionally induced by drugs (e.g., vancomycin, carbamazepine, ceftriaxone, and cyclosporine), malignancies, infections, and other causes. So far, only a few cases of IgA bullous dermatosis coexisting with IgA nephropathy have been reported. A 64-year-old female receiving intravenous ceftriaxone and metronidazole for liver abscess had purpuric macules and papules on her extremities. One week later, she had generalized edema and skin rash with bullae and was diagnosed with concurrent linear IgA dermatosis and IgA nephropathy. After steroid treatment, the skin lesion subsided within two weeks, and kidney function slowly returned to normal. As both diseases occurred after a common possible cause, we predict their pathogeneses are associated.

  5. High glucose repatterns human podocyte energy metabolism during differentiation and diabetic nephropathy

    Science.gov (United States)

    Imasawa, Toshiyuki; Obre, Emilie; Bellance, Nadège; Lavie, Julie; Imasawa, Tomoko; Rigothier, Claire; Delmas, Yahsou; Combe, Christian; Lacombe, Didier; Benard, Giovanni; Claverol, Stéphane; Bonneu, Marc; Rossignol, Rodrigue

    2017-01-01

    Podocytes play a key role in diabetic nephropathy pathogenesis, but alteration of their metabolism remains unknown in human kidney. By using a conditionally differentiating human podocyte cell line, we addressed the functional and molecular changes in podocyte energetics during in vitro development or under high glucose conditions. In 5 mM glucose medium, we observed a stepwise activation of oxidative metabolism during cell differentiation that was characterized by peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α)–dependent stimulation of mitochondrial biogenesis and function, with concomitant reduction of the glycolytic enzyme content. Conversely, when podocytes were cultured in high glucose (20 mM), stepwise oxidative phosphorylation biogenesis was aborted, and a glycolytic switch occurred, with consecutive lactic acidosis. Expression of the master regulators of oxidative metabolism transcription factor A mitochondrial, PGC-1α, AMPK, and serine–threonine liver kinase B1 was altered by high glucose, as well as their downstream signaling networks. Focused transcriptomics revealed that myocyte-specific enhancer factor 2C (MEF2C) and myogenic factor 5 (MYF5) expression was inhibited by high glucose levels, and endoribonuclease-prepared small interfering RNA–mediated combined inhibition of those transcription factors phenocopied the glycolytic shift that was observed in high glucose conditions. Accordingly, a reduced expression of MEF2C, MYF5, and PGC-1α was found in kidney tissue sections that were obtained from patients with diabetic nephropathy. These findings obtained in human samples demonstrate that MEF2C-MYF5–dependent bioenergetic dedifferentiation occurs in podocytes that are confronted with a high-glucose milieu.—Imasawa, T., Obre, E., Bellance, N., Lavie, J., Imasawa, T., Rigothier, C., Delmas, Y., Combe, C., Lacombe, D., Benard, G., Claverol, S., Bonneu, M., Rossignol, R. High glucose repatterns human podocyte energy

  6. 泼尼松联合霉酚酸酯结合中药治疗重症 IgA 肾病%Prednisone and Mycophenolate Mofetil Combined with Traditional Chinese Medicine for Treatment of Severe IgA Nephropathy

    Institute of Scientific and Technical Information of China (English)

    王丽伟

    2013-01-01

    目的:比较泼尼松联合霉酚酸酯(MMF)结合中药汤剂与泼尼松联合环磷酰胺(CYC)治疗重症IgA肾病的临床疗效。方法:84例重症IgA肾病患者根据入院先后顺序按随机原则分别给予泼尼松联合MMF结合中药汤剂治疗(MMF组,n=42),或采用泼尼松联合CYC治疗(CYC组n=42),持续12个月。两组患者基础病情无差异,随访时间18个月,观察两组患者临床缓解率以及相应实验室指标如24 h尿蛋白定量、血肌酐、血浆白蛋白、总蛋白、血脂变化,并比较两组治疗的不良反应。结果:1)临床缓解率:治疗18个月时MMF组临床总有效率高于CYC组,分别为85.7% VS 61.8%(P<0.05);2)观察期末,MMF组患者24 h尿蛋白定量(0.6±0.3)明显低于CYC组(1.4±0.5)(P<0.05),血浆白蛋白和总蛋白(43.2±4.3和70.2±8.1)均显著高于CYC组患者(36.9±3.6和60.3±7.6)(P<0.05);3)血脂变化:MMF组血脂较治疗前明显降低,而CYC组无变化(P<0.05);4)不良反应发生率:MMF组不良反应发生率(4.76%)明显低于CYC组(19.0%)。结论:泼尼松联合MMF治结合中药汤剂疗重症IgA肾病,临床缓解率高于泼尼松联合CYC静脉滴注疗法,能更有效降低患者24 h尿蛋白定量,改善患者血脂和血浆白蛋白水平,维持患者肾功能稳定,并且MMF不良反应发生率显著低于CYC疗法。%Objective:To compare efficacy of 1) Prednisone and mycophenolate mofetil (MMF) and herbal decoctions with 2) predni-sone and cyclophosphamide ( CYC ) for treating severe IgA nephropathy .Methods:Eighty-four patients with severe IgA nephropathy were randomly given prednisone and MMF and herbal decoction (MMF group, n=42), or treated with prednisone and CYC (CYC group n=42), for 12 months.Patients were of no difference in terms of basic illness severity .In 18-month followups, observe clinical effective rate and the

  7. Cross-reactive saliva IgA antibodies to oxidized LDL and periodontal pathogens in humans.

    Science.gov (United States)

    Akhi, Ramin; Wang, Chunguang; Kyrklund, Mikael; Kummu, Outi; Turunen, Sini Pauliina; Hyvärinen, Kati; Kullaa, Arja; Salo, Tuula; Pussinen, Pirkko J; Hörkkö, Sohvi

    2017-07-01

    Oxidized low-density lipoproteins (oxLDL) are formed as a result of lipid peroxidation and are highly immunogenic and proatherogenic. In this study, saliva antibodies binding to oxLDL, Porphyromonas gingivalis (Pg) and Aggregatibacter actinomycetemcomitans (Aa) were characterized and their cross-reactivity was evaluated. Resting and stimulated saliva samples were collected from 36 healthy adults (mean age 26 years). Saliva IgA, IgG and IgM autoantibody levels to copper oxidized LDL (CuOx-LDL) and malondialdehyde acetaldehyde-modified LDL (MAA-LDL) were determined with chemiluminescence immunoassay. Saliva IgA and IgG antibodies binding to MAA-LDL and CuOx-LDL were detected in all samples and they were associated with the saliva levels of IgA and IgG to P. gingivalis and A. actinomycetemcomitans. Competitive immunoassay showed that saliva antibodies to MAA-LDL cross-reacted specifically with P. gingivalis. The autoantibody levels to oxLDL in saliva were not associated with the autoantibody levels to oxLDL in plasma or with saliva apolipoprotein B 100 levels. Saliva contains IgA and IgG binding to oxLDL, which showed cross-reactive properties with the periodontal pathogens Porphyromonas gingivalis (P.g). The data suggest that secretory IgA to P.g may participate in immune reactions involved in LDL oxidation through molecular mimicry. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. Clinical Significance of Serum IgA,C3 Levels and IgA/C3 Ratio in IgA Nephropathy%血清IgA、C3及IgA/C3比值在IgA肾病中的临床意义

    Institute of Scientific and Technical Information of China (English)

    鲍玲玲; 柴华旗

    2013-01-01

      目的探讨血清IgA、C3水平及IgA/C3比值在原发性IgA肾病中的临床意义。方法以透射免疫比浊法测定69例经肾穿刺活检确诊为原发性IgA肾病患者和58例非IgA原发性肾小球肾炎患者血清IgA及C3水平,按Haas分级标准评估IgA肾病的病理分型,同时对结果进行分析。结果原发性IgA肾病患者与非IgA原发性肾小球肾炎患者血清IgA水平分别为[(3.01±0.91)vs(2.51±1.05)g/L,P<0.01];血清C3水平分别为[(1.00±0.22)vs(1.14±0.27)g/L,P<0.01];IgA/C3比值分别为(3.14±1.19 vs 2.26±0.93,P<0.01)。Haas分型为Ⅰ、Ⅱ型患者与Ⅲ、Ⅳ、Ⅴ型患者血清IgA水平分别为[(2.87±0.82)vs(3.26±1.03)g/L,P>0.05];血清C3水平分别为[(0.98±0.20)vs(1.04±0.25)g/L,P>0.05];IgA/C3比值分别为(3.05±1.03 vs 3.31±1.45,P>0.05)。结论血清IgA、C3水平及IgA/C3比值可作为鉴别原发性IgA肾病与非IgA肾病的参考指标。%Objective To analyze the difference of serum IgA,C3 levels and IgA/ C3 ratio between the patients with primary IgA nephropathy(IgAN) and non-IgA nephropathy and observe the correlation of these parameters with Haas’s grading system in patients with IgA nephropathy.Methods 69 patients with primary IgA nephropathy and 58 patients with non-IgA nephropathy were diagnosed by renal biopsy,the levels of serum IgA,C3 were detected with turbidimetric method in all patients.Patho-grading was evaluated according to the standard of Haas grading.Results The levels of serum IgA in the patients with IgAN were significantly higher than those in patients with non-IgA nephropathy(3.01±0.91 vs 2.51±1.05g/L,P0.05),C3 levels(0.98±0.20 vs 1.04±0.25g/L,P>0.05) and IgA/ C3 ratio(3.05±1.03 vs 3.31±1.45,P>0.05) of the patients with class Ⅲ,Ⅳ,Ⅴ was higher than classⅠand Ⅱ,but the differences between groups was not statistically significant.Conclusion The serum IgA,C3 levels and IgA/ C3

  9. Enhanced expression of two discrete isoforms of matrix metalloproteinase-2 in experimental and human diabetic nephropathy

    Science.gov (United States)

    Bae, Sun Sik; Lee, Min Young; Rhee, Harin; Kim, Il Young; Seong, Eun Young; Lee, Dong Won; Lee, Soo Bong; Kwak, Ihm Soo; Lovett, David H.

    2017-01-01

    Background We recently reported on the enhanced expression of two isoforms of matrix metalloproteinase-2 (MMP-2) in human renal transplantation delayed graft function. These consist of the conventional secreted, full length MMP-2 isoform (FL-MMP-2) and a novel intracellular N-Terminal Truncated isoform (NTT-MMP-2) generated by oxidative stress-mediated activation of an alternate promoter in the MMP-2 first intron. Here we evaluated the effect of hyperglycemia and diabetes mellitus on the in vitro and in vivo expression of the two MMP-2 isoforms. Methods We quantified the abundance of the FL-MMP-2 and NTT-MMP-2 transcripts by qPCR in HK2 cells cultured in high glucose or 4-hydroxy-2-hexenal (HHE) and tested the effects of the NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC). The streptozotocin (STZ) murine model of Type I diabetes mellitus and renal biopsies of human diabetic nephropathy were used in this study. Results Both isoforms of MMP-2 in HK2 cells were upregulated by culture in high glucose or with HHE. PDTC treatment did not suppress high glucose-mediated FL-MMP-2 expression but potently inhibited NTT-MMP-2 expression. With STZ-treated mice, renal cortical expression of both isoforms was increased (FL-MMP-2, 1.8-fold; NTT-MMP-2, greater than 7-fold). Isoform-specific immunohistochemical staining revealed low, but detectable levels of the FL-MMP-2 isoform in controls, while NTT-MMP-2 was not detected. While there was a modest increase in tubular epithelial cell staining for FL-MMP-2 in STZ-treated mice, NTT-MMP-2 was intensely expressed in a basolateral pattern. FL-MMP-2 and NTT-MMP-2 isoform expression as quantified by qPCR were both significantly elevated in renal biopsies of human diabetic nephropathy (12-fold and 3-fold, respectively). Conclusions The expression of both isoforms of MMP-2 was enhanced in an experimental model of diabetic nephropathy and in human diabetic nephropathy. Selective MMP-2 isoform inhibition could offer a novel approach for

  10. Clinical and pathological analysis of IgA nephropathy with acute kidney injury%原发性IgA肾病患儿伴发急性肾损伤19例临床分析

    Institute of Scientific and Technical Information of China (English)

    陈敏广; 叶晓华; 梁海燕; 杨青

    2016-01-01

    Objective To investigate the incidence,etiology,clinico-pathological characteristics and prognosis in primary IgA nephropathy (IgAN) children with acute kidney injury (AKI).Method Retrospective analysis of the clinical and pathological manifestations and follow-up results of 19 Chlidren,who were associated with AKI in 196 cases of children with IgA nephropathy treated in our department from January,1996 to Jun,2012 was performed.Result (1) The 19 cases associated with AKI accounted for 9.7% of all 196 Chlidren with IgAN.Within the 19 cases,there were gross hematuria in 17 cases,massive proteinuria in 16 cases,hypoalbuminemia in 10 cases,edema in 10 cases and hypertension in one case.The peak serum creatinine was from 94.5 μmol/ L to 282 μmol/L.(2) Histological changes:with the formation of crescent in 10 cases,diffuse endocapillary proliferation in 5 cases,15 cases had renal tubular injury,10 cases had red blood cell and protein cast,1 case with acute interstitial nephritis.(3) The cause of IgA nephropathy with AKI:13 patients had severe glomerular damage,including crescentic glomerulonephritis and diffuse endocapillary proliferation;1 case was complicated with acute interstitial nephritis after being treated with antibiotics,2 patients had decreased glomerular filtration rate because of taking benazepril or oral indomethacin,1 case with renal tubular injury induced by gross hematuria,and the other two cases the reason was not clear.(4) Multivariate Logistic regression analysis showed that massive proteinuria was independent risk factor of IgAN in children with AKI (OR =27.370,95% confidence interval was 3.151-237.740,P < 0.01).(5) None of the patients were on dialysis,steroid therapy was used in 13 cases (including 7 cases of methylprednisolone pulse therapy),6 cases were treated with combined cyclophosphamide treatment.Except 1 cases no significant improvement,the renal functiones of all patients recovered or improved within 1-2 months after treatment

  11. M-Type Phospholipase A2 Receptor as Target Antigen in Idiopathic Membranous Nephropathy

    Science.gov (United States)

    Beck, Laurence H.; Bonegio, Ramon G.B.; Lambeau, Gérard; Beck, David M.; Powell, David W.; Cummins, Timothy D.; Klein, Jon B.; Salant, David J.

    2009-01-01

    BACKGROUND Idiopathic membranous nephropathy, a common form of the nephrotic syndrome, is an antibody-mediated autoimmune glomerular disease. Serologic diagnosis has been elusive because the target antigen is unknown. METHODS We performed Western blotting of protein extracts from normal human glomeruli with serum samples from patients with idiopathic or secondary membranous nephropathy or other proteinuric or autoimmune diseases and from normal controls. We used mass spectrometry to analyze the reactive protein bands and confirmed the identity and location of the target antigen with a monospecific antibody. RESULTS Serum samples from 26 of 37 patients (70%) with idiopathic but not secondary membranous nephropathy specifically identified a 185-kD glycoprotein in non-reduced glomerular extract. Mass spectrometry of the reactive protein band detected the M-type phospholipase A2 receptor (PLA2R). Reactive serum specimens recognized recombinant PLA2R and bound the same 185-kD glomerular protein as did the monospecific anti-PLA2R antibody. Anti-PLA2R autoantibodies in serum samples from patients with membranous nephropathy were mainly IgG4, the predominant immunoglobulin subclass in glomerular deposits. PLA2R was expressed in podocytes in normal human glomeruli and colocalized with IgG4 in immune deposits in glomeruli of patients with membranous nephropathy. IgG eluted from such deposits in patients with idiopathic membranous nephropathy, but not in those with lupus membranous or IgA nephropathy, recognized PLA2R. CONCLUSIONS A majority of patients with idiopathic membranous nephropathy have antibodies against a conformation-dependent epitope in PLA2R. PLA2R is present in normal podocytes and in immune deposits in patients with idiopathic membranous nephropathy, indicating that PLA2R is a major antigen in this disease. PMID:19571279

  12. Clinical differential diagnosis value of detecting serum underglycosylated IgA1 in IgA nephropathy%血清低半乳糖化IgA1测定对鉴别IgA肾病的临床价值

    Institute of Scientific and Technical Information of China (English)

    邱强; 列才华; 曹翠明; 谢院生; 陈香美

    2008-01-01

    目的 确定血清低半乳糖化IgA1对鉴别诊断IgA肾病的临床价值.方法 以原发性肾小球疾病患者91例为研究对象,接受肾活检并留取血清;以健康体检者20例血清作为对照.血清标本先用装有耦联蚕豆凝集素的微球进行微量离心柱法分离并洗脱,获得低半乳糖化IgA1.再以凝集素HAA(Helix aspersa)用ELISA法定量检测异常糖基化IgA1(HAA-IgA1).分析血清低半乳糖IgA1升高在鉴别诊断IgA肾病方面的临床价值.结果 48例IgA肾病患者HAA-IgA1水平[(83.7±41.0)U]高于健康对照组[(52.6±22.9)U]及43例其他原发性肾小球疾病患者组[(49.2±27.3)U](均P<0.01).而该43例中,非IgA系膜增殖性肾炎患者22例(51%)的HAA-IgA1水平[(47.6±21.5)U]亦显著低于IgA肾病患者.以肾穿刺病理诊断为金标准,所绘制ROC曲线面积为0.797,面积的标准误为0.047(P<0.01);鉴别诊断IgA肾病的灵敏度为72.9%,特异度为72.1%,准确度为72.5%.结论 应用微量离心柱法联合ELISA法检测IgA肾病患者血清低半乳糖IgA1对于鉴别诊断IgA肾病具有一定临床价值.%Objective To evaluate the clinical value of detecting serum underglycosylated IgA1 in diagnosis and differentiation of lgA nephropathy (IgAN). Methods Serum underglycosylated IgA1 was isolated by microspincolumn coupled with vicia villosa lectin (VVL) from 48 cases with IgAN and 43 cases with other primary glomemlonephritis. All the patients were diagnosed by renal biopsy. Sera from 20 healthy persons were used as control group. After isolation, the eluant with rich underglycosylated lgAl was detected by incubation with biotin- labeled horseradish peroxidase (HRP) and Helix aspersa (HAA, recognizing N-acetylgalactosamine specifically)in enzyme-linked immunosorbent assay (ELISA). The sensitivity and specificity of diagnosis and differentiation of IgAN with elevated serum underglycosylated IgA1 were analyzed. Results The level of serum underglycosylated IgA1 in IgAN patients [(83

  13. Peptide mimetics of immunoglobulin A (IgA) and FcαRI block IgA-induced human neutrophil activation and migration.

    Science.gov (United States)

    Heineke, Marieke H; van der Steen, Lydia P E; Korthouwer, Rianne M; Hage, J Joris; Langedijk, Johannes P M; Benschop, Joris J; Bakema, Jantine E; Slootstra, Jerry W; van Egmond, Marjolein

    2017-07-24

    The cross-linking of the IgA Fc receptor (FcαRI) by IgA induces release of the chemoattractant LTB4, thereby recruiting neutrophils in a positive feedback loop. IgA autoantibodies of patients with autoimmune blistering skin diseases therefore induce massive recruitment of neutrophils, resulting in severe tissue damage. To interfere with neutrophil mobilization and reduce disease morbidity, we developed a panel of specific peptides mimicking either IgA or FcαRI sequences. CLIPS technology was used to stabilize three-dimensional structures and to increase peptides' half-life. IgA and FcαRI peptides reduced phagocytosis of IgA-coated beads, as well as IgA-induced ROS production and neutrophil migration in in vitro and ex vivo (human skin) experiments. Since topical application would be the preferential route of administration, Cetomacrogol cream containing an IgA CLIPS peptide was developed. In the presence of a skin permeation enhancer, peptides in this cream were shown to penetrate the skin, while not diffusing systemically. Finally, epitope mapping was used to discover sequences important for binding between IgA and FcαRI. In conclusion, a cream containing IgA or FcαRI peptide mimetics, which block IgA-induced neutrophil activation and migration in the skin may have therapeutic potential for patients with IgA-mediated blistering skin diseases. © 2017 The Authors. European Journal of Immunology published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Lessons From the KK-Ay Mouse, a Spontaneous Animal Model for the Treatment of Human Type 2 Diabetic Nephropathy.

    Science.gov (United States)

    Tomino, Yasuhiko

    2012-01-01

    Diabetic nephropathy is a major cause of end-stage kidney disease (ESKD) in patients with type 1 and type 2 diabetes throughout the world. In human glomeruli, expansion of diffuse mesangial matrices, exudative lesions and/or segmental nodular sclerosis are pathological features of diabetic nephropathy. There have been many reports on the pathogenesis and treatment of type 2 diabetes using various animal models. It appears that KK-Ay mice, especially in terms of their immunohistological findings, are a suitable animal model for human type 2 diabetic nephropathy. Many compounds have been reported to be advanced glycation end product (AGE) inhibitors such as aminoguanidine, angiotensin II receptor inhibitors and pyridoxamine, and these are useful in therapeutic interventions for reducing AGEs. Pyridoxamine ameliorates lipid peroxidation and insulin resistance in KK-Ay mice. Combination therapy with angiotensin converting inhibitors (ACE-I) and angiotensin II type 1 receptor blockers (ARB), including an ARB and 1,25-dihydroxyvitamin D3, i.e. anti-hypertensive and anti-reactive oxygen species effects, or with eicosapentaenoic acid (EPA), i.e. anti-microinflammation effect, have shown efficacy in the treatment of diabetic nephropathy in KK-Ay mice. It appears that KK-Ay mice are a useful spontaneous animal model for the evaluation of pathogenesis and treatment in patients with type 2 diabetic nephropathy.

  15. The Kinetics of Glomerular Deposition of Nephritogenic IgA

    Science.gov (United States)

    Yamaji, Kenji; Suzuki, Yusuke; Suzuki, Hitoshi; Satake, Kenji; Horikoshi, Satoshi; Novak, Jan; Tomino, Yasuhiko

    2014-01-01

    Whether IgA nephropathy is attributable to mesangial IgA is unclear as there is no correlation between intensity of deposits and extent of glomerular injury and no clear mechanism explaining how these mesangial deposits induce hematuria and subsequent proteinuria. This hinders the development of a specific therapy. Thus, precise events during deposition still remain clinical challenge to clarify. Since no study assessed induction of IgA nephropathy by nephritogenic IgA, we analyzed sequential events involving nephritogenic IgA from IgA nephropathy-prone mice by real-time imaging systems. Immunofluorescence and electron microscopy showed that serum IgA from susceptible mice had strong affinity to mesangial, subepithelial, and subendothelial lesions, with effacement/actin aggregation in podocytes and arcade formation in endothelial cells. The deposits disappeared 24-h after single IgA injection. The data were supported by a fluorescence molecular tomography system and real-time and 3D in vivo imaging. In vivo imaging showed that IgA from the susceptible mice began depositing along the glomerular capillary from 1 min and accumulated until 2-h on the first stick in a focal and segmental manner. The findings indicate that glomerular IgA depositions in IgAN may be expressed under the balance between deposition and clearance. Since nephritogenic IgA showed mesangial as well as focal and segmental deposition along the capillary with acute cellular activation, all glomerular cellular elements are a plausible target for injury such as hematuria. PMID:25409466

  16. Hepatic-associated immunoglobulin-A nephropathy in a child with liver cirrhosis and portal hypertension.

    Science.gov (United States)

    Alghamdi, Sharifa A; Saadah, Omar I; Almatury, Nesreen; Al-Maghrabi, Jaudah

    2012-01-01

    Hepatic-associated immunoglobulin A (IgA) nephropathy is a relatively common condition that occurs in adults with liver cirrhosis and portal hypertension. However, it is rare in children. This condition is characterized by the deposition of IgA in the renal glomeruli. The present report describes a 14-year-old boy with cryptogenic liver cirrhosis and portal hypertension who presented with hematuria and proteinuria associated with histological changes of IgA nephropathy.

  17. Hepatic-associated immunoglobulin-A nephropathy in a child with liver cirrhosis and portal hypertension

    Directory of Open Access Journals (Sweden)

    Sharifa A Alghamdi

    2012-01-01

    Full Text Available Hepatic-associated immunoglobulin A (IgA nephropathy is a relatively common condition that occurs in adults with liver cirrhosis and portal hypertension. However, it is rare in children. This condition is characterized by the deposition of IgA in the renal glomeruli. The present report describes a 14-year-old boy with cryptogenic liver cirrhosis and portal hypertension who presented with hematuria and proteinuria associated with histological changes of IgA nephropathy.

  18. 六味地黄汤对IgA肾病大鼠α-SMA及FN表达的影响%Effects of Liuwei Dihuang Decoction onthe Expression of α-SMA and FN in IgA Nephropathy Rats

    Institute of Scientific and Technical Information of China (English)

    彭亚军; 李旭华; 何泽云; 廖春来; 何雅琴; 胡淑娟

    2015-01-01

    〔Abstract〕 Objective To observe the effects of Liuwei Dihuang Decoction on the expression of α-SMA and fibronectin (FN) in IgA nephropathy rats, and further investigate its possible mechanism. Methods Forty SD rats were equally randomly divided into 4 groups: the normal group, model group, tripterygium glycosides tablets group and Liuwei Dihuang Decoction group. IgAN rat models were established with bovine serum albumin (BSA), lipopolysaccharide (LPS) and carbon tetrachloride (CCl4). The successfully established models were given 4 weeks of continuous perfusion. The proteinuria and urinary red blood cell count were detected every week, respectively. At fourth weekend, all the rats were killed for kidney function test. The α-SMA and FN protein expression of each group were detected by using immunohistochemistry and Western blot, and semi-quantitative analysis was made. Results The urine protein and urine red blood cell countsin each group were compared, the model group was higher significantly than that of normal group (P <0.05), while compared with mode group, Liuwei Dihuang Decoction group was decreased significantly (P<0.05), the difference was statistically significant.The α-SMA and FN expression in model group were increased than that in the normal group, while the expression of Liuwei Dihuang decoction group was decreased comparing with the model group (P<0.05), the difference was statistically significant. Conclusion Liuwei Dihuang Decoction can reduce the urine protein and urine red blood cell count of IgA nephropathy rats and improve the kidney function, which may be related with down-regulation of α-SMA and FN expression.%目的:观察六味地黄汤对IgA肾病大鼠α-平滑肌肌动蛋白(α-smooth muscle actin,α-SMA)及纤维连接蛋白(fibronectin, FN)表达的影响,进一步探讨其可能作用机制。方法 SD 大鼠40只随机分为正常对照组、模型组、雷公藤多苷片组,六味地黄汤组。除正常对

  19. Identification of cross-species shared transcriptional networks of diabetic nephropathy in human and mouse glomeruli.

    Science.gov (United States)

    Hodgin, Jeffrey B; Nair, Viji; Zhang, Hongyu; Randolph, Ann; Harris, Raymond C; Nelson, Robert G; Weil, E Jennifer; Cavalcoli, James D; Patel, Jignesh M; Brosius, Frank C; Kretzler, Matthias

    2013-01-01

    Murine models are valuable instruments in defining the pathogenesis of diabetic nephropathy (DN), but they only partially recapitulate disease manifestations of human DN, limiting their utility. To define the molecular similarities and differences between human and murine DN, we performed a cross-species comparison of glomerular transcriptional networks. Glomerular gene expression was profiled in patients with early type 2 DN and in three mouse models (streptozotocin DBA/2, C57BLKS db/db, and eNOS-deficient C57BLKS db/db mice). Species-specific transcriptional networks were generated and compared with a novel network-matching algorithm. Three shared human-mouse cross-species glomerular transcriptional networks containing 143 (Human-DBA STZ), 97 (Human-BKS db/db), and 162 (Human-BKS eNOS(-/-) db/db) gene nodes were generated. Shared nodes across all networks reflected established pathogenic mechanisms of diabetes complications, such as elements of Janus kinase (JAK)/signal transducer and activator of transcription (STAT) and vascular endothelial growth factor receptor (VEGFR) signaling pathways. In addition, novel pathways not previously associated with DN and cross-species gene nodes and pathways unique to each of the human-mouse networks were discovered. The human-mouse shared glomerular transcriptional networks will assist DN researchers in selecting mouse models most relevant to the human disease process of interest. Moreover, they will allow identification of new pathways shared between mice and humans.

  20. [Standardization of ELISA IgM and IgA for immunodiagnosis of human trichinosis].

    Science.gov (United States)

    Contreras, M C; Acevedo, E; Aguilera, S; Sandoval, L; Salinas, P

    1999-01-01

    An ELISA test for trichinosis using as antigen a larvae soluble fraction from Trichinella spiralis was carried out for the detection of IgM and IgA specific antibodies in 45 serum samples from patients confirmed or suspected to have trichinosis by strong clinical and epidemiological evidences. All the patients had positive serology detected by precipitin test, bentonite floculation test, indirect hemagglutination test and ELISA IgG test. The cut-off value was determined using two criteria. Criterion A was determined in each plate, using three positive controls and two negative ones; the average of the negative controls and the weakest positive control, multiplied by a 1.2 factor was, considered the cut-off value. Criterion B was determined using the average plus three standard deviations from 64 apparently healthy persons serum samples. In both cases, three serum dilutions (1:10, 1:100 and 1:500) were used. The sensitivity of ELISA IgM was 100.0, 93.3 and 82.2% using serum dilutions of 1:10, 1:100 and 1:500 respectively (criterion A) and 100.0, 97.8 and 95.6% for the same dilutions (criterion B), whereas the values for ELISA IgA were: 100.0, 91.1 and 86.7% (criterion A) and 100.0, 100.0 and 91.1% (criterion B). In order to find out the specificity of ELISA IgM and ELISA IgA, additional 118 serum samples from individuals with other parasitoses, such as cysticercosis (18) hydatidosis (39), fascioliasis (12), toxocariasis (30), Chagas' disease (12) and individuals with non-specific eosinophilia (7), were also tested. ELISA IgM presented a specificity of 92.3, 93.4 and 97.3% (criterion A) and 96.2, 97.8 and 97.8% (criterion B) whereas the results for ELISA IgA were 97.8, 98.9 and 99.4% (criterion A) and 98.4% for the 1:10 and 1:100 dilutions and 100.0% for the 1:500 dilution (criterion B). The positive predictive values of ELISA IgM were 76.3, 77.8 and 88.1% (criterion A) and 86.5, 91.7 and 91.5% (criterion B) whereas the negative ones were 100.0, 98.3 and 95

  1. Psammomys obesus, a particularly important animal model for the study of the human diabetic nephropathy

    Science.gov (United States)

    Scherzer, Pnina; Katalan, Shachaf; Got, Gay; Pizov, Galina; Londono, Irene; Gal-Moscovici, Anca; Popovtzer, Mordecai M.; Ziv, Ehud

    2011-01-01

    The Psammomys obesus lives in natural desert habitat on low energy (LE) diet, however when maintained in laboratory conditions with high energy (HE) diet it exhibits pathological metabolic changes resembling those of type 2 diabetes. We have evaluated and correlated the histopathology, metabolic and functional renal alterations occurring in the diabetic Psammomys. Renal function determined by measuring glomerular filtration rate (GFR), protein excretion, protein/creatinine ratio and morpho-immunocytochemical evaluations were performed on HE diet diabetic animals and compared to LE diet control animals. The diabetic animals present a 54% increase in GFR after one month of hyperglycemic condition and a decrease of 47% from baseline values after 4 months. Protein excretion in diabetic animals was 5 folds increased after 4 months. Light microscopy showed an increase in glomeruli size in the diabetic Psammomys, and electron microscopy and immunocytochemical quantitative evaluations revealed accumulation of basement membrane material as well as frequent splitting of the glomerular basement membrane. In addition, glycogen-filled Armanni-Ebstein clear cells were found in the distal tubules including the thick ascending limbs of the diabetic animals. These renal complications in the Psammomys, including changes in GFR with massive proteinuria sustained by physiological and histopathological changes, are very similar to the diabetic nephropathy in human. The Psamommys obesus represents therefore a reliable animal model of diabetic nephropathy. PMID:22025969

  2. Psammomys obesus, a particularly important animal model for the study of the human diabetic nephropathy.

    Science.gov (United States)

    Scherzer, Pnina; Katalan, Shachaf; Got, Gay; Pizov, Galina; Londono, Irene; Gal-Moscovici, Anca; Popovtzer, Mordecai M; Ziv, Ehud; Bendayan, Moise

    2011-09-01

    The Psammomys obesus lives in natural desert habitat on low energy (LE) diet, however when maintained in laboratory conditions with high energy (HE) diet it exhibits pathological metabolic changes resembling those of type 2 diabetes. We have evaluated and correlated the histopathology, metabolic and functional renal alterations occurring in the diabetic Psammomys. Renal function determined by measuring glomerular filtration rate (GFR), protein excretion, protein/creatinine ratio and morpho-immunocytochemical evaluations were performed on HE diet diabetic animals and compared to LE diet control animals. The diabetic animals present a 54% increase in GFR after one month of hyperglycemic condition and a decrease of 47% from baseline values after 4 months. Protein excretion in diabetic animals was 5 folds increased after 4 months. Light microscopy showed an increase in glomeruli size in the diabetic Psammomys, and electron microscopy and immunocytochemical quantitative evaluations revealed accumulation of basement membrane material as well as frequent splitting of the glomerular basement membrane. In addition, glycogen-filled Armanni-Ebstein clear cells were found in the distal tubules including the thick ascending limbs of the diabetic animals. These renal complications in the Psammomys, including changes in GFR with massive proteinuria sustained by physiological and histopathological changes, are very similar to the diabetic nephropathy in human. The Psamommys obesus represents therefore a reliable animal model of diabetic nephropathy.

  3. Protection of Human Colon Cells from Shiga Toxin by Plant-based Recombinant Secretory IgA

    Science.gov (United States)

    Nakanishi, Katsuhiro; Morikane, Shota; Ichikawa, Shiori; Kurohane, Kohta; Niwa, Yasuo; Akimoto, Yoshihiro; Matsubara, Sachie; Kawakami, Hayato; Kobayashi, Hirokazu; Imai, Yasuyuki

    2017-01-01

    Shiga toxin is a major virulence factor of food-poisoning caused by Escherichia coli such as O157:H7. Secretory immunoglobulin (Ig) A (SIgA) is supposed to prevent infection of the mucosal surface and is a candidate agent for oral immunotherapy. We previously established a recombinant monoclonal antibody (mAb) consisting of variable regions from a mouse IgG mAb specific for the binding subunit of Shiga toxin 1 (Stx1) and the Fc region of mouse IgA. Here we produced a secretory form of the recombinant IgA (S-hyIgA) with transgenic Arabidopsis thaliana plant. All the S-hyIgA cDNAs (heavy, light, J chain and secretory component) were expressed under the control of a bidirectional promoter of a chlorophyll a/b-binding protein of A. thaliana without using a viral promoter. The plant-based S-hyIgA exhibited antigen binding, and was modified with plant-specific N-linked sugar chains. The Ig heavy chain and secretory components were observed in an intracellular protein body-like structure of the transgenic leaves on immuno-electron microscopy. An extract of the transgenic leaves neutralized the cytotoxicity of Stx1 toward butyrate-treated Caco-2 cells, a human colon carcinoma cell line. These results will contribute to the development of edible therapeutic antibodies such as those for the treatment of mucosal infection. PMID:28368034

  4. 不同性别原发性IgA肾病患者的临床与病理特点研究%Study of the Clinical and Pathological Features of Patients with Primary IgA Nephropathy of Different Genders

    Institute of Scientific and Technical Information of China (English)

    吴小群; 廖学渊

    2013-01-01

    目的 分析不同性别原发性IgA肾病(IgAN)患者的临床、病理特点,了解性别与该病临床、病理特点的关系.方法 选择2009年1月至2011年12月梅州市人民医院经肾穿刺活检确诊的原发性IgAN患者158例的临床表现、检测指标及病理分级数据进行统计分析.结果 临床特点中,仅水肿在性别上差异有统计学意义(P<0.05);临床指标中,收缩压、舒张压、血尿酸、三酰甘油、白蛋白及补体C3在性别上分析差异均有统计学意义(P<0.05);病理分级中,男性组与女性组比较,差异无统计学意义(P>0.05).结论 性别对IgAN的临床表现及病理分级影响不大,但是临床指标水平在性别上有统计学意义,应加强男性相关指标监测,控制病情.%Objective To analyze the clinical and pathological features of primary IgA nephropathy patients of different genders,find out the relationship between gender and clinical and pathological features of the disease. Methods The clinical manifestations,indicators and pathological classification of 158 IgA nephropathy patients confirmed by renal biopsy were collected for statistical analysis. Results As for the clinical manifestations, there was significant difference in edema between different genders( P 0. 05 ). Conclusion The clinical manifestations and pathological grading of IgA nephropathy are affected less by the gender,but there are statistically significant difference in the clinical indicators. We should strengthen the monitoring of the related indicators of the male patients to control the disease.

  5. Balkan Endemic Nephropathy - Still continuing enigma, risk assessment and underestimated hazard of joint mycotoxin exposure of animals or humans.

    Science.gov (United States)

    Stoev, Stoycho D

    2017-01-05

    The spreading of mycotoxic nephropathy in animals/humans was studied. The possible etiological causes provoking this nephropathy were carefully reviewed and analyzed. The natural content of the most frequent nephrotoxic mycotoxins in target feedstuffs/foods were investigated, in addition to their significance for development of renal damages in endemic areas. An estimation of the level of exposure of humans to the nephrotoxic mycotoxin, ochratoxin A (OTA), is made. The possible synergism or additive effects between some target mycotoxins in the development of nephropathy is also covered. The significance of joint mycotoxin interaction and masked mycotoxins, in addition to some newly isolated fungal toxic agents in the complicated etiology of mycotoxic nephropathy ranged in Balkan countries is discussed. The importance of some target fungal species which can induce kidney damages was evaluated. The morphological/ultrastructural, functional and toxicological similarities between human and animal nephropathy are studied. The possible hazard of low content of combinations of some target mycotoxins in food or feedstuff ingested by pigs, chickens or humans under natural conditions is evaluated and a risk assessment was made. Some different but more effective manners of prophylaxis and/or prevention against OTA contamination of feedstuffs/foods are suggested. A survey was made in regard to the best possible ways of veterinary hygiene control of OTA-exposed animals at slaughter time for preventing the entrance of OTA in commercial feedstuffs/food channels with a view to reduce the possible health hazard for humans. The economic efficacy and applicability of such preventive measures is additionally discussed and some practical suggestions are made.

  6. Idiopathic erythrocytosis in IgA nephropathy

    Science.gov (United States)

    Mahesh, E.; Madhyastha, P. R.; Kalashetty, M.; Gurudev, K. C.; Bande, S.; John, M. M.

    2017-01-01

    We report a case of idiopathic erythrocytosis in a 31-year-old male who was incidentally detected to have hypertension during his preemployment checkup. Urine routine showed proteinuria and hematuria. Biochemical parameters revealed raised serum creatinine, and histological findings of the renal biopsy showed IgAN.

  7. Salivary production of IgA and IgG to human herpes virus 8 latent and lytic antigens by patients in whom Kaposi's sarcoma has regressed.

    Science.gov (United States)

    Mbopi-Keou, Francois-Xavier; Legoff, Jerome; Piketty, Christophe; Hocini, Hakim; Malkin, Jean-Elie; Inoue, Naoki; Scully, Crispian M; Porter, Stephen R; Teo, Chong-Gee; Belec, Laurent

    2004-01-23

    IgG and IgA antibodies with specificities to a latent and a lytic antigen of human herpes virus 8 (HHV-8) were detectable in the saliva and serum of eight patients whose Kaposi's sarcoma had regressed, seven of whom were HIV-1 infected. The measurement of antibody-specific activity and secretion rate, and the detection of secretory IgA all indicate anti-HHV-8 antibody activity in saliva. The specific humoral responses possibly influence mucosal replication of HHV-8, and in turn, that of HIV.

  8. The recent research of pathogenesis of IgA nephropathy%IgA 肾病的遗传易感性和黏膜免疫应答异常

    Institute of Scientific and Technical Information of China (English)

    王金泉

    2016-01-01

    众所周知,遗传风险因素和黏膜免疫异常在IgA肾病致病机制中起重要作用。近年来,系列研究已发现新的IgA肾病易感遗传位点,以及遗传风险因素和IgA肾病各方面,包括起病、临床表现、组织病理学、对治疗反应和预后之间的新关系。与此同时,肠道黏膜免疫异常在IgA肾病致病中的作用重新引起了人们的关注。肠道免疫耐受缺陷会削弱机体对微生物肠道屏障功能、增加食物抗原和细菌毒素的吸收、激活黏膜相关淋巴组织导致亚临床肠道炎症。遗传致病机制的进一步阐明和“肠道-肾关系”学说赋予IgA肾病新的治疗理念,如治疗亚临床肠道炎症或调控肠道微生物菌群,也利于进一步探索干预IgA的新靶目标和更加个体化的治疗。%It is known that genetic risk factors and mucosal immunity play vary important role in the pathogenesis of IgA ne-phropathy ( IgAN) .Recent years, new susceptibility loci of IgAN and relationships among genetic risk factors and each field of IgAN, which includes onset, clinical manifestation, histopathology, response to treatment and prognosis, have been found.Meanwhile, a re-surgence of interest has addressed the role of intestinal immunity facing dietary components, like gluten or the complex intestinal flora, the microbiota.A defective immune tolerance might favor an abnormal response to microbiota with alterations of the intestinal barrier, including increased alimentary antigens and bacterial toxins absorption, triggering mucosal-associated lymphoid tissue ( MALT) activa-tion and subclinical intestinal inflammation.The genetic pathogenesis and the new hypothesis for a strong intestine-kidney connection in IgAN are tempting, because they offer new treatment options, such as targeted to subclinical intestinal inflammation or microbiota modi-fications, and favor for further exploring new targets of IgAN intervention.

  9. Juvenile nephropathy in a Boxer dog resembling the human nephronophthisis-medullary cystic kidney disease complex.

    Science.gov (United States)

    Basile, Angelo; Onetti-Muda, Andrea; Giannakakis, Konstantinos; Faraggiana, Tullio; Aresu, Luca

    2011-12-01

    A juvenile nephropathy in a 4-year-old male Boxer dog, closely resembling the Nephronophthisis (NPHP)-Medullary Cystic Kidney Disease Complex (MCKD) in humans is described. Gross examination of the kidneys revealed several multiple cysts at the corticomedullary junction and in the medulla. Histological examination was characterized by a widespread tubular atrophy and dilatation, with a marked thickening of the tubular basement membrane, interstitial lymphocytic infiltration and fibrosis. Ultrastructural studies revealed dilated tubules with irregular basement membrane thickening and splitting. Lectin histochemistry investigation revealed that the cysts originated in the distal convoluted tubule and collecting duct. Having excluded all other known cystic diseases of the kidney, and based on the lectin histochemistry results, the macroscopic and histological findings of our case are highly compatible with a diagnosis of the NPHP-MCKD complex. To our knowledge, this is the first report describing this particular lesion.

  10. Membranous nephropathy

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/000472.htm Membranous nephropathy To use the sharing features on this page, please enable JavaScript. Membranous nephropathy is a kidney disorder that leads to changes ...

  11. Location and distribution of bone marrow mesenchymal stem cells in the kidney of IgA nephropathy rats%骨髓间充质干细胞在IgA肾病大鼠肾脏中的定位与分布

    Institute of Scientific and Technical Information of China (English)

    彭伟; 刘郑荣

    2011-01-01

    背景:由于骨髓间充质干细胞缺乏特异性表面抗原,常根据其贴壁生长、成骨成脂分化等生物学特点来鉴定.目的:观察骨髓间充质干细胞在IgA肾病大鼠肾脏中的定位与分布情况.方法:以牛血清白蛋白+葡萄球菌肠毒素B+皮下注射四氯化碳的改良法建立SD大鼠IgA肾病模型.造模成功分别经尾静脉移植大鼠骨髓间充质干细胞或生理盐水,并设立不造模的正常对照组.移植后1,4周观察各组大鼠的尿蛋白、肾功能、肾脏病理变化、IgA荧光沉积变化,并通过免疫组织化学观察BrdU标记的骨髓间充质干细胞在肾组织中的分布情况.结果与结论:移植后1周,骨髓间充质干细胞组尿蛋白、血肌酐明显低于生理盐水组;移植后4周,骨髓间充质干细胞组肾脏病理变化、IgA荧光沉积与生理盐水组比较差异有显著性意义.提示骨髓间充质干细胞输注可促进大鼠IgA肾病的修复,并可定位于肾小球系膜区及少数肾小管间质区,但随时间延长,BrdU标记的髓间充质干细胞在肾组织中分布却逐渐减少.%BACKGROUND: Bone marrow mesenchymal stem cells (BMSCs) without specific surface antigens are often identified according to adhesive growth, osteogenic differentiation, adipogenic differentiation and other biological characteristics. OBJECTIVE: to observe the location and distribution of BMSCs in IgA nephropathy rats.METHODS: Sprague-Dawley rats were randomly divided into three groups: BMSCs group, saline group and control group. IgA nephropathy model was established by the improving method with bovine serum albumin+staphylococcal enterotoxin B+subcutaneous injection of carbon tetrachloride in the former two groups. At the 1st and 4th weeks after BMSCs injection, the changes of urine protein, renal function, histopathology and IgA immunofluorescence were observed. BrdU-labeled BMSCs were detected by immunohistochemistry to observe the disposition in the kidney

  12. Large Scale Generation and Characterization of Anti-Human IgA Monoclonal Antibody in Ascitic Fluid of Balb/c Mice

    Directory of Open Access Journals (Sweden)

    Fatemeh Ezzatifar

    2015-03-01

    Full Text Available Purpose: Monoclonal antibodies are potentially powerful tools used in biomedical research, diagnosis, and treatment of infectious diseases and cancers. The monoclonal antibody against Human IgA can be used as a diagnostic application to detect infectious diseases. The aim of this study was to improve an appropriate protocol for large-scale production of mAbs against IgA. Methods: For large-scale production of the monoclonal antibody, hybridoma cells that produce monoclonal antibodies against Human IgA were injected intraperitoneally into Balb/c mice that were previously primed with 0.5 ml Pristane. After ten days, ascitic fluid was harvested from the peritoneum of each mouse. The ELISA method was carried out for evaluation of the titration of produced mAbs. The ascitic fluid was investigated in terms of class and subclass by a mouse mAb isotyping kit. MAb was purified from the ascitic fluid by ion exchange chromatography. The purity of the monoclonal antibody was confirmed by SDS-PAGE, and the purified monoclonal antibody was conjugated with HRP. Results: Monoclonal antibodies with high specificity and sensitivity against Human IgA were prepared by hybridoma technology. The subclass of antibody was IgG1 and its light chain was the kappa type. Conclusion: This conjugated monoclonal antibody could have applications in designing ELISA kits in order to diagnose different infectious diseases such as toxoplasmosis and H. Pylori.

  13. 肾小管肝型脂肪酸结合蛋白对小鼠IgA肾病的肾脏保护作用%Protective effects of tubular liver-type fatty acid binding protein on murine IgA nephropathy

    Institute of Scientific and Technical Information of China (English)

    佐楠; 李艳秋; 王力宁; 李子龙; 王均; 冯江敏; 马健飞; 范秋灵; 姚丽

    2011-01-01

    目的 探讨近曲小管肝型脂肪酸结合蛋白(L-FABP)对骨髓移植诱导的小鼠IgAN的肾脏保护作用.方法 通过骨髓移植在肾小管高表达人类L-FABP(hL-FABP)基因的转基因鼠(Tg)和相同背景的野生鼠(WT)上重建IgAN.受体鼠分别在骨髓移植后第6和12周处死,留取肾脏标本.用实时荧光定量PCR方法检测肾脏hL-FABP、纤连蛋白(FN)和单核细胞趋化蛋白1(MCP-1)的mRNA表达;免疫组化法检测hL-FABP和FN的蛋白表达分布;Western印迹法检测hL-FABP、4-羟壬烯醛(4-HNE)、血红素加氧酶1(HO-1)、FN、Ⅳ型胶原的蛋白表达水平;ELISA法检测血清IgA、尿白蛋白和尿hL-FABP水平.结果 骨髓移植在受体转基因鼠(Tg-ddY)和野生鼠(WT-ddY)上均重建了IgAN,血清IgA水平升高伴有系膜区IgA沉积,组间差异无统计学意义.正常Tg鼠的肾小管表达hL-FABP.与正常Tg鼠相比,骨髓移植后第6周,Tg-ddY鼠肾脏hL-FABP的mRNA(1.62±0.32比0.46±0.09,P<0.01)和蛋白(1.74±0.76比1.14±0.31,P<0.01)表达水平显著上调,伴有尿hL-FABP水平(μg/g肌酐)显著升高(59.87±26.75比31.01±14.86,P<0.05).与Tg-ddY鼠相比,WT-ddY鼠在第12周出现明显的白蛋白尿(mg/L)(828±656比82±22,P<0.01)、明显的系膜基质扩张(P<0.01),并在肾小球出现更多的FN及Ⅳ型胶原沉积.Tg-ddY鼠的肾脏HO-1和4-HNE修饰蛋白(均P<0.05)以及MCP-1 mRNA的表达(P<0.01)被显著抑制.结论 肾小管L-FABP可能通过抑制氧化应激和炎性介质的产生减轻肾小球损伤,在IgAN早期发挥了肾脏保护作用.%Objective To investigate the renoprotection of tubular L-FABP in murine IgA nephropathy (IgAN) induced by bone marrow transplantation(BMT). Methods IgAN models were reconstituted by BMT from IgAN-prone mice into mice (Tg) transgenically tubular overexpressing human L-FABP (hL-FABP) and wild type (WT) mice. These recipients were sacrificed at 6 and 12 weeks after BMT and their kidneys were collected. The expressions

  14. Dioxins, furans and dioxin-like PCBs in human blood: causes or consequences of diabetic nephropathy?

    Science.gov (United States)

    Everett, Charles J; Thompson, Olivia M

    2014-07-01

    Nephropathy, or kidney disease, is a major, potential complication of diabetes. We assessed the association of 6 chlorinated dibenzo-p-dioxins, 9 chlorinated dibenzofurans and 8 polychlorinated biphenyls (PCBs) in blood with diabetic nephropathy in the 1999-2004 National Health and Nutrition Examination Survey (unweighted N=2588, population estimate=117,658,357). Diabetes was defined as diagnosed or undiagnosed (glycohemoglobin ≥ 6.5%) and nephropathy defined as urinary albumin to creatinine ratio >30 mg/g, representing microalbuminuria or macroalbuminuria. For the 8 chemicals analyzed separately, values above the 75th percentile were considered elevated, whereas for the other 15 compounds values above the maximum limit of detection were considered elevated. Seven of 8 dioxins and dioxin-like compounds, analyzed separately, were found to be associated with diabetic nephropathy. The chemicals associated with diabetic nephropathy were: 1,2,3,6,7,8-Hexachlorodibenzo-p-dioxin; 1,2,3,4,6,7,8,9-Octachlorodibenzo-p-dioxin; 2,3,4,7,8-Pentachlorodibenzofuran; PCB 126; PCB 169; PCB 118; and PCB 156. Three of the 8 dioxins and dioxin-like compounds; 1,2,3,4,6,7,8,9-Octachlorodibenzo-p-dioxin; 2,3,4,7,8-Pentachlorodibenzofuran and PCB 118; expressed as log-transformed continuous variables; were associated with diabetes without nephropathy. When 4 or more of the 23 chemicals were elevated the odds ratios were 7.00 (95% CI=1.80-27.20) for diabetic nephropathy and 2.13 (95% CI=0.95-4.78) for diabetes without nephropathy. Log-transformed toxic equivalency (TEQ) was associated with both diabetic nephropathy, and diabetes without nephropathy, the odds ratios were 2.35 (95% CI=1.57-3.52) for diabetic nephropathy, and 1.44 (95% CI=1.11-1.87) for diabetes without nephropathy. As the kidneys function to remove waste products from the blood, diabetic nephropathy could be either the cause or the consequence (or both) of exposure to dioxins, furans and dioxin-like PCBs. Copyright © 2014

  15. Mouse Models of Diabetic Nephropathy

    OpenAIRE

    Brosius, Frank C.; Alpers, Charles E.; Bottinger, Erwin P.; Breyer, Matthew D.; Coffman, Thomas M.; Gurley, Susan B.; Harris, Raymond C.; Kakoki, Masao; Kretzler, Matthias; Leiter, Edward H.; Levi, Moshe; McIndoe, Richard A.; Sharma, Kumar; Smithies, Oliver; Susztak, Katalin

    2009-01-01

    Diabetic nephropathy is the major cause of end-stage renal disease worldwide. Despite its prevalence, identification of specific factors that cause or predict diabetic nephropathy has been delayed in part by lack of reliable animal models that mimic the disease in humans. The Animal Models of Diabetic Complications Consortium (AMDCC) was created 8 years ago by the National Institutes of Health to develop and characterize models of diabetic nephropathy and other complications. This interim rep...

  16. 免疫抑制治疗IgA肾病远期疗效的Meta分析%Meta analysis for the long-term efficacy and safety of immunosuppression on the progression of IgA nephropathy

    Institute of Scientific and Technical Information of China (English)

    田磊; 邵兴华; 谢园园; 王琴; 王玲; 倪兆慧; 牟姗

    2014-01-01

    Objective To access the long-term efficacy and safety of immunosuppression on the progression of IgA nephropathy (IgAN) by Meta analysis.Methods Databases EMBASE,Pubmed,Elsevier Science Direct,Scopus,Web of Science,Google Scholar,Cochrane Library,China National Knowledge Infrastructure,WanFang and VIP Data were retrieved to collect the randomized controlled trials (RCTs) at least 3 years follow-up on immunosuppression for IgAN published before May 2014.The literatures were screened independently by two reviewers according to the inclusion and exclusion criteria,and the methodological quality was assessed.Statistic software Stata 12.0 was used to conduct analysis.Results Nine articles were included in this study with a total of 568 patients.Immurnosuppression could lowered the risk for the progression to ESRD (RR=0.32,95%CI:0.20-0.49,P < 0.01).As far as the efficacy of immunosuppression,subgroup analysis indicated that three studies with more than 7 year follow-up (RR=0.28,95%CI:0.13-0.59,P < 0.01) were similar with 7 studies followed by for less than 7 years (RR=0.34,95% CI:0.19-0.59,P<0.01); six adopted immunosuppressor monotherapy (RR=0.29,95% CI:0.15-0.58,P< 0.01) were similar to two used corticosteroids plus other immunosuppression (RR=0.33,95%CI:0.18-0.59,P < 0.01); There were no significant differences between four studies from Europe (RR=0.27,95%CI:0.14-0.53,P < 0.01) and five from Asia (RR=0.35,95% CI:0.19-0.65,P<0.01).Immunosuppression was associated with an increased risk for adverse events (RR=2.33,95% CI:1.33-4.09,P<0.01).Conclusion Immunosuppression for IgAN may reduce long-term risk of progression to ESRD,but increase the risk of adverse events to some extent.%目 的应用Meta分析的方法评价IgA肾病免疫抑制治疗的远期疗效.方法 采用计算机检索EMBASE、Pubmed、Elsevier Science Direct、Scopus、Web of Science、Google Scholar、Cochrane图书馆、中国知网期刊、万方、维普等数据

  17. Clinicopathological analysis of IgA nephropathy patients with mild proteinuria and/or hematuria%少量蛋白尿和(或)血尿IgA肾病临床病理分析

    Institute of Scientific and Technical Information of China (English)

    萨茹拉; 傅辰生; 陈利明; 袁敏; 丁小强; 刘红; 於佳炜; 章晓燕; 蒋素华; 邹建洲; 滕杰; 吉俊; 钟一红

    2010-01-01

    Objective To clarify the relationship between clinical manifestation and pathological features of IgA nephropathy (IgAN) patients with mild proteinuria and/or hematuria.Methods Clinicopathological data from 316 biopsy-proven IgAN cases (proteinuria<1 g/24 h and/or hematuria, and Scr<133 μmol/L) from our hospital between January 1993 and October 2009 were studied retrospectively. The renal histopathology was quantified according to Lee's grading and Katafuchi's semi-quantitative standard, and the risk factors for renal pathological lesions were evaluated using multifactor logistic regression analysis. Results Among these 316 patients, 123 were male and 193 patients were female. The mean age at the time of renal biopsy was (33.10±10.69) years old. Clinical features were found as follows: hematuria with proteinuria was found in 267 patients (84.5%), isolated hematuria in 24 patients (7.6%), and isolated proteinuria in 25 patients (7.9%). 16.5% of patients had hypertension. The percentages of CKD stage Ⅰ, Ⅱ, Ⅲ were 76.9%, 20.9% and 2.2%, respectively. 31.3% of patients presented Lee's grade Ⅲ or more severe.52.8% of patients had various degrees of glomerulosclerosis. Crescent formation was observed in 20.3% of patients. 22.5% of patients showed tubular atrophy;16.8% showed interstitial fibrosis and 24.7% also had renal vascular lesions. The extent of glomerulosclerosis was negatively correlated with eGFR levels, but positively correlated with the amount of proteinuria and mean arterial pressure (MAP) level (P<0.05). The score of tubulointerstitial lesion was positively correlated with the amount of proteinuria and negatively correlated with eGFR and hemoglobin (Hb)level (P<0.05). The degree of renal vascular lesion was also correlated to MAP level positively and eGFR level negatively (P<0.05). Multifactor logistic regression analysis revealed that proteinuria, Scr and Hb at the time of renal biopsy were independent risk factors for severe renal

  18. The Application of AN Electronic Nose as a Predictive Technique against Human Diabetic Nephropathy

    Science.gov (United States)

    Mohamed, E. I.; Festuccia, A. M.; Martinelli, E.; Andreoli, A.; Martini, A.; di Natale, C.; de Lorenzo, A.

    2000-12-01

    The aim of this study is to apply electronic nose (EN) technology as an alternative method for fast monitoring of metabolic clearances and nephropathy insurgence in diabetics. This will be performed through urine analyses of diabetic patients and healthy subjects.

  19. Lack of cleavage of immunoglobulin A (IgA) from rhesus monkeys by bacterial IgA1 proteases.

    OpenAIRE

    Reinholdt, J; Kilian, M.

    1991-01-01

    Bacterial immunoglobulin A1 (IgA1) proteases cleaving IgA1 and secretory IgA1 molecules in the hinge region are believed to be important virulence factors. Previous studies have indicated that IgA of humans, gorillas, and chimpanzees are the exclusive substrates of these enzymes. In a recent study, IgA from the rhesus monkey was found to be susceptible to the IgA1 protease activity of Streptococcus pneumoniae. In an attempt to reproduce this observation, we found that neither five isolates of...

  20. Radiogenic nephropathy; Radiogene Nephropathie

    Energy Technology Data Exchange (ETDEWEB)

    Gotthardt, M. [Univ. Medisch Centrum St Radboud, Nijmegen (Netherlands). Nucleaire Geneeskunde

    2010-07-01

    Patient-individual dosimetric analyses are a useful tool in external beam radiotherapy (EBR) to protect patients from side effects such as radiogenic nephropathy. At this point in time, individual dosimetry is not used as a standard in patient treated with radiolabelled antibody fragments or polypeptides. The reasons are a number of problems, which make patient dosimetry more challenging than in EBR. While in EBR, the dose is distributed evenly in the organ and the organ volume can exactly be determined, in internal radiotherapy the tracer is not evenly distributed within the organ leading to a non-uniform dose distribution. In addition, the dose rate of the most commonly used radionuclides is lower than in EBR and the range of their radiation differ, so that the radiobiological effects are differing considerably in comparison to EBR. Conclusion: More complex models have to be used for clinical kidney dosimetry in internal radiotherapy. In this paper, we give a concise overview of the reasons for accumulation of radiotracers in the kidney, the most recent developments in kidney dosimetry, and approaches to reduce the kidney uptake of radiotracers in order to avoid radiogenic nephropathy. (orig.)

  1. A double antibody radioimmunoassay for measurement of IgG, IgA and IgM synthesized by human lymphocytes in vitro.

    Directory of Open Access Journals (Sweden)

    Asano,Taro

    1981-11-01

    Full Text Available To investigate cellular interactions between human T and B lymphocytes in various diseases, we established a technique to prove terminal differentiation of B lymphocytes into immunoglobulin synthesizing and secreting cells. We also established a double antibody radioimmunoassay to measure the amount of IgG, IgA and IgM synthesized and secreted in culture supernatants. Purified immunoglobulins were obtained from sera of patients with myeloma or macroglobulinemia. The peripheral blood lymphocytes from 25 normal individuals had the geometric mean synthetic rates of 1886 ng for IgG, 1607 ng for IgA and 1173 ng for IgM per 1 X 10(6 cells when cultured for nine days in the presence of pokeweed mitogen. The method is simple and sensitive, and is thought to be useful for examining human lymphocyte function in vitro.

  2. Renal disease in human immunodeficiency virus - Not just HIV-associated nephropathy.

    Science.gov (United States)

    Vali, P S; Ismal, K; Gowrishankar, S; Sahay, M

    2012-03-01

    The aim of the study was to determine the various histopathological lesions in human immunodeficiency virus (HIV) patients with renal dysfunction and to establish clinicopathological correlation. Over a period of two years from January 2008 to March 2010, 27 HIV positive patients with renal dysfunction were subjected to renal biopsy. Of the 27 patients, 23 were males and four were females (85.2% males, 14.8% females). Mean age was 38.2 ± 10.36 (range 20 - 60) years. The probable mode of acquisition of HIV infection was sexual in 22 patients (81.5%). Thirteen patients (48%) had nephrotic proteinuria. The CD4 count ranged from 77 to 633/microliter. The kidneys were of normal size in 19 (70.4%) and bulky in eight (29.6%) patients. Thirteen patients required renal replacement therapy. Eleven patients had acute tubule-interstitial lesions (40.7%) while 15 (55.5%) had glomerular lesions. The various glomerular lesions were, focal segmental glomerulosclerosis in five, amyloidosis in three, diffuse proliferative GN in two, and membranoproliferative glomerulonephritis (GN), membranous GN, minimal change disease, diabetic nephropathy, crescentic GN, and thrombotic microangiopathy were seen in one each. None of the clinical or laboratory variables, except hypertension, was found to predict glomerular versus non-glomerular lesions on biopsy. In conclusion we show that a variety of glomerular and tubulointerstitial lesions can be seen on renal histology. Hence, renal biopsy is indicated in renal dysfunction associated with HIV for making proper diagnosis and therapy.

  3. Circulating human CD27-IgA+ memory-B cells recognize bacteria with polyreactive immunoglobulins1

    Science.gov (United States)

    Berkowska, Magdalena A.; Schickel, Jean-Nicolas; Grosserichter-Wagener, Christina; de Ridder, Dick; Ng, Yen Shing; van Dongen, Jacques J.M.; Meffre, Eric; van Zelm, Menno C.

    2015-01-01

    The vast majority of immunoglobulin (Ig)A production occurs in mucosal tissue following T-cell dependent and T-cell independent antigen responses. To study the nature of each of these responses, we analyzed the gene expression and Ig reactivity profiles of T-cell dependent CD27+IgA+ and T-cell independent CD27−IgA+ circulating memory-B cells. Gene expression profiles of IgA+ subsets were highly similar to each other and to IgG+ memory-B-cell subsets with typical upregulation of activation markers and downregulation of inhibitory receptors. However, we identified the mucosa-associated CCR9 and RUNX2 genes to be specifically upregulated in CD27−IgA+ B cells. We also found that CD27−IgA+ B cells expressed antibodies with distinct Ig repertoire and reactivity than those from CD27+IgA+ B cells. Indeed, antibodies from CD27−IgA+ B cells were weakly mutated, often utilized Igλ chain and were enriched in polyreactive clones recognizing various bacterial species. Hence, T-cell independent IgA responses are likely involved in the maintenance of gut homeostasis through the production of polyreactive mutated IgA antibodies with crossreactive anti-commensal reactivity. PMID:26150533

  4. 尿蛋白标志物对儿童IgA肾病和IgM肾病肾脏病理损伤的预测价值%Urinary protein markers predict the severity of renal histological lesions in children with IgA nephropathy and IgM nephropathy

    Institute of Scientific and Technical Information of China (English)

    王雪芹; 李梦霞; 李晓忠; 朱雪明; 封其华; 李艳红

    2015-01-01

    目的 比较儿童IgM肾病(IgMN)和IgA肾病(IgAN)的临床表现、病理损伤及尿蛋白标志物水平变化,探讨尿蛋白标志物对IgAN和IgMN患儿肾脏病理损伤严重程度的预测价值.方法 选择2002年1月至2014年10月行肾组织活检的74例患儿为研究对象.检测活检当日晨尿中IgG、清蛋白(Alb)、转铁蛋白(TRF)、α1-微球蛋白(α1-MG)、β2-微球蛋白(β2-MG)和N-乙酰-β-葡萄糖苷酶(NAG)水平.采用系膜细胞增生(MC)、肾小球硬化(GS)、肾小管间质损伤(TID)的评分半定量评估肾脏病理损伤严重程度.以多因素Logistic回归分析评估在校正混杂因素后尿液蛋白与肾脏病理损伤的关系,用受试者工作特征曲线下面积(AUC)评价尿液蛋白对肾脏病理损伤严重程度的预测价值.结果 74例患儿中,IgAN 44例,IgMN 30例.IgAN患儿尿oα1-MG和Alb水平高于IgMN患儿;然而,校正年龄后,差异无统计学意义.多因素Logistic回归分析显示,尿液蛋白中TRF与IgAN和IgMN患儿严重MC(>5个系膜细胞/系膜区)显著相关(B=0.010);Alb与严重GS(≥10%肾小球节段性黏连或硬化)显著相关(B=0.001);NAG与严重TID(局灶或弥散性肾小管间质病变)显著相关(B =0.038).尿β2-MG与严重MC、GS、TID无显著相关.尿TRF预测严重MC的AUC值为0.85(P <0.001).尿Alb预测严重GS的AUC值为0.78 (P =0.002).尿NAG预测严重TID的AUC值为0.78(P =0.003).结论 尿蛋白标志物是预测儿童IgAN和IgMN肾脏病理损伤严重程度的指标.其中尿TRF、Alb和NAG具有更好的预测价值.%Objective To compare the clinical manifestations,renal histological lesions,and the levels of urinary protein markers between the children with IgA nephropathy (IgAN) and those with IgM nephropathy (IgMN), and to determine whether urinary protein markers could predict the severity of renal histological lesions in children with IgAN and IgMN.Methods Seventy-four children with renal biopsy-proven IgAN and IgMN from

  5. Effect of tripterygium glycosides on serum ion and β2-GPI/ox-LDL in patients with IgA nephropathy%雷公藤多苷对IgAN患者血清离子及β2-GPI/ox-LDL影响

    Institute of Scientific and Technical Information of China (English)

    彭健韫; 苏震

    2015-01-01

    目的:探讨雷公藤多苷对IgA肾病(IgA nephropathy,IgAN)患者血清离子及β2糖蛋白I(β2-glycoprotein,β2-GPI)/氧化低密度脂蛋白( oxidized low density lipoprotein ,ox-LDL)的影响。方法收集丽水市人民医院肾内科2014年1月~2015年4月收治的原发性IgAN患者54例,随机分为对照组和实验组,每组27例,对照组患者常规给予盐酸贝那普利片10 mg,1次/天口服;给予双嘧达莫片50 mg,3次/天口服,实验组在对照组基础上给予雷公藤多苷片20 mg,3次/天口服。2组患者均治疗6个月。治疗结束后,对所有患者的血清Ca、P、β2-GPI/ox-LDL水平及肾功能相关指标进行检测。结果与对照组治疗后比较,实验组患者血清Ca水平较高,血清P水平较低(P<0.05);实验组患者的血清β2-GPI/ox-LDL水平较低(P<0.05);实验组患者的血清Scr、BUN水平较低(P<0.05)。结论雷公藤多苷能够显著降低IgAN患者血清P、β2-GPI/ox-LDL、Scr及BUN水平,提高血清Ca水平,改善肾功能。%Objective To analyse effect of tripterygium glycosides on serum ion and β2-GPI/ox-LDL in patients with IgA nephropathy. Methods 54 patients who were diagnosed with primary IgA nephropathy in our hospital were collected.All patients were randomly divided into experimental group and control group, 27 cases in each group.Control group was given conventional Benazepri1 Hydrochloride Tablets 10 mg, 1 times per day orally;given Dipyridamole Tablets 50 mg, 3 times per day orally, patients in experimental group were given tripterygium glycosides 20 mg on the basis of control group treatment orally,3 times per day.All the patients were treated for 6 month.After the treatment, the serum levels of Ca,P,β2-GPI/ox-LDL and renal function related index were detected in all patients.Results Compared with control group post-treatment, the serum level of Ca was higher(P<0.05); and the serum level of P

  6. Risk factor analysis of blood pressure circadian rhythm abnormality in IgA nephropathy patients with hypertension%126例IgA肾病伴高血压患者血压昼夜节律异常的危险因素分析

    Institute of Scientific and Technical Information of China (English)

    林利容; 张炜炜; 黄坤; 杨聚荣; 张建国; 李开龙; 何娅妮

    2013-01-01

    Objective To investigate the risk factors for blood pressure circadian rhythm abnormality in the IgA nephropathy ( IgAN) patients with hypertension. Methods The study enrolled 126 adult IgA nephropathy patients with hypertension,all of them underwent renal biopsy and ambulatory blood pressure monitoring. Patients were excluded if they were treated by antihypertensive drugs or glucocorti-coids. Baseline patient characteristics and clinical data were collected. Risk factors of blood pressure rhythm abnormality were determined by Spearman correlation analysis and Logistic regression analysis. Results The prevalence of non-dipper blood pressure was 73. 8% for IgAN patients with hypertension. Uric acid,serum creatinine,urine protein/creatinine,nocturnal urinary sodium,urinary chlorine excretion levels were higher in patients with non-dipper hypertension than those with dipper hypertension. Patients with non-dipper hypertension had significantly lower eGFR than those with non-dipper hypertension. Of logistic regression analysis showed that high uric acid,urine protein/creatinine≥ 1.84 mg/mg,24 h urinary sodium > 62. 5 mmol/L,eGFR < 60 ml/min/1. 73 m2 were risk factors for blood pressure circadian rhythm abnormality in the IgA nephropathy patients with hypertension. Conclusion Kidney lesion not only leads to hypertension,also plays a crucial role in the regulation of blood pressure rhythm abnormalities.%目的 分析IrA肾病伴高血压患者血压昼夜节律异常的危险因素.方法 收集成人IrA肾病伴高血压患者126例,均行肾活检及动态血压监测,排除服用降压药物、糖皮质激素者.采用单因素及多因素Logistic回归分析血压昼夜节律异常的危险因素.结果 (1)成人IgA肾病伴高血压患者非勺型血压患病率为73.8%;(2)与勺型血压组比较,非勺型血压患者总胆固醇、血尿酸、血清肌酐、尿蛋白/肌酐、夜间尿钠、尿氯排泄水平均显著增高,肾小球滤过率(eGFR)

  7. 伴有牙周炎的IgA肾病患者牙周治疗前后血清TNF-α与IL-8变化分析%Changes in levels of serum TNF-α and IL-8 before and after periodontal therapy for patients of IgA nephropathy with periodontitis

    Institute of Scientific and Technical Information of China (English)

    许志鹏; 宋勇; 孙燕

    2015-01-01

    Objective To examine the levels of serum tumor necrosis factor-α(TNF-α) and interleukin-8 (IL-8) for IgA nephropathy patients with periodontitis before and after periodontal therapy. Methods Fifty pa-tients of IgA nephropathy with chronic periodontitis (study group) and 30 healthy individuals (control group) were in-cluded in this study. The study group was treated by ultrasonic and VECTOR periodontal therapy apparatus, whereas the control group received no special treatment. We measured the periodontal indexes, and serum TNF-αand IL-8 lev-els by enzyme-linked immunosorbent assay (ELISA) at the visit of doctor in the control group as well as before treat-ment and 4 weeks after treatment in the study group. Results After periodontal therapy, the periodontal status was significantly improved, with the levels of periodontal indexes and serum TNF-α and IL-8 significantly decreased. Compared with the control group, the periodontal indexes and the serum TNF-αand IL-8 were still significantly higher. Conclusion Periodontal treatment can not only effectively improve the periodontal lesions and promote the recovery of periodontitis, but also reduce the levels of serum TNF-αand IL-8 and benefit the treatment for IgA nephropathy.%目的:观察伴有慢性牙周炎的IgA肾病患者牙周治疗前后血清肿瘤坏死因子-α(TNF-α)和白细胞介素-8(IL-8)变化。方法选取伴有慢性牙周炎的IgA肾病患者50例(治疗组)和健康者30例(对照组)。对照组不予特殊处理,治疗组采用超声洁牙和VECTOR牙周治疗仪进行牙周治疗,对照组于初诊时,治疗组于治疗前及治疗后4周,分别检测两组受试者的牙周指数和血清TNF-α与IL-8的浓度。血清中TNF-α与IL-8的浓度采用酶联免疫吸附法测定。结果治疗组患者经过牙周治疗后,牙周状况明显好转,血清TNF-α与IL-8浓度与治疗前比较均明显降低,差异均有统计学意义(P<0.05),但是牙周指数、TNF-α和IL-8

  8. Study on the Regularity of Prescription for IgA Nephropathy Basing on Text Mining Technique with Chinese Patent Medicine and West Medicine%基于文本挖掘技术的中成药及西药治疗IgA肾病用药规律研究

    Institute of Scientific and Technical Information of China (English)

    蔡峰; 郑光; 郭洪涛; 姜淼; 谭勇; 杨静; 张弛; 张志华; 吕爱平

    2011-01-01

    Objective:To explore the data to reveal meaningful regularity of Chinese patent medicine and west medicine. Methods: Papers from large data sets of IgA nephropathy were used to set the Acess database. And then,these articles were used to data processing by the SQL. After article denoise,the regulation of IgA nephropathy was analyzed about the TCM medicine and the west medicine. Results:Glucoside Tripterygium Total, Huangkui Capsule ,hemostasis tablets,Bailing Capsule were the commonly used Chinese patent medicine. Im-munosuppressive agents, ACEI, glucocorticoids, ARB were of the core west medicine. Glucoside Tripterygium Total, Huangkui Capsule and ACEI,ARB,glucocorticoids were often used in conjunction with Chinese patent medicine and western medicine. Conclusion:The result,which provides an objective basis with text mining technique, not only reflects the actual clinical use,but also expands the scope of clinical medicine for the scientific and rational use of Chinese proprietary medicine and west medicine.%目的 利用文本挖掘技术探索中成药及西药治疗IgA肾病的用药规律.方法在中国生物医学文献数据库(CBM)中采集治疗IgA肾病的相关文献,建立Access数据库,运用SQL对数据进行处理,结合人工降噪后,分析中成药及西药治疗IgA肾病的用药规律.结果雷公藤多苷片、黄葵胶囊、止血片、百令胶囊等依次为治疗IgA肾病的高频中成药;免疫抑制剂、ACEI、糖皮质激素、ARB等依次为治疗IgA肾病的高频西药;雷公藤多苷片、黄葵胶囊和ACEI、ARB、糖皮质激素分别是联用时常用的中成药和西药.结论文本挖掘能够分析中成药及西药治疗IgA肾病的用药规律,获得的结果不仅反映了临床用药实际,而且拓展了临床用药的范畴与思路,为科学合理地使用中成药及西药提供了客观依据.

  9. Acute Cresentric IgA Nephritis in a Patient with Hodgkin's Lymphoma

    Directory of Open Access Journals (Sweden)

    Ebru GÖK OĞUZ

    2014-09-01

    Full Text Available In glomerular diseases, the occurence of lymphoma is mostly observed in the form of both minimal change disease and Hodgkin’s lymphoma. The coocurrence of Membranous nephropathy and membranoproliferative glomerulonephritis are generally associated with non-Hodgkin’s lymphoma. While Ig A nephropathy-lymphoma association is rare, it is generally observed in the form of non- Hodgkin’s lymphoma, and there are also cases proposed the cooccurence of Ig A nephropathy and cutaneous T-cell lymphoma. In this case, it is emphasized that IgA nephropathy presented with cresentric glomerulonephritis should be considered in patients with hodgkin’s lymphoma who have sudden renal disorder.

  10. Effects of C1 GALT1 and Cosmc mRNA Expression of Liuwei Dihuang Decoction on IgA Nephropathy Rat Peripheral Blood%六味地黄汤对IgA肾病大鼠外周血C1 GALT1及Cosmc mRNA表达影响研究∗

    Institute of Scientific and Technical Information of China (English)

    彭亚军; 李旭华; 何泽云; 廖春来; 何雅琴; 胡淑娟

    2016-01-01

    目的:观察六味地黄汤对IgA肾病大鼠外周血C1GALT1及Cosmc mRNA表达,探讨其对IgA糖基化的影响。方法:SD大鼠40只随机分为正常对照组,模型组,雷公藤多苷片组,六味地黄汤组。除正常对照组外均采用运用牛血清白蛋白+脂多糖+四氯化碳方法建立实验性IgA肾病模型。造模成功后连续灌胃4周。将各组大鼠外周血分离的PBMC悬液,采用实时荧光定量PCR检测C1GALT1及Cosmc mRNA的表达,ELISA法测定外周血中IgA含量,凝集素亲和 ELISA 法检测IgA1异常糖基化程度,并进行定量分析。结果:各组C1GALT1mRNA表达量并差异无统计学意义(P>0.05);在各组Cosmc mRNA表达中,六味地黄汤组及雷公藤多苷片组表达均较模型组升高(P0. 05); In each group Cosmc mRNA expression, Liuwei Dihuang decoction group and tripterygium glycosides tablets more expression were higher in the model group (P<0. 05), but express Liuwei Dihuang decoction group lower than tripterygium glycosides tablets group (P<0. 05). The IgA content and the degree of abnormal glycosylation of the rats in each group were compared. The Liuwei Dihuang decoction group were significantly lower than the model group, the difference was statistically significant (P<0. 05). Conclusion:Liuwei Dihuang decoction can regulate the expression of Cosmc and mRNA, in-crease the activity of C1GALT1, improve the IgA1 abnorant glycosylation, which down regulate theIgA1 content, to avoid further dep-osition in kidney, and delay the progression of IgA nephropathy.

  11. 血清IgA及IgA/C3 比值在IgA肾病诊断中的价值%Value of serum IgA,IgA/C3 ratio in diagnosis of IgA nephropathy

    Institute of Scientific and Technical Information of China (English)

    张郁苒; 于青; 姚建

    2009-01-01

    @@ IgA肾病(IgA nephropathy,IgAN)是我国最常见的原发性肾小球肾炎,但至今其确切发病机制仍不明确.免疫反应和补体系统可能在IgAN的发生、发展中起重要作用,9%~70%的IgAN患者血清IgA升高[1],其血清C3水平是否下降仍有争议.

  12. Diabetic nephropathy

    Directory of Open Access Journals (Sweden)

    Zelmanovitz Themis

    2009-09-01

    Full Text Available Abstract Diabetic nephropathy is the leading cause of chronic renal disease and a major cause of cardiovascular mortality. Diabetic nephropathy has been categorized into stages: microalbuminuria and macroalbuminuria. The cut-off values of micro- and macroalbuminuria are arbitrary and their values have been questioned. Subjects in the upper-normal range of albuminuria seem to be at high risk of progression to micro- or macroalbuminuria and they also had a higher blood pressure than normoalbuminuric subjects in the lower normoalbuminuria range. Diabetic nephropathy screening is made by measuring albumin in spot urine. If abnormal, it should be confirmed in two out three samples collected in a three to six-months interval. Additionally, it is recommended that glomerular filtration rate be routinely estimated for appropriate screening of nephropathy, because some patients present a decreased glomerular filtration rate when urine albumin values are in the normal range. The two main risk factors for diabetic nephropathy are hyperglycemia and arterial hypertension, but the genetic susceptibility in both type 1 and type 2 diabetes is of great importance. Other risk factors are smoking, dyslipidemia, proteinuria, glomerular hyperfiltration and dietary factors. Nephropathy is pathologically characterized in individuals with type 1 diabetes by thickening of glomerular and tubular basal membranes, with progressive mesangial expansion (diffuse or nodular leading to progressive reduction of glomerular filtration surface. Concurrent interstitial morphological alterations and hyalinization of afferent and efferent glomerular arterioles also occur. Podocytes abnormalities also appear to be involved in the glomerulosclerosis process. In patients with type 2 diabetes, renal lesions are heterogeneous and more complex than in individuals with type 1 diabetes. Treatment of diabetic nephropathy is based on a multiple risk factor approach, and the goal is retarding the

  13. [Analgesic nephropathy].

    Science.gov (United States)

    Pintér, I; Nagy, J

    1998-11-22

    Analgesic nephropathy is a slowly progressive disease caused by the chronic abuse of analgesic mixtures containing two analgesic components combined with potentially addictive substances (coffeine and/or codeine). Pathologically, the nephropathy is characterized by renal papillary necrosis with calcification and chronic interstitial nephritis sometimes in association with transitional-cell carcinoma of the uroepithelium. In the early stage, the clinical characteristics are polyuria, sterile pyuria, sometimes renal colic and haematuria. With further progression of the disease, there are the nonspecific symptoms of advanced renal failure. The incidence of classic analgesic nephropathy among Hungarian patients on chronic renal replacement therapy has proven. There is an urgent need for the estimation of analgesic nephropathy among patients with chronic renal disease and among patients with chronic pain presumably regularly taking analgesics in Hungary. As long as analgesic mixtures containing phenacetin or paracetamol and/or nonsteroidal antiinflammatory drugs and addictive substances are available "over-the-counter", analgesic nephropathy will continue to be a problem also in our country.

  14. Passive administration of purified secretory IgA from human colostrum induces protection against Mycobacterium tuberculosis in a murine model of progressive pulmonary infection

    Directory of Open Access Journals (Sweden)

    Alvarez Nadine

    2013-02-01

    Full Text Available Abstract Background Immunoglobulin A is the most abundant isotype in secretions from mucosal surfaces of the gastrointestinal, respiratory and genitourinary tracts and in external secretions such as colostrum, breast milk, tears and saliva. The high concentration of human secretory IgA (hsIgA in human colostrum strongly suggests that it should play an important role in the passive immune protection against gastrointestinal and respiratory infections. Materials and methods Human secretory IgA was purified from colostrum. The reactivity of hsIgA against mycobacterial antigens and its protective capacity against mycobacterial infection was evaluated. Results The passive administration of hsIgA reduces the pneumonic area before challenge with M. tuberculosis. The intratracheal administration of M. tuberculosis preincubated with hsIgA to mice greatly reduced the bacterial load in the lungs and diminished lung tissue injury. Conclusions HsIgA purified from colostrum protects against M. tuberculosis infection in an experimental mouse model.

  15. Minimal Change Disease and IgA Deposition: Separate Entities or Common Pathophysiology?

    Directory of Open Access Journals (Sweden)

    Brandon S. Oberweis

    2013-01-01

    Full Text Available Introduction. Minimal Change Disease (MCD is the most common cause of nephrotic syndrome in children, while IgA nephropathy is the most common cause of glomerulonephritis worldwide. MCD is responsive to glucocorticoids, while the role of steroids in IgA nephropathy remains unclear. We describe a case of two distinct clinical and pathological findings, raising the question of whether MCD and IgA nephropathy are separate entities or if there is a common pathophysiology. Case Report. A 19-year old man with no medical history presented to the Emergency Department with a 20-day history of anasarca and frothy urine, BUN 68 mg/dL, Cr 2.3 mg/dL, urinalysis 3+ RBCs, 3+ protein, and urine protein : creatinine ratio 6.4. Renal biopsy revealed hypertrophic podocytes on light microscopy, podocyte foot process effacement on electron microscopy, and immunofluorescent mesangial staining for IgA. The patient was started on prednisone and exhibited dramatic improvement. Discussion. MCD typically has an overwhelming improvement with glucocorticoids, while the resolution of IgA nephropathy is rare. Our patient presented with MCD with the uncharacteristic finding of hematuria. Given the improvement with glucocorticoids, we raise the question of whether there is a shared pathophysiologic component of these two distinct clinical diseases that represents a clinical variant.

  16. Minimal change disease and IgA deposition: separate entities or common pathophysiology?

    Science.gov (United States)

    Oberweis, Brandon S; Mattoo, Aditya; Wu, Ming; Goldfarb, David S

    2013-01-01

    Introduction. Minimal Change Disease (MCD) is the most common cause of nephrotic syndrome in children, while IgA nephropathy is the most common cause of glomerulonephritis worldwide. MCD is responsive to glucocorticoids, while the role of steroids in IgA nephropathy remains unclear. We describe a case of two distinct clinical and pathological findings, raising the question of whether MCD and IgA nephropathy are separate entities or if there is a common pathophysiology. Case Report. A 19-year old man with no medical history presented to the Emergency Department with a 20-day history of anasarca and frothy urine, BUN 68 mg/dL, Cr 2.3 mg/dL, urinalysis 3+ RBCs, 3+ protein, and urine protein : creatinine ratio 6.4. Renal biopsy revealed hypertrophic podocytes on light microscopy, podocyte foot process effacement on electron microscopy, and immunofluorescent mesangial staining for IgA. The patient was started on prednisone and exhibited dramatic improvement. Discussion. MCD typically has an overwhelming improvement with glucocorticoids, while the resolution of IgA nephropathy is rare. Our patient presented with MCD with the uncharacteristic finding of hematuria. Given the improvement with glucocorticoids, we raise the question of whether there is a shared pathophysiologic component of these two distinct clinical diseases that represents a clinical variant.

  17. 替米沙坦对大鼠IgA肾病模型肾小管间质损伤及PPARγ表达的影响%Effect of telmisartan on tubulointerstital injury and expression of PPARγin rat renal tissue of IgA nephropathy model

    Institute of Scientific and Technical Information of China (English)

    邢丽; 柏林; 禹程远; 解汝娟

    2010-01-01

    Objective To observe the effect of telmisartan on the expression of PPARγin rat renal tissue of IgA nephropathy model and clarify the possible mechanism of telmisartan in tubulointerstitial injury.Methods The experimental rat model with IgA nephropathy was induced by bovine serum albumin ( BSA),lipopolysaccharide(LPS)and carbon tetrachloride(CCl4). Forty male SD rats were randomly divided into control group, IgA model group, rosiglitazone group, telmisartan group and losartan group. At preadministration, Weeks 4, 8 and 10, the quantity of 24-hour proteinuria was measured. The morphologic changes of renal tissues were evaluated by electron microscope. Immunohistochemistry was used to observe the expressions of PPARγ, TGF-β1 and α-smooth muscle actin (α-SMA) in different groups and RT-PCR to detect the expressions of PPARγ, TGF-β1 and monocyte chemoattractant protein-1 ( MCP-1 ) in different groups. Results Compared with control group, 24-hour proteinuria(mg) increased markedly in IgA model group( 14. 14 ± 1.99 vs 1.59 ±0. 18), but rosiglitazone group(2. 35 ±0. 33), telmisartan group( 1.88 ±0. 09)and losartan group( 2. 82 ± 0. 34 ) was much lower and telmisartan had the most significant effect (all P <0. 05). Compared with control group, there were varying degrees of mesangial proliferation and infiltration of inflammatory cell in IgA model group(3. 10 ±0. 18). The tubulointerstitial injury was notably alleviated in rosiglitazone group( 1.97 ±0. 23), telmisartan group( 1.57 ±0. 14) and losartan group (2. 15 ±0. 22) while telmisartan had the most significant effect (all P < 0.01 =. With immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR), PPARγ, TGF-β1, α-SMA and MCP-1 had minimal expression on tubule and interstitium in normal group. But there was a high expression in model group. There was no difference between losartan and model groups. There was a lowered expression in rosiglitazone and telmisartan groups

  18. 15.4.Interstitial nephritis and interstitial nephropathy

    Institute of Scientific and Technical Information of China (English)

    1992-01-01

    920149 The relationship between renal tis-sue subsets of lymphocytes and clinicalfeatures in IgA nephropathy.LIU Zhihong (刘志红),et al.Dept Nephrol,Jinling Hosp,Nanjing(210002).Chin J Nephrol 1991; 7 (4): 230.Amount of CD4+,CD8+ and B cells in the

  19. Effects of leflunomide on renal pathology and expression of MCP-1 in renal tissue in rat experimental IgA nephropathy model%Leflunomide对实验性IgA肾病大鼠肾脏病理及MCP-1表达的影响

    Institute of Scientific and Technical Information of China (English)

    汤颖; 娄探奇; 成彩联; 陈珠江; 张俊

    2006-01-01

    目的观察leflunomide对实验性IgA肾病(IgA nephropathy IgA N)大鼠肾脏病理及肾组织单核细胞趋化因子(monocyte chemoattractive peptide1,MCP-1)表达的影响,了解其作用机制.方法建立IgAN大鼠模型,随机分成leflunomide组,强的松组,模型对照组,并同时设立正常对照组.行免疫荧光、光镜检查,并用免疫组化和RT-PCR方法分别检测肾组织MCP-1蛋白和基因水平的表达.结果与模型对照组相比,leflunomide组免疫复合物在肾脏的沉积明显减少,系膜区基质增生程度显著减轻(P<0.01);Leflunomide在基因和蛋白水平均能够有效抑制MCP-1在肾组织的表达(P<0.05).结论Leflunomide能够减少免疫复合物在肾脏的沉积,减轻系膜区基质增生,并且下调MCP-1在肾脏的表达,减少局部炎症反应,减轻肾脏损害,保护肾脏.

  20. Suppression subtractive hybridization to obtain differential genes associated kidney yang defficiency of IgA nephropathy%运用消减杂交技术构建IgA肾病肾阳虚证的相关基因文库

    Institute of Scientific and Technical Information of China (English)

    李玉萍; 罗仁; 孙晓敏; 聂晓莉; 赵晓山; 杨海文

    2011-01-01

    Objective To construct cDNA substractive library of kidney yang defficiency of IgA nephropathy ( IgAN)by suppression subtractive hybridization ( SSH).Methods The research related genes of kidney yang defficiency syndrome of IgAN.Microamount RNA was amplified.SSH and gene cloning were used to obtain differential genes associated kidney yang defficiency of IgAN.Result A Total of 537 clones were obtained.276 from the forward subtractive library and 261 from the reverse subtractive library.Conclusion The cDNA subtractive library is successfully constructed and it may provide a solid foundation for screening and cloning the genes of kidney yang defficiency.%目的 采用抑制性消减杂交技术构建汉族人IgA肾病肾阳虚证cDNA消减文库.方法 以辨病与辨证相结合,以IgA肾病肾阳虚证入手,应用RNA微量扩增、抑制性消减杂交、基因克隆等技术和方法,构建IgA肾病肾阳虚证消减文库.结果 该研究成功地构建了IgA肾病肾阳虚证的cDNA消减文库,其中正向消减文库获得276个阳性克隆,反向消减文库获得261个阳性克隆.结论 该研究初步构建了IgA肾病肾阳虚证的cDNA消减文库,为进一步筛选和克隆肾阳虚证的相关基因奠定了基础.

  1. 激素联合血管紧张素转换酶抑制剂治疗中度蛋白尿IgA肾病的随机对照研究%Corticosteroids Plus Angiotensin Converting Enzyme Inhibitor in Treating IgA Nephropathy: A Randomized Control Trial

    Institute of Scientific and Technical Information of China (English)

    熊子波; 梁伟; 王勇强; 侯霜; 张帆; 贺丽娟; 罗琼

    2012-01-01

    目的 探讨激素与血管紧张素转换酶抑制剂(ACEI)联合治疗中度蛋白尿IgA肾病患者的疗效及其影响因素.方法 选择2003年5月-2009年1月在北京大学深圳医院住院的102例IgA肾病患者,均满足血肌酐<133 μmol/L,尿蛋白为1.0 ~3.5 g/24 h.按照随机数字表分为试验组和对照组.对照组(50例)给予ACEI类药物治疗(洛汀新10 mg/d),试验组(52例)在此基础上口服泼尼松0.5 mg/kg,隔日给药,治疗12 个月,并在治疗的第1、3、5个月初分别给予甲基泼尼松龙0.5 g/d,冲击3 d.对肾脏病理改变进行分级并对各种病变进行半定量分析.结果 在0、2、4、6、8、10、12个月时两组患者平均24 h尿蛋白水平分别为:试验组(2.07±0.88)g/24 h、(0.82±0.66)g/24 h、(0.63±0.53)g/24 h、(0.56±0.51)g/24 h、(0.58±0.47)g/24 h、(0.57±0.48)g/24 h及(0.64±0.54) g/24 h;对照组(1.88±0.67)g/24 h、(1.67±0.75)g/24 h、(1.55±0.81)g/24 h、(1.24±0.77)g/24 h、(1.44±0.92)g/24 h、(1.31±0.79)g/24 h及(1.28±0.85) g/24 h,两组在治疗2个月后尿蛋白水平间差异有统计学意义(P<0.01);而试验组和对照组的血肌酐水平在治疗期间均稳定,且两组间差异无统计学意义(P>0.05).多因素分析显示激素联合ACEI治疗的疗效与肾小球硬化积分及肾小管间质积分呈负相关.结论 激素联合ACEI治疗中度蛋白尿IgA肾病,能更有效降低尿蛋白,稳定肾功能.其中影响疗效的主要因素为肾小球硬化率及肾小管间质病变程度.%Objective To evaluate the efficacy of the corticosteroids plus angiotensin converting enzyme inhibitor ( ACEI ) in treating IgA nephropathy and its influencing factors. Methods Totally 102 inpatients with IgA nephropathy hospitalized in Peking University Shenzhen Hospital were randomly enrolled. All of them met the inclusion criteria: serum creatinine a-bove 133 |j,mol/L and urine proteins 1.0 - 3. 5 g/24 h. These patients were divided into two groups: control group

  2. Risk factors analysis of prognosis of microalbuminuria IgA nephropathy patients with decreased ;serum C3 level%表现为微量白蛋白尿IgA肾病伴低C3血症患者的预后危险因素分析

    Institute of Scientific and Technical Information of China (English)

    郭宗运; 李霞; 周世菊; 赵东; 刘金彦; 吴玉梅

    2016-01-01

    proliferation (RR = 0.872, 95% CI: 0.491- 1.275, P =0.042), crescentic (RR = 1.528, 95% CI: 1.073- 2.385, P = 0.009) affected prognosis of microalbuminuria IgA nephropathy as the independent risk factors. Conclusions The clinical and pathological features in patients of microalbuminuria IgA nephropathy with decreased serum C3 level is more severe, and the prognosis is poor. The patients should be followed up closely and early intervention treatment and early active control of microalbuminuria should be done at the same time.%目的:对表现为微量白蛋白尿IgA肾病伴低C3血症患者的临床资料以及预后进行分析,探讨低C3血症在微量白蛋白尿IgA肾病中的意义。方法分析肾活检确诊且随访时间大于6个月的135例微量白蛋白尿IgA肾病患者的临床资料,依据血清C3水平,分为低C3组(34例)和正常C3组(101例)。以24 h尿蛋白定量大于1 g或肾穿刺时血清肌酐(SCr)值正常者出现SCr异常或肾穿刺时SCr异常者出现SCr升高1倍以上为随访终点,用Kaplan-Meier法分析肾脏生存率,应用Cox回归模型分析影响预后的相关危险因素。结果随访时间(53.4±21.9)个月,低C3组有27例(79.41%)、正常C3组有32例(31.68%)进入随访终点。通过Kaplan-Meier生存分析显示低C3组肾脏中位生存时间显著短于正常C3组[(46.7±9.1)个月比(68.4±9.9)个月,P=0.014]。应用Cox回归方法分析显示血清Scr异常(RR=1.147,95%CI:1.129~1.395,P=0.008)、低C3血症(RR=1.028,95%CI:0.672~1.495,P=0.039)、尿蛋白定量>1 g/24 h(RR=2.066,95%CI:1.242~3.838,P=0.006)以及肾穿刺时的病理指标Lee分级Ⅲ~Ⅴ级(RR=2.820,95%CI:1.249~5.638,P=0.041)、节段性肾小球硬化或粘连(RR=1.232,95%CI:1.065~1.520,P=0.040)、肾小管萎缩或间质纤维化(RR=2.604,95%CI:1.748~4.104,P=0.037)、毛细血管内细胞增生(RR=0

  3. Scorpion sting nephropathy

    OpenAIRE

    2011-01-01

    Scorpion envenomations are ubiquitous, but nephropathy is a rare manifestation, reported mainly from the Middle East and North Africa. Rapid venom redistribution from blood, delayed excretion from the kidneys, direct toxicity of venom enzymes, cytokine release and afferent arteriolar constriction have been seen in experimental animals. Haemoglobinuria, acute tubular necrosis, interstitial nephritis and haemolytic–uraemic syndrome have been documented in human victims of scorpion envenomation....

  4. Nodular lesions and mesangiolysis in diabetic nephropathy.

    Science.gov (United States)

    Wada, Takashi; Shimizu, Miho; Yokoyama, Hitoshi; Iwata, Yasunori; Sakai, Yoshio; Kaneko, Shuichi; Furuichi, Kengo

    2013-02-01

    Diabetic nephropathy is a leading cause of end-stage renal failure all over the world. Advanced human diabetic nephropathy is characterized by the presence of specific lesions including nodular lesions, doughnut lesions, and exudative lesions. Thus far, animal models precisely mimicking advanced human diabetic nephropathy, especially nodular lesions, remain to be fully established. Animal models with spontaneous diabetic kidney diseases or with inducible kidney lesions may be useful for investigating the pathogenesis of diabetic nephropathy. Based on pathological features, we previously reported that diabetic glomerular nodular-like lesions were formed during the reconstruction process of mesangiolysis. Recently, we established nodular-like lesions resembling those seen in advanced human diabetic nephropathy through vascular endothelial injury and mesangiolysis by administration of monocrotaline. Here, in this review, we discuss diabetic nodular lesions and its animal models resembling human diabetic kidney lesions, with our hypothesis that endothelial cell injury and mesangiolysis might be required for nodular lesions.

  5. Salmon consumption during pregnancy alters fatty acid composition and secretory IgA concentration in human breast milk.

    Science.gov (United States)

    Urwin, Heidi J; Miles, Elizabeth A; Noakes, Paul S; Kremmyda, Lefkothea-Stella; Vlachava, Maria; Diaper, Norma D; Pérez-Cano, Francisco J; Godfrey, Keith M; Calder, Philip C; Yaqoob, Parveen

    2012-08-01

    Fish oil supplementation during pregnancy alters breast milk composition, but there is little information about the impact of oily fish consumption. We determined whether increased salmon consumption during pregnancy alters breast milk fatty acid composition and immune factors. Women (n = 123) who rarely ate oily fish were randomly assigned to consume their habitual diet or to consume 2 portions of farmed salmon per week from 20 wk of pregnancy until delivery. The salmon provided 3.45 g long-chain (LC) (n-3) PUFA/wk. Breast milk fatty acid composition and immune factors [soluble CD14, transforming growth factor-β (TGFβ)1, TGFβ2, and secretory IgA] were analyzed at 1, 5, 14, and 28 d postpartum (PP). Breast milk from the salmon group had higher proportions of EPA (80%), docosapentaenoic acid (30%), and DHA (90%) on d 5 PP compared with controls (P < 0.01). The LC (n-6) PUFA:LC (n-3) PUFA ratio was lower for the salmon group on all days of PP sampling (P ≤ 0.004), although individual (n-6) PUFA proportions, including arachidonic acid, did not differ. All breast milk immune factors decreased between d 1 and 28 PP (P < 0.001). Breast milk secretory IgA (sIgA) was lower in the salmon group (d 1-28 PP; P = 0.006). Salmon consumption during pregnancy, at the current recommended intakes, increases the LC (n-3) PUFA concentration of breast milk in early lactation, thus improving the supply of these important fatty acids to the breast-fed neonate. The consequence of the lower breast milk concentration of sIgA in the salmon group is not clear.

  6. Causes of reduced expression of Cosmc gene in IgA nephropathy patients%IgA肾病患者Cosmc基因表达低下原因探讨

    Institute of Scientific and Technical Information of China (English)

    秦伟; 钟翔; 张颖娟; 谭淳予; 杨立川; 樊均明

    2008-01-01

    目的 探讨IgA肾病(IgAN)患者核心1β1,3半乳糖基转移酶伴侣蛋白(Cosmc)表达低下的原因,到底是基因突变还是外源性抑制.方法 40例IgAN患者、16例非IgAN肾小球肾炎患者、21例健康对照被纳入本研究.直接测序方法测定Cosmc基因外显子区域的核酸序列.免疫磁珠分离IgAN患者、非IgAN肾小球.肾炎患者和健康对照者外周血B淋巴细胞,并分别在RPMI-1640及RPMI-1640+脂多糖(LPS)中培养72 h.实时荧光RT-PCR方法测定Cosmc基因的mRNA表达水平.结果 (1)IgAN患者Cosmc基因外显子区域没有共同突变位点,仅在2例患者中发现2处错义突变和2处无意义突变,而且这些突变并不影响患者cosmc基因的表达.(2)IgAN患者外周血B淋巴细胞的基础Cosmc基因表达显著降低,为健康对照组的31%.(3)经RPMI-1640培养后,IgAN患者Cosmc基因的表达水平升高至基础值的219%.RPMI-1640+LPS组Cosmc基因的h调受到明显抑制.(4)健康对照Cosmc基因的表达不受RPMI-1640和LPS的影响.结论 IgAN患者外周血B淋巴细胞Cosmc基因表达低下可能与基因突变无关,而是受外源性抑制囚素影响所致.%Objective To clarify whether the Cosmc gene down-regnhtion in lgA nephropathy (IgAN) patients is resulted from genetic disorders or external suppressions. Methods Forty IgAN patients, 16 non-IgAN glomerulonephritis patients and 21 healthy controls were enrolled in the study. Genomie DNA was extracted and then Cosmc gene was amplified and sequenced. Peripheral B lymphoeytes were isolated and cultured with RPMI-1640 alone or plus lipopolysaecharide (LPS). The Cosmc mRNA expression levels at baseline, after RPMI-1640 culture or RPMI-1640+LPS treatment were measured respectively by real-time RT-PCR. Results (1) Only 2 missense mutations and 2 silent mutations were detected in coding frame region of Cosine gene in 2 IgAN patients. (2) The baseline Cosmc gene expression level was significantly lower in IgAN patients (31% of

  7. Working mechanism of immunoglobulin A1 (IgA1) protease: cleavage of IgA1 antibody to Neisseria meningitidis PorA requires de novo synthesis of IgA1 Protease

    DEFF Research Database (Denmark)

    Vidarsson, G; Overbeeke, N; Stemerding, AM

    2005-01-01

    Neisseria meningitidis secretes a protease that specifically cleaves the hinge region of immunoglobulin A1 (IgA1), releasing the effector (Fc) domain of IgA1 from the antigen binding (Fab) determinants. Theoretically, the remaining Fab fragments can block pathogen receptors or toxins and still...... provide protection. Here, we describe binding of V-gene-matched human IgA1 and IgA2 to PorA of strain H44/76. On live meningococci, efficient cleavage of IgA1, but not cleavage of IgA2, was observed, and up to approximately 80% of the IgA1 Fc tails were lost from the meningococcal surface within 30 min....... No cleavage of IgA1 was found on an isogenic H44/76 strain lacking IgA1 protease. Furthermore, our data indicate that PorA-bound IgA1 is masked by the serogroup B polysaccharide capsule, rendering the IgA1 less accessible to degradation by secreted IgA1 protease present in the bacterial surroundings...

  8. 内蒙地区 IgA 肾病患者血清IgA1 分子N-乙酰半乳糖胺异常与其病理表现关系探讨%Discussion of the Relationship between Serum IgA1 Molecular N-Acetlygalactosamine Abnormality and its Pathological Manifestations in IgA Nephropathy in Inner Mongolia Region

    Institute of Scientific and Technical Information of China (English)

    徐秀芝; 王新; 肖秀清; 王巧莲

    2009-01-01

    目的 探讨内蒙地区蒙古族与汉族人群IgA肾病患者血清IgA1分子N-乙酰半乳糖胺异常程度与肾脏病理表现的关系.方法将入选的60 例IgA肾病患者,用ELISA法测定蚕豆凝集素(VVL)与IgA1分子铰链区上N-乙酰半乳糖胺(GalNAc)的总结合力,即VVL总结合力,同时计算VVL与IgA1的结合力.将20例原发性肾病综合征微小病变与膜性肾病患者设为对照组,根据IgA1与VVL结合力的均值加减2个标准差为界,将IgA肾病组分为正常糖基化与低糖基化,同时进行常规肾活检.结果 IgA1肾病组VVL总结合力、VVL与IgA1结合力情况与对照组比较有显著性差异(P<0.05);蒙古族与汉族IgA1糖基化程度、肾脏病理情况、年龄及血肌酐比较,无显著性差异(P>0.05).结论内蒙地区蒙古族与汉族人群中IgA1低糖基化程度与肾脏病理轻重无明显的相关关系,IgA肾病患者血清IgA1糖基化异常,血清低糖基化程度重者发病年龄较轻但肾小球滤过功能损伤较重.IgA1低糖基化程度尚不能推测肾脏病理轻重,并且在蒙古族与汉族人群中,低糖基化IgA1对IgA肾病的致病作用亦无差别.

  9. Detection of parasite-specific IgG and IgA in paired serum and saliva samples for diagnosis of human strongyloidiasis in northern Paraná state, Brazil.

    Science.gov (United States)

    Bosqui, Larissa R; Gonçalves, Ana Lúcia R; Gonçalves-Pires, Maria do Rosário F; Custodio, Luiz Antonio; de Menezes, Maria Cláudia N D; Murad, Valter A; de Paula, Fabiana M; Pavanelli, Wander R; Conchon-Costa, Ivete; Costa-Cruz, Julia Maria; Costa, Idessania N

    2015-10-01

    Human strongyloidiasis is an infection caused by the helminth Strongyloides stercoralis that can be fatal, especially in immunosuppressed patients. The aim of this study is to evaluate parasite-specific IgG and IgA levels using S. venezuelensis third-stage (L3) infective larvae alkaline extract as a heterologous antigen by ELISA in paired serum and saliva samples with improved sensitivity and specificity. Individuals from northern Paraná state, Brazil were divided into three groups: 30 patients copropositive for S. stercoralis (Group I); 30 clinically healthy individuals (Group II); and 30 patients copropositive for other parasites (Group III). The area under ROC curve (AUC), an overall index of diagnostic accuracy, and Kappa index were calculated. Data were analyzed using analysis of variance (ANOVA) followed by a Kruskal-Wallis test. Probability (p) values of <0.05 were regarded as significant. In Group I, IgG was detected in 96.7% serum and in 6.7% saliva samples. IgG was not detected in Group II. In Group III, cross-reactivity was observed for serum IgG in 26.7% and in 6.7% for saliva samples. In Group I, IgA was detected in 76.7% serum and 56.7% saliva samples. In Group II, 3.3% were positive for IgA in serum, whereas IgA was not detected in any saliva samples. Group III showed 6.7% serum and 26.7% saliva-positive samples. The sensitivity values for detection of IgG and IgA in serum samples were 96.7% and 76.7%, respectively. In saliva samples, the sensitivity values for detection of IgG and IgA were 6.7% and 56.7%, respectively. The specificity value was 100% for the detection of IgG in serum and for detection of IgG and IgA in saliva, and 96.7% for detection of IgA in serum samples. The proper choice of immunological diagnosis to supplement parasitological methods is essential to estimate the true prevalence of the parasite, and will permit analysis of population immune response profiles, particularly in northern Paraná state, where there are no previous

  10. Clinical application value of urinary transforming growth factor-beta 1 in predicting IgA nephropathy progress%尿转化生长因子-β1在预测IgA肾病进展中的临床应用价值

    Institute of Scientific and Technical Information of China (English)

    周金金; 徐家云; 彭霞; 邵叶青

    2016-01-01

    Objective Through analyzing relevance of urinary transforming growth factor-beta 1(TGF-β1)and clinicopathological characteristics of IgA nephropathy, study clinical significance of urinary TGF- beta 1 in IgAN pathogenesis and progress.Methods Choose 30 cases primary IgAN patients hospitalized in nephrology department of The First Affiliated Hospital of Henan University of Science and Technology from March 2013 to May 2015; and 5 cases healthy control subjects. Test urine TGF - 1 level by ELISA method, and test other clinical indicators including serum creatinine, urine creatinine, 24h urinary protein quantitative. Result 1 urinary TGF- beta 1/ urinary Cr ratio was higher than normal controls of IgAN patients (P<0.05); 2 urinary TGF- beta 1/urinary Cr level of IgAN patients were positively related with pathological grading, 24h urinary protein, CKD classification.Conclusion Urinary TGF- beta 1 level can be used as early molecular biological indicator of IgAN activity and progress.%目的:通过分析IgA肾病(IgAN)尿转化生长因子β1(TGF-β1)与临床病理的相关性,探讨尿TGF-β1在IgAN发病和进展中的临床意义。方法选择2013年3月至2015年5月间在河南科技大学第一附属医院肾内科住院的原发性IgAN患者30例,健康对照者5例,采用ELISA法检测尿TGF-β1水平,同时测定血、尿肌酐,24h尿蛋白定量等临床指标。结果1、IgAN患者尿TGF-β1/尿Cr比值高于正常对照者(P<0.05);2、IgAN患者尿 TGF-β1/尿Cr水平分别与病理分级、24h尿蛋白定量、CKD分期呈正相关。结论尿TGF-β1水平可作为反映IgAN活动和进展的早期分子生物学指标。

  11. IMMUNOGLOBULIN A (IgA AND ITS RECEPTORS

    Directory of Open Access Journals (Sweden)

    V. B. Klimovich

    2006-01-01

    Full Text Available Abstract. Daily IgA production in human organism comprises 3 to 5 g, thus exceeding total synthesis of other Ig classes. IgA in human body is presented by 9 structural variants. Its molecules belong to two subclasses, IgA1 and IgA2, the latter represented by two allotypes. In human serum, IgA1 monomers predominate, that are produced by the bone marrow cells. Mucosa-associated lymphoid tissues produce dimeric IgA1 and IgA2 molecules containing an accessory polypeptide J-chain. When transported across epithelial layer to the mucosal surface, an extracellular segment of polymeric IgA receptor (pIgAR is joining the dimeric IgA1, which becomes a ‘secretory’ component being a part cesretory IgA (sIgA molecule. The main function of sIgA is to bind bacteria and viruses at the mucosal surfaces, thus preventing pathogens to invade the internal spaces of the organism (immune exclusion. If transferred across epithelium, IgA may neutralize the viruses penetrating the cells, like as bind and deliver proteins and other antigens to the mucosal surface. The leukocyte IgA receptor (FcαRI, CD89 is expressed on the neutrophils, eosinophiles, monocytes/macrophages, as well as dendritic and Kupffer cells. The cytoplasmic domain FcαRI is devoid of an activation ITAM motif. To transduce signal, an FcαRI-associated chain of Fcγ receptor is used. Due to this mechanism, IgA binding leads to activation of phagocytosis, endocytosis, antigen presentation, synthesis of proinflammatory mediator and other immune functions. Fcα/μR receptor is a structural homologue of pIgR, and it is able to bind IgA and IgM, being, however, expressed only at the surface of mature B lymphocytes and macrophages. Interaction of IgA with asialoglycoprotein and transferrin (CD71 receptors, like as with some other molecules, that have yet undetermined role in immune defense and development of pathological events.

  12. [Lithium nephropathy].

    Science.gov (United States)

    Kaczmarczyk, Ireneusz; Sułowicz, Władysław

    2013-01-01

    Lithium salts are the first-line drug therapy in the treatment of uni- and bipolar disorder since the sixties of the twentieth century. In the mid-70s, the first information about their nephrotoxicity appeared. Lithium salts have a narrow therapeutic index. Side effects during treatment are polyuria, polydipsia and nephrogenic diabetes insipidus. Accidental intoxication can cause acute renal failure requiring renal replacement therapy while receiving long-term lithium salt can lead to the development of chronic kidney disease. The renal biopsy changes revealed a type of chronic tubulointerstitial nephropathy. The imaging studies revealed the presence of numerous symmetric microcysts. Care of the patient receiving lithium should include regular determination of serum creatinine, creatinine clearance and monitoring of urine volume. In case of deterioration of renal function reducing the dose should be considered.

  13. Silica Nephropathy

    Directory of Open Access Journals (Sweden)

    N Ghahramani

    2010-06-01

    Full Text Available Occupational exposure to heavy metals, organic solvents and silica is associated with a variety of renal manifestations. Improved understanding of occupational renal disease provides insight into environmental renal disease, improving knowledge of disease pathogenesis. Silica (SiO2 is an abundant mineral found in sand, rock, and soil. Workers exposed to silica include sandblasters, miners, quarry workers, masons, ceramic workers and glass manufacturers. New cases of silicosis per year have been estimated in the US to be 3600–7300. Exposure to silica has been associated with tubulointerstitial disease, immune-mediated multisystem disease, chronic kidney disease and end-stage renal disease. A rare syndrome of painful, nodular skin lesions has been described in dialysis patients with excessive levels of silicon. Balkan endemic nephropathy is postulated to be due to chronic intoxication with drinking water polluted by silicates released during soil erosion. The mechanism of silica nephrotoxicity is thought to be through direct nephrotoxicity, as well as silica-induced autoimmune diseases such as scleroderma and systemic lupus erythematosus. The renal histopathology varies from focal to crescentic and necrotizing glomerulonephritis with aneurysm formation suggestive of polyarteritis nodosa. The treatment for silica nephrotoxicity is non-specific and depends on the mechanism and stage of the disease. It is quite clear that further research is needed, particularly to elucidate the pathogenesis of silica nephropathy. Considering the importance of diagnosing exposure-related renal disease at early stages, it is imperative to obtain a thorough occupational history in all patients with renal disease, with particular emphasis on exposure to silica, heavy metals, and solvents.

  14. Parathyroid hormone-related protein is a hypertrophy factor for human mesangial cells: Implications for diabetic nephropathy.

    Science.gov (United States)

    Ortega, Arantxa; Romero, Montserrat; Izquierdo, Adriana; Troyano, Nuria; Arce, Yolanda; Ardura, Juan Antonio; Arenas, María Isabel; Bover, Jordi; Esbrit, Pedro; Bosch, Ricardo J

    2012-05-01

    Hypertrophy of human mesangial cells (HMC) is among the earliest characteristics in patients with diabetic nephropathy (DN). Recently, we observed the upregulation of parathyroid hormone (PTH)-related protein (PTHrP) in experimental DN, associated with renal hypertrophy. Herein, we first examined whether PTHrP was overexpressed in human DN, and next assessed the putative role of this protein on high glucose (HG)-induced HMC hypertrophy. As previously found in mice, kidneys from diabetic patients showed an increased tubular and glomerular immunostaining for PTHrP. In HMC, HG medium increased PTHrP protein expression associated with the development of hypertrophy as assessed by cell protein content. This effect was also induced by PTHrP(1-36). HG and PTHrP(1-36)-induced hypertrophy were associated with an increase in cyclin D1 and p27Kip1 protein expression, a decreased cyclin E expression, and the prevention of cyclin E/cdk2 complex activation. Both PTHrP neutralizing antiserum (α-PTHrP) and the PTH/PTHrP receptor antagonist (JB4250) were able to abolish HG induction of hypertrophy, the aforementioned changes in cell cycle proteins, and also TGF-β1 up-regulation. Moreover, the capability of both HG and PTHrP(1-36) to induce HMC hypertrophy was abolished by α-TGFβ1. These data show for the first time that PTHrP is upregulated in the kidney of patients with DN. Our findings also demonstrate that PTHrP acts as an important mediator of HG-induced HMC hypertrophy by modulating cell cycle regulatory proteins and TGF-β1. Copyright © 2011 Wiley Periodicals, Inc.

  15. Exposures influencing total IgA level in colostrum.

    Science.gov (United States)

    Munblit, D; Sheth, S; Abrol, P; Treneva, M; Peroni, D G; Chow, L-Y; Boner, A L; Pampura, A; Warner, J O; Boyle, R J

    2016-02-01

    Immunoglobulin A (IgA) is a predominant immunoglobulin present in human breast milk and is known to play an important role in infant gut immunity maturation. Breast milk composition varies between populations, but the environmental and maternal factors responsible for these variations are still unclear. We examined the relationship between different exposures and levels of IgA in colostrum. The objective of this study was to examine whether exposures analysed influence levels of IgA in colostrum. The present study used 294 colostrum samples from the MecMilk International cohort, collected from women residing in London, Moscow and Verona. Samples were analysed in automated Abbott Architect Analyser. We found an inverse correlation between time postpartum and colostrum total IgA level (r=-0.49, PIgA levels were influenced by colostrum collection time (PIgA (P=0.01). We conclude that the concentration of IgA in colostrum drops rapidly after birth and future studies should always consider this factor in analysis. IgA concentration varied significantly between countries, with the highest level detected in Moscow and lowest in Verona. Mode of delivery effect should be confirmed on larger cohorts. Further work is needed to determine ways to correct for IgA decline over time in colostrum, and to find the cause of variations in IgA levels between the countries.

  16. Expression of IgA Proteases by Haemophilus influenzae in the Respiratory Tract of Adults With Chronic Obstructive Pulmonary Disease.

    Science.gov (United States)

    Murphy, Timothy F; Kirkham, Charmaine; Jones, Megan M; Sethi, Sanjay; Kong, Yong; Pettigrew, Melinda M

    2015-12-01

    Immunoglobulin (Ig)A proteases of Haemophilus influenzae are highly specific endopeptidases that cleave the hinge region of human IgA1 and also mediate invasion and trafficking in human respiratory epithelial cells, facilitating persistence of H. influenzae. Little is known about the expression of IgA proteases in clinical settings of H. influenzae infection. We identified and characterized IgA protease genes in H. influenzae and studied their expression and proteolytic specificity, in vitro and in vivo in 169 independent strains of H. influenzae collected longitudinally over 10 years from adults with chronic obstructive pulmonary disease. The H. influenzae pangenome has 2 alleles of IgA protease genes; all strains have igaA, and 40% of strains have igaB. Each allele has 2 variants with differing proteolytic specificities for human IgA1. A total of 88% of 169 strains express IgA protease activity. Expression of the 4 forms of IgA protease varies among strains. Based on the presence of IgA1 fragments in sputum samples, each of the different forms of IgA protease is selectively expressed in the human airways during infection. Four variants of IgA proteases are variably expressed by H. influenzae during infection of the human airways. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  17. The action of NIR (808nm) laser radiation and gold nanorods labeled with IgA and IgG human antibodies on methicillin-resistant and methicillin sensitive strains of Staphylococcus aureus

    Science.gov (United States)

    Tuchina, Elena S.; Petrov, Pavel O.; Ratto, Fulvio; Centi, Sonia; Pini, Roberto; Tuchin, Valery V.

    2015-03-01

    The effect of NIR laser radiation (808 nm) on methicillin-sensitive and methicillin resistant strains of Staphylococcus aureus incubated with gold nanorods is studied. Nanorods having length of 44 (± 4) nm and diameter of 10 (± 3) nm with the absorption maximum in the NIR (800 nm), functionalized with human immunoglobulins IgA and IgG, were synthesized and used in the studies. The killing ability up to 97% of the microorganism populations by using this nanotechnology was shown.

  18. Mesangial cell-derived tumor necrosis factor α up-regulates the expression of tubular liver type fatty acid binding-protein and its renoprotective role in IgA nephropathy%系膜细胞源性肿瘤坏死因子α上调IgA肾病肾小管肝型脂肪酸结合蛋白的表达及其肾脏保护作用

    Institute of Scientific and Technical Information of China (English)

    佐楠; 栗霄立; 王力宁; 李子龙; 王均; 冯江敏; 马健飞; 范秋灵; 姚丽

    2011-01-01

    Objective To explore the mechanism of up-regulation of tubular liver-type fatty acid binding-protein (L-FABP) in IgA nephropathy (IgAN) and its renoprotective role.Methods Murine mesangial cells (MCs) from primary cell culture were cultured with aggregated IgA (AIgA) (10 to 250 mg/L) for 48 hours. The supernatant after culture was collected as AIgA-MC medium. Murine proximal tubular cell line (mProx) stably expressing human L-FABP (hL-FABP) by transfection (mProx-L) were cultured with AIgA, AIgA-MC medium and /or neutralizing anti-TNF-α antibody and recombinant murine TNF-α, respectively. AIgA-MC medium (AIgA final concentration was 25 mg/L) was cultured with mProx and mProx-L cells. The mRNA expressions of hL-FABP and MCP-1 of the cells were detected by real-time PCR. The protein expressions of hL-FABP and 4-HNE of the cells were detected by Western blotting. Results (1) The hL-FABP mRNA and protein expression stimulated by AIgA-MC medium was significantly higher as compared to AIgA (P<0.01). (2) Pre-incubation of neutralizing anti-TNF-α antibody (final concentration was 1 and 5 mg/L) with mProx-L cells could significantly suppress the up-regulation of hL-FABP protein expression induced by AlgA-MC medium (P<0.05 and P<0.01).(3) Recombinant murine TNF-α (final concentration was 50 and 250 ng/L) also induced a significant up-regulation of hL-FABP expression (P<0.01). (4) After the stimulation of AIgA-MC medium, both 4-HNE protein expression and MCP-1 mRNA expression were significantly suppressed in mProx-L cells compared to those of mProx cells (P <0.05 and P<0.01). Conclusion Mesangial cell-derived TNF-α can induce up-regulation of tubular L-FABP expression. Overexpression of tubular L-FABP may lessen the progression of IgAN by reducing oxidative stress and inflammatory mediators.%目的 探讨体外近曲小管肝型脂肪酸结合蛋白(L-FABP)在IgA肾病(IgAN)中的上调机制及其对肾脏的保护作用.方法 原代培养的小鼠系膜

  19. Comparison of mucosal lining fluid sampling methods and influenza-specific IgA detection assays for use in human studies of influenza immunity.

    Science.gov (United States)

    de Silva, Thushan I; Gould, Victoria; Mohammed, Nuredin I; Cope, Alethea; Meijer, Adam; Zutt, Ilse; Reimerink, Johan; Kampmann, Beate; Hoschler, Katja; Zambon, Maria; Tregoning, John S

    2017-10-01

    We need greater understanding of the mechanisms underlying protection against influenza virus to develop more effective vaccines. To do this, we need better, more reproducible methods of sampling the nasal mucosa. The aim of the current study was to compare levels of influenza virus A subtype-specific IgA collected using three different methods of nasal sampling. Samples were collected from healthy adult volunteers before and after LAIV immunization by nasal wash, flocked swabs and Synthetic Absorptive Matrix (SAM) strips. Influenza A virus subtype-specific IgA levels were measured by haemagglutinin binding ELISA or haemagglutinin binding microarray and the functional response was assessed by microneutralization. Nasosorption using SAM strips lead to the recovery of a more concentrated sample of material, with a significantly higher level of total and influenza H1-specific IgA. However, an equivalent percentage of specific IgA was observed with all sampling methods when normalized to the total IgA. Responses measured using a recently developed antibody microarray platform, which allows evaluation of binding to multiple influenza strains simultaneously with small sample volumes, were compared to ELISA. There was a good correlation between ELISA and microarray values. Material recovered from SAM strips was weakly neutralizing when used in an in vitro assay, with a modest correlation between the level of IgA measured by ELISA and neutralization, but a greater correlation between microarray-measured IgA and neutralizing activity. In conclusion we have tested three different methods of nasal sampling and show that flocked swabs and novel SAM strips are appropriate alternatives to traditional nasal washes for assessment of mucosal influenza humoral immunity. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Occurrence of vascular IgA deposits in clinically normal skin of patients with renal disease.

    Science.gov (United States)

    Faille-Kuyper, E H; Kater, L; Kuijten, R H; Kooiker, C J; Wagenaar, S S; van der Zouwen, P; Mees, E J

    1976-05-01

    Skin and kidney biopsies were performed on 262 patients with various nephropathies. In 45 skin biopsy specimens finely granular deposits of predominantly IgA and late-acting complement factors were detected in the walls of superficial capillaries, sometimes concomitantly with IgM, IgG, C4 or a combination of these proteins. Twelve of the 45 patients presented with anaphylactoid purpura and the majority of the other 33 patients had either recurrent macroscopic or microscopic hematuria. The renal lesions in 32 of these 45 patients consisted of focal segmental intracapillary proliferation. In 35 the kidney biopsy specimen showed mesangial deposits of IgA; in one case IgA was deposited along the glomerular basement membrane. In only three of the remaining 217 patients without cutaneous IgA deposits were typical mesangial IgA deposits found. The close correlation between IgA deposits in cutaneous vessels and focal segmental intracapillary proliferation with mesangial IgA deposits suggests that immunofluorescence examination of skin biopsy specimens could prove of diagnostic value. The results provide additional evidence for a close pathogenic relationship between IgA-associated glomerulonephritis and anaphylactoid purpura.

  1. Approaching Biomarkers of Membranous Nephropathy from a Murine Model to Human Disease

    Directory of Open Access Journals (Sweden)

    Chia-Chao Wu

    2011-01-01

    Full Text Available Background. Membranous glomerulonephropathy (MN is the most prevalent cause of nephrotic syndrome in adult humans. However, the specific biomarkers of MN have not been fully elucidated. We examined the alterations in gene expression associated with the development of MN. Methods. Murine MN was induced by cationic bovine serum albumin (cBSA. After full-blown MN, cDNA microarray analysis was performed to identify gene expression changes, and highly expressed genes were evaluated as markers both in mice and human kidney samples. Results. MN mice revealed clinical proteinuria and the characteristic diffuse thickening of the glomerular basement membrane. There were 175 genes with significantly different expressions in the MN kidneys compared with the normal kidneys. Four genes, metallothionein-1 (Mt1, cathepsin D (CtsD, lymphocyte 6 antigen complex (Ly6, and laminin receptor-1 (Lamr1, were chosen and quantified. Mt1 was detected mainly in tubules, Lamr1 was highly expressed in glomeruli, and CtsD was detected both in tubules and glomeruli. The high expressions of Lamr1 and CtsD were also confirmed in human kidney biopsies. Conclusion. The murine MN model resembled the clinical and pathological features of human MN and may provide a tool for investigating MN. Applying cDNA microarray analysis may help to identify biomarkers for human MN.

  2. Influence of Personalized Nursing Mode on the Emotions and Quality of Life in Different Classification IgA Nephropathy Patients%个性化护理模式对不同分级IgA肾病患者情绪及生活质量的影响

    Institute of Scientific and Technical Information of China (English)

    尹晓丽; 王丽; 韩梦雨; 金娟; 朱俊

    2013-01-01

    目的:探讨个性化护理模式对不同分级IgA肾病(IgAN)患者负性情绪及生活质量的影响。方法将80例住院诊断IgAN患者,随机分为观察组和对照组,各40例。对照组采用常规护理。观察组采用个性化护理模式。比较两组干预前后负性情绪及生活质量情况。结果观察组干预后焦虑及抑郁评分明显下降(P<0.01),观察组较对照组干预后的焦虑及抑郁评分明显下降(P<0.01);观察组生活质量评分(除疼痛和肾病负担外)优于对照组(P<0.001)。结论针对不同分级IgAN患者实行个性化护理模式,可以明显改善患者的负性情绪,提高其生活质量。%Objective To evaluate the effect of personalized nursing mode on negative emotions and quality of life in different classification IgA nephropathy (IgAN) patients and observe its clinical value .Methods 80 cases of IgAN patients were randomly di-vided into observation group and control group .Used conventional care for the control group and the patients in observation group were given the model of personalized care .And then compared the negative emotions and quality of life before and after intervention in two groups .Results The negative emotions ,such as anxiety and depression scores in observation group before and after interven-tion improved significantly (P<0 .01) ,the observation group after the intervention of anxiety and depression scores improved signif-icantly compared with the control group (P<0 .01) .Overall health ,society and physical function ,functions of physical and emo-tional ,energy and emotional state ,social cognitive function ,symptoms and discomfort ,kidney affect ,sexual function ,sleep quali-ty ,comprehensive health evaluation and patient satisfaction in the observation group were better than that in control group signifi -cantly(P<0 .001) .Conclusions The personalized nursing mode in different classification of IgAN patients can

  3. Diabetic nephropathy and antioxidants.

    Science.gov (United States)

    Tavafi, Majid

    2013-01-01

    Oxidative stress has crucial role in pathogenesis of diabetic nephropathy (DN). Despite satisfactory results from antioxidant therapy in rodent, antioxidant therapy showed conflicting results in combat with DN in diabetic patients. Directory of Open Access Journals (DOAJ), Google Scholar,Pubmed (NLM), LISTA (EBSCO) and Web of Science have been searched. Treatment of DN in human are insufficient with rennin angiotensin system (RAS) blockers, so additional agent ought to combine with this management. Meanwhile based on DN pathogenesis and evidences in experimental and human researches, the antioxidants are the best candidate. New multi-property antioxidants may be improved human DN that show high power antioxidant capacity, long half-life time, high permeability to mitochondrion, improve body antioxidants enzymes activity and anti-inflammatory effects. Based on this review and our studies on diabetic rats, rosmarinic acid a multi-property antioxidant may be useful in DN patients, but of course, needs to be proven in clinical trials studies.

  4. Crystalglobulin-induced nephropathy.

    Science.gov (United States)

    Gupta, Vinay; El Ters, Mireille; Kashani, Kianoush; Leung, Nelson; Nasr, Samih H

    2015-03-01

    Crystalline nephropathy refers to renal parenchymal deposition of crystals leading to kidney damage. The most common forms of crystalline nephropathy encountered in renal pathology are nephrocalcinosis and oxalate nephropathy. Less frequent types include urate nephropathy, cystinosis, dihydroxyadeninuria, and drug-induced crystalline nephropathy (e.g., caused by indinavir or triamterene). Monoclonal proteins can also deposit in the kidney as crystals and cause tissue damage. This occurs in conditions such as light chain proximal tubulopathy, crystal-storing histiocytosis, and crystalglobulinemia. The latter is a rare complication of multiple myeloma that results from crystallization of monoclonal proteins in the systemic vasculature, leading to vascular injury, thrombosis, and occlusion. In this report, we describe a case of crystalglobulin-induced nephropathy and discuss its pathophysiology and the differential diagnosis of paraprotein-induced crystalline nephropathy.

  5. Effects of SGLT2 inhibition in human kidney proximal tubular cells--renoprotection in diabetic nephropathy?

    Directory of Open Access Journals (Sweden)

    Usha Panchapakesan

    Full Text Available Sodium/glucose cotransporter 2 (SGLT2 inhibitors are oral hypoglycemic agents used to treat patients with diabetes mellitus. SGLT2 inhibitors block reabsorption of filtered glucose by inhibiting SGLT2, the primary glucose transporter in the proximal tubular cell (PTC, leading to glycosuria and lowering of serum glucose. We examined the renoprotective effects of the SGLT2 inhibitor empagliflozin to determine whether blocking glucose entry into the kidney PTCs reduced the inflammatory and fibrotic responses of the cell to high glucose. We used an in vitro model of human PTCs. HK2 cells (human kidney PTC line were exposed to control 5 mM, high glucose (HG 30 mM or the profibrotic cytokine transforming growth factor beta (TGFβ1; 0.5 ng/ml in the presence and absence of empagliflozin for up to 72 h. SGLT1 and 2 expression and various inflammatory/fibrotic markers were assessed. A chromatin immunoprecipitation assay was used to determine the binding of phosphorylated smad3 to the promoter region of the SGLT2 gene. Our data showed that TGFβ1 but not HG increased SGLT2 expression and this occurred via phosphorylated smad3. HG induced expression of Toll-like receptor-4, increased nuclear deoxyribonucleic acid binding for nuclear factor kappa B (NF-κB and activator protein 1, induced collagen IV expression as well as interleukin-6 secretion all of which were attenuated with empagliflozin. Empagliflozin did not reduce high mobility group box protein 1 induced NF-κB suggesting that its effect is specifically related to a reduction in glycotoxicity. SGLT1 and GLUT2 expression was not significantly altered with HG or empagliflozin. In conclusion, empagliflozin reduces HG induced inflammatory and fibrotic markers by blocking glucose transport and did not induce a compensatory increase in SGLT1/GLUT2 expression. Although HG itself does not regulate SGLT2 expression in our model, TGFβ increases SGLT2 expression through phosphorylated smad3.

  6. Injection of recombinant Fc alpha RI/CD89 in mice does not induce mesangial IgA deposition

    NARCIS (Netherlands)

    van der Boog, PJM; van Kooten, C; van Zandbergen, G; Klar-Mohamad, N; Oortwijn, B; Bos, NA; van Remoortere, A; Hokke, CH; de Fijter, JW; Daha, MR

    2004-01-01

    Background. Earlier studies have suggested that complexes of the human IgA receptor FcalphaRI/CD89 with mouse IgA are pathogenic upon deposition in the renal mesangium. Transgenic mice expressing FcalphaRI/CD89 on macrophages/monocytes developed massive mesangial IgA deposition and a clinical

  7. Injection of recombinant Fc alpha RI/CD89 in mice does not induce mesangial IgA deposition

    NARCIS (Netherlands)

    van der Boog, PJM; van Kooten, C; van Zandbergen, G; Klar-Mohamad, N; Oortwijn, B; Bos, NA; van Remoortere, A; Hokke, CH; de Fijter, JW; Daha, MR

    2004-01-01

    Background. Earlier studies have suggested that complexes of the human IgA receptor FcalphaRI/CD89 with mouse IgA are pathogenic upon deposition in the renal mesangium. Transgenic mice expressing FcalphaRI/CD89 on macrophages/monocytes developed massive mesangial IgA deposition and a clinical pictur

  8. Histopathological Study of the Lungs of Mice Receiving Human Secretory IgA and Challenged with Mycobacterium tuberculosis.

    Science.gov (United States)

    Alvarez, Nadine; Infante, Juan Francisco; Borrero, Reinier; Mata, Dulce; Payan, Jorge Barrios-; Hossain, Md Murad; Mohd Nor, Norazmi; Sarmiento, María Elena; Hernandez-Pando, Rogelio; Acosta, Armando

    2014-05-01

    Humoral and cellular immune responses are associated with protection against extracellular and intracellular pathogens, respectively. In the present study, we evaluated the effect of receiving human secretory immunoglobulin A (hsIgA) on the histopathology of the lungs of mice challenged with virulent Mycobacterium tuberculosis. The hsIgA was purified from human colostrum and administered to Balb/c mice by the intranasal route prior to infection with M. tuberculosis or in a pre-incubated formulation with mycobacteria, with the principal aim to study its effect on qualitative pulmonary histopathology. The intranasal administration of hsIgA and the pre-incubation of mycobacteria with this preparation was associated with the presence of organised granulomas with signs of immune activation and histological features related to efficient disease control. This effect was highly evident during the late stage of infection (60 days), as demonstrated by numerous organised granulomas with numerous activated macrophages in the lungs of treated mice. The administration of hsIgA to mice before intratracheal infection with M. tuberculosis or the pre-incubation of the bacteria with the antibody formulation induced the formation of well-organised granulomas and inflammatory lesions in lungs compared with non-treated animals which correlates with the protective effect already demonstrated by these antibody formulations.

  9. Computational modeling of the Fc αRI receptor binding in the Fc α domain of the human antibody IgA: Normal Modes Analysis (NMA) study

    Science.gov (United States)

    Jayasinghe, Manori; Posgai, Monica; Tonddast-Navaei, Sam; Ibrahim, George; Stan, George; Herr, Andrew; George Stan Group Collaboration; Herr's Group Team

    2014-03-01

    Fc αRI receptor binding in the Fc α domain of the antibody IgA triggers immune effector responses such as phagocytosis and antibody-dependent cell-mediated cytotoxicity in eukaryotic cells. Fc α is a dimer of heavy chains of the IgA antibody and each Fc α heavy chain which consisted of two immunoglobulin constant domains, CH2 and CH3, can bind one Fc αRI molecule at the CH2-CH3 interface forming a 2:1 stoichiometry. Experimental evidences confirmed that Fc αRI binding to the Fc α CH2-CH3 junction altered the kinetics of HAA lectin binding at the distant IgA1 hinge. Our focus in this research was to understand the conformational changes and the network of residues which co-ordinate the receptor binding dynamics of the Fc α dimer complex. Structure-based elastic network modeling was used to compute normal modes of distinct Fc α configurations. Asymmetric and un-liganded Fc α configurations were obtained from the high resolution crystal structure of Fc α-Fc αRI 2:1 symmetric complex of PDB ID 1OW0. Our findings confirmed that Fc αRI binding, either in asymmetric or symmetric complex with Fc α, propagated long-range conformational changes across the Fc domains, potentially also impacting the distant IgA1 hinge.

  10. HIV Associated Lupus Like Nephropathy

    OpenAIRE

    2014-01-01

    Background Human immunodeficiency virus type 1 (HIV-1)-seropositive patients are at a high risk for the development of a variety of acute and chronic renal diseases. Most patients with HIVAN are of African descent, presenting late in the course of their HIV-1 infection. The only reliable test to establish or rule out the presence of HIVAN (HIV associated nephropathy) is renal biopsy. The most common lesion associated with HIV is a focal segmental glomeruloscelerosis, but several times, other ...

  11. Blood Test: Immunoglobulin A (IgA)

    Science.gov (United States)

    ... to 2-Year-Old Blood Test: Immunoglobulin A (IgA) KidsHealth > For Parents > Blood Test: Immunoglobulin A (IgA) Print A A A What's in this article? ... Questions en español Análisis de sangre: inmunoglobulina A (IgA) What It Is An IgA test measures the ...

  12. 呈慢性肾炎的IgA肾病96例临床病理和预后分析%Analysis of clinico-pathological characteristics and prognosis in 96 patients of IgA nephropathy with chronic glomerulonephritis

    Institute of Scientific and Technical Information of China (English)

    徐晓燕; 黄朝兴

    2011-01-01

    Objective: To discuss the early diagnostic criterion of chronic glomerulonephritis in primary IgA Nephropathy (IgAN). Methods: From march 1993 to august 2009, 96 biopsy-proven IgAN patients from The First Affiliated Hospital of Wenzhou Medical College with serum creatinine level above the upper limit (Scr≥ 105 μ mol/L by picric kinetic method) were enrolled in this study. The patients were divided into two groups according to creatinine clearance rate (Ccr): Group A (Ccr≥ 60 mL/min, n=43), and group B (Ccr<60 mL/min, n=53). Two groups of patients with clinico-pathological characteristics and prognosis were compared and analyzed. Endpoint was defined as double of baseline serum creatinine or Ccr<15 mL/min.Results:Among 96 cases with IgAN, incidence of proteinuria>1.O g/day, severe glomerular sclerosis, moderate to severe tubelointerstitial lesions was 73.0%,82.3%and 76.0%respectively,and the average Ccr at renal biopsy was (59.15± 20.73) mL/min. All cases with a median followup of 18.5 months, 21 patients developed to ESRD. The incidence of intermediate to severe tubulointerstitial lesions and nephrotic-range proteinuria in group B was significantly higher than that in group A (84.9% vs 65.1%, P<O.05 and 41.5% vs 18.6%, P<O.05, respectively).Patients in B and A groups were followed-up for a median duration of 33 and 21 months,respectively, 28,0% and 14.0% patients reaching the endpoint. Conclusion: For patients with IgAN, the fundamental clinico-pathological features of chronic glomerulonephritis are as follows:①durative proteinuria>1.O g/day; ②lasting Ccr decrease; ③moderate to severe tubulointerstitial lesions accompanied with severe glomerular sclerosis. The three items mentioned above may be used as the early diagnostic criterion for chronic glomerulonephritis.%目的:探讨在原发性IgA肾病(IgAN)中如何早期作出慢性肾小球肾炎(慢性肾炎)的临床诊断.方法:于1993年3月-2009年8月我院肾活检

  13. Clinical study on treatment of IgA nephropathy with renal insufficiency by corticosteroid, corticosteroid combined with cyclophosphamide and corticosteroid combined with mycophenolate mofetil%单纯激素、激素联合环磷酰胺和激素联合麦考酚酯治疗肾功能不全IgA肾病的临床研究

    Institute of Scientific and Technical Information of China (English)

    王伟铭; 贾晓媛; 潘晓霞; 沈平雁; 刘剑; 徐丽梨; 李娅; 王朝晖; 李晓

    2013-01-01

    Objective To investigate the clinical efficacy and safety of corticosteroid, corticosteroid combined with cyclophosphamide ( CTX) and corticosteroid combined with mycophenolate mofetil ( MMF) in IgA nephropathy (IgAN) with renal insufficiency. Methods Patients confirmed as primary IgAN by renal biopsy were selected, with chronic renal disease (CKD) of 3-4 stage and moderate renal lesions. Sixty patients were enrolled, and randomly received corticosteroid therapy (corticosteroid group, re =20), corticosteroid combined with CTX therapy (corticosteroid + CTX group, n=20) and corticosteroid combined with MMF therapy ( corticosteroid + MMF group, n = 20) . The 24 h urine protein, renal function parameters and adverse effect were observed during treatment. Results With the time of treatment, 24 h urine protein was gradually reduced in each group, and 24 h urine protein in corticosteroid group and corticosteroid + CTX group 3, 6 and 12 months after treatment and in corticosteroid + MMF group 12 months after treatment was significantly lower than the baseline (P 0. 05). Eight patients (8/20) in corticosteroid + MMF group suffered from serious pulmonary infection during treatment for 3 to 4 months, the baseline eGFR of whom was significantly lower than that of patients without serious pulmonary infection in corticosteroid + MMF group (P <0. 05). Conclusion Twenty-four hour urine protein can be significantly decreased with corticostsroid therapy, corticosteroid combined with CTX therapy and corticosteroid combined with MMF therapy in patients with IgAN and impaired renal function, and stable renal function can be maintained during treatment. Intensive follow-up should be carried out in the treatment with MMF due to the possibility of occurrence of serious pulmonary infection.%目的 观察单纯激素、激素联合环磷酰胺(CTX)、激素联合霉酚酸酯(MMF)治疗伴慢性肾功能不全原发性IgA肾病(IgAN)患者的临床效果和安全性.方法 选取经肾穿

  14. Diabetic nephropathy: a national dialogue.

    Science.gov (United States)

    Breyer, Matthew D; Coffman, Thomas M; Flessner, Michael F; Fried, Linda F; Harris, Raymond C; Ketchum, Christian J; Kretzler, Matthias; Nelson, Robert G; Sedor, John R; Susztak, Katalin

    2013-09-01

    The National Institute of Diabetes and Digestive and Kidney Diseases-supported Kidney Research National Dialogue (KRND) asked the scientific community to formulate and prioritize research objectives that would improve our understanding of kidney function and disease. Several high-priority objectives for diabetic nephropathy were identified in data and sample collection, hypothesis generation, hypothesis testing, and translation promotion. The lack of readily available human samples linked to comprehensive phenotypic, clinical, and demographic data remains a significant obstacle. With data and biological samples in place, several possibilities exist for using new technologies to develop hypotheses. Testing novel disease mechanisms with state-of-the-art tools should continue to be the foundation of the investigative community. Research must be translated to improve diagnosis and treatment of people. The objectives identified by the KRND provide the research community with future opportunities for improving the prevention, diagnosis, and treatment of diabetic nephropathy.

  15. Immunoglobulin A nephropathy: Basic characteristics

    Directory of Open Access Journals (Sweden)

    Petrović Lada

    2003-01-01

    Full Text Available Introduction Immunoglobulin A nephropathy (IgAN is one of the most common forms of primary glomerulonephritis in many countries. Most clinical features of IgAN point to a renal problem, such as recurrent macroscopic hematuria or asymptomatic microscopic hematuria and proteinuria. Pathologic features of IgAN present with different types and different degrees of glomerular tubulointerstitial and vascular lesions. The aim of this study was detailed analysis of clinical and laboratory findings, as well as findings of immunofluorescence and light microscopy. We also investigated associations between these factors. Material and methods We investigated 60 patients who underwent renal biopsy. The study was partly retrospective and partly prospective. Results The average age of patients was 34.19 years. Male female ratio was 2.33:1. IgAN was most frequently asymptomatic (83.33% as microhematuria and proteinuria, while gross hematuria was found in 16.667%. Renal biopsy material was analyzed by light microscopy revealing changes in all glomerular structures. Immunofluorescence microscopy demonstrated dominant IgA deposits. This study established association of glomerulosclerosis with clinical features of disease. Discussion and conclusions IgAN frequently develops in the 4th decade of life, mostly in males and presents as asymptomatic (83.33%. Patohistological changes include all glomerular structures. There is no specific serological test for IgAN, but pathological changes affect clinical features of the disease, as proteinuria and increase of creatinine concentration.

  16. Genetics of diabetic nephropathy

    DEFF Research Database (Denmark)

    Parving, H H; Tarnow, L; Rossing, P

    1996-01-01

    Diabetic nephropathy is a clinical syndrome characterized by persistent albuminuria, a relentless decline in GFR, raised arterial blood pressure, and increased relative mortality for cardiovascular diseases. Diabetic nephropathy is a leading cause of end-stage renal failure. The pathogenesis of d...

  17. The Gastrointestinal Frontier: IgA and Viruses

    Science.gov (United States)

    Blutt, Sarah E.; Conner, Margaret E.

    2013-01-01

    Viral gastroenteritis is one of the leading causes of diseases that kill ~2.2 million people worldwide each year. IgA is one of the major immune effector products present in the gastrointestinal tract yet its importance in protection against gastrointestinal viral infections has been difficult to prove. In part this has been due to a lack of small and large animal models in which pathogenesis of and immunity to gastrointestinal viral infections is similar to that in humans. Much of what we have learned about the role of IgA in the intestinal immune response has been obtained from experimental animal models of rotavirus infection. Rotavirus-specific intestinal IgA appears to be one of the principle effectors of long term protection against rotavirus infection. Thus, there has been a focus on understanding the immunological pathways through which this virus-specific IgA is induced during infection. In addition, the experimental animal models of rotavirus infection provide excellent systems in which new areas of research on viral-specific intestinal IgA including the long term maintenance of viral-specific IgA. PMID:24348474

  18. Increased renal gene transcription of protein kinase C-beta in human diabetic nephropathy: relationship to long-term glycaemic control

    DEFF Research Database (Denmark)

    Langham, R.G.; Kelly, D.J.; Gow, R.M.;

    2008-01-01

    was examined in renal biopsies (n=25) with classical histological features of diabetic nephropathy and compared with that in normal control tissue (n=6). Peptide localisation of PKC-alpha, PKC-beta and the activated forms phosphorylated PKC-alpha and -beta was also performed on matched paraffin......-embedded sections of renal biopsies using immunohistochemistry. The effects of high glucose on PRKC-beta expression and peptide production in cultured human proximal tubular epithelial cells were assessed. RESULTS: Quantitative real-time PCR demonstrated a 9.9-fold increase in PRKC-beta mRNA in kidney biopsies...... quantitative analysis of mRNA from archival, formalin-fixed, paraffin-embedded tissue sections. RNA was extracted from scraped 6 microm sections of biopsy tissue, and PRKC-alpha and PRKC-beta (also known as PRKCA and PRKCB) mRNA measured using real-time PCR. Expression of genes encoding PKC isoforms...

  19. Recognition of galactose-deficient O-glycans in the hinge region of IgA1 by N-acetylgalactosamine-specific snail lectins: a comparative binding study.

    Science.gov (United States)

    Gomes, Michelle M; Suzuki, Hitoshi; Brooks, Monica T; Tomana, Milan; Moldoveanu, Zina; Mestecky, Jiri; Julian, Bruce A; Novak, Jan; Herr, Andrew B

    2010-07-13

    Aberrancies in IgA1 glycosylation have been linked to the pathogenesis of IgA nephropathy (IgAN), a kidney disease characterized by deposits of IgA1-containing immune complexes in the glomerular mesangium. IgA1 from IgAN patients is characterized by the presence of galactose (Gal)-deficient O-glycans in the hinge region that can act as epitopes for anti-glycan IgG or IgA1 antibodies. The resulting circulating immune complexes are trapped in the glomerular mesangium of the kidney where they trigger localized inflammatory responses by activating mesangial cells. Certain lectins recognize the terminal N-acetylgalactosamine (GalNAc)-containing O-glycans on Gal-deficient IgA1 and can be potentially used as diagnostic tools. To improve our understanding of GalNAc recognition by these lectins, we have conducted binding studies to assess the interaction of Helix aspersa agglutinin (HAA) and Helix pomatia agglutinin (HPA) with Gal-deficient IgA1. Surface plasmon resonance spectroscopy revealed that both HAA and HPA bind to a Gal-deficient synthetic hinge region glycopeptide (HR-GalNAc) as well as various aberrantly glycosylated IgA1 myeloma proteins. Despite having six binding sites, both HAA and HPA bind IgA1 in a functionally bivalent manner, with the apparent affinity for IgA1 related to the number of exposed GalNAc groups in the IgA1 hinge. Finally, HAA and HPA were shown to discriminate very effectively between the IgA1 secreted by cell lines derived from peripheral blood cells of patients with IgAN and that from cells of healthy controls. These studies provide insight into lectin recognition of the Gal-deficient IgA1 hinge region and lay the groundwork for the development of reliable diagnostic tools for IgAN.

  20. Rodent models of diabetic nephropathy: their utility and limitations.

    Science.gov (United States)

    Kitada, Munehiro; Ogura, Yoshio; Koya, Daisuke

    2016-01-01

    Diabetic nephropathy is the most common cause of end-stage renal disease. Therefore, novel therapies for the suppression of diabetic nephropathy must be developed. Rodent models are useful for elucidating the pathogenesis of diseases and testing novel therapies, and many type 1 and type 2 diabetic rodent models have been established for the study of diabetes and diabetic complications. Streptozotocin (STZ)-induced diabetic animals are widely used as a model of type 1 diabetes. Akita diabetic mice that have an Ins2+/C96Y mutation and OVE26 mice that overexpress calmodulin in pancreatic β-cells serve as a genetic model of type 1 diabetes. In addition, db/db mice, KK-Ay mice, Zucker diabetic fatty rats, Wistar fatty rats, Otsuka Long-Evans Tokushima Fatty rats and Goto-Kakizaki rats serve as rodent models of type 2 diabetes. An animal model of diabetic nephropathy should exhibit progressive albuminuria and a decrease in renal function, as well as the characteristic histological changes in the glomeruli and the tubulointerstitial lesions that are observed in cases of human diabetic nephropathy. A rodent model that strongly exhibits all these features of human diabetic nephropathy has not yet been developed. However, the currently available rodent models of diabetes can be useful in the study of diabetic nephropathy by increasing our understanding of the features of each diabetic rodent model. Furthermore, the genetic background and strain of each mouse model result in differences in susceptibility to diabetic nephropathy with albuminuria and the development of glomerular and tubulointerstitial lesions. Therefore, the validation of an animal model reproducing human diabetic nephropathy will significantly facilitate our understanding of the underlying genetic mechanisms that contribute to the development of diabetic nephropathy. In this review, we focus on rodent models of diabetes and discuss the utility and limitations of these models for the study of diabetic

  1. GWAS for serum galactose-deficient IgA1 implicates critical genes of the O-glycosylation pathway.

    Directory of Open Access Journals (Sweden)

    Krzysztof Kiryluk

    2017-02-01

    Full Text Available Aberrant O-glycosylation of serum immunoglobulin A1 (IgA1 represents a heritable pathogenic defect in IgA nephropathy, the most common form of glomerulonephritis worldwide, but specific genetic factors involved in its determination are not known. We performed a quantitative GWAS for serum levels of galactose-deficient IgA1 (Gd-IgA1 in 2,633 subjects of European and East Asian ancestry and discovered two genome-wide significant loci, in C1GALT1 (rs13226913, P = 3.2 x 10-11 and C1GALT1C1 (rs5910940, P = 2.7 x 10-8. These genes encode molecular partners essential for enzymatic O-glycosylation of IgA1. We demonstrated that these two loci explain approximately 7% of variability in circulating Gd-IgA1 in Europeans, but only 2% in East Asians. Notably, the Gd-IgA1-increasing allele of rs13226913 is common in Europeans, but rare in East Asians. Moreover, rs13226913 represents a strong cis-eQTL for C1GALT1 that encodes the key enzyme responsible for the transfer of galactose to O-linked glycans on IgA1. By in vitro siRNA knock-down studies, we confirmed that mRNA levels of both C1GALT1 and C1GALT1C1 determine the rate of secretion of Gd-IgA1 in IgA1-producing cells. Our findings provide novel insights into the genetic regulation of O-glycosylation and are relevant not only to IgA nephropathy, but also to other complex traits associated with O-glycosylation defects, including inflammatory bowel disease, hematologic disease, and cancer.

  2. Proliferative retinopathy predicts nephropathy

    DEFF Research Database (Denmark)

    Karlberg, Charlotte; Falk, Christine; Green, Anders;

    2012-01-01

    We wanted to examine proliferative retinopathy as a marker of incident nephropathy in a 25-year follow-up study of a population-based cohort of Danish type 1 diabetic patients and to examine cross-sectional associations between nephropathy and retinopathy in long-term surviving patients of the same...... photographs at follow-up. Single spot urine was used to evaluate nephropathy at both examinations. Proliferative retinopathy was present in 29 patients (15.8%) at baseline. At follow-up, these patients were more likely to macroalbuminuria (20.7% vs. 6.5%) than patients without proliferative retinopathy...... at baseline. In a multivariate logistic regression adjusted for baseline age, sex, duration of diabetes, smoking, HbA(1,) systolic and diastolic blood pressure, odds ratio of nephropathy (micro- and macroalbuminuria combined) was 2.98 (95% confidence interval 1.18-7.51, p = 0.02) for patients...

  3. Kidney Disease (Nephropathy)

    Science.gov (United States)

    ... Text Size: A A A Listen En Español Kidney Disease (Nephropathy) Kidneys are remarkable organs. Inside them ... resulting in kidney disease. How Does Diabetes Cause Kidney Disease? When our bodies digest the protein we ...

  4. Purification and functional characterization of mucosal IgA from vaccinated and SIV-infected rhesus macaques

    Science.gov (United States)

    Musich, Thomas; Demberg, Thorsten; Morgan, Ian L.; Estes, Jacob D.; Franchini, Genoveffa; Robert-Guroff, Marjorie

    2015-01-01

    Vaccine-induced mucosal antibodies are often evaluated using small volumes of secretory fluids. However, fecal matter containing mucosal IgA is abundant. We purified fecal IgA from five SIV-vaccinated and five SIV-infected rhesus macaques by sequential affinity chromatography. The purified IgA was dimeric by native PAGE, contained secretory component, and was analogous to IgA in colostrum and vaginal fluid by western blot. IgA from one infected and four vaccinated animals neutralized H9-derived SIVmac251 with IC50s as low as 1µg/mL. Purified IgAs inhibited transcytosis and exhibited phagocytic activity, the latter significantly correlated with SIVmac251 Env-specific IgA in the purified samples. Among different affinity resins, peptide M was optimal compared to jacalin, anti-monkey IgA and SSL7 for IgA purification, as confirmed using tandem peptide M/anti-monkey IgA columns. Fecal IgA provided material sufficient for several assays relevant to protective efficacy, and was shown to be multifunctional. Our approach is potentially applicable to human clinical studies. PMID:25840105

  5. Purification and functional characterization of mucosal IgA from vaccinated and SIV-infected rhesus macaques.

    Science.gov (United States)

    Musich, Thomas; Demberg, Thorsten; Morgan, Ian L; Estes, Jacob D; Franchini, Genoveffa; Robert-Guroff, Marjorie

    2015-06-01

    Vaccine-induced mucosal antibodies are often evaluated using small volumes of secretory fluids. However, fecal matter containing mucosal IgA is abundant. We purified fecal IgA from five SIV-vaccinated and five SIV-infected rhesus macaques by sequential affinity chromatography. The purified IgA was dimeric by native PAGE, contained secretory component, and was analogous to IgA in colostrum and vaginal fluid by western blot. IgA from one infected and four vaccinated animals neutralized H9-derived SIV(mac)251 with IC(50)s as low as 1 μg/mL. Purified IgAs inhibited transcytosis and exhibited phagocytic activity, the latter significantly correlated with SIV(mac)251 Env-specific IgA in the purified samples. Among different affinity resins, peptide M was optimal compared to jacalin, anti-monkey IgA and SSL7 for IgA purification, as confirmed using tandem peptide M/anti-monkey IgA columns. Fecal IgA provided material sufficient for several assays relevant to protective efficacy, and was shown to be multifunctional. Our approach is potentially applicable to human clinical studies.

  6. Characterisation of kidney lesions in early schistosomal-specific nephropathy.

    Science.gov (United States)

    Sobh, M A; Moustafa, F E; Sally, S M; Deelder, A M; Ghoniem, M A

    1988-01-01

    In this work 42 patients with active Schistosoma mansoni infection and renal involvement were examined. Of these, 16 had asymptomatic proteinuria (group I) and 26 had the nephrotic syndrome (group II). Fifteen nonschistosomal patients with idiopathic nephrotic syndrome were included as control cases (group III). Renal biopsy specimens were obtained from all patients and controls. These were examined by light microscopy (LM), by direct immunofluorescence microscopy using antisera against human IgG, IgM, IgA, C3, C4, C1q, and fibrinogen, and by indirect immunofluorescence microscopy using monoclonal antibodies directed against the circulating schistosome antigens, circulating anodic antigen (CCA) and circulating cathodic antigen (CCA). Schistosomal-specific deposits were seen in the renal glomeruli in 24 of the 42 schistosomal patients but in none of the 15 control patients. Although schistosomal-specific deposits were seen in seven of the 16 patients presenting with asymptomatic proteinuria, no morphological changes could be seen by LM. On the other hand, schistosomal-specific deposits could be seen in the kidneys of 17 of the 26 patients presenting with the nephrotic syndrome. All but one specimen showed morphological changes when examined by LM. These were consistent with mesangioproliferative glomerulonephritis in seven, focal segmental glomerulosclerosis in five, mesangiocapillary glomerulonephritis in two, membranous glomerulonephritis in one, and focal segmental hyalinosis in one patient. The present study clearly suggests that (a) schistosomal-specific nephropathy does exist in human settings, (b) it is an immune complex disease, and (c) CAA and CCA are major responsible antigens.

  7. A Systems Biology Overview on Human Diabetic Nephropathy: From Genetic Susceptibility to Post-Transcriptional and Post-Translational Modifications.

    Science.gov (United States)

    Conserva, Francesca; Gesualdo, Loreto; Papale, Massimo

    2016-01-01

    Diabetic nephropathy (DN), a microvascular complication occurring in approximately 20-40% of patients with type 2 diabetes mellitus (T2DM), is characterized by the progressive impairment of glomerular filtration and the development of Kimmelstiel-Wilson lesions leading to end-stage renal failure (ESRD). The causes and molecular mechanisms mediating the onset of T2DM chronic complications are yet sketchy and it is not clear why disease progression occurs only in some patients. We performed a systematic analysis of the most relevant studies investigating genetic susceptibility and specific transcriptomic, epigenetic, proteomic, and metabolomic patterns in order to summarize the most significant traits associated with the disease onset and progression. The picture that emerges is complex and fascinating as it includes the regulation/dysregulation of numerous biological processes, converging toward the activation of inflammatory processes, oxidative stress, remodeling of cellular function and morphology, and disturbance of metabolic pathways. The growing interest in the characterization of protein post-translational modifications and the importance of handling large datasets using a systems biology approach are also discussed.

  8. A Systems Biology Overview on Human Diabetic Nephropathy: From Genetic Susceptibility to Post-Transcriptional and Post-Translational Modifications

    Directory of Open Access Journals (Sweden)

    Francesca Conserva

    2016-01-01

    Full Text Available Diabetic nephropathy (DN, a microvascular complication occurring in approximately 20–40% of patients with type 2 diabetes mellitus (T2DM, is characterized by the progressive impairment of glomerular filtration and the development of Kimmelstiel-Wilson lesions leading to end-stage renal failure (ESRD. The causes and molecular mechanisms mediating the onset of T2DM chronic complications are yet sketchy and it is not clear why disease progression occurs only in some patients. We performed a systematic analysis of the most relevant studies investigating genetic susceptibility and specific transcriptomic, epigenetic, proteomic, and metabolomic patterns in order to summarize the most significant traits associated with the disease onset and progression. The picture that emerges is complex and fascinating as it includes the regulation/dysregulation of numerous biological processes, converging toward the activation of inflammatory processes, oxidative stress, remodeling of cellular function and morphology, and disturbance of metabolic pathways. The growing interest in the characterization of protein post-translational modifications and the importance of handling large datasets using a systems biology approach are also discussed.

  9. Iga viies SVH on ennetatav

    Index Scriptorium Estoniae

    2009-01-01

    ONTARGET uuring tõestab, et telmisartaan kaitseb kõrge kardiovaskulaarse riskiga patsiente sama tõhusalt kui ramipriil, kuid on paremini talutav. Uuringust võib järeldada, et telmisartaaniga saab ennetada iga viiendat tõsist kardiovaskulaarset juhtumit. Eesti arstidele tutvustati uuringut 6. mail toimunud sümpoosiumil

  10. Iga viies SVH on ennetatav

    Index Scriptorium Estoniae

    2009-01-01

    ONTARGET uuring tõestab, et telmisartaan kaitseb kõrge kardiovaskulaarse riskiga patsiente sama tõhusalt kui ramipriil, kuid on paremini talutav. Uuringust võib järeldada, et telmisartaaniga saab ennetada iga viiendat tõsist kardiovaskulaarset juhtumit. Eesti arstidele tutvustati uuringut 6. mail toimunud sümpoosiumil

  11. Novel Role of Parathyroid Hormone-Related Protein in the Pathophysiology of the Diabetic Kidney: Evidence from Experimental and Human Diabetic Nephropathy

    Directory of Open Access Journals (Sweden)

    Montserrat Romero

    2013-01-01

    Full Text Available Parathyroid hormone-related protein (PTHrP and its receptor type 1 (PTH1R are extensively expressed in the kidney, where they are able to modulate renal function. Renal PTHrP is known to be overexpressed in acute renal injury. Recently, we hypothesized that PTHrP involvement in the mechanisms of renal injury might not be limited to conditions with predominant damage of the renal tubulointerstitium and might be extended to glomerular diseases, such as diabetic nephropathy (DN. In experimental DN, the overexpression of both PTHrP and the PTH1R contributes to the development of renal hypertrophy as well as proteinuria. More recent data have shown, for the first time, that PTHrP is upregulated in the kidney from patients with DN. Collectively, animal and human studies have shown that PTHrP acts as an important mediator of diabetic renal cell hypertrophy by a mechanism which involves the modulation of cell cycle regulatory proteins and TGF-β1. Furthermore, angiotensin II (Ang II, a critical factor in the progression of renal injury, appears to be responsible for PTHrP upregulation in these conditions. These findings provide novel insights into the well-known protective effects of Ang II antagonists in renal diseases, paving the way for new therapeutic approaches.

  12. Novel role of parathyroid hormone-related protein in the pathophysiology of the diabetic kidney: evidence from experimental and human diabetic nephropathy.

    Science.gov (United States)

    Romero, Montserrat; Ortega, Arantxa; Olea, Nuria; Arenas, María Isabel; Izquierdo, Adriana; Bover, Jordi; Esbrit, Pedro; Bosch, Ricardo J

    2013-01-01

    Parathyroid hormone-related protein (PTHrP) and its receptor type 1 (PTH1R) are extensively expressed in the kidney, where they are able to modulate renal function. Renal PTHrP is known to be overexpressed in acute renal injury. Recently, we hypothesized that PTHrP involvement in the mechanisms of renal injury might not be limited to conditions with predominant damage of the renal tubulointerstitium and might be extended to glomerular diseases, such as diabetic nephropathy (DN). In experimental DN, the overexpression of both PTHrP and the PTH1R contributes to the development of renal hypertrophy as well as proteinuria. More recent data have shown, for the first time, that PTHrP is upregulated in the kidney from patients with DN. Collectively, animal and human studies have shown that PTHrP acts as an important mediator of diabetic renal cell hypertrophy by a mechanism which involves the modulation of cell cycle regulatory proteins and TGF- β 1. Furthermore, angiotensin II (Ang II), a critical factor in the progression of renal injury, appears to be responsible for PTHrP upregulation in these conditions. These findings provide novel insights into the well-known protective effects of Ang II antagonists in renal diseases, paving the way for new therapeutic approaches.

  13. Contrast induced nephropathy in urology

    Directory of Open Access Journals (Sweden)

    Viji Samuel Thomson

    2009-01-01

    Full Text Available Intravenous contrast agents have a distinct role in urological imaging: to study precise anatomical delineation, vascularity, and to assess the function of the renal unit. Contrast induced nephropathy (CIN is a known adverse effect of intravenous contrast administration. The literature on incidence, pathophysiology, clinical features, and current preventive strategies available for CIN relevant to urologists was reviewed. A search of the PubMed database was done using the keywords nephropathy and media, prevention and control or prevention Contrast media (explode, all adverse effects, and kidney diseases (explode. An online search of the EMBASE database for the time ranging from 1977 to February 2009 was performed using the keywords ionic contrast medium, adverse drug reaction, major or controlled clinical study, human, nephrotoxicity, and kidney disease. Current publications and data most relevant to urologists were examined. CIN was the third most common cause of hospital-acquired renal failure. The incidence is less common with intravenous contrast administration as compared with intra-arterial administration. The pathogenesis of contrast mediated nephropathy is due to a combination of toxic injury to renal tubules and medullary ischemic injury mediated by reactive oxygen species. CIN most commonly manifests as a nonoliguric and asymptomatic transient decline in renal function. Patients who developed CIN were found to have increased mortality, longer hospital stay, and complicated clinical course. An overview of risk factors and risk prediction score for prognostication of CIN are elaborated. Preventive strategies including choice of contrast agents, maximum tolerated dose, role of hydration, hydration regime, etc. are discussed. The role of N- acetyl cysteine, Theophylline, Fenoldapam, Endothelin receptor antagonists, iloprost, atrial natriuretic peptide, and newer therapies such as targeted renal therapy (TRT are discussed. A working

  14. OBSTRUCTIVE NEPHROPATHY: ITS PHYSIOPATHOLOGY

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    Musso C

    2011-01-01

    Full Text Available Obstructive nephropathy is the functional and /or parenchymal renal damage secondary to the urinary tract occlusion at any part of it. The inducing urinary obstruction diseases can vary depending on the patient´s age and gender. There are many renal dysfunction inducing mechanisms involved in this entity: increase in the intra-luminal pressure, ureteral dilatation with ineffective ureteral peristalsis, glomerular ultrafiltration net pressure reduction, intra-renal glomerular blood flux reduction due to vasoconstriction, and local disease of chemotactic substances. Obstructive nephropathy can also lead to hypertension (vasoconstriction-hypervolemia, hyperkalemia, metabolic acidosis (aldosterone resistance, diabetes insipidus (vasopressine resistance. In conclusion, since obstructive nephropathy is a potentially reversible cause of renal dysfunction, it should always be taken into account among the differential diagnosis of renal failure inducing mechanisms.

  15. Glyco-engineering for the production of recombinant IgA1 with distinct mucin-type O-glycans in plants.

    Science.gov (United States)

    Dicker, Martina; Maresch, Daniel; Strasser, Richard

    2016-11-01

    IgA nephropathy (IgAN) is a common autoimmune disease that is characterized by formation and deposition of IgA1-containing immune complexes frequently leading to end-stage kidney disease. The IgA1 in these immune complexes carries aberrantly glycosylated O-glycans. In circulating IgA1 these galactose-deficient mucin-type O-glycans are bound by autoantibodies and thus, contribute to immune complex formation and pathogenesis. Even though the disease is associated with the overproduction of aberrant O-glycans on IgA1, specific structure-function-studies of mucin-type O-glycans are limited. Compared to other expression hosts, plants offer the opportunity for de novo synthesis of O-glycans on recombinant glycoproteins as they are lacking the mammalian O-glycosylation pathway. Recently, we demonstrated that Nicotiana benthamiana are suitable for the generation of distinct O-glycans on recombinant IgA1. Here, we expand our engineering repertoire by in planta generation of galactose-deficient and α2,6-sialylated O-glycans which are the prevailing glycans detected on IgA1 from patients with IgAN.

  16. CagA, a major virulence factor of Helicobacter pylori, promotes the production and underglycosylation of IgA1 in DAKIKI cells

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Man [Department of Nephrology, The First Affiliated Hospital of Chengdu Medical College, Chengdu City 610500 (China); Li, Fu-gang [Department of Nephrology, Affiliated Hospital of Luzhou Medical College, Luzhou City 646000 (China); Xie, Xi-sheng [Department of Nephrology, Second Clinical Medical Institution of North Sichuan Medical College (Nanchong Central Hospital), Nanchong City 637400 (China); Wang, Shao-qing [Department of Nephrology, The First Affiliated Hospital of Chengdu Medical College, Chengdu City 610500 (China); Fan, Jun-ming, E-mail: junmingfan@163.com [Department of Nephrology, The First Affiliated Hospital of Chengdu Medical College, Chengdu City 610500 (China); Department of Nephrology, Affiliated Hospital of Luzhou Medical College, Luzhou City 646000 (China)

    2014-02-07

    Highlights: • CagA stimulated cell proliferation and the production of IgA1 in DAKIKI cells. • CagA promoted the underglycosylation of IgA1 in DAKIKI cells. • CagA decreased the expression of C1GALT1 and its chaperone Cosmc in DAKIKI cells. • Helicobacter pylori infection may participate in the pathogenesis of IgAN via CagA. - Abstract: While Helicobacter pylori (Hp) infection is closely associated with IgA nephropathy (IgAN), the underlying molecular mechanisms remain to be elucidated. This study was to investigate the effect of cytotoxin associated gene A protein (CagA), a major virulence factor of Hp, on the production and underglycosylation of IgA1 in the B cell line DAKIKI cells. Cells were cultured and treated with recombinant CagA protein. We found that CagA stimulated cell proliferation and the production of IgA1 in a dose-dependent and time-dependent manner. Moreover, CagA promoted the underglycosylation of IgA1, which at least partly attributed to the downregulation of β1,3-galactosyltransferase (C1GALT1) and its chaperone Cosmc. In conclusion, we demonstrated that Hp infection, at least via CagA, may participate in the pathogenesis of IgAN by influencing the production and glycosylation of IgA1 in B cells.

  17. Preventing diabetic nephropathy

    DEFF Research Database (Denmark)

    Hansen, H P; Lund, S S; Rossing, P

    2001-01-01

    In type 1 diabetic patients with microalbuminuria not receiving antihypertensive treatment, an increase in urinary albumin excretion rate (AER) of 6% to 14%/year and a risk for the development of diabetic nephropathy of 3% to 30%/year have previously been reported. The aim of the present study wa...

  18. The Protective Role of Nrf2 in Streptozotocin-Induced Diabetic Nephropathy

    OpenAIRE

    Jiang, Tao; Huang, Zheping; Lin, Yifeng; Zhang, Zhigang; Fang, Deyu; Zhang, Donna D.

    2010-01-01

    OBJECTIVE Diabetic nephropathy is one of the major causes of renal failure, which is accompanied by the production of reactive oxygen species (ROS). Nrf2 is the primary transcription factor that controls the antioxidant response essential for maintaining cellular redox homeostasis. Here, we report our findings demonstrating a protective role of Nrf2 against diabetic nephropathy. RESEARCH DESIGN AND METHODS We explore the protective role of Nrf2 against diabetic nephropathy using human kidney ...

  19. Role of IGFBP7 in Diabetic Nephropathy: TGF-β1 Induces IGFBP7 via Smad2/4 in Human Renal Proximal Tubular Epithelial Cells.

    Directory of Open Access Journals (Sweden)

    Jun Watanabe

    Full Text Available Tubular injury is one of the important determinants of progressive renal failure in diabetic nephropathy (DN, and TGF-β1 has been implicated in the pathogenesis of tubulointerstitial disease that characterizes proteinuric renal disease. The aim of this study was to identify novel therapeutic target molecules that play a role in the tubule damage of DN. We used an LC-MS/MS-based proteomic technique and human renal proximal epithelial cells (HRPTECs. Urine samples from Japanese patients with type 2 diabetes (n = 46 were used to quantify the candidate protein. Several proteins in HRPTECs in cultured media were observed to be driven by TGF-β1, one of which was 33-kDa IGFBP7, which is a member of IGFBP family. TGF-β1 up-regulated the expressions of IGFBP7 mRNA and protein in a dose- and time-dependent fashion via Smad2 and 4, but not MAPK pathways in HRPTECs. In addition, the knockdown of IGFBP7 restored the TGF-β1-induced epithelial to mesenchymal transition (EMT. In the immunohistochemical analysis, IGFBP7 was localized to the cytoplasm of tubular cells but not that of glomerular cells in diabetic kidney. Urinary IGFBP7 levels were significantly higher in the patients with macroalbuminuria and were correlated with age (r = 0.308, p = 0.037, eGFR (r = -0.376, p = 0.01, urinary β2-microglobulin (r = 0.385, p = 0.008, and urinary N-acetyl-beta-D-glucosaminidase (NAG (r = 0.502, p = 0.000. A multivariate regression analysis identified urinary NAG and age as determinants associated with urinary IGFBP7 levels. In conclusion, our data suggest that TGF-β1 enhances IGFBP7 via Smad2/4 pathways, and that IGFBP7 might be involved in the TGF-β1-induced tubular injury in DN.

  20. Localized linear IgA dermatosis induced by UV light-treatment for herpes zoster.

    Science.gov (United States)

    He, Chundi; Xu, Honghui; Xiao, Ting; Geng, Long; Chen, Hong-Duo

    2007-05-01

    We report a case of localized linear IgA dermatosis (LID). The patient suffered from herpes zoster on the right waist and received three localized ultraviolet (UV) light treatments. One month later he presented with bullae on the same site. Direct immunofluorescence showed deposition of linear IgA and weak C3 along the basement membrane zone. Indirect immunofluorescence on the salt-split human skin demonstrated that IgA antibodies were bound to the epidermal side. To our knowledge, this is the first case of localized LID induced by UV light treatment for herpes zoster. It is also the third case of LID induced by UV light.

  1. Cadmium nephropathy: monitoring for early evidence of renal dysfunction

    Energy Technology Data Exchange (ETDEWEB)

    Murray, T. (Univ. of Pennsylvania, Philadelphia); Walker, B.R.; Spratt, D.M.; Chappelka, R.

    1981-07-01

    Prospective studies in humans comparing various tests of cadmium-induced nephropathy have not been reported. Consequently, it is not possible to ascertain which screening methods should be followed in order to detect early nephropathy at a reversible stage. To obtain such data, the authors studied 23 cadmium workers with periodic analyses of blood/urine cadmium levels, hair cadmium content, urinary cytologies, creatinine clearance and urinary levels of lysozyme, ..beta..-2-microglobulins, immunoglobulins, and aminoacids. Blood/urine levels were useful only as indices of acute environmental exposure and not as predictors of total body content or possible nephropathy. Hair content was elevated in most works. Urine cytology was not reliable. Until further data are available, it is suggested that all five measures of renal function be used in screening and follow-up of cadmium workers for preventing nephropathy.

  2. Ichthyosiform mycosis fungoides with alopecia and atypical membranous nephropathy

    Directory of Open Access Journals (Sweden)

    Qiang Zhou

    2011-01-01

    Full Text Available We describe here a rare case of variant of mycosis fungoides (MF: ichthyosiform MF with alopecia and atypical membranous nephropathy. The diagnosis was made based on the following findings: generalized ichthyosis-like eruption, alopecia, enlarged superficial lymph nodes, proteinuria, and hematuria, the histological features of the skin biopsy from both ichthyotic and alopecic lesions with immunohistochemical staining, and the renal biopsy examination with immunofluorescence. The histological examination of ichthyotic and alopecic lesions displayed a predominant infiltration of atypical lymphocytes in the upper dermis with the characteristics of epidermotropism and folliculotropism. Immunohistochemical studies demonstrated that most infiltrated atypical lymphocytes were CD3, CD4, and CD45RO positive, whereas negative for CD5, CD7, CD20, CD30, and CD56. A renal biopsy examination revealed atypical membranous nephropathy with deposition of immunoglobulin G (IgG, IgM, IgA, C1q, and C3. In this case atypical membranous nephropathy was involved, which is very uncommon and has never been presented in the literature to date. Although ichthyosiform MF usually features a relatively favorable course, diffuse alopecia and the renal involvement in this case might indicate aggressive disease and poor prognosis.

  3. Rodent models of diabetic nephropathy: their utility and limitations

    Directory of Open Access Journals (Sweden)

    Kitada M

    2016-11-01

    Full Text Available Munehiro Kitada,1,2 Yoshio Ogura,2 Daisuke Koya1,2 1Division of Anticipatory Molecular Food Science and Technology, Medical Research Institute, 2Department of Diabetology and Endocrinology, Kanazawa Medical University, Uchinada, Ishikawa, Japan Abstract: Diabetic nephropathy is the most common cause of end-stage renal disease. Therefore, novel therapies for the suppression of diabetic nephropathy must be developed. Rodent models are useful for elucidating the pathogenesis of diseases and testing novel therapies, and many type 1 and type 2 diabetic rodent models have been established for the study of diabetes and diabetic complications. Streptozotocin (STZ-induced diabetic animals are widely used as a model of type 1 diabetes. Akita diabetic mice that have an Ins2+/C96Y mutation and OVE26 mice that overexpress calmodulin in pancreatic β-cells serve as a genetic model of type 1 diabetes. In addition, db/db mice, KK-Ay mice, Zucker diabetic fatty rats, Wistar fatty rats, Otsuka Long-Evans Tokushima Fatty rats and Goto-Kakizaki rats serve as rodent models of type 2 diabetes. An animal model of diabetic nephropathy should exhibit progressive albuminuria and a decrease in renal function, as well as the characteristic histological changes in the glomeruli and the tubulointerstitial lesions that are observed in cases of human diabetic nephropathy. A rodent model that strongly exhibits all these features of human diabetic nephropathy has not yet been developed. However, the currently available rodent models of diabetes can be useful in the study of diabetic nephropathy by increasing our understanding of the features of each diabetic rodent model. Furthermore, the genetic background and strain of each mouse model result in differences in susceptibility to diabetic nephropathy with albuminuria and the development of glomerular and tubulointerstitial lesions. Therefore, the validation of an animal model reproducing human diabetic nephropathy will

  4. Development of the gut microbiota and mucosal IgA responses in twins and gnotobiotic mice.

    Science.gov (United States)

    Planer, Joseph D; Peng, Yangqing; Kau, Andrew L; Blanton, Laura V; Ndao, I Malick; Tarr, Phillip I; Warner, Barbara B; Gordon, Jeffrey I

    2016-06-09

    Immunoglobulin A (IgA), the major class of antibody secreted by the gut mucosa, is an important contributor to gut barrier function. The repertoire of IgA bound to gut bacteria reflects both T-cell-dependent and -independent pathways, plus glycans present on the antibody's secretory component. Human gut bacterial taxa targeted by IgA in the setting of barrier dysfunction are capable of producing intestinal pathology when isolated and transferred to gnotobiotic mice. A complex reorientation of gut immunity occurs as infants transition from passively acquired IgA present in breast milk to host-derived IgA. How IgA responses co-develop with assembly of the microbiota during this period remains poorly understood. Here, we (1) identify a set of age-discriminatory bacterial taxa whose representations define a program of microbiota assembly and maturation during the first 2 postnatal years that is shared across 40 healthy twin pairs in the USA; (2) describe a pattern of progression of gut mucosal IgA responses to bacterial members of the microbiota that is highly distinctive for family members (twin pairs) during the first several postnatal months then generalizes across pairs in the second year; and (3) assess the effects of zygosity, birth mode, and breast feeding. Age-associated differences in these IgA responses can be recapitulated in young germ-free mice, colonized with faecal microbiota obtained from two twin pairs at 6 and 18 months of age, and fed a sequence of human diets that simulate the transition from milk feeding to complementary foods. Most of these responses were robust to diet, suggesting that 'intrinsic' properties of community members play a dominant role in dictating IgA responses. The approach described can be used to define gut mucosal immune development in health and disease states and to help discover ways of repairing or preventing perturbations in this facet of host immunity.

  5. Development of a standardized ELISA for the determination of autoantibodies against human M-type phospholipase A2 receptor in primary membranous nephropathy

    NARCIS (Netherlands)

    Dahnrich, C.; Komorowski, L.; Probst, C.; Seitz-Polski, B.; Esnault, V.; Wetzels, J.F.M.; Hofstra, J.M.; Hoxha, E.; Stahl, R.A.K.; Lambeau, G.; Stocker, W.; Schlumberger, W.

    2013-01-01

    BACKGROUND: Autoantibodies against the M-type phospholipase A2 receptor (PLA2R1) are specific markers for primary membranous nephropathy (pMN) and anti-PLA2R1 serum levels may be useful to monitor disease activity. So far, a recombinant cell-based indirect immunofluorescence assay (RC-IFA) using rec

  6. Development of a standardized ELISA for the determination of autoantibodies against human M-type phospholipase A2 receptor in primary membranous nephropathy

    NARCIS (Netherlands)

    Dahnrich, C.; Komorowski, L.; Probst, C.; Seitz-Polski, B.; Esnault, V.; Wetzels, J.F.M.; Hofstra, J.M.; Hoxha, E.; Stahl, R.A.K.; Lambeau, G.; Stocker, W.; Schlumberger, W.

    2013-01-01

    BACKGROUND: Autoantibodies against the M-type phospholipase A2 receptor (PLA2R1) are specific markers for primary membranous nephropathy (pMN) and anti-PLA2R1 serum levels may be useful to monitor disease activity. So far, a recombinant cell-based indirect immunofluorescence assay (RC-IFA) using

  7. Staphylococcus Infection-Associated GN - Spectrum of IgA Staining and Prevalence of ANCA in a Single-Center Cohort.

    Science.gov (United States)

    Satoskar, Anjali A; Suleiman, Sarah; Ayoub, Isabelle; Hemminger, Jessica; Parikh, Samir; Brodsky, Sergey V; Bott, Cherri; Calomeni, Edward; Nadasdy, Gyongyi M; Rovin, Brad; Hebert, Lee; Nadasdy, Tibor

    2017-01-06

    Staphylococcus infection-associated GN (SAGN) is a well recognized disease entity, particularly because of the frequent IgA-dominant glomerular immunoglobulin staining on kidney biopsy. Biopsy features can resemble two other disease entities - primary IgA nephropathy and Henoch-Schönlein purpura nephritis - posing a diagnostic pitfall. This is clinically relevant because of the crucial difference in the therapeutic approach. The diagnosis of SAGN is further complicated by the variability in the degree of glomerular IgA (and C3) staining, the extent of electron dense immune-type deposits, and positive ANCA serology in some patients. We performed a thorough histopathologic review of our single-center cohort of 78 culture-proven SAGN biopsies to assess the spectrum of IgA staining, prevalence of ANCA serology, prevalence of subepithelial "humps," and other histologic features to distinguish from primary IgA nephropathy. Among the 78 SAGN biopsies, IgA staining was trace in 25%, mild in 19%, moderate in 44%, and strong in 12% of the cases. C3 was frequently moderate-to-strong but was trace in 14% of the biopsies. Concomitantly trace IgA, IgG, and C3 (pauci-immune pattern) was seen in 13%. Crescents were present in 35% of the SAGN biopsies. Out of 41 patients tested for ANCA, nine (22%) were positive, including patients with endocarditis and other infections. Subepithelial humps were identified in only 31% of the SAGN biopsies. SAGN biopsies show marked variability in IgA immunofluorescence staining and low frequency of subepithelial humps compared with poststreptococcal GN. Occasional ANCA positivity is present in cases of SAGN, even in infections other than endocarditis. Therefore, biopsy diagnosis can be difficult particularly when clinical symptoms of infection are subtle. Both the pathologist and the nephrologist should be aware of these diagnostic pitfalls. Copyright © 2016 by the American Society of Nephrology.

  8. Re-thinking the functions of IgA+ plasma cells

    Science.gov (United States)

    Gommerman, Jennifer L; Rojas, Olga L; Fritz, Jörg H

    2014-01-01

    The intestinal mucosa harbors the largest population of antibody (Ab)-secreting plasma cells (PC) in the human body, producing daily several grams of immunoglobulin A (IgA). IgA has many functions, serving as a first-line barrier that protects the mucosal epithelium from pathogens, toxins and food antigens (Ag), shaping the intestinal microbiota, and regulating host–commensal homeostasis. Signals induced by commensal colonization are central for regulating IgA induction, maintenance, positioning and function and the number of IgA+ PC is dramatically reduced in neonates and germ-free (GF) animals. Recent evidence demonstrates that the innate immune effector molecules tumor necrosis factor α (TNFα) and inducible nitric oxide synthase (iNOS) are required for IgA+ PC homeostasis during the steady state and infection. Moreover, new functions ascribed to PC independent of Ab secretion continue to emerge, suggesting that PC, including IgA+ PC, should be re-examined in the context of inflammation and infection. Here, we outline mechanisms of IgA+ PC generation and survival, reviewing their functions in health and disease. PMID:25483334

  9. Progression of diabetic nephropathy

    DEFF Research Database (Denmark)

    Hovind, P; Rossing, P; Tarnow, L

    2001-01-01

    BACKGROUND: Diabetic nephropathy is a major cause of renal failure. The decline in glomerular filtration rate (GFR) is highly variable, ranging from 2 to 20, with a median of 12 mL/min/year. The risk factors of losing filtration power (progression promoters) have not been clearly identified...... mm Hg and 9.2%, respectively) revealed a rate of decline in GFR of only 1.5 mL/min/year in the lowest stratum compared with 6.1 mL/min/year in the highest stratum (P past decades, predominantly because of effective...... antihypertensive treatment. Genuine normotensive patients have a slow progression of nephropathy. Several modifiable variables have been identified as progression promoters....

  10. Light chain nephropathy

    Directory of Open Access Journals (Sweden)

    Sihem Darouich

    2015-01-01

    Full Text Available Light chain deposition disease (LCDD is characterized by the tissue deposition of monotypic immunoglobulin light chains of either kappa or lambda isotype. It is the archetypal systemic disease that is most frequently diagnosed on a kidney biopsy, although the deposits may involve several other organs. This brief review focuses on the clinicopathological features of LCDD-associated nephropathy with an emphasis on the diagnostic and therapeutic difficulties related to this elusive condition.

  11. Contrast-induced nephropathy

    Directory of Open Access Journals (Sweden)

    Ricardo A. García Hernández

    2016-06-01

    Full Text Available Contrast-induced nephropathy is an important complication associated with the use of contrast media. Favoring factors for the development of contrast-induced nephronpathy have been widely described, being diabetes mellitus and previous renal disease the greatest risk. The pathophysiology is a complex process where the medullary hypoxia represents the trigger element. Previous hydration and the use of low osmolality contrast are the most recommended measures to prevent its development.

  12. IgA as therapeutic antibody

    NARCIS (Netherlands)

    Leusen, Jeanette H W

    2015-01-01

    This review is focused on the promises of IgA as a new therapeutic antibody. For more than 30 years IgG molecules have been used in the clinic in the fields of oncology, hematology, auto immune diseases and infections. However, IgA might be a good alternative, since it recruits different effector ce

  13. [Clinical symptoms in IgA deficiency].

    Science.gov (United States)

    De Oliveira-Serra, Flavio Augusto; Mosca, Tainá; Santos de Menezes, Maria da Conceição; Carvalho-Neves Forte, Wilma

    2017-01-01

    Antecedentes: La deficiencia de inmunoglobulina A (IgA) es la inmunodeficiencia primaria más frecuente. El diagnóstico oportuno y el seguimiento clínico pueden mejorar la calidad de vida de los portadores. Para ello, deben estudiarse y entenderse las manifestaciones clínicas de este trastorno. Objetivo: Determinar las manifestaciones clínicas de la deficiencia de IgA. Métodos: Estudio transversal, retrospectivo, exploratorio, realizado mediante análisis de expedientes de 39 pacientes con deficiencia de IgA. Resultados: De los pacientes analizados, 10 fueron diagnosticados con deficiencia total de IgA y 29 con deficiencia parcial. Las principales manifestaciones clínicas fueron rinoconjuntivitis y asma alérgicas. En los pacientes con deficiencia total de IgA, además de las enfermedades alérgicas se observó un mayor número de cuadros infecciosos de rinosinusitis, amigdalitis y conjuntivitis (p IgA fueron los cuadros alérgicos de rinoconjuntivitis y el asma; además, los pacientes portadores de deficiencia total de IgA presentaron aumento significativo de cuadros infecciosos de rinosinusitis, amigdalitis y conjuntivitis, comparados con los pacientes con deficiencia parcial de IgA.

  14. Differential expression of laminin isoforms in diabetic nephropathy and other renal diseases.

    Science.gov (United States)

    Setty, Suman; Michael, Alfred A; Fish, Alfred J; Michael Mauer, S; Butkowski, Ralph J; Virtanen, Ismo; Kim, Youngki

    2012-06-01

    Laminin a non-collagenous glycoprotein is a major component of the renal glomerular basement membrane and mesangium. Thus far eleven distinct chains have been described, permutations of which make up 15 laminin isoforms. Laminin molecules interact with cells and other matrix molecules during organ development and differentiation. We studied the distribution of laminin isoforms in patients with type 1 diabetic nephropathy, membranous nephropathy, membranoproliferative glomerulonephritis and IgA nephropathy/ Henoch-Schönlein purpura. Immunofluorescence microscopic studies with laminin-chain-specific antibodies to the α1, α2, α5, β1, β2 and γ1 chains detected α2, β1 and γ1 chain expression in the normal mesangium and α5, β2 and γ1 in normal glomerular basement membrane. Significantly, constituents of the glomerular basement membrane, α5, β2 and γ1 chains were overexpressed in kidneys with diabetic nephropathy. Initially the constituents of the mesangium increased commensurate with the degree of mesangial expansion and degree of diabetic nephropathy. Reduction in α2 chain intensity was observed with severe mesangial expansion and in the areas of nodular glomerulosclerosis. In addition, with late disease aberrant expression of α2 and β2 chains was observed in the mesangium. Glomerular basement membrane in renal disease overexpressed molecules normally present in that location. In summary, the alterations in basement membrane composition in various renal diseases seem to not only reflect the balance between synthesis and degradation of normal basement membrane constituents, but also their aberrant expression.

  15. Functional Flexibility of Intestinal IgA – Broadening the Fine Line

    Science.gov (United States)

    Slack, Emma; Balmer, Maria Luisa; Fritz, Jörg H.; Hapfelmeier, Siegfried

    2012-01-01

    Intestinal bacteria outnumber our own human cells in conditions of both health and disease. It has long been recognized that secretory antibody, particularly IgA, is produced in response to these microbes and hypothesized that this must play an important role in defining the relationship between a host and its intestinal microbes. However, the exact role of IgA and the mechanisms by which IgA can act are only beginning to be understood. In this review we attempt to unravel the complex interaction between so-called “natural,” “primitive” (T-cell-independent), and “classical” IgA responses, the nature of the intestinal microbiota/intestinal pathogens and the highly flexible dynamic homeostasis of the mucosal immune system. Such an analysis reveals that low-affinity IgA is sufficient to protect the host from excess mucosal immune activation induced by harmless commensal microbes. However, affinity-maturation of “classical” IgA is essential to provide protection from more invasive commensal species such as segmented filamentous bacteria and from true pathogens such as Salmonella typhimurium. Thus a correlation is revealed between “sophistication” of the IgA response and aggressiveness of the challenge. A second emerging theme is that more-invasive species take advantage of host inflammatory mechanisms to more successfully compete with the resident microbiota. In many cases, the function of IgA may be to limit such inflammatory responses, either directly by coagulating or inhibiting virulence of bacteria before they can interact with the host or by modulating immune signaling induced by host recognition. Therefore IgA appears to provide an added layer of robustness in the intestinal ecosystem, promoting “commensal-like” behavior of its residents. PMID:22563329

  16. Comparative analysis of plant-produced, recombinant dimeric IgA against cell wall β-glucan of pathogenic fungi.

    Science.gov (United States)

    Capodicasa, Cristina; Catellani, Marcello; Moscetti, Ilaria; Bromuro, Carla; Chiani, Paola; Torosantucci, Antonella; Benvenuto, Eugenio

    2017-08-19

    Immunoglobulins A (IgA) are crucially involved in protection of human mucosal surfaces from microbial pathogens. In this work, we devised and expressed in plants recombinant chimeric antifungal antibodies (Abs) of isotype A (IgA1, IgA2, and scFvFcA1), derived from a murine mAb directed to the fungal cell wall polysaccharide β-glucan which had proven able to confer protection against multiple pathogenic fungi. All recombinant IgA (rIgA) were expressed and correctly assembled in dimeric form in plants and evaluated for yield, antigen-binding efficiency and antifungal properties in vitro, in comparison with a chimeric IgG1 version. Production yields and binding efficiency to purified β-glucans showed significant variations not only between Abs of different isotypes but also between the different IgA formats. Moreover, only the dimeric IgA1 was able to strongly bind cells of the fungal pathogen Candida albicans and to restrain its adhesion to human epithelial cells. Our data indicate that IgG to IgA switch and differences in molecular structure among different rIgA formats can impact expression in plant and biological activity of anti-β-glucans Abs and provide new insights for the design of recombinant IgA as anti-infective immunotherapeutics, whose potential is still poorly investigated. © 2017 Wiley Periodicals, Inc.

  17. Amadori albumin in diabetic nephropathy

    Directory of Open Access Journals (Sweden)

    Km. Neelofar

    2015-01-01

    Full Text Available Nonenzymatic glycation of macromolecules in diabetes mellitus (DM is accelerated due to persistent hyperglycemia. Reducing sugar such as glucose reacts non enzymatically with free €- amino groups of proteins through series of reactions forming Schiff bases. These bases are converted into Amadori product and further into AGEs. Non enzymatic glycation has the potential to alter the biological, structural and functional properties of macromolecules both in vitro and in vivo. Studies have suggested that amadori as well as AGEs are involved in the micro-macro vascular complications in DM, but most studies have focused on the role of AGEs in vascular complications of diabetes. Recently putative AGE-induced patho-physiology has shifted attention from the possible role of amadori-modified proteins, the predominant form of the glycated proteins in the development of the diabetic complications. Human serum albumin (HSA, the most abundant protein in circulation contains 59 lysine and 23 arginine residues that could, in theory be involved in glycation. Albumin has dual nature, first as a marker of intermediate glycation and second as a causative agent of the damage of tissues. Among the blood proteins, hemoglobin and albumin are the most common proteins that are glycated. HSA with a shorter half life than RBC, appears to be an alternative marker of glycemic control as it can indicate blood glucose status over a short period (2-3 weeks and being unaffected by RBCs life span and variant haemoglobin, anemia etc which however, affect HbA1c. On the other hand, Amadori albumin may accumulate in the body tissues of the diabetic patients and participate in secondary complications. Amadori-albumin has potential role in diabetic glomerulosclerosis due to long term hyperglycaemia and plays an important role in the pathogenesis of diabetic nephropathy. This review is an approach to compile both the nature of glycated albumin as a damaging agent of tissues and as an

  18. Nlrp3-inflammasome activation in non-myeloid-derived cells aggravates diabetic nephropathy.

    Science.gov (United States)

    Shahzad, Khurrum; Bock, Fabian; Dong, Wei; Wang, Hongjie; Kopf, Stefan; Kohli, Shrey; Al-Dabet, Moh'd Mohanad; Ranjan, Satish; Wolter, Juliane; Wacker, Christian; Biemann, Ronald; Stoyanov, Stoyan; Reymann, Klaus; Söderkvist, Peter; Groß, Olaf; Schwenger, Vedat; Pahernik, Sascha; Nawroth, Peter P; Gröne, Herman-Josef; Madhusudhan, Thati; Isermann, Berend

    2015-01-01

    Diabetic nephropathy is a growing health concern with characteristic sterile inflammation. As the underlying mechanisms of this inflammation remain poorly defined, specific therapies targeting sterile inflammation in diabetic nephropathy are lacking. Intriguingly, an association of diabetic nephropathy with inflammasome activation has recently been shown, but the pathophysiological relevance of this finding remains unknown. Within glomeruli, inflammasome activation was detected in endothelial cells and podocytes in diabetic humans and mice and in glucose-stressed glomerular endothelial cells and podocytes in vitro. Abolishing Nlrp3 or caspase-1 expression in bone marrow-derived cells fails to protect mice against diabetic nephropathy. Conversely, Nlrp3-deficient mice are protected against diabetic nephropathy despite transplantation of wild-type bone marrow. Pharmacological IL-1R antagonism prevented or even reversed diabetic nephropathy in mice. Mitochondrial reactive oxygen species (ROS) activate the Nlrp3 inflammasome in glucose or advanced glycation end product stressed podocytes. Inhibition of mitochondrial ROS prevents glomerular inflammasome activation and nephropathy in diabetic mice. Thus, mitochondrial ROS and Nlrp3-inflammasome activation in non-myeloid-derived cells aggravate diabetic nephropathy. Targeting the inflammasome may be a potential therapeutic approach to diabetic nephropathy.

  19. Diabetic nephropathy : pathology, genetics and carnosine metabolism

    NARCIS (Netherlands)

    Mooyaart, Antien Leonora

    2011-01-01

    My thesis concerns different aspects of diabetic nephropathy. A pathologic classification of diabetic nephropathy is developed, a meta-analyis of genes in diabetic nephropathy is developed and the other chapters are about the CNDP1 gene in relation to kidney disease, mainly diabetic nephropathy.

  20. [Classification of Diabetic Nephropathy 2014].

    Science.gov (United States)

    Haneda, Masakazu; Utsunomiya, Kazunori; Koya, Daisuke; Babazono, Tetsuya; Moriya, Tatsumi; Makino, Hirofumi; Kimura, Kenjiro; Suzuki, Yoshiki; Wada, Takashi; Ogawa, Susumu; Inaba, Masaaki; Kanno, Yoshihiko; Shigematsu, Takashi; Masakane, Ikuto; Tsuchiya, Ken; Honda, Keiko; Ichikawa, Kazuko; Shide, Kenichiro

    2014-01-01

    The Committee on Diabetic Nephropathy revised the classification of diabetic nephropathy in view of the current status of eGFR and CKD in Japan. To make revisions for the classification of diabetic nephropathy 2014, the Committee carefully evaluated the report of the Research Group on Diabetic Nephropathy, Ministry of Health, Labour, and Welfare of Japan. The major revisions made were as follows: 1. eGFR can be used for the evaluation of GFR; 2. In stage 3 (overt nephropathy), A and B were combined; 3. Stage 4 (renal failure) was defined as GFR less than 30 mL/min/1.73 m2, regardless of albuminuria; and 4. The importance of differential diagnosis was stressed in all stages.

  1. IgA deficiency in wolves.

    Science.gov (United States)

    Frankowiack, Marcel; Hellman, Lars; Zhao, Yaofeng; Arnemo, Jon M; Lin, Miaoli; Tengvall, Katarina; Møller, Torsten; Lindblad-Toh, Kerstin; Hammarström, Lennart

    2013-06-01

    Low mean concentrations of serum immunoglobulin A (IgA) and an increased frequency of overt IgA deficiency (IgAD) in certain dog breeds raises the question whether it is a breeding-enriched phenomenon or a legacy from the dog's ancestor, the gray wolf (Canis lupus). The IgA concentration in 99 serum samples from 58 free-ranging and 13 captive Scandinavian wolves, was therefore measured by capture ELISA. The concentrations were markedly lower in the wolf serum samples than in the dog controls. Potential differences in the IgA molecule between dogs and wolves were addressed by sequencing the wolf IgA heavy chain constant region encoding gene (IGHA). Complete amino acid sequence homology was found. Detection of wolf and dog IgA was ascertained by showing identity using double immunodiffusion. We suggest that the vast majority of wolves, the ancestor of the dog, are IgA deficient. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. Characterization of the ligand binding site of the bovine IgA Fc receptor (bFc alpha R).

    Science.gov (United States)

    Morton, H Craig; Pleass, Richard J; Woof, Jenny M; Brandtzaeg, Per

    2004-12-24

    Recently, we identified a bovine IgA Fc receptor (bFc alpha R), which shows high homology to the human myeloid Fc alpha R, CD89. IgA binding has previously been shown to depend on several specific residues located in the B-C and F-G loops of the membrane-distal extracellular domain 1 of CD89. To compare the ligand binding properties of these two Fc alpha Rs, we have mapped the IgA binding site of bFc alpha R. We show that, in common with CD89, Tyr-35 in the B-C loop is essential for IgA binding. However, in contrast to earlier observations on CD89, mutation of residues in the F-G loop did not significantly inhibit IgA binding.

  3. Heroin crystal nephropathy.

    Science.gov (United States)

    Bautista, Josef Edrik Keith; Merhi, Basma; Gregory, Oliver; Hu, Susie; Henriksen, Kammi; Gohh, Reginald

    2015-06-01

    In this paper we present an interesting case of acute kidney injury and severe metabolic alkalosis in a patient with a history of heavy heroin abuse. Urine microscopy showed numerous broomstick-like crystals. These crystals are also identified in light and electron microscopy. We hypothesize that heroin crystalizes in an alkaline pH, resulting in tubular obstruction and acute kidney injury. Management is mainly supportive as there is no known specific therapy for this condition. This paper highlights the utility of urine microscopy in diagnosing the etiology of acute kidney injury and proposes a novel disease called heroin crystal nephropathy.

  4. Contrast induced nephropathy

    DEFF Research Database (Denmark)

    Stacul, Fulvio; van der Molen, Aart J; Reimer, Peter

    2011-01-01

    measures used to reduce the incidence of CIN, and the management of patients receiving metformin. Key Points • Definition, risk factors and prevention of contrast medium induced nephropathy are reviewed. • CIN risk is lower with intravenous than intra-arterial iodinated contrast medium. • eGFR of 45 ml....../min/1.73 m (2) is CIN risk threshold for intravenous contrast medium. • Hydration with either saline or sodium bicarbonate reduces CIN incidence. • Patients with eGFR ≥ 60 ml/min/1.73 m (2) receiving contrast medium can continue metformin normally....

  5. Contrast induced nephropathy

    DEFF Research Database (Denmark)

    Stacul, Fulvio; van der Molen, Aart J; Reimer, Peter

    2011-01-01

    measures used to reduce the incidence of CIN, and the management of patients receiving metformin. Key Points • Definition, risk factors and prevention of contrast medium induced nephropathy are reviewed. • CIN risk is lower with intravenous than intra-arterial iodinated contrast medium. • eGFR of 45 ml....../min/1.73 m (2) is CIN risk threshold for intravenous contrast medium. • Hydration with either saline or sodium bicarbonate reduces CIN incidence. • Patients with eGFR = 60 ml/min/1.73 m (2) receiving contrast medium can continue metformin normally....

  6. Circadian clock-dependent increase in salivary IgA secretion modulated by sympathetic receptor activation in mice.

    Science.gov (United States)

    Wada, Misaki; Orihara, Kanami; Kamagata, Mayo; Hama, Koki; Sasaki, Hiroyuki; Haraguchi, Atsushi; Miyakawa, Hiroki; Nakao, Atsuhito; Shibata, Shigenobu

    2017-08-18

    The salivary gland is rhythmically controlled by sympathetic nerve activation from the suprachiasmatic nucleus (SCN), which functions as the main oscillator of circadian rhythms. In humans, salivary IgA concentrations reflect circadian rhythmicity, which peak during sleep. However, the mechanisms controlling this rhythmicity are not well understood. Therefore, we examined whether the timing of parasympathetic (pilocarpine) or sympathetic (norepinephrine; NE) activation affects IgA secretion in the saliva. The concentrations of saliva IgA modulated by pilocarpine activation or by a combination of pilocarpine and NE activation were the highest in the middle of the light period, independent of saliva flow rate. The circadian rhythm of IgA secretion was weakened by an SCN lesion and Clock gene mutation, suggesting the importance of the SCN and Clock gene on this rhythm. Adrenoceptor antagonists blocked both NE- and pilocarpine-induced basal secretion of IgA. Dimeric IgA binds to the polymeric immunoglobulin receptor (pIgR) on the basolateral surface of epithelial cells and forms the IgA-pIgR complex. The circadian rhythm of Pigr abundance peaked during the light period, suggesting pIgR expression upon rhythmic secretion of IgA. We speculate that activation of sympathetic nerves during sleep may protect from bacterial access to the epithelial surface through enhanced secretion of IgA.

  7. Histological changes of kidney in diabetic nephropathy.

    Science.gov (United States)

    Pourghasem, Mohsen; Shafi, Hamid; Babazadeh, Zahra

    2015-01-01

    Diabetes mellitus is the most common cause of chronic renal disorders and end-stage kidney disease in developed countries. It is the major cause of dialysis and transplantation. Failure in renal function causes wide disorders in the body. Diabetes results in wide range of alterations in the renal tissue. It is believed that early histological changes in diabetic nephropathy are detectable 2 years after diabetes is diagnosed. The glomerular alterations are the most important lesions in the diabetic nephropathy (DN). The Renal Pathology Society provides a new pathological classification for the detection of histopathology of DN. It divides diabetic nephropathy into four hierarchical glomerular lesions. Alloxan or streptozotocin induced diabetic rat is the one most widely used specie to study DN. Histological changes in the rat DN closely resemble the human disease and the most information of this review was obtained through the study of rat DN. All cell types of the kidney such as mesangial cells, podocytes and tubulointerstitial cells are liable to be affected in the event of DN. Severity of renal lesions is associated to the clinical aspect of renal outcome, but the aim of this article was only to review the histological changes of kidney in diabetes mellitus.

  8. Rotavirus vaccination and infection induce VP6-specific IgA responses.

    Science.gov (United States)

    Lappalainen, Suvi; Blazevic, Vesna; Malm, Maria; Vesikari, Timo

    2017-02-01

    Rotavirus (RV) is the leading cause of severe gastroenteritis (GE) in young children, but RVGE has drastically been reduced with the introduction of live oral RV vaccines into childhood immunization program in many countries. Serum IgA antibody is a marker of clinical protection against severe RVGE after RV infection and vaccination. This study investigated VP6-specificity of anti-RV IgA antibody levels in Finnish children aged 6-23 months before and after introduction of RotaTeq® into national immunization program. Although RV inner capsid protein VP6 is considered as antigenic target in clinical and seroepidemiological studies, at present VP6 protein is not commonly employed as a primary ELISA-antigen. Thus, sera from 20 unvaccinated and 19 vaccinated children were examined in ELISA with recombinant VP6 (rVP6) protein, and the VP6-specific responses were compared to responses observed with human RV Wa and bovine RV WC3 cell culture antigens. Moreover, fecal antibodies were tested with rVP6 and Wa cell culture antigen. Equal levels of serum anti-RV IgA antibodies were detected by the three antigens. Fecal IgA titers against rVP6 and Wa antigen showed a correlation with the corresponding serum levels. The results suggest that the IgA response measured by virus-capture ELISA is mainly directed to VP6 protein, supporting the usage of rVP6 in detection of anti-RV IgA antibodies. Natural RV infections and vaccinations induced similar levels of serum VP6-specific IgA antibodies. Serum IgA antibodies after RotaTeq® vaccination showed sustained levels up to two years of age in line with long term protection. J. Med. Virol. 89:239-245, 2017. © 2016 Wiley Periodicals, Inc.

  9. Regulation of intestinal IgA responses

    Science.gov (United States)

    Xiong, Na; Hu, Shaomin

    2015-01-01

    The intestine harbors enormous numbers of commensal bacteria and is under frequent attack from food-borne pathogens and toxins. A properly regulated immune response is critical for homeostatic maintenance of commensals and for protection against infection and toxins in the intestine. IgA isotype antibodies function specifically in mucosal sites such as the intestines to help maintain intestinal health by binding to and regulating commensal microbiota, pathogens and toxins. IgA antibodies are produced by intestinal IgA antibody-secreting plasma cells generated in gut-associated lymphoid tissues from naïve B cells in response to stimulations of the intestinal bacteria and components. Research on generation, migration, and maintenance of IgA-secreting cells is important in our effort to understand the biology of IgA responses and to help better design vaccines against intestinal infections. PMID:25837997

  10. Haridus - iga lapse õigus / Gerd Tarand

    Index Scriptorium Estoniae

    Tarand, Gerd, 1985-

    2009-01-01

    MTÜ Mondo alustas veebruaris maailmaharidusprojektiga „Haridus - iga lapse õigus“, mille üldine eesmärk on tõsta Eesti elanikkonna, eriti noorte huvi arengumaade vastu ning teadmisi ja arusaamist arengumaade haridusega seonduvatest probleemidest

  11. Haridus - iga lapse õigus / Gerd Tarand

    Index Scriptorium Estoniae

    Tarand, Gerd, 1985-

    2009-01-01

    MTÜ Mondo alustas veebruaris maailmaharidusprojektiga „Haridus - iga lapse õigus“, mille üldine eesmärk on tõsta Eesti elanikkonna, eriti noorte huvi arengumaade vastu ning teadmisi ja arusaamist arengumaade haridusega seonduvatest probleemidest

  12. Buckling analysis of nanoplates using IGA

    Science.gov (United States)

    Phung-Van, P.; Abdel-Wahab, M.; Nguyen-Xuan, H.

    2017-05-01

    Isogeometric analysis (IGA) based on HSDT is used to simulate buckling analysis of nanoplates. The material properties of nanoplates based on the Mori-Tanaka schemes and the rule of mixture are used. The differential nonlocal equations with size effect are utilized. The nonlocal governing equations are approximated according to IGA, that satisfies naturally the higher-order derivatives continuity requirement in weak form of nanoplates. Several numerical results are presented to demonstrate the reliability of the proposed method.

  13. A proton nuclear magnetic resonance-based metabonomics study of metabolic profiling in immunoglobulin a nephropathy

    Energy Technology Data Exchange (ETDEWEB)

    Sui, Weiguo; Che, Wenti; Guimai, Zuo; Chen, Jiejing [181st Hospital Guangxi, Central Laboratory, Laboratory of Metabolic Diseases Research, Guangxi Province (China); Li, Liping [Guangxi Normal University, The Life Science College, Guangxi Province (China); Li, Wuxian [Key Laboratory of Laboratory Medical Diagnostics of Education Ministry, Chongqiong Medical University, Chongqing (China); Dai, Yong [Clinical Medical Research Center, the Second Clinical Medical College of Jinan University (Shenzhen People' s Hospital), Shenzhen, Guangdong Province (China)

    2012-07-01

    Objectives: Immunoglobulin A nephropathy is the most common cause of chronic renal failure among primary glomerulonephritis patients. The ability to diagnose immunoglobulin A nephropathy remains poor. However, renal biopsy is an inconvenient, invasive, and painful examination, and no reliable biomarkers have been developed for use in routine patient evaluations. The aims of the present study were to identify immunoglobulin A nephropathy patients, to identify useful biomarkers of immunoglobulin A nephropathy and to establish a human immunoglobulin A nephropathy metabolic profile. Methods: Serum samples were collected from immunoglobulin A nephropathy patients who were not using immunosuppressants. A pilot study was undertaken to determine disease-specific metabolite biomarker profiles in three groups: healthy controls (N = 23), low-risk patients in whom immunoglobulin A nephropathy was confirmed as grades I-II by renal biopsy (N = 23), and high-risk patients with nephropathies of grades IV-V (N = 12). Serum samples were analyzed using proton nuclear magnetic resonance spectroscopy and by applying multivariate pattern recognition analysis for disease classification. Results: Compared with the healthy controls, both the low-risk and high-risk patients had higher levels of phenylalanine, myo-inositol, lactate, L6 lipids ( CH-CH{sub 2}-CH = O), L5 lipids (-CH{sub 2}-C = O), and L3 lipids (-CH{sub 2}-CH{sub 2}-C = O) as well as lower levels of {beta}-glucose, {alpha}-glucose, valine, tyrosine, phosphocholine, lysine, isoleucine, glycerolphosphocholine, glycine, glutamine, glutamate, alanine, acetate, 3-hydroxybutyrate, and 1-methylhistidine. Conclusions: These metabolites investigated in this study may serve as potential biomarkers of immunoglobulin A nephropathy. Point scoring of pattern recognition analysis was able to distinguish immunoglobulin A nephropathy patients from healthy controls. However, there were no obvious differences between the low-risk and high

  14. A proton nuclear magnetic resonance-based metabonomics study of metabolic profiling in immunoglobulin a nephropathy

    Directory of Open Access Journals (Sweden)

    Weiguo Sui

    2012-01-01

    Full Text Available OBJECTIVES: Immunoglobulin A nephropathy is the most common cause of chronic renal failure among primary glomerulonephritis patients. The ability to diagnose immunoglobulin A nephropathy remains poor. However, renal biopsy is an inconvenient, invasive, and painful examination, and no reliable biomarkers have been developed for use in routine patient evaluations. The aims of the present study were to identify immunoglobulin A nephropathy patients, to identify useful biomarkers of immunoglobulin A nephropathy and to establish a human immunoglobulin A nephropathy metabolic profile. METHODS: Serum samples were collected from immunoglobulin A nephropathy patients who were not using immunosuppressants. A pilot study was undertaken to determine disease-specific metabolite biomarker profiles in three groups: healthy controls (N = 23, low-risk patients in whom immunoglobulin A nephropathy was confirmed as grades I-II by renal biopsy (N = 23, and high-risk patients with nephropathies of grades IV-V (N = 12. Serum samples were analyzed using proton nuclear magnetic resonance spectroscopy and by applying multivariate pattern recognition analysis for disease classification. RESULTS: Compared with the healthy controls, both the low-risk and high-risk patients had higher levels of phenylalanine, myo-Inositol, lactate, L6 lipids ( = CH-CH2-CH = O, L5 lipids (-CH2-C = O, and L3 lipids (-CH2-CH2-C = O as well as lower levels of β -glucose, α-glucose, valine, tyrosine, phosphocholine, lysine, isoleucine, glycerolphosphocholine, glycine, glutamine, glutamate, alanine, acetate, 3-hydroxybutyrate, and 1-methylhistidine. CONCLUSIONS: These metabolites investigated in this study may serve as potential biomarkers of immunoglobulin A nephropathy. Point scoring of pattern recognition analysis was able to distinguish immunoglobulin A nephropathy patients from healthy controls. However, there were no obvious differences between the low-risk and high-risk groups in our

  15. Outcomes of renal transplantation in patients with immunoglobulin A nephropathy in India

    Directory of Open Access Journals (Sweden)

    Chacko B

    2007-01-01

    Full Text Available Background: There is a paucity of data on the course of renal transplant in patients with immunoglobulin A (IgA nephropathy (IgAN from India. While the natural history of IgAN in the Indian context is rapidly progressive, the post-transplant course remains speculative. Aim: To study the graft survival in renal transplant recipients whose native kidney disease was IgAN and the incidence and correlates of recurrent disease. Settings and Designs: Retrospective case control study from a Nephrology unit of a large tertiary care center. Materials and Methods: The outcomes of 56 transplant patients (58 grafts with biopsy-proven IgAN and of 116 patients without IgAN or diabetic nephropathy, transplanted during the same period were analyzed. Correlates of biopsy-confirmed recurrent disease were determined. Statistical Analysis: Means were analyzed by Student′s t test and Mann-Whitney test; proportions were determined by Chi-square analysis and graft survival curves were generated using the Kaplan-Meier. Results: Five-year graft survival for IgA patients was not significantly different from that in the reference group (90% and 79%, P = 0.6. During a mean follow-up of 42 months (range, 1-144, 28 event graft biopsies were required in 20 grafts of IgAN. Histological recurrence was diagnosed in five of the 20 available biopsies (25% after a mean duration of 28 months. Recurrence did not correlate with donor status, HLA B35 and A2, recipient age, gender or immunosuppression. Conclusions: Renal transplantation is an appropriate treatment modality for IgA nephropathy patients with end-stage renal disease in India, despite the potential for recurrent disease. The posttransplant course is an indolent one when compared to the malignant pretransplant phase.

  16. GENETICS ASPECTS OF DIABETIC NEPHROPATHY

    Directory of Open Access Journals (Sweden)

    Oana-Elena Sauca

    2010-09-01

    Full Text Available Diabetic nephropathy is a clinical syndrome characterized by persistent albuminuria, a relentless decline in GFR, raised arterial blood pressure, and increased relative mortality for cardiovascular diseases. The pathogenesis of diabetic nephropathy is multifactorial, with contributions from metabolic abnormalities, hemodynamic alteration, and various growth and genetic factors. The identification of the main genes would allow the detection of those individuals at high risk for diabetic nephropathy and better understanding of its pathophysiologyas well.The present review discusses the main information available in literature regarding some genetic variants (involved in the renin-angiotensin system, glucose and lipid metabolism and some cytoskeleton proteins that reaffirms the importance of genetic factors in diabetic nephropathy.

  17. ANTIOXIDANT STATUS IN DIABETIC NEPHROPATHY

    Directory of Open Access Journals (Sweden)

    Giriraja

    2015-12-01

    Full Text Available BACKGROUND Hyperglycemia and dislipidemia in DM induce increased lipid peroxdation and free radical formation. This is an important mechanism of microangiopathy. AIM To measure the antioxidant status in type 2 DM with nephropathy and compared with nondiabetic control group. MATERIALS AND METHODS 50 type 2 DM patients aged between 50 to 70 years according to national diabetes data group criteria with nephropathy diagnosed on the basis of history, physical examination and biochemical parameters were included. 50 age and sex matched apparently healthy individuals with normal plasma glucose, normal renal parameters and with no symptoms suggestive of DM were taken as controls. RESULTS Antioxidant status was significantly less in patients with diabetic nephropathy. CONCLUSION Data suggests that alteration in antioxidant status may help predict the risk of diabetic nephropathy.

  18. Diabetic Nephropathy without Diabetes

    Directory of Open Access Journals (Sweden)

    Katia López-Revuelta

    2015-07-01

    Full Text Available Diabetic nephropathy without diabetes (DNND, previously known as idiopathic nodular glomerulosclerosis, is an uncommon entity and thus rarely suspected; diagnosis is histological once diabetes is discarded. In this study we describe two new cases of DNND and review the literature. We analyzed all the individualized data of previous publications except one series of attached data. DNND appears to be favored by recognized cardiovascular risk factors. However, in contrast with diabetes, apparently no factor alone has been demonstrated to be sufficient to develop DNND. Other factors not considered as genetic and environmental factors could play a role or interact. The most plausible hypothesis for the occurrence of DNND would be a special form of atherosclerotic or metabolic glomerulopathy than can occur with or without diabetes. The clinical spectrum of cardiovascular risk factors and histological findings support this theory, with hypertension as one of the characteristic clinical features.

  19. IgA autoantibodies in the pemphigoids and linear IgA bullous dermatosis

    NARCIS (Netherlands)

    Horvath, Barbara; Niedermeier, Andrea; Podstawa, Eva; Mueller, Ralf; Hunzelmann, Nicolas; Karpati, Sarolta; Hertl, Michael

    2010-01-01

    Background: Patients with bullous pemphigoid (BP), mucous membrane pemphigoid (MMP) and pemphigoid gestationis (PG) have IgG antibodies against BP180 and BP230, components of the hemidesmosomes. Patients with linear IgA bullous dermatosis (LABD) have IgA autoantibodies against a 97/120-kDa protein w

  20. Is there any association between secretory IgA and lactoferrin concentration in mature human milk and food allergy in breastfed children.

    Science.gov (United States)

    Hogendorf, Anna; Stańczyk-Przyłuska, Anna; Sieniwicz-Luzeńczyk, Katarzyna; Wiszniewska, Magdalena; Arendarczyk, Jerzy; Banasik, Małgorzata; Fendler, Wojciech; Kowalski, Marek; Zeman, Krzysztof

    2013-01-01

    Breastfeeding is recommended as a protective method against the development of allergy. However, some studies have reported an increased risk of allergies development in breastfed infants of atopic mothers, which implies that atopic mothers may have an altered composition of breast milk. The aim of the study was to determine the concentration of secretory immunoglobulin A (S-IgA) and lactoferrin in human mature milk and to evaluate the association between the levels of these proteins in breast milk with food allergy in children, depending on the allergy status of the breastfeeding mother. Medical data was collected from birth to 24 months of age from 84 mother-child pairs participating in an EU-funded project "EuroPrevall - The prevalence, cost and basis of food allergy across Europe". The diagnosis of food allergy in children was based on the positive result of a double-blind placebo-controlled food challenge (DBPCFC). S-IgA and lactoferrin levels were measured in the whey of mature breast milk with commercial enzyme-linked immunosorbent assay (ELISA) kits. Statistical analysis (the U Mann-Whitney and Kruskal-Wallis tests as well as the Spearman's rank correlation coefficient) was performed using STATISTICA 8.0 PL (Statsoft, Tulsa, USA). Ten out of eighty four participating children had positive skin prick tests (SPT) and/or sIgE to food antigens and in 7 (8.4%) DBPCFC confirmed food allergy. the median concentration of S-IgA was 476,83 μg/ml (range 6.51-1359.61 μg/ml). the median concentration of Lf was 15.68 μg/ml (range 11.68-36.43 μg/ml). The concentrations of S-IgA and Lf showed a moderate, negative, correlation R=-0.28; p=0.05. Mature breast milk of mothers of children with food allergy and of healthy children showed similar concentrations of both proteins. The level of S-IgA in the mature milk of mothers with atopic allergy was significantly lower, compared to non-atopic mothers. More studies are needed to reveal the mystery of the lack of protective

  1. Vascular Endothelial Growth Factor-A165b Is Protective and Restores Endothelial Glycocalyx in Diabetic Nephropathy.

    Science.gov (United States)

    Oltean, Sebastian; Qiu, Yan; Ferguson, Joanne K; Stevens, Megan; Neal, Chris; Russell, Amy; Kaura, Amit; Arkill, Kenton P; Harris, Kirstie; Symonds, Clare; Lacey, Katja; Wijeyaratne, Lihini; Gammons, Melissa; Wylie, Emma; Hulse, Richard P; Alsop, Chloe; Cope, George; Damodaran, Gopinath; Betteridge, Kai B; Ramnath, Raina; Satchell, Simon C; Foster, Rebecca R; Ballmer-Hofer, Kurt; Donaldson, Lucy F; Barratt, Jonathan; Baelde, Hans J; Harper, Steven J; Bates, David O; Salmon, Andrew H J

    2015-08-01

    Diabetic nephropathy is the leading cause of ESRD in high-income countries and a growing problem across the world. Vascular endothelial growth factor-A (VEGF-A) is thought to be a critical mediator of vascular dysfunction in diabetic nephropathy, yet VEGF-A knockout and overexpression of angiogenic VEGF-A isoforms each worsen diabetic nephropathy. We examined the vasculoprotective effects of the VEGF-A isoform VEGF-A165b in diabetic nephropathy. Renal expression of VEGF-A165b mRNA was upregulated in diabetic individuals with well preserved kidney function, but not in those with progressive disease. Reproducing this VEGF-A165b upregulation in mouse podocytes in vivo prevented functional and histologic abnormalities in diabetic nephropathy. Biweekly systemic injections of recombinant human VEGF-A165b reduced features of diabetic nephropathy when initiated during early or advanced nephropathy in a model of type 1 diabetes and when initiated during early nephropathy in a model of type 2 diabetes. VEGF-A165b normalized glomerular permeability through phosphorylation of VEGF receptor 2 in glomerular endothelial cells, and reversed diabetes-induced damage to the glomerular endothelial glycocalyx. VEGF-A165b also improved the permeability function of isolated diabetic human glomeruli. These results show that VEGF-A165b acts via the endothelium to protect blood vessels and ameliorate diabetic nephropathy.

  2. A comparison of anti-HER2 IgA and IgG1 in vivo efficacy is facilitated by high N-glycan sialylation of the IgA.

    Science.gov (United States)

    Rouwendal, Gerard Ja; van der Lee, Miranda M; Meyer, Saskia; Reiding, Karli R; Schouten, Jan; de Roo, Guy; Egging, David F; Leusen, Jeanette Hw; Boross, Peter; Wuhrer, Manfred; Verheijden, Gijs F; Dokter, Wim H; Timmers, Marco; Ubink, Ruud

    2016-01-01

    Monomeric IgA has been proposed as an alternative antibody format for cancer therapy. Here, we present our studies on the production, purification and functional evaluation of anti-HER2 IgA antibodies as anti-cancer agents in comparison to the anti-HER2 IgG1 trastuzumab. MALDI-TOF MS analysis showed profound differences in glycosylation traits across the IgA isotypes and cell lines used for production, including sialylation and linkage thereof, fucosylation (both core and antennary) and the abundance of high-mannose type species. Increases in sialylation proved to positively correlate with in vivo plasma half-lives. The polymerization propensity of anti-HER2 IgA2m2 could be suppressed by an 18-aa deletion of the heavy chain tailpiece - coinciding with the loss of high-mannose type N-glycan species - as well as by 2 cysteine to serine mutations at positions 320 and 480. The HER2 F(ab')2-mediated anti-proliferative effect of the IgA2m1 and IgA2m2 subtypes was similar to IgG1, whereas the IgA1 isotype displayed considerably lower potency and efficacy. The Fc-mediated induction of antibody-dependent cell-mediated cytotoxicity (ADCC) using human whole blood ADCC assays did not demonstrate such clear differences between the IgA isotypes. However, the potency of the anti-HER2 IgA antibodies in these ADCC assays was found to be significantly lower than that of trastuzumab. In vivo anti-tumor activity of the anti-HER2 IgA antibodies was compared to that of trastuzumab in a BT-474 breast cancer xenograft model. Multiple dosing and sialylation of the IgA antibodies compensated for the short in vivo half-life of native IgA antibodies in mice compared to a single dose of IgG1. In the case of the IgA2m2 antibody, the resulting high plasma exposure levels were sufficient to cause clear tumor stasis comparable to that observed for trastuzumab at much lower plasma exposure levels.

  3. IgA pemphigus showing IgA antibodies to desmoglein 1 and 3.

    Science.gov (United States)

    Hegazy, Salama; Bouchouicha, Sana; Khaled, Aida; Laadher, Lilia; Sellami, Maryem Kallel; Zeglaoui, Faten

    2016-10-01

    IgA pemphigus is a rare autoimmune vesiculo-pustular skin disease. Only approximately 70 cases have been reported to date. We report a case of IgA pemphigus with IgA antibodies to desmoglein 1 (Dsg1) and desmoglein 3 (Dsg3). We report the case of an 60-year-old man with intraepidermal neutrophilic IgA pemphigus with IgA antibodies to Dsg1 and Dsg3. Histologic examination revealed subcorneal neutrophilic pustules with few acantholytic cells. The disease was not effectively controlled by conventional therapeutic regimens (colchicine, dapsone). Systemic treatment with isotretinoin 25 mg/d and prednisone 20 mg/d achieved only a slight effect after six months. Our case confirmed the recalcitrant nature of IgA pemphigus in response to distinct therapies, indicating that further research focusing on therapeutic approaches for this type of pemphigus is needed. Physicians should keep IgA pemphigus in mind when approaching patients with bullous eruption.

  4. Towards microRNA-based therapeutics for diabetic nephropathy.

    Science.gov (United States)

    Alvarez, M L; DiStefano, J K

    2013-03-01

    There is no cure for diabetic nephropathy and the molecular mechanisms underlying disease aetiology remain poorly understood. While current paradigms for clinical management of diabetic nephropathy are useful in delaying disease onset and preventing its progression, they do not do so for a significant proportion of diabetic individuals, who eventually end up developing renal failure. Thus, novel therapeutic targets are needed for the treatment and prevention of the disease. MicroRNAs (miRNAs), a class of non-coding RNAs that negatively regulate gene expression, have recently been identified as attractive targets for therapeutic intervention. It is widely recognised that dysregulation of miRNA expression or action contributes to the development of a number of different human diseases, and evidence of a role for miRNAs in the aetiology of diabetic nephropathy is emerging. The discovery that modulation of miRNA expression in vivo is feasible, combined with recent results from successful clinical trials using this technology, opens the way for future novel therapeutic applications. For instance, inhibition of miRNAs that are commonly upregulated in diabetic nephropathy decreases albuminuria and mesangial matrix accumulation in animal models, suggesting that a therapeutic agent against these molecules may help to prevent the development of diabetic nephropathy. Certain challenges, including the development of safe and reliable delivery systems, remain to be overcome before miRNA-based therapeutics become a reality. However, the findings accumulated to date, in conjunction with newly emerging results, are expected to yield novel insights into the complex pathogenesis of diabetic nephropathy, and may eventually lead to the identification of improved therapeutic targets for treatment of this disease.

  5. [Novel biomarkers for diabetic nephropathy].

    Science.gov (United States)

    Araki, Shin-ichi

    2014-02-01

    Diabetic nephropathy is a leading cause of end-stage renal disease worldwide. An early clinical sign of this complication is an increase of urinary albumin excretion, called microalbuminuria, which is not only a predictor of the progression of nephropathy, but also an independent risk factor for cardiovascular disease. Although microalbuminuria is clinically important to assess the prognosis of diabetic patients, it may be insufficient as an early and specific biomarker of diabetic nephropathy because of a large day-to-day variation and lack of a good correlation of microalbuminuria with renal dysfunction and pathohistological changes. Thus, more sensitive and specific biomarkers are needed to improve the diagnostic capability of identifying patients at high risk. The factors involved in renal tubulo-interstitial damage, the production and degradation of extracellular matrix, microinflammation, etc., are investigated as candidate molecules. Despite numerous efforts so far, the assessment of these biomarkers is still a subject of ongoing investigations. Recently, a variety of omics and quantitative techniques in systems biology are rapidly emerging in the field of biomarker discovery, including proteomics, transcriptomics, and metabolomics, and they have been applied to search for novel putative biomarkers of diabetic nephropathy. Novel biomarkers or their combination with microalbuminuria provide a better diagnostic accuracy than microalbuminuria alone, and may be useful for establishing personal medicine. Furthermore, the identification of novel biomarkers may provide insight into the mechanisms underlying diabetic nephropathy.

  6. Differences in serum IgA responses to HIV-1 gp41 in elite controllers compared to viral suppressors on highly active antiretroviral therapy.

    Science.gov (United States)

    Nabi, Rafiq; Moldoveanu, Zina; Wei, Qing; Golub, Elizabeth T; Durkin, Helen G; Greenblatt, Ruth M; Herold, Betsy C; Nowicki, Marek J; Kassaye, Seble; Cho, Michael W; Pinter, Abraham; Landay, Alan L; Mestecky, Jiri; Kozlowski, Pamela A

    2017-01-01

    Mechanisms responsible for natural control of human immunodeficiency type 1 (HIV) replication in elite controllers (EC) remain incompletely defined. To determine if EC generate high quality HIV-specific IgA responses, we used Western blotting to compare the specificities and frequencies of IgA to HIV antigens in serum of gender-, age- and race-matched EC and aviremic controllers (HC) and viremic noncontrollers (HN) on highly active antiretroviral therapy (HAART). Concentrations and avidity of IgA to HIV antigens were measured using ELISA or multiplex assays. Measurements for IgG were performed in parallel. EC were found to have stronger p24- and V1V2-specific IgG responses than HN, but there were no IgG differences for EC and HC. In contrast, IgA in EC serum bound more frequently to gp160 and gag proteins than IgA in HC or HN. The avidity of anti-gp41 IgA was also greater in EC, and these subjects had stronger IgA responses to the gp41 heptad repeat region 1 (HR1), a reported target of anti-bacterial RNA polymerase antibodies that cross react with gp41. However, EC did not demonstrate greater IgA responses to E. coli RNA polymerase or to peptides containing the shared LRAI sequence, suggesting that most of their HR1-specific IgA antibodies were not induced by intestinal microbiota. In both EC and HAART recipients, the concentrations of HIV-specific IgG were greater than HIV-specific IgA, but their avidities were comparable, implying that they could compete for antigen. Exceptions were C1 peptides and V1V2 loops. IgG and IgA responses to these antigens were discordant, with IgG reacting to V1V2, and IgA reacting to C1, especially in EC. Interestingly, EC with IgG hypergammaglobulinemia had greater HIV-specific IgA and IgG responses than EC with normal total IgG levels. Heterogeneity in EC antibody responses may therefore be due to a more focused HIV-specific B cell response in some of these individuals. Overall, these data suggest that development of HIV-specific IgA

  7. [Linear IgA bullous dermatosis].

    Science.gov (United States)

    Lorette, Gérard; Georgesco, Gabriella

    2010-10-01

    The linear IgA bullous dermatosis can have various aspects involving erythema and bullous lesions. It is a rare disease. Two peaks of frequency are noticed in children before puberty and in adults around 60 years of age. The histological and immunological characterisation is infraepidermal bullous lesions and linear deposits of IgA along the dermoepidermal basement membrane. There are some targets antigens. There is often a medical condition that seems to trigger. The link with drugs in particular with vancomycin was established. The mainstay of treatment is dapsone generally associated with steroids.

  8. Chronic allograft nephropathy.

    Science.gov (United States)

    Vadivel, Nidyanandh; Tullius, Stefan G; Chandraker, Anil

    2007-07-01

    Chronic allograft nephropathy (CAN) remains the Achilles heel of renal transplantation. In spite of the significant strides achieved in one-year renal allograft survival with newer immunosuppressant strategies, the fate of long-term renal allograft survival remains unchanged. The number of renal transplant recipients returning to dialysis has doubled in the past decade. This is especially important since these patients pose a significantly increased likelihood of dying while on the waiting list for retransplantation, due to increasing disparity between donor organ availability versus demand and longer waiting time secondary to heightened immunologic sensitization from their prior transplants. In this review we analyze the latest literature in detail and discuss the definition, natural history, pathophysiology, alloantigen dependent and independent factors that play a crucial role in CAN and the potential newer therapeutic targets on the horizon. This article highlights the importance of early identification and careful management of all the potential contributing factors with particular emphasis on prevention rather than cure of CAN as the core management strategy.

  9. Non-Proteinuric Diabetic Nephropathy

    Science.gov (United States)

    Robles, Nicolas Roberto; Villa, Juan; Hernandez Gallego, Roman

    2015-01-01

    Diabetic nephropathy patients traditionally show significant macroalbuminuria prior to the development of renal impairment. However, this clinical paradigm has recently been questioned. Epidemiological surveys confirm that chronic kidney disease (CKD) diagnosed by a low glomerular filtration rate (GFR) is more common in diabetic patients than in the non-diabetic population but a low number of patients had levels of proteinuria above that which traditionally defines overt diabetic nephropathy (>500 mg/g). The large number of patients with low levels of proteinuria suggests that the traditional clinical paradigm of overt diabetic nephropathy is changing since it does not seem to be the underlying renal lesion in most of diabetic subjects with CKD. PMID:26371050

  10. Interstitial nephritis and interstital nephropathy

    Institute of Scientific and Technical Information of China (English)

    1993-01-01

    930154 Plasma thromboxane B2 and 6-keto-prostaglandin F1 alpha in diabetic nephropathyWANG Yao(王尧),et al,Dept Endocrinol,1stAffil Hosp,Nanjihng Railway Med Coll.210009.Chin J Nephrol 1992;8(5):275-277.The plasma levels of TXB2 and 6-keto-PGF1were measured by RIA in 14 diabetics with and49 diabetics without nephropathy and 35 normalsubjects.The results showed that the levels ofplasma TXB2 and the ratio of TXB2/6-keto-PGF.were increased both in diabetics with or

  11. Do we need to measure total serum IgA to exclude IgA deficiency in coeliac disease?

    Science.gov (United States)

    Sinclair, D; Saas, M; Turk, A; Goble, M; Kerr, D

    2006-01-01

    Background Screening for IgA deficiency in patients with coeliac disease is essential because of the increased incidence of IgA deficiency associated with the disease, which usually relies on the estimation of IgA levels in each case. Aim To devise a method of excluding IgA deficiency without measuring total serum IgA in each case. Materials and methods The optical density readings on enzyme‐linked immunosorbent assay (ELISA) of 608 routine samples received for tissue transglutaminase (TTG) antibody testing for coeliac disease were compared with their total IgA concentrations. Dilution experiments were also carried out to ensure linear relationships between optical density on ELISA and IgA concentrations and to compare the sensitivities for TTG and endomysium antibodies in TTG‐positive samples. Results and discussion A clear relationship was shown between total IgA concentration and TTG optical density readings by ELISA. To ensure a positive TTG result if antibodies are present, it was possible to recommend an optical density level above which all samples have sufficient IgA. Samples with optical density <0.05 should be investigated further by estimating total IgA and, if low, samples should be subjected to immunofluorescence microscopy testing for IgA and IgG endomysium antibodies. Conclusions An easier, more cost‐effective and practical way of excluding IgA deficiency in the investigation on coeliac disease is reported. PMID:16489174

  12. IgA Antibodies in Rett Syndrome

    Science.gov (United States)

    Reichelt, K. L.; Skjeldal, O.

    2006-01-01

    The level of IgA antibodies to gluten and gliadin proteins found in grains and to casein found in milk, as well as the level of IgG to gluten and gliadin, have been examined in 23 girls with Rett syndrome and 53 controls. Highly statistically significant increases were found for the Rett population compared to the controls. The reason for this…

  13. Linear IgA Bullous Dermatosis

    DEFF Research Database (Denmark)

    Lings, Kristina; Bygum, Anette

    2015-01-01

    Linear IgA bullous dermatosis (LAD) is an autoimmune, chronic bullous disease affecting primarily young children and adults. Studies on LAD are relatively sparse and from Scandinavia we could only find a few case reports. Therefore we decided to conduct a retrospective investigation of patients...

  14. IgA Antibodies in Rett Syndrome

    Science.gov (United States)

    Reichelt, K. L.; Skjeldal, O.

    2006-01-01

    The level of IgA antibodies to gluten and gliadin proteins found in grains and to casein found in milk, as well as the level of IgG to gluten and gliadin, have been examined in 23 girls with Rett syndrome and 53 controls. Highly statistically significant increases were found for the Rett population compared to the controls. The reason for this…

  15. Podocyte Pathology and Nephropathy

    Directory of Open Access Journals (Sweden)

    Sandra eMerscher

    2014-07-01

    Full Text Available Sphingolipids are components of the lipid rafts in plasma membranes, which are important for proper function of podocytes, a key element of the glomerular filtration barrier. Research revealed an essential role of sphingolipids and sphingolipid metabolites in glomerular disorders of genetic and non-genetic origin. The discovery that glucocerebrosides accumulate in Gaucher disease in glomerular cells and are associated with clinical proteinuria initiated intensive research into the function of other sphingolipids in glomerular disorders. The accumulation of sphingolipids in other genetic diseases including Tay-Sachs, Sandhoff, Fabry, hereditary inclusion body myopathy 2, Niemann-Pick and nephrotic syndrome of the Finnish type and its implications with respect to glomerular pathology will be discussed. Similarily, sphingolipid accumulation occurs in glomerular diseases of non-genetic origin including diabetic kidney disease (DKD, HIV-associated nephropathy, focal segmental glomerulosclerosis (FSGS and lupus nephritis. Sphingomyelin metabolites, such as ceramide, sphingosine and sphingosine-1-phosphate have also gained tremendous interest. We recently described that sphingomyelin phosphodiesterase acid-like 3b (SMPDL3b is expressed in podocytes where it modulates acid sphingomyelinase (ASMase activity and acts as a master modulator of danger signaling. Decreased SMPDL3b expression in post-reperfusion kidney biopsies from transplant recipients with idiopathic FSGS correlates with the recurrence of proteinuria in patients and in experimental models of xenotransplantation. Increased SMPDL3b expression is associated with DKD. The consequences of differential SMPDL3b expression in podocytes in these diseases with respect to their pathogenesis will be discussed. Finally, the role of sphingolipids in the formation of lipid rafts in podocytes and their contribution to the maintenance of a functional slit diaphragm in the glomerulus will be discussed.

  16. Clonal antibody dominance after influenza vaccination in IgA nephropathy patients and controls

    NARCIS (Netherlands)

    Radl, J.; Hoogeveen, C.M.; Wall Bake, A.W.L. van den; Mestecky, J.

    1995-01-01

    Chemicals/CAS: hemagglutinin, 37333-12-3; sialidase, 9001-67-6; Antibodies, Monoclonal; Antibodies, Viral; Hemagglutinins, Viral; Immunoglobulin A; Immunoglobulin G; Influenza Vaccine; Neuraminidase, EC 3.2.1.18

  17. Evaluation of Children with IgA Nephropathy According to the Oxford Classification

    Directory of Open Access Journals (Sweden)

    Yel, Sibel

    2013-01-01

    Full Text Available OBJECTIVE: In this study, we aim to evaluate the clinical findings and short term results of our patients with IgAN according to Oxford classification.MATERIAL and METHODS: The medical records and the renal biopsy findings of 25 patients with IgAN were retrospectively reviewed. According to the pathological findings in Oxford classification, those without obvious disorder were accepted as Group 1 (n=16, and those with obvious disorders were accepted as Group 2 (n=9.These groups were compared for gender, age of onset, age of diagnosis, mean blood pressure and estimated glomerular filtration rate (GFR at diagnosis and follow-up, proteinuria, clinical presentation and prognosis.RESULTS: The most common complaint of the patients at presentation was hematuria. The most common histopathological renal finding was the proliferation of mesengial cells in varying degrees. Statistically no significant differences of mean blood pressure, GRF changes, protenuria, clinical findings, and prognosis were detected at presentation and follow-up.CONCLUSION: We could not show short-term effectiveness to predict clinical and laboratory findings, and prognosis of the patients of Oxford classification in children with IgAN.

  18. Visceral leishmaniasis in adults with nephropathy

    Directory of Open Access Journals (Sweden)

    H Kaaroud El Jeri

    2017-01-01

    Full Text Available The aim of this study is to evaluate the features of visceral leishmaniasis (VL in adults with nephropathy, who were not infected with the human immunodeficiency virus. This is a retrospective study of 14 adults hospitalized between 2000 and 2014, with VL and renal involvement. Clinical, biological, and therapeutic data were collected from the patients′ medical files. Eleven women and three men, most of whom were from the North of the country, with a mean age of 40.5 years were studied. Lupus was present in five cases, the Sicca syndrome in three cases, diabetes in one case, renal failure on dialysis in two cases, and there were three renal transplant recipients. Major clinical symptoms were fever and weakness in all cases. Enlargement of the spleen was present in eight cases and hepatomegaly in six cases. Biologic inflammatory syndrome and anemia were present in all cases, and pancytopenia was present in seven cases. Renal insufficiency was noted in all cases. Diagnosis of VL was confirmed by bone marrow examination or serology. Treatment consisted of antimoniate in 10 cases and amphotericin B in four cases. Seven deaths were recorded. Clinical symptoms of VL are atypical in patients with nephropathy and therefore, the diagnosis should be suspected in such patients because VL is still endemic in our country.

  19. ELISA detection of specific functional antibodies in human serum to Escherichia coli, tetanus toxoid, and diphtheria-tetanus toxoids: normal values for IgG, IgA, and IgM.

    Science.gov (United States)

    Moen, R C; Oemichen, S L; Kiggens, A J; Hong, R

    1986-01-01

    An inexpensive, easily performed enzyme-linked immunosorbent assay (ELISA) was developed to measure specific IgG, IgA, and IgM antibodies to the common antigens Escherichia coli, diphtheria-tetanus toxoid, and tetanus toxoid. Normal values were established. Classical antibody deficiency disease states were confirmed and delineated by these assays. Additionally, several instances were discovered when functional antibody levels were abnormal when the serum immunoglobulin levels were normal. The use of ELISA assays for antibodies to common antigens provides a useful technique to measure and monitor isotype responses of the humoral immune system.

  20. B-1 cells as a source of IgA.

    Science.gov (United States)

    Meyer-Bahlburg, Almut

    2015-12-01

    Immunoglobulin A (IgA) is the most abundantly produced immunoglobulin found primarily on mucosal surfaces. The generation of IgA and its involvement in mucosal immune responses have been intensely studied over the past years. IgA can be generated in T cell-dependent and T cell-independent pathways, and it has an important impact on maintaining homeostasis within the mucosal immune system. There is good evidence that B-1 cells contribute substantially to the production of mucosal IgA and thus play an important role in regulating commensal microbiota. However, whether B-1 cells produce antigen-specific or only nonspecific IgA remains to be determined. This review will discuss what is currently known about IgA production by B-1 cells and the functional relevance of B-1 cell-derived IgA both in vitro and in vivo.

  1. Impaired Podocyte Autophagy Exacerbates Proteinuria in Diabetic Nephropathy.

    Science.gov (United States)

    Tagawa, Atsuko; Yasuda, Mako; Kume, Shinji; Yamahara, Kosuke; Nakazawa, Jun; Chin-Kanasaki, Masami; Araki, Hisazumi; Araki, Shin-Ichi; Koya, Daisuke; Asanuma, Katsuhiko; Kim, Eun-Hee; Haneda, Masakazu; Kajiwara, Nobuyuki; Hayashi, Kazuyuki; Ohashi, Hiroshi; Ugi, Satoshi; Maegawa, Hiroshi; Uzu, Takashi

    2016-03-01

    Overcoming refractory massive proteinuria remains a clinical and research issue in diabetic nephropathy. This study was designed to investigate the pathogenesis of massive proteinuria in diabetic nephropathy, with a special focus on podocyte autophagy, a system of intracellular degradation that maintains cell and organelle homeostasis, using human tissue samples and animal models. Insufficient podocyte autophagy was observed histologically in patients and rats with diabetes and massive proteinuria accompanied by podocyte loss, but not in those with no or minimal proteinuria. Podocyte-specific autophagy-deficient mice developed podocyte loss and massive proteinuria in a high-fat diet (HFD)-induced diabetic model for inducing minimal proteinuria. Interestingly, huge damaged lysosomes were found in the podocytes of diabetic rats with massive proteinuria and HFD-fed, podocyte-specific autophagy-deficient mice. Furthermore, stimulation of cultured podocytes with sera from patients and rats with diabetes and massive proteinuria impaired autophagy, resulting in lysosome dysfunction and apoptosis. These results suggest that autophagy plays a pivotal role in maintaining lysosome homeostasis in podocytes under diabetic conditions, and that its impairment is involved in the pathogenesis of podocyte loss, leading to massive proteinuria in diabetic nephropathy. These results may contribute to the development of a new therapeutic strategy for advanced diabetic nephropathy.

  2. Lithium nephropathy: a case report

    OpenAIRE

    Raphael Reis Pereira-Silva; Debora Esperancini-Tebar

    2014-01-01

    Although widely used in the management of bipolar disorder, lithium may cause adverse kidney effects. The importance of the present study is to report the case of a 59-year-old woman who was under regular treatment with lithium for bipolar disorder and whose imaging studies demonstrated the presence of multiple renal microcysts, suggesting lithium nephropathy as main diagnostic hypothesis.

  3. Lithium nephropathy: a case report

    Directory of Open Access Journals (Sweden)

    Raphael Reis Pereira-Silva

    2014-01-01

    Full Text Available Although widely used in the management of bipolar disorder, lithium may cause adverse kidney effects. The importance of the present study is to report the case of a 59-year-old woman who was under regular treatment with lithium for bipolar disorder and whose imaging studies demonstrated the presence of multiple renal microcysts, suggesting lithium nephropathy as main diagnostic hypothesis.

  4. Release from Th1-type immune tolerance in spleen and enhanced production of IL-5 in Peyer's patch by cholera toxin B induce the glomerular deposition of IgA.

    Science.gov (United States)

    Yamanaka, Takahiro; Tamauchi, Hidekazu; Suzuki, Yusuke; Suzuki, Hitoshi; Horikoshi, Satoshi; Terashima, Masazumi; Iwabuchi, Kazuya; Habu, Sonoko; Okumura, Ko; Tomino, Yasuhiko

    2016-04-01

    We examined the pathogenesis of glomerular damage in Th2 type-dependent GATA-3 transgenic (GATA-3 Tg) mice with IgA nephropathy (IgAN). GATA-3 Tg mice were immunized orally using OVA plus cholera toxin B (CTB), and measurement of the serum IgA antibody level and histopathological examination were performed. Marked increases in the serum levels of OVA-specific IgA antibody, IgA and IgG, C3 deposits analogous to those seen in IgAN, and expansion of the matrix in association with mesangial cell proliferation were observed. Furthermore, glomerular IgA deposits were co-localized with mannan-binding lectin (MBL) deposits, which might actually have been abnormal IgA deposits. In GATA-3/TCR-Tg mice that had been orally sensitized with CTB plus OVA and were re-stimulated with OVA in vitro, cultured Peyer's patch cells showed the enhanced production of IL-5 and supernatants from cultures of spleen cells showed a reduction of TGF-β production with a simultaneous increase in IL-2 production and the recovery of IFN-γ formation. The amount of TGF-β produced by the spleen cells was found to be correlated with the amount of IFN-γ and IL-IL-2 produced by the cells. Also, the percentage of regulatory T cells (Treg) in the spleens of mice sensitized with OVA plus CTB was lower than that in mice orally sensitized with OVA alone. These results suggest that the increased production of IL-5 from Peyer's patch cells (PPc) and the restored Th1-type immune response might cause the production of abnormal IgA and might induce the deposition of IgA in glomeruli.

  5. Induction of Staphylococcus aureus-specific IgA and agglutination potency in milk of cows by mucosal immunization.

    Science.gov (United States)

    Tempelmans Plat-Sinnige, Marjan J; Verkaik, Nelianne J; van Wamel, Willem J B; de Groot, Nanda; Acton, Dennis S; van Belkum, Alex

    2009-06-19

    Lactating cows were immunized with inactivated Staphylococcus aureus strains and concentrated culture supernatants. Application of a repeated mucosal immunization scheme resulted in significant levels of S. aureus-specific IgA in milk of dairy cows. Average IgA titers against whole cell S. aureus increased during the first 10 weeks of immunization after which a plateau level was reached and maintained during lactation. Immune whey agglutinated both bovine and human S. aureus strains including methicillin-resistant S. aureus (MRSA) strains and recognized extracted S. aureus proteins on Western blot. ELISAs to quantify milk IgA reactive with a number of S. aureus virulence proteins (e.g. enterotoxins, microbial surface component recognizing adhesive matrix molecules (MSCRAMMs) and immune modulating proteins) and cell wall components, demonstrated the polyclonality of the IgA. Correlations observed between agglutination and specific IgA titers for whey and for purified IgA suggested functionality of the induced antibodies. Milk from immunized cows may provide a way of producing potentially therapeutic polyclonal antibodies against S. aureus colonization and infection.

  6. A disease model of diabetic nephropathy in a glomerulus-on-a-chip microdevice.

    Science.gov (United States)

    Wang, Li; Tao, Tingting; Su, Wentao; Yu, Hao; Yu, Yue; Qin, Jianhua

    2017-05-16

    Diabetic nephropathy is a major chronic renal complication of diabetes mellitus, and is the leading cause of end-stage kidney diseases. Establishing a disease model of diabetic nephropathy in vitro can accelerate the understanding of its mechanisms and pharmaceutical development. We provide the proof-of-principle for using a glomerulus-on-a-chip microdevice that reconstitutes organ-level kidney functions to create a human disease model of early stage diabetic nephropathy on chip. The microfluidic device, which recapitulates the glomerular microenvironment, consists of parallel channels lined by isolated primary glomerular microtissues that experience fluid flow to mimic the glomerular filtration barrier (GFB), including glomerular endothelial cells, 3D basement membrane and podocytes. This device was used to reproduce high glucose-induced critical pathological responses in diabetic nephropathy as observed in humans. The results reveal that hyperglycemia plays a crucial role in the development of increased barrier permeability to albumin and glomerular dysfunction that lead to proteinuria. This organ-on-a-chip microdevice mimics the critical pathological responses of glomerulus that are characteristic of diabetic nephropathy that has not been possible by cell-based and animal models, providing a useful platform for studying the mechanism of diabetic nephropathy and developing an effective therapy in glomerular diseases.

  7. Simultaneous detection of celiac disease-specific IgA antibodies and total IgA.

    Science.gov (United States)

    Grossmann, Kai; Röber, Nadja; Hiemann, Rico; Rödiger, Stefan; Schierack, Peter; Reinhold, Dirk; Laass, Martin W; Conrad, Karsten; Roggenbuck, Dirk

    2016-12-01

    Celiac disease (CD) serology requires analysis of tissue transglutaminase type-2 (TG2autoAbs), deamidated gliadin (DGAbs), and as reference endomysial autoantibodies (EmA). Total IgA assessment helps to determine IgA-deficient CD patients. The novel multiplex indirect immunofluorescence (IIF) technique CytoBead was used to develop the first quantitative one-step serological CD assay comprising both simultaneous IgA autoAb and total IgA testing. CytoBead CeliAK detecting TG2autoAb, DGAb, EmA, and simultaneously total IgA uses fluorescent microparticles for antigen and antibody immobilization along with monkey-esophagus tissue sections on glass slides. The assay was interpreted visually by classical fluorescent microscopy and digital IIF using AKLIDES(®). Overall, 380 samples (155 CD patients, 5 with IgA deficiency, 68 with cystic fibrosis, 59 with eye disease, 93 blood donors) were run for performance analysis. Data were compared with classical IgA autoAb analysis by ELISA and IIF. Comparing CD-specific IgA autoAb testing by CytoBead with classical IIF and ELISA, very good agreements for EmA, TG2autoAb, and DGAb were determined (Cohen's κ = 0.98, 0.96, 0.85, respectively). The difference between multiplex and single testing revealed a significant difference for TG2autoAb testing only (McNemar, p = 0.0078). Four CD patients and 4 controls demonstrated TG2autoAb positivity by ELISA but were negative by CytoBead. Further, 140/155 (90.9 %) CD patients demonstrated TG2autoAb levels above ten times the upper normal and all five IgA-deficient samples IgA levels IgA deficiency analyses comparable with classical testing by single-parameter assays. Thus, comprehensive CD serology by CytoBead can alleviate the workload in routine laboratories.

  8. Transient glyco-engineering to produce recombinant IgA1 with defined N- and O-glycans in plants

    Directory of Open Access Journals (Sweden)

    Martina eDicker

    2016-01-01

    Full Text Available The production of therapeutic antibodies to combat pathogens and treat diseases such as cancer is of great interest for the biotechnology industry. The recent development of plant-based expression systems has demonstrated that plants are well-suited for the production of recombinant monoclonal antibodies with defined glycosylation. Compared to immunoglobulin G (IgG, less effort has been undertaken to express immunoglobulin A (IgA, which is the most prevalent antibody class at mucosal sites and a promising candidate for novel recombinant biopharmaceuticals with enhanced anti-tumour activity. Here, we transiently expressed recombinant human IgA1 against the VP8* rotavirus antigen in glyco-engineered deltaXT/FT Nicotiana benthamiana plants. Mass spectrometric analysis of IgA1 glycopeptides revealed the presence of complex biantennary N-glycans with terminal N-acetylglucosamine present on the N-glycosylation site of the CH2 domain in the IgA1 alpha chain. Analysis of the peptide carrying nine potential O-glycosylation sites in the IgA1 alpha chain hinge region showed the presence of plant-specific modifications including hydroxyproline formation and the attachment of pentoses. By co-expression of enzymes required for initiation and elongation of human O-glycosylation it was possible to generate disialylated mucin-type core 1 O-glycans on plant-produced IgA1. Our data demonstrate that deltaXT/FT Nicotiana benthamiana plants can be engineered towards the production of recombinant IgA1 with defined human-type N- and O-linked glycans.

  9. Transient Glyco-Engineering to Produce Recombinant IgA1 with Defined N- and O-Glycans in Plants.

    Science.gov (United States)

    Dicker, Martina; Tschofen, Marc; Maresch, Daniel; König, Julia; Juarez, Paloma; Orzaez, Diego; Altmann, Friedrich; Steinkellner, Herta; Strasser, Richard

    2016-01-01

    The production of therapeutic antibodies to combat pathogens and treat diseases, such as cancer is of great interest for the biotechnology industry. The recent development of plant-based expression systems has demonstrated that plants are well-suited for the production of recombinant monoclonal antibodies with defined glycosylation. Compared to immunoglobulin G (IgG), less effort has been undertaken to express immunoglobulin A (IgA), which is the most prevalent antibody class at mucosal sites and a promising candidate for novel recombinant biopharmaceuticals with enhanced anti-tumor activity. Here, we transiently expressed recombinant human IgA1 against the VP8* rotavirus antigen in glyco-engineered ΔXT/FT Nicotiana benthamiana plants. Mass spectrometric analysis of IgA1 glycopeptides revealed the presence of complex biantennary N-glycans with terminal N-acetylglucosamine present on the N-glycosylation site of the CH2 domain in the IgA1 alpha chain. Analysis of the peptide carrying nine potential O-glycosylation sites in the IgA1 alpha chain hinge region showed the presence of plant-specific modifications including hydroxyproline formation and the attachment of pentoses. By co-expression of enzymes required for initiation and elongation of human O-glycosylation it was possible to generate disialylated mucin-type core 1 O-glycans on plant-produced IgA1. Our data demonstrate that ΔXT/FT N. benthamiana plants can be engineered toward the production of recombinant IgA1 with defined human-type N- and O-linked glycans.

  10. Advances in Murine Models of Diabetic Nephropathy

    Science.gov (United States)

    Kong, Li-li; Wu, Hao; Cui, Wen-peng; Zhou, Wen-hua; Luo, Ping; Sun, Jing; Yuan, Hang; Miao, Li-ning

    2013-01-01

    Diabetic nephropathy (DN) is one of the microvascular complications of both type 1 and type 2 diabetes, which is also associated with a poor life expectancy of diabetic patients. However, the pathogenesis of DN is still unclear. Thus, it is of great use to establish appropriate animal models of DN for doing research on pathogenesis and developing novel therapeutic strategies. Although a large number of murine models of DN including artificially induced, spontaneous, and genetically engineered (knockout and transgenic) animal models have been developed, none of them develops renal changes sufficiently reflecting those seen in humans. Here we review the identified murine models of DN from the aspects of genetic background, type of diabetes, method of induction, gene deficiency, animal age and gender, kidney histopathology, and phenotypic alterations in the hope of enhancing our comprehension of genetic susceptibility and molecular mechanisms responsible for this disease and providing new clues as to how to choose appropriate animal models of DN. PMID:23844375

  11. Advances in Murine Models of Diabetic Nephropathy

    Directory of Open Access Journals (Sweden)

    Li-li Kong

    2013-01-01

    Full Text Available Diabetic nephropathy (DN is one of the microvascular complications of both type 1 and type 2 diabetes, which is also associated with a poor life expectancy of diabetic patients. However, the pathogenesis of DN is still unclear. Thus, it is of great use to establish appropriate animal models of DN for doing research on pathogenesis and developing novel therapeutic strategies. Although a large number of murine models of DN including artificially induced, spontaneous, and genetically engineered (knockout and transgenic animal models have been developed, none of them develops renal changes sufficiently reflecting those seen in humans. Here we review the identified murine models of DN from the aspects of genetic background, type of diabetes, method of induction, gene deficiency, animal age and gender, kidney histopathology, and phenotypic alterations in the hope of enhancing our comprehension of genetic susceptibility and molecular mechanisms responsible for this disease and providing new clues as to how to choose appropriate animal models of DN.

  12. Lithium clearance in chronic nephropathy

    DEFF Research Database (Denmark)

    Kamper, A L; Holstein-Rathlou, N H; Leyssac, P P

    1989-01-01

    1. Lithium clearance measurements were made in 72 patients with chronic nephropathy of different aetiology and moderate to severely reduced renal function. 2. Lithium clearance was strictly correlated with glomerular filtration rate, and there was no suggestion of distal tubular reabsorption...... of lithium or influence of osmotic diuresis. 3. Fractional reabsorption of lithium was reduced in most patients with glomerular filtration rates below 25 ml/min. 4. Calculated fractional distal reabsorption of sodium was reduced in most patients with glomerular filtration rates below 50 ml/min. 5. Lithium...... that lithium clearance may be a measure of the delivery of sodium and water from the renal proximal tubule. With this assumption it was found that adjustment of the sodium excretion in chronic nephropathy initially takes place in the distal parts of the nephron (loop of Henle, distal tubule and collecting duct...

  13. Lithium clearance in chronic nephropathy

    DEFF Research Database (Denmark)

    Kamper, A L; Holstein-Rathlou, N H; Leyssac, P P

    1989-01-01

    1. Lithium clearance measurements were made in 72 patients with chronic nephropathy of different aetiology and moderate to severely reduced renal function. 2. Lithium clearance was strictly correlated with glomerular filtration rate, and there was no suggestion of distal tubular reabsorption...... clearance data were independent of whether renal disease was of primarily glomerular or tubular origin and, further, were not influenced by long-term conventional antihypertensive treatment. 6. It is concluded that, even with a reduced kidney function, the data are compatible with the suggestion...... that lithium clearance may be a measure of the delivery of sodium and water from the renal proximal tubule. With this assumption it was found that adjustment of the sodium excretion in chronic nephropathy initially takes place in the distal parts of the nephron (loop of Henle, distal tubule and collecting duct...

  14. Endemic Nephropathy Around the World.

    Science.gov (United States)

    Gifford, Fiona J; Gifford, Robert M; Eddleston, Michael; Dhaun, Neeraj

    2017-03-01

    There have been several global epidemics of chronic kidney disease of unknown etiology (CKDu). Some, such as Itai-Itai disease in Japan and Balkan endemic nephropathy, have been explained, whereas the etiology of others remains unclear. In countries such as Sri Lanka, El Salvador, Nicaragua, and India, CKDu is a major public health problem and causes significant morbidity and mortality. Despite their geographical separation, however, there are striking similarities between these endemic nephropathies. Young male agricultural workers who perform strenuous labor in extreme conditions are the worst affected. Patients remain asymptomatic until end-stage renal failure. Biomarkers of tubular injury are raised, and kidney biopsy shows chronic interstitial nephritis with associated tubular atrophy. In many of these places access to dialysis and transplantation is limited, leaving few treatment options. In this review we briefly describe the major historic endemic nephropathies. We then summarize the epidemiology, clinical features, histology and clinical course of CKDu in Mesoamerica, Sri Lanka, India, Egypt, and Tunisia. We draw comparisons between the proposed etiologies and supporting research. Recognition of the similarities may reinforce the international drive to establish causality and to effect prevention.

  15. Endemic Nephropathy Around the World

    Directory of Open Access Journals (Sweden)

    Fiona J. Gifford

    2017-03-01

    Full Text Available There have been several global epidemics of chronic kidney disease of unknown etiology (CKDu. Some, such as Itai-Itai disease in Japan and Balkan endemic nephropathy, have been explained, whereas the etiology of others remains unclear. In countries such as Sri Lanka, El Salvador, Nicaragua, and India, CKDu is a major public health problem and causes significant morbidity and mortality. Despite their geographical separation, however, there are striking similarities between these endemic nephropathies. Young male agricultural workers who perform strenuous labor in extreme conditions are the worst affected. Patients remain asymptomatic until end-stage renal failure. Biomarkers of tubular injury are raised, and kidney biopsy shows chronic interstitial nephritis with associated tubular atrophy. In many of these places access to dialysis and transplantation is limited, leaving few treatment options. In this review we briefly describe the major historic endemic nephropathies. We then summarize the epidemiology, clinical features, histology and clinical course of CKDu in Mesoamerica, Sri Lanka, India, Egypt, and Tunisia. We draw comparisons between the proposed etiologies and supporting research. Recognition of the similarities may reinforce the international drive to establish causality and to effect prevention.

  16. Linear IgA disease: clinical presentation, diagnosis, and pathogenesis.

    Science.gov (United States)

    Venning, Vanessa A

    2012-05-01

    Linear IgA disease is one of the rarer subepidermal blistering diseases. Linear IgA disease is a chronic, acquired, autoimmune blistering disease that is characterized by subepidermal blistering and linear deposition of IgA basement membrane antibodies. The disease affects both children and adults and, although there are some differences in their clinical presentations, there is considerable overlap with shared immunopathology and immunogenetics. Copyright © 2012 Elsevier Inc. All rights reserved.

  17. TCM Differential Treatment of IgA Nephrosis

    Institute of Scientific and Technical Information of China (English)

    聂莉芳

    2005-01-01

    @@ IgA nephrosis, with an incidence of 38%-49% in the primary glomerulopathy in China, is one of the main causes for the late renal failure. In view of the fact that there are no specific Western remedies for IgA nephrosis characterized by hematuria, the researches on TCM differential treatment of IgA nephrosis have been listed in the major projects of "the Scientific Technologies in thel0th 5-year plan of China".

  18. Oral manifestations caused by the linear IgA disease.

    Science.gov (United States)

    Eguia del Valle, Asier; Aguirre Urízar, José Manuel; Martínez Sahuquillo, Angel

    2004-01-01

    The Linear IgA deposit related disease or Linear IgA disease (LAD) is a chronic, uncommon and autoimmunological mucocutaneous disease, characterised by linear IgA deposits along the basement membrane zone. In mainly cases, moreover cutaneous lesions, there are oral mucosal and other mucosal lesions. There are also, some cases published of Linear IgA disease limited to oral mucosa. The known of this disease is important for the establishment of a correct differential diagnosis in cases of blistering mucocutaneous diseases. In this paper, we analyze the most important features of this disease, attending specially to the oral manifestations.

  19. IgA deficiency in wolves from Canada and Scandinavia.

    Science.gov (United States)

    Frankowiack, Marcel; Olsson, Mia; Cluff, H Dean; Evans, Alina L; Hellman, Lars; Månsson, Johan; Arnemo, Jon M; Hammarström, Lennart

    2015-05-01

    Immunoglobulin A deficiency (IgAD) is the most common primary immunodeficiency in both humans and selected breeds of domestic dogs. In both species, IgAD is associated with recurrent infections and immune mediated diseases. Previous results imply that IgAD is also common in the wild ancestor of domestic dogs, the gray wolf. Here, we report that serum IgA concentrations are significantly different in Scandinavian and Canadian wolves (p = 3.252e-15) with an increased prevalence for IgAD in Scandinavian wolves (60%), which is as high as those found in high-risk dog breeds. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Association of genetic variants with diabetic nephropathy