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Sample records for autoimmune lymphoproliferative syndrome

  1. Recurrent Oral Inflammation in Autoimmune Lymphoproliferative Syndrome

    OpenAIRE

    Pac, Malgorzata; Olczak-Kowalczyk, Dorota; Wolska-Kuśnierz, Beata; Piątosa, Barbara; Górska, Renata; Bernatowska, Ewa

    2014-01-01

    Abstract   Background and aim: Autoimmune lymphoproliferative syndrome (ALPS) is a disorder of abnormal lymphocyte survival caused by dysregulation of the Fas apoptotic pathway. In ALPS defective lymphocyte apoptosis manifests as a chronic, nonmalignant lymphadenopathy and/or splenomegaly/hepatosplenomegaly, expansion of double negative T cell (DNTC) – CD4-CD8-TCRαβ+ T cells, autoimmune cytopenias and other autoimmune diseases.  Patients demonstrate oral lesions which have not yet been repo...

  2. Tubulointerstitial Nephritis in a Patient With Probable Autoimmune Lymphoproliferative Syndrome

    DEFF Research Database (Denmark)

    Glerup, Mia; Herlin, Troels; Rittig, Søren

    2013-01-01

    Autoimmune lymphoproliferative syndrome (ALPS) is caused by a nonmalignant defective Fas-mediated apoptosis. The main clinical manifestations are chronic lymphadenopathy, splenomegaly, and autoimmune cytopenia. Most patients with ALPS have a FAS germline mutation. ALPS has occasionally been......-vessel vasculitis with normal glomeruli and inflammation in the interstitium. The patient responded to prednisolone treatment and obtained a full renal recovery. Symptoms of connective tissue disorder supervened and after the development of more pronounced splenomegaly, a diagnosis of ALPS was confirmed....

  3. Autoimmune Lymphoproliferative Syndrome: A Rare Cause of Disappearing HDL Syndrome

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    Swetha Sriram

    2016-01-01

    Full Text Available The term disappearing HDL syndrome refers to development of severe high density lipoprotein cholesterol (HDL-C deficiency in noncritically ill patients with previously normal HDL-C and triglyceride levels. Autoimmune lymphoproliferative syndrome (ALPS is a disorder of the immune system due to an inability to regulate lymphocyte homeostasis resulting in lymphadenopathy and hepatosplenomegaly. We describe a 17-year-old boy who was evaluated in the lipid clinic for history of undetectable or low HDL-C and low density lipoprotein cholesterol (LDL-C levels. Past medical history was significant for ALPS IA diagnosed at 10 years of age when he presented with bilateral cervical adenopathy. He was known to have a missense mutation in one allele of the FAS protein extracellular domain consistent with ALPS type 1A. HDL-C and LDL-C levels had been undetectable on multiple occasions, though lipids had not been measured prior to the diagnosis of ALPS. He had been receiving sirolimus for immunosuppression. The HDL-C and LDL-C levels correlated with disease activity and improved to normal levels during times when the activity of ALPS was controlled. This case highlights the importance of considering ALPS as a cause of low HDL-C and LDL-C levels in a child with evidence of lymphoproliferation.

  4. Diagnosis of autoimmune lymphoproliferative syndrome caused by FAS deficiency in adults

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    Lambotte, Olivier; Neven, Bénédicte; Galicier, Lionel; Magerus-Chatinet, Aude; Schleinitz, Nicolas; Hermine, Olivier; Meyts, Isabelle; Picard, Capucine; Godeau, Bertrand; Fischer, Alain; Rieux-Laucat, Frédéric

    2013-01-01

    A diagnosis of autoimmune lymphoproliferative syndrome caused by FAS deficiency during adulthood is unusual. We analyzed 17 cases of autoimmune lymphoproliferative syndrome caused by FAS deficiency diagnosed during adulthood in French reference centers for hereditary immunodeficiencies and for immune cytopenias. Twelve of the 17 patients had developed their first symptoms during childhood. The diagnosis of autoimmune lymphopro-liferative syndrome had been delayed for a variety of reasons, including unusual clinical manifestations, late referral to a reference center, and the occurrence of somatic FAS mutations. The 5 other patients presented their first symptoms after the age of 16 years. In these patients, three germline heterozygous FAS mutations were predicted to be associated with haploinsufficiency and a somatic event on the second FAS allele was observed in 2 cases. Autoimmune lymphoproliferative syndrome may well be diagnosed in adulthood. The occurrence of additional genetic events may account for the delayed disease onset. PMID:22983577

  5. Approaches to managing cytopenias in Autoimmune Lymphoproliferative Syndrome (ALPS.

    Directory of Open Access Journals (Sweden)

    V. Koneti eRao

    2015-07-01

    Full Text Available Autoimmune Lymphoproliferative Syndrome (ALPS is a rare disorder frequently due to mutations in FAS (TNFRSF6 gene. Unlike most of the self limiting autoimmune cytopenias sporadically seen in childhood, multi lineage cytopenias due to ALPS are often refractory as their inherited genetic defect is not going to go away. Historically more ALPS patients have died due to overwhelming sepsis following splenectomy to manage their chronic cytopenias than due to any other cause, including malignancies. Hence current recommendations underscore the importance of avoiding splenectomy in ALPS, by long-term use of corticosteroid sparing immunosuppressive agents like mycophenolate mofetil and sirolimus. Paradigms learnt from managing ALPS patients in recent years is highlighted here and can be extrapolated to manage refractory cytopenias in patients with as yet undetermined genetic bases for their ailments. It is also desirable to develop international registries for children with rare and complex immune problems associated with chronic multilineage cytopenias in order to elucidate their natural history and long-term comorbidities due to their disease and its treatments.

  6. Deregulation of Fas ligand expression as a novel cause of autoimmune lymphoproliferative syndrome-like disease.

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    Nabhani, Schafiq; Ginzel, Sebastian; Miskin, Hagit; Revel-Vilk, Shoshana; Harlev, Dan; Fleckenstein, Bernhard; Hönscheid, Andrea; Oommen, Prasad T; Kuhlen, Michaela; Thiele, Ralf; Laws, Hans-Jürgen; Borkhardt, Arndt; Stepensky, Polina; Fischer, Ute

    2015-09-01

    Autoimmune lymphoproliferative syndrome is frequently caused by mutations in genes involved in the Fas death receptor pathway, but for 20-30% of patients the genetic defect is unknown. We observed that treatment of healthy T cells with interleukin-12 induces upregulation of Fas ligand and Fas ligand-dependent apoptosis. Consistently, interleukin-12 could not induce apoptosis in Fas ligand-deficient T cells from patients with autoimmune lymphoproliferative syndrome. We hypothesized that defects in the interleukin-12 signaling pathway may cause a similar phenotype as that caused by mutations of the Fas ligand gene. To test this, we analyzed 20 patients with autoimmune lymphoproliferative syndrome of unknown cause by whole-exome sequencing. We identified a homozygous nonsense mutation (c.698G>A, p.R212*) in the interleukin-12/interleukin-23 receptor-component IL12RB1 in one of these patients. The mutation led to IL12RB1 protein truncation and loss of cell surface expression. Interleukin-12 and -23 signaling was completely abrogated as demonstrated by deficient STAT4 phosphorylation and interferon γ production. Interleukin-12-mediated expression of membrane-bound and soluble Fas ligand was lacking and basal expression was much lower than in healthy controls. The patient presented with the classical symptoms of autoimmune lymphoproliferative syndrome: chronic non-malignant, non-infectious lymphadenopathy, splenomegaly, hepatomegaly, elevated numbers of double-negative T cells, autoimmune cytopenias, and increased levels of vitamin B12 and interleukin-10. Sanger sequencing and whole-exome sequencing excluded the presence of germline or somatic mutations in genes known to be associated with the autoimmune lymphoproliferative syndrome. Our data suggest that deficient regulation of Fas ligand expression by regulators such as the interleukin-12 signaling pathway may be an alternative cause of autoimmune lymphoproliferative syndrome-like disease. Copyright© Ferrata Storti

  7. Association of severe myoclonic epilepsy of infancy (SMEI with probable autoimmune lymphoproliferative syndrome-variant

    Directory of Open Access Journals (Sweden)

    A. Berio

    2014-12-01

    Full Text Available The paper reported on a case of severe myoclonic epilepsy of infancy (SMEI associated with a probable autoimmune lymphoproliferative syndrome variant (Dianzani autoimmune lymphoproliferative disease (DALD. A male patient with typical features of SMEI and a SCN1A gene variant presented in the first year of life with multiple lymph nodes, palpable liver at 2 cm from the costal margin, neutropenia, dysgammaglobulinemia, relative and sometimes absolute lymphocytosis. Subsequently the patient presented with constantly raised IgA in serum and positive antinuclear and thyroid antimicrosomal antibodies. The diagnosis of probable autoimmune lymphoproliferative syndrome was made; arthritis, skin and throat blisters, which appeared subsequently led to the diagnosis of linear IgA disease. On the basis of these unique associations, the Authors hypothesized that autoimmunity may be partly responsible of the severe epileptic symptomatology, perhaps mediated by autoantibodies against sodium channels or by accompanying cytotoxic T-lymphocytes. Corticosteroid treatment ameliorated the epilepsy and laboratory tests. Future studies will be necessary to evaluate the relevance of autoimmunity in SMEI.

  8. Autoimmune lymphoproliferative syndrome: more than a FAScinating disease [version 1; referees: 3 approved

    Directory of Open Access Journals (Sweden)

    Karen Bride

    2017-11-01

    Full Text Available Autoimmune lymphoproliferative syndrome (ALPS is an inherited syndrome characterized by abnormal lymphocyte survival caused by failure of apoptotic mechanisms to maintain lymphocyte homeostasis. This failure leads to the clinical manifestations of non-infectious and non-malignant lymphadenopathy, splenomegaly, and autoimmune pathology, most commonly, autoimmune cytopenias. Since ALPS was first characterized in the early 1990s, insights in disease biology have improved both diagnosis and management of this syndrome. Sirolimus is the best-studied and most effective corticosteroid-sparing therapy for ALPS and should be considered first-line for patients in need of chronic treatment. This review highlights practical clinical considerations for the diagnosis and management of ALPS. Further studies could reveal new proteins and regulatory pathways that are critical for lymphocyte activation and apoptosis.

  9. Autoimmune Lymphoproliferative Syndrome (ALPS)

    Science.gov (United States)

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  10. Mapping the x-linked lymphoproliferative syndrome

    International Nuclear Information System (INIS)

    Skare, J.C.; Milunsky, A.; Byron, K.S.; Sullivan, J.L.

    1987-01-01

    The X-linked lymphoproliferative syndrome is triggered by Epstein-Barr virus infection and results in fatal mononucleosis, immunodeficiency, and lymphoproliferative disorders. This study shows that the mutation responsible for X-linked lymphoproliferative syndrome is genetically linked to a restriction fragment length polymorphism detected with the DXS42 probe (from Xq24-q27). The most likely recombination frequency between the loci is 4%, and the associated logarithm of the odds is 5.26. Haplotype analysis using flanking restriction fragment length polymorphism markers indicates that the locus for X-linked lymphoproliferative syndrome is distal to probe DXS42 but proximal to probe DXS99 (from Xq26-q27). It is now possible to predict which members of a family with X-linked lymphoproliferative syndrome are carrier females and to diagnose the syndrome prenatally

  11. Sirolimus for Autoimmune Disease of Blood Cells

    Science.gov (United States)

    2017-11-02

    Autoimmune Pancytopenia; Autoimmune Lymphoproliferative Syndrome (ALPS); Evans Syndrome; Idiopathic Thrombocytopenic Purpura; Anemia, Hemolytic, Autoimmune; Autoimmune Neutropenia; Lupus Erythematosus, Systemic; Inflammatory Bowel Disease; Rheumatoid Arthritis

  12. Frequency of a FAS ligand gene variant associated with inherited feline autoimmune lymphoproliferative syndrome in British shorthair cats in New Zealand.

    Science.gov (United States)

    Aberdein, D; Munday, J S; Dittmer, K E; Heathcott, R W; Lyons, L A

    2017-11-01

    AIMS To determine the frequency of the FAS-ligand gene (FASLG) variant associated with feline autoimmune lymphoproliferative syndrome (FALPS) and the proportion of carriers of the variant in three British shorthair (BSH) breeding catteries in New Zealand. METHODS Buccal swabs were collected from all cats in two BSH breeding catteries from the South Island and one from the North Island of New Zealand. DNA was extracted and was tested for the presence of the FASLG variant using PCR. Cats with the FASLG variant were identified and the frequency of the FASLG variant allele calculated. Pedigree analysis was performed and inbreeding coefficients were calculated for cats with the FASLG variant. RESULTS Of 32 BSH cats successfully tested for the presence of the FASLG variant, one kitten (3%) was homozygous (FALPS-affected), and seven (22%) cats were heterozygous (carriers) for the FASLG variant allele, and 24 (75%) cats were homozygous for the wild type allele. The overall frequency of the FASLG variant allele in these 32 cats was 0.14. Cats carrying the FASLG variant were from all three breeding catteries sampled, including two catteries that had not previously reported cases of FALPS. Pedigree analysis revealed common ancestry of FALPS-affected and carrier cats within six generations, as well as frequent inbreeding, with inbreeding coefficients >0.12 for five cats with the FASLG variant. CONCLUSIONS AND CLINICAL RELEVANCE There was a high frequency of the FASLG variant allele (0.14) in this small sample of BSH cats, with 22% of healthy cats identified as carriers of the FASLG variant. For an inherited disease, lethal at a young age, in a small population in which inbreeding is common, these results are significant. To prevent future cases of disease and stop further spread of the FASLG variant allele within the BSH population in New Zealand, it is recommended that all BSH and BSH-cross cats be tested for the presence of the FASLG variant before mating. Cats identified as

  13. Autoimmune lymphoproliferative syndrome and non-Hodgkin lymphoma: what 18F-fluorodeoxyglucose positron emission tomography/computed tomography can do in the management of these patients? Suggestions from a case report.

    Science.gov (United States)

    Cistaro, A; Pazè, F; Durando, S; Cogoni, M; Faletti, R; Vesco, S; Vallero, S; Quartuccio, N; Treglia, G; Ramenghi, U

    2014-01-01

    A young patient with undefined autoimmune lymphoproliferative syndrome (ALPS-U) and low back pain underwent a CT and MRI study that showed enhancing vertebral lesions, some pulmonary nodules and diffuse latero-cervical lymphadenopathy. A (18)F-FDG-PET/CT scan showed many areas of intense (18)F-FDG uptake in multiple vertebrae, in some ribs, in the sacrum, in the liver, in both lungs, in multiple lymph nodes spread in the cervical, thoracic and abdominal chains. A bone marrow biopsy showed a "lymphomatoid granulomatosis", a rare variant of B-cell non-Hodgkin lymphoma (NHL). After the treatment, the (18)F-FDG-PET/CT scan showed a complete metabolic response. Copyright © 2013 Elsevier España, S.L. and SEMNIM. All rights reserved.

  14. Genetics Home Reference: autoimmune lymphoproliferative syndrome

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    ... NBK1108/ Citation on PubMed Dowdell KC, Niemela JE, Price S, Davis J, Hornung RL, Oliveira JB, Puck JM, ... on PubMed or Free article on PubMed Central Price S, Shaw PA, Seitz A, Joshi G, Davis J, ...

  15. [Polyglandular autoimmune syndromes : An overview].

    Science.gov (United States)

    Komminoth, P

    2016-05-01

    Polyglandular autoimmune syndromes (PGAS), also known as autoimmune polyendocrinopathy syndromes (APS), are a heterogeneous group of rare, genetically caused diseases of the immune system which lead to inflammatory damage of various endocrine glands resulting in malfunctions. In addition, autoimmune diseases of non-endocrine organs may also be found. Early diagnosis of PGAS is often overlooked because of heterogeneous symptoms and the progressive occurrence of the individual diseases. The two most important forms of PGAS are the juvenile and adult types. The juvenile type (PGAS type 1) is caused by mutations in the autoimmune regulator (AIRE) gene on chromosome 21, exhibits geographic variations in incidence and is defined by the combination of mucocutaneous candidiasis, Addison's disease and hypoparathyroidism. In addition, autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) syndrome and other autoimmune diseases can also occur. The adult form of PGAS (PGAS type 2) is a multigenetic disorder associated with some HLA haplotypes, is more common than the juvenile type, shows female predominance and exhibits the combination of type 1 diabetes, autoimmune thyroid disease, Addison's disease and other autoimmune disorders. The histological alterations in affected organs of PGAS patients are similar to findings in sporadically occurring autoimmune diseases of these organs but there are no pathognomic fine tissue findings. If patients exhibit autoimmune changes in two different endocrine glands or if there are indications of several autoimmune disorders from the patient history, it is important to consider PGAS and inform the clinicians of this suspicion.

  16. Autoimmune diseases and myelodysplastic syndromes.

    Science.gov (United States)

    Komrokji, Rami S; Kulasekararaj, Austin; Al Ali, Najla H; Kordasti, Shahram; Bart-Smith, Emily; Craig, Benjamin M; Padron, Eric; Zhang, Ling; Lancet, Jeffrey E; Pinilla-Ibarz, Javier; List, Alan F; Mufti, Ghulam J; Epling-Burnette, Pearlie K

    2016-05-01

    Immune dysregulation and altered T-cell hemostasis play important roles in the pathogenesis of myelodysplastic syndromes (MDS). Recent studies suggest an increased risk of MDS among patients with autoimmune diseases. Here, we investigated the prevalence of autoimmune diseases among MDS patients, comparing characteristics and outcomes in those with and without autoimmune diseases. From our study group of 1408 MDS patients, 391 (28%) had autoimmune disease, with hypothyroidism being the most common type, accounting for 44% (n = 171) of patients (12% among all MDS patients analyzed). Other autoimmune diseases with ≥5% prevalence included idiopathic thrombocytopenic purpura in 12% (n = 46), rheumatoid arthritis in 10% (n = 41), and psoriasis in 7% (n = 28) of patients. Autoimmune diseases were more common in female MDS patients, those with RA or RCMD WHO subtype, and those who were less dependent on red blood cell transfusion. Median overall survival (OS) was 60 months (95% CI, 50-70) for patients with autoimmune diseases versus 45 months (95% CI, 40-49) for those without (log-rank test, P = 0.006). By multivariate analysis adjusting for revised IPSS and age >60 years, autoimmune diseases were a statistically significant independent factor for OS (HR 0.78; 95% CI, 0.66-0.92; P = 0.004). The rate of acute myeloid leukemia (AML) transformation was 23% (n = 89) in MDS patients with autoimmune disease versus 30% (n = 301) in those without (P = 0.011). Patient groups did not differ in response to azacitidine or lenalidomide treatment. Autoimmune diseases are prevalent among MDS patients. MDS patients with autoimmune diseases have better OS and less AML transformation. © 2016 Wiley Periodicals, Inc.

  17. Multiple autoimmune syndrome with celiac disease.

    Science.gov (United States)

    Harpreet, Singh; Deepak, Jain; Kiran, B

    Multiple autoimmune syndrome (MAS) is a condition characterised by three or more autoimmune disorders in a same individual. Familial, immunologic and infectious factors are implicated in the development of MAS. Here we report a case of a 32-year-old woman with co-existence of four auto-immune diseases, namely autoimmune hypothyroidism, Sjögren's syndrome, systemic lupus erythematosus (SLE) and celiac disease which leads to the final diagnosis of multiple autoimmune syndrome type 3 with celiac disease. Patients with single autoimmune disorder are at 25% risk of developing other autoimmune disorders. The present case emphasises to clinicians that there is a need for continued surveillance for the development of new autoimmune disease in predisposed patients.

  18. Polyglandular autoimmune syndrome type I.

    Science.gov (United States)

    Proust-Lemoine, Emmanuelle; Saugier-Veber, Pascale; Wémeau, Jean-Louis

    2012-12-01

    Polyglandular Autoimmune Syndrom type 1 (PAS-1) or Autoimmune PolyEndocrinopathy Candidiasis-Ectodermal-Dystrophy (APECED) is a rare recessive autosomal disease related to Autoimmune Regulator (AIRE) gene mutations. AIRE is mainly implicated in central and peripheric immune tolerance. Diagnosis was classically based on presence of at least two out of three "majors" criterions of Whitaker's triad (candidiasis, autoimmune hypoparathyroidism and adrenal insufficiency). Presence of one criterion was sufficient when a sibling was previously diagnosed. However, some atypic or poorly symptomatic variants do not correspond to these criterions. As a matter of fact, digestive (malabsorption, pernicious anemia, hepatitis), cutaneous (alopecia, vitiligo, enamel dysplasia) or ophtalmological (keratitis) components could prevail. In these cases, diagnosis could be made by molecular genetics. Prognosis is influenced by genetic (AIRE mutations, HLA), hormonal and environmental (infections) factors. Potentially letal components (hepatitis and severe malabsorption) could be treated by immunosuppressors. Candidiasis and other infections should be carefully screened and treated before beginning those therapies, in order to avoid severe systemic infections. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  19. Autoimmune polyendocrine syndrome and thrombocytosis.

    Science.gov (United States)

    Atquet, V; Lienart, F; Vaes, M

    2015-12-01

    We describe a woman aged 37  years, affected with Hashimoto's thyroiditis, detected since the age of 17, with gonadic insufficiency with anti-ovarian antibodies since the age of 22  years and Addison's disease since 24  years old. At that moment, the diagnosis of autoimmune polyendocrine syndrome (APS) was made. Concomitant to this diagnosis, thrombocytosis was detected and aetiological assessment revealed an atrophy of the spleen. Differential diagnoses of APS and hyposplenism will be discussed. We will look at a possible association between these two pathologies. Indeed, asplenism is found in approximately 20% of adults affected by type 1 APS, also called auto-immune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) syndrome. The most likely aetiology for this atrophy of the spleen is a destruction of auto-immunological origin. However, in our patient, the search for a mutation of the autoimmune regulator (AIRE) gene proved negative. This mutation is commonly, but not systematically, present in type 1 APS. A type 2 APS should then be considered.

  20. Autoimmune diseases in women with Turner's syndrome

    DEFF Research Database (Denmark)

    Jørgensen, Kristian T; Rostgaard, Klaus; Bache, Iben

    2010-01-01

    OBJECTIVE: In terms of number of X chromosomes, women with Turner's syndrome cytogenetically resemble men. An increased risk of autoimmune diseases has been observed among women with Turner's syndrome. This study was undertaken to investigate whether the autoimmune disease profile in women with T...

  1. [Type 2 autoimmune polyendocrine syndromes (APS-2)].

    Science.gov (United States)

    Vialettes, Bernard; Dubois-Leonardon, Noémie

    2013-01-01

    Type 2 autoimmune polyendocrine syndromes (APS-2) are the most frequent disorders associating several organ-specific autoimmune diseases. Their high prevalence is due to the fact that the main manifestations of APS-2, such as thyroidal autoimmunity, type 1 diabetes, autoimmune gastric atrophy and vitiligo, are common diseases. APS-2 represents a clinical model that can serve to help unravel the mechanisms underlying autoimmunity. Diagnosis of APS-2 is a challenge for the clinician, especially in poorly symptomatic forms, and may require systematic screening based on measurement of autoantibodies and functional markers.

  2. Treatment of the X-linked lymphoproliferative, Griscelli and Chédiak-Higashi syndromes by HLH directed therapy

    DEFF Research Database (Denmark)

    Trottestam, Helena; Beutel, Karin; Meeths, Marie

    2009-01-01

    BACKGROUND: Griscelli syndrome type 2 (GS2), the X-linked lymphoproliferative (XLP) and the Chédiak-Higashi (CHS) syndromes are diseases that all may develop hemophagocytic syndromes. We wanted to investigate whether the treatment protocols for hemophagocytic lymphohistiocytosis (HLH) can also...

  3. Thyroid Autoimmunity in Girls with Turner Syndrome.

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    Witkowska-Sędek, Ewelina; Borowiec, Ada; Kucharska, Anna; Chacewicz, Karolina; Rumińska, Małgorzata; Demkow, Urszula; Pyrżak, Beata

    2017-01-01

    Turner syndrome is associated with increased incidence of autoimmune diseases, especially those of the thyroid gland. The aim of this study was to assess the prevalence of thyroid autoimmunity among pediatric patients with Turner syndrome. The study was retrospective and included 41 girls with Turner syndrome aged 6-18 years. Free thyroxine (FT4), thyroid stimulating hormone (TSH), anti-thyroid peroxidase (TPO-Ab) antibodies, anti-thyroglobulin (TG-Ab) antibodies, and karyotype were investigated. The correlation between karyotype and incidence of thyroid autoimmunity was also examined. Eleven patients (26.8%) were positive for TPO-Ab and/or TG-Ab. Three girls from that subgroup were euthyroid, 5 had subclinical hypothyroidism, and 3 were diagnosed with overt hypothyroidism. Out of these 11 patients affected by thyroid autoimmunity, 6 girls had mosaic karyotype with X-isochromosome (n = 4) or with deletions (n = 2), and 5 had the 45,X karyotype. The study findings confirmed a high incidence of thyroid autoimmunity in girls with Turner syndrome, but we failed to observe an association between the incidence of thyroid autoimmunity and karyotype. We conclude that it is important to monitor thyroid function in patients with Turner syndrome because they are prone to develop hypothyroidism.

  4. Autoimmune channelopathies in paraneoplastic neurological syndromes.

    Science.gov (United States)

    Joubert, Bastien; Honnorat, Jérôme

    2015-10-01

    Paraneoplastic neurological syndromes and autoimmune encephalitides are immune neurological disorders occurring or not in association with a cancer. They are thought to be due to an autoimmune reaction against neuronal antigens ectopically expressed by the underlying tumour or by cross-reaction with an unknown infectious agent. In some instances, paraneoplastic neurological syndromes and autoimmune encephalitides are related to an antibody-induced dysfunction of ion channels, a situation that can be labelled as autoimmune channelopathies. Such functional alterations of ion channels are caused by the specific fixation of an autoantibody upon its target, implying that autoimmune channelopathies are usually highly responsive to immuno-modulatory treatments. Over the recent years, numerous autoantibodies corresponding to various neurological syndromes have been discovered and their mechanisms of action partially deciphered. Autoantibodies in neurological autoimmune channelopathies may target either directly ion channels or proteins associated to ion channels and induce channel dysfunction by various mechanisms generally leading to the reduction of synaptic expression of the considered channel. The discovery of those mechanisms of action has provided insights on the regulation of the synaptic expression of the altered channels as well as the putative roles of some of their functional subdomains. Interestingly, patients' autoantibodies themselves can be used as specific tools in order to study the functions of ion channels. This article is part of a Special Issue entitled: Membrane channels and transporters in cancers. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. A new combination of multiple autoimmune syndrome? Coexistence of vitiligo, autoimmune thyroid disease and ulcerative colitis

    Directory of Open Access Journals (Sweden)

    Firdevs Topal

    2011-09-01

    Full Text Available The occurrence of three or more autoimmune disorders in one patient defines multiple autoimmune syndrome. The pathogenesis of multiple autoimmune syndrome is not known yet and environmental triggers and genetic susceptibility have been suggested to be involved. Herein, we report a 47-year-old woman who had Hashimoto’s thyroiditis, vitiligo and newly diagnosed ulcerative colitis. Diagnosis of ulcerative colitis was confirmed with histopathologic examination. This case presents a new combination of multiple autoimmune syndrome.

  6. Oral cyclophosphamide was effective for Coombs-negative autoimmune hemolytic anemia in CD16+CD56- chronic lymphoproliferative disorder of NK-cells.

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    Sekiguchi, Nodoka; Nishina, Sayaka; Kawakami, Toru; Sakai, Hitoshi; Senoo, Noriko; Senoo, Yasushi; Ito, Toshiro; Saito, Hiroshi; Nakazawa, Hideyuki; Koizumi, Tomonobu; Ishida, Fumihiro

    2017-06-01

    An 84-year-old woman was referred to our hospital presenting anemia. Her hemoglobin level was 5.8 g/dL, and white blood cell count was 9400/μL, consisting of 82% lymphocytes. Given the lymphocyte phenotype (CD2+, CD3-, CD16+, and CD56-) and negative whole blood EBV viral load, we made a diagnosis of chronic lymphoproliferative disorder of NK cells (CLPD-NK). We suspected hemolytic anemia because of the high levels of reticulocytes in the peripheral blood and the low haptoglobin value. Although the direct Coombs test was negative and there was no cold agglutination, we examined her red-blood-cell-bound IgG (RBC-IgG), which was elevated. She was diagnosed as having as Coombs-negative autoimmune hemolytic anemia (AIHA). We report the effectiveness of oral cyclophosphamide for Coombs-negative autoimmune hemolytic anemia in CLPD-NK.

  7. Increased prevalence of autoimmunity in Turner syndrome

    DEFF Research Database (Denmark)

    Mortensen, K H; Cleemann, L; Hjerrild, B E

    2009-01-01

    Individuals with Turner syndrome (TS) are prone to develop autoimmune conditions such as coeliac disease (CD), thyroiditis and type 1 diabetes (T1DM). The objective of the present study was to examine TS of various karyotypes for autoantibodies and corresponding diseases. This was investigated...

  8. Is Tourette's syndrome an autoimmune disease?

    NARCIS (Netherlands)

    Hoekstra, P; Limburg, P; Kallenberg, C; Minderaa, R; Battistin, L

    2004-01-01

    Tourette's syndrome is a childhood-onset neuropsychiatric disorder characterized by the presence of both multiple motor and vocal tics. While its pathogenesis at a molecular and cellular level remains unknown, recent research findings point to the possible involvement of autoimmunity in at least a

  9. Autoimmune polyendocrine syndrome type 1 and NALP5, parathyroid autoantigen

    NARCIS (Netherlands)

    Alimohammadi, Mohammad; Bjorklund, Peyman; Hallgren, Asa; Pontynen, Nora; Szinnai, Gabor; Shikama, Noriko; Keller, Marcel P.; Ekwall, Olov; Kinkel, Sarah A.; Husebye, Eystein S.; Gustafsson, Jan; Rorsman, Fredrik; Peltonen, Leena; Betterle, Corrado; Perheentupa, Jaakko; Akerstrom, Goran; Westin, Gunnar; Scott, Hamish S.; Hollaender, Georg A.; Kampe, Olle

    2008-01-01

    Background: Autoimmune polyendocrine syndrome type 1 (APS-1) is a multiorgan autoimmune disorder caused by mutations in AIRE, the autoimmune regulator gene. Though recent studies concerning AIRE deficiency have begun to elucidate the molecular pathogenesis of organ-specific autoimmunity in patients

  10. Primary biliary cirrhosis--autoimmune hepatitis overlap syndrome associated with dermatomyositis, autoimmune thyroiditis and antiphospholipid syndrome.

    Science.gov (United States)

    Pamfil, Cristina; Candrea, Elisabeta; Berki, Emese; Popov, Horațiu I; Radu, Pompilia I; Rednic, Simona

    2015-03-01

    Autoimmune liver diseases may be associated with extrahepatic autoimmune pathology. We report the case of a 52-year old woman who initially presented to the gastroenterology department for extreme fatigue, pale stools, dark urine and pruritus. Laboratory tests showed significant cholestasis and elevation of aminotransferase levels. Immunological tests revealed positive antinuclear (ANA=1:320) and antimitochondrial antibodies (AMA=1:40) with negative anti-smooth muscle and liver kidney microsomal type 1 antibodies. The biopsy was compatible with overlap syndrome type 1. The patient was commenced on immunosuppressive therapy according to standard of care (azathioprine 50mg, ursodeoxycholic acid and prednisone 0.5mg/kg), with moderate biochemical improvement. She subsequently developed proximal symmetrical weakness and cutaneous involvement and was diagnosed with biopsy-proven dermatomyositis. The immunosuppressive regimen was intensified to 150 mg azathioprine. At the three-month follow-up, her symptoms subsided and aminotransferases and muscle enzymes normalized. Upon further investigation the patient was diagnosed with autoimmune thyroiditis and antiphospholipid syndrome. To our knowledge, this is the first case of primary biliary cirrhosis - autoimmune hepatitis overlap syndrome associated with dermatomyositis, autoimmune thyroiditis and antiphospholipid syndrome.

  11. [Coexistence of autoimmune polyglandular syndrome type 3 with diabetes insipidus].

    Science.gov (United States)

    Krysiak, Robert; Okopień, Bogusław

    2015-01-01

    Autoimmune polyglandular syndromes are conditions characterized by the combination of two or more organ-specific disorders. The underestimation oftheir real frequency probable results from physicians' inadequate knowledge of these clinical entities and sometimes their atypical clinical presentation. Because they comprise a wide spectrum of autoimmune disorders, autoimmune polyglandular syndromes are divided into four types, among which type-3 is the most common one. In this article, we report the case of a young female, initially diagnosed with diabetes mellitus who several years later developed full-blown autoimmune polyglandular syndrome type 3 consisting of autoimmune thyroid disorder and latent autoimmune diabetes in adults.The discussed case suggests that in selected patients diabetes insipidus may coexist with autoimmune endocrinopathies and nonendocrine autoimmunopathies, as well as that in some patients idiopathic diabetes insipidus may be secondary to lymphocytic infiltration and destruction of the hypothalamic supraoptic and paraventricular nuclei and/or the supraoptic-hypophyseal tract

  12. The autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy or autoimmune polyglandular syndrome type 1.

    Science.gov (United States)

    Lankisch, Tim O; Jaeckel, Elmar; Strassburg, Christian P

    2009-08-01

    Autoimmune polyglandular syndromes are rare autoimmune endocrinopathies that are associated with nonendocrine autoimmunopathies. Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), also named autoimmune polyglandular syndrome type 1 (APS-1), is distinguished from autoimmune polyglandular syndrome 2 (APS-2). Major disease components of APECED are adrenal insufficiency, hypoparathyroidism, and candidiasis. The diagnosis is established by the presence of two out of the three components. Minor clinical features include autoimmune hepatitis, which occurs in up to 20% of APECED patients, and ranges from a mild to a fulminant course. The disease mostly affects juvenile patients from Sardegna, Italy, Finland, and Iran (Iranian Jews), but it also occurs in other ethnic groups. The AIRE gene responsible for APECED is expressed in cells involved in induction and maintenance of immune tolerance. Genetic alterations of the single gene are associated with APECED. Because a specific therapy is not currently available, treatment consists of hormone replacement and caring for clinical symptoms. Copyright Thieme Medical Publishers.

  13. AIRE variations in Addison's disease and autoimmune polyendocrine syndromes (APS)

    DEFF Research Database (Denmark)

    Bøe Wolff, A S; Oftedal, B; Johansson, S

    2008-01-01

    Autoimmune Addison's disease (AAD) is often associated with other components in autoimmune polyendocrine syndromes (APS). Whereas APS I is caused by mutations in the AIRE gene, the susceptibility genes for AAD and APS II are unclear. In the present study, we investigated whether polymorphisms...

  14. Autoimmune polyglandular syndrome in a 13-year old girl

    DEFF Research Database (Denmark)

    Borgwardt, L.; Pedersen, P.; Peitersen, B.

    2008-01-01

    Autoimmune polyglandular syndrome (APS) is an entity, defined by autoimmunity towards two or more endocrine organs. APS is classified in 3 subgroups (type-1, type-2a, type-2b), according to the organs involved. A case is presented of a 13-year old girl referred to the Department of Paediatrics...

  15. Type 1 diabetes and polyglandular autoimmune syndrome: A review

    Science.gov (United States)

    Hansen, Martin P; Matheis, Nina; Kahaly, George J

    2015-01-01

    Type 1 diabetes (T1D) is an autoimmune disorder caused by inflammatory destruction of the pancreatic tissue. The etiopathogenesis and characteristics of the pathologic process of pancreatic destruction are well described. In addition, the putative susceptibility genes for T1D as a monoglandular disease and the relation to polyglandular autoimmune syndrome (PAS) have also been well explored. The incidence of T1D has steadily increased in most parts of the world, especially in industrialized nations. T1D is frequently associated with autoimmune endocrine and non-endocrine diseases and patients with T1D are at a higher risk for developing several glandular autoimmune diseases. Familial clustering is observed, which suggests that there is a genetic predisposition. Various hypotheses pertaining to viral- and bacterial-induced pancreatic autoimmunity have been proposed, however a definitive delineation of the autoimmune pathomechanism is still lacking. In patients with PAS, pancreatic and endocrine autoantigens either colocalize on one antigen-presenting cell or are expressed on two/various target cells sharing a common amino acid, which facilitates binding to and activation of T cells. The most prevalent PAS phenotype is the adult type 3 variant or PAS type III, which encompasses T1D and autoimmune thyroid disease. This review discusses the findings of recent studies showing noticeable differences in the genetic background and clinical phenotype of T1D either as an isolated autoimmune endocrinopathy or within the scope of polyglandular autoimmune syndrome. PMID:25685279

  16. Polyglandular Autoimmune Syndrome Type III with Primary Hypoparathyroidism

    Directory of Open Access Journals (Sweden)

    Sang Jin Kim

    2013-09-01

    Full Text Available Polyglandular autoimmune syndrome is defined as multiple endocrine gland insufficiencies accompanied by autoimmune diseases of the endocrine and nonendocrine system. After Schmidt introduced a case of nontuberculosis adrenal gland dysfunction with thyroiditis in 1926, Neufeld defined polyglandular autoimmune syndrome by I, II, and III subtypes in 1980 by their presentation of occurrence age, heredity methods, relationship with human leukocyte antigen, and accompanying diseases. We report a case of a 32-year-old female with polyglandular autoimmune syndrome III accompanied by type 1 diabetes mellitus that was treated with insulin (36 units per day for 11 years. She had insulin deficiency and Hashimoto thyroiditis as an autoimmune disorder. In addition, she had several features similar to Albright's hereditary osteodystrophy including short stature, truncal obesity, round face, short neck, low intelligence (full IQ 84, and decreased memory. Although Albright's hereditary osteodystrophy is morphological evidence of pseudohypoparathyroidism or pseudopseudohypoparathyroidism, she had primary hypoparathyroidism on laboratory results. Here, we report a case of polyglandular autoimmune syndrome III with type 1 diabetes mellitus, autoimmune thyroiditis, and primary hypoparathyroidism, accompanied by clinical features similar to Albright's hereditary osteodystrophy.

  17. A rare combination of type 3 autoimmune polyendocrine syndrome (APS-3) or multiple autoimmune syndrome (MAS-3).

    Science.gov (United States)

    Betterle, Corrado; Garelli, Silvia; Coco, Graziella; Burra, Patrizia

    2014-06-01

    Type 3 autoimmune polyendocrine syndrome (APS-3) is defined by the presence of an autoimmune thyroid disease and another autoimmune illness, excluding Addison's disease; this is a frequent combination. We report the case of a 55 years old female patient with APS-3, with seven clinical or latent autoimmune manifestations. At 49 years of age she was admitted at the General Hospital for leukopenia, weight loss, tremors, anxiety and diarrhea. The personal history revealed ulcerative colitis and, during the last year, episodes of fever with migrant arthralgia and cutaneous lesions. The patient was evaluated for thyroid function and imaging, mielobiopsy, glycaemic control, gastrointestinal and rheumatologic disorders with specific biochemical tests, imaging and endoscopic procedures. We concluded that the patient was affected by APS-3, characterized by the association of Graves' disease, autoimmune leukopenia, latent autoimmune diabetes of the adult (LADA), autoimmune gastritis, ulcerative colitis, Sjögren's and anti-phospholipid syndromes. The patient started low doses of corticosteroid drugs for leukopenia, underwent (131)I therapy for hyperthyroidism and later started substitutive thyroid therapy with l-thyroxine, insulin therapy for LADA, mesalazine for ulcerative colitis and artificial tears for Sjögren's syndrome. In this article we report a complex case of APS-3, characterized by the association of seven different autoimmune diseases, which required a complex therapeutic strategy.

  18. HELLP syndrome: a complication or a new autoimmune syndrome?

    Directory of Open Access Journals (Sweden)

    Paola Triggianese

    2014-11-01

    Full Text Available The HELLP (hemolysis, elevated liver enzymes, low platelets syndrome is a pregnancy-specific disease characterized by hemolysis with elevated lactate dehydrogenase, elevated liver enzymes, and decreased platelet count. It is considered a severe variant of the hypertensive disorders that occur during pregnancy together with the pre-eclampsia (PE and the eclampsia giving symptoms in the mother from 20 weeks’ gestation onward. All these conditions are multi-system pregnancy-related diseases associated with an increase in blood pressure and in both the perinatal and the maternal morbidity/mortality. Observational studies suggest that steroid treatment in HELLP syndrome may improve the hematological and biochemical features in the mother and the perinatal outcome. The present review aims to show that the HELLP syndrome may be considered as an autoimmune disorder itself. Biomarkers of the immune system can be a useful tool improving the diagnostic and therapeutic management of women with HELLP by delineating the underlying etiology of this syndrome.

  19. DRESS syndrome with autoimmune hepatitis from strontium ranelate.

    Science.gov (United States)

    di Meo, Nicola; Gubertini, Nicoletta; Crocè, Lory; Tiribelli, Claudio; Trevisan, Giusto

    2016-05-01

    Strontium ranelate, which is used for postmenopausal osteoporosis, has been associated with drug rash with eosinophilia and systemic symptoms (DRESS) syndrome, a severe, acute, potentially fatal, multisystem adverse drug reaction characterized by skin rash, fever, hematological abnormalities, and lymphadenopathy with involvement of several internal organs. We report the case of a woman who developed DRESS syndrome with a generalized maculopapular rash, eosinophilia, dyspnea, bilateral cervical lymphadenopathy, and reactivation of Epstein-Barr virus (EBV) with liver damage 3 weeks after administration of strontium ranelate for postmenopausal osteoporosis. Approximately 6 months after total remission of cutaneous symptoms, the patient developed autoimmune hepatitis. This case confirms that strontium ranelate should be considered as a possible factor in the etiopathology of DRESS syndrome as well as in the subsequent development of autoimmune hepatitis. The possibility of developing autoimmune hepatitis as a part of DRESS syndrome related to strontium ranelate use can occur months after the acute episode.

  20. Autoimmune Basis for Postural Tachycardia Syndrome

    Science.gov (United States)

    2018-01-23

    Postural Orthostatic Tachycardia Syndrome; Postural Tachycardia Syndrome; Tachycardia; Arrhythmias, Cardiac; Autonomic Nervous System Diseases; Orthostatic Intolerance; Cardiovascular Diseases; Primary Dysautonomias

  1. Splenectomy in two children with autoimmune lymphoproliferative syndrome and massive splenomegaly

    DEFF Research Database (Denmark)

    Glerup, Mia; Thelle, Thomas; Grønbaek, Kirsten

    2009-01-01

    Treatment of patients with ALPS has varied but presently there is no consensus about the optimal therapy. Splenectomy is an option but data regarding the postsplenectomy outcome in pediatric ALPS patients remain very limited. We present two children who suffered from anemia and physical discomfort...... from the large spleen. Both patients underwent uneventful splenectomy and experienced significant improvement in cytopenia, daily activity and well-being. Furthermore the youngest patient showed a significant catch-up growth. We conclude that in selected patients with marked splenomegaly and ALPS......, splenectomy may be considered a treatment option....

  2. [Oral diseases in auto-immune polyendocrine syndrome type 1].

    Science.gov (United States)

    Proust-Lemoine, Emmanuelle; Guyot, Sylvie

    2017-09-01

    Auto-immune polyendocrine syndrome type 1 (APS1) also called Auto-immune Polyendocrinopathy Candidiasis Ectodermal Dystrophy (APECED) is a rare monogenic childhood-onset auto-immune disease. This autosomal recessive disorder is caused by mutations in the auto-immune regulator (AIRE) gene, and leads to autoimmunity targeting peripheral tissues. There is a wide variability in clinical phenotypes in patients with APSI, with auto-immune endocrine and non-endocrine disorders, and chronic mucocutaneous candidiasis. These patients suffer from oral diseases such as dental enamel hypoplasia and candidiasis. Both are frequently described, and in recent series, enamel hypoplasia and candidiasis are even the most frequent components of APS1 together with hypoparathyroidism. Both often occur during childhood (before 5 years old for canrdidiasis, and before 15 years old for enamel hypoplasia). Oral candidiasis is recurrent all life long, could become resistant to azole antifungal after years of treatment, and be carcinogenic, leading to severe oral squamous cell carcinoma. Oral components of APS1 should be diagnosed and rigorously treated. Dental enamel hypoplasia and/or recurrent oral candidiasis in association with auto-immune diseases in a young child should prompt APS1 diagnosis. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  3. Autoimmune Polyglandular Syndrome Type 2: An Unusual Presentation

    Directory of Open Access Journals (Sweden)

    Hamdollah Karamifar

    2010-05-01

    Full Text Available "nAutoimmune polyglandular syndrome (APS type 2 is characterized by the presence of Addison's disease, in association with autoimmune thyroid disease and/or type 1 diabetes mellitus. APS type 2 occurs most often in middle aged females and is rare in children. Here an 11 year old boy is reported with Addison's disease who developed symptom's of diabetes mellitus, goiter, malabsorption, macrocytic anemia and keratitis. APS type 2 occurs most often in middle aged females and is quite rare in children but one should think to autoimmune poly glandular syndrome type II in patient at any age especially in patients with Addison's disease.

  4. Is Tourette's syndrome an autoimmune disease?

    NARCIS (Netherlands)

    Hoekstra, PJ; Kallenberg, CGM; Korf, J; Minderaa, RB

    2002-01-01

    We provide a review of recent research findings which support the involvement of autoimmunity in childhood-onset tic disorders, in particular the presence of antineuronal autoantibodies, D8/17 B lymphocyte overexpression, a marker of chorea associated with streptococcal infection, and possible

  5. Overlapping humoral autoimmunity links rheumatic fever and the antiphospholipid syndrome

    DEFF Research Database (Denmark)

    Blank, M; Krause, I; Magrini, L

    2006-01-01

    Rheumatic fever (RF) and the antiphospholipid syndrome (APS) are autoimmune diseases that share similar cardiac and neurological pathologies. We assessed the presence of shared epitopes between M protein, N-acetyl-beta-D-glucosamine (GlcNAc) and beta2 glycoprotein-I (beta2GPI), the pathogenic...

  6. [Apeced syndrome or autoimmune polyendocrine syndrome Type 1].

    Science.gov (United States)

    Proust-Lemoine, Emmanuelle; Wémeau, Jean-Louis

    2008-01-01

    Apeced syndrome is a rare disease, with autosomal recessive transmission and associated with mutations of the AIRE gene, which is involved in central and peripheral immune tolerance mechanisms. Its diagnosis is classically based on the combination of any two of the following three major criteria: chronic mucocutaneous candidiasis, hypoparathyroidism and autoimmune chronic adrenocortical insufficiency (Addison disease). One single criterion is sufficient to diagnosis a sibling of a patient already diagnosed. Because of its great phenotypic variability, some atypical or oligosymptomatic forms may not be recognized. In the presence of one of the three major criteria, it is thus important to look for other clinical manifestations--digestive, cutaneous (including keratinized appendages) and ophthalmological (until then considered minor). In these atypical forms, the diagnosis depends on molecular genetics. Prognosis is influenced by different factors that may be genetic (AIRE mutations, HLA), hormonal (sex) or environmental (infections). Potentially fatal disease (hepatitis or severe malabsorption) requires immunosuppressant therapy. Before beginning this aggressive treatment, underlying infectious foci, especially of candidiasis, must be sought and treated to prevent the development of extremely serious systemic infections in this context. A workup for splenic atrophy is also recommended.

  7. Paraneoplastic autoimmune multiorgan syndrome (paraneoplastic pemphigus) with unusual manifestations and without detectable autoantibodies

    OpenAIRE

    Jimena Sanz-Bueno; Daniella Cullen; Carlos Zarco; Francisco Vanaclocha

    2014-01-01

    We describe a patient with paraneoplastic autoimmune multiorgan syndrome (PAMS) secondary to a lymphoblastic T- cell lymphoma who presented with a lichenoid dermatitis and vitiligo, later developing bronchiolitis obliterans and autoimmune hepatitis. Notably, he had no detectable autoantibodies. The development of vitiligo and autoimmune hepatic involvement probably indicate a role for cytotoxic T- cell lymphocytes in the pathogenesis of this syndrome.

  8. Paraneoplastic autoimmune multiorgan syndrome (paraneoplastic pemphigus with unusual manifestations and without detectable autoantibodies

    Directory of Open Access Journals (Sweden)

    Jimena Sanz-Bueno

    2014-01-01

    Full Text Available We describe a patient with paraneoplastic autoimmune multiorgan syndrome (PAMS secondary to a lymphoblastic T- cell lymphoma who presented with a lichenoid dermatitis and vitiligo, later developing bronchiolitis obliterans and autoimmune hepatitis. Notably, he had no detectable autoantibodies. The development of vitiligo and autoimmune hepatic involvement probably indicate a role for cytotoxic T- cell lymphocytes in the pathogenesis of this syndrome.

  9. Autoimmune polyglandular syndrome type 1 in a 12-year-old ...

    African Journals Online (AJOL)

    2011-12-20

    Dec 20, 2011 ... Case Study: Autoimmune polyglandular syndrome type 1 in a 12-year-old Ugandan girl. 65. 2013 Volume 18 ... Autoimmune polyglandular syndrome type 1 (APS-1), also known as autoimmune polyendocrinopathy-candidiasis- ectodermal dystrophy ... Serum phosphorus, magnesium and vitamin D levels ...

  10. Autoimmune Progesterone Dermatitis Presenting as Stevens-Johnson Syndrome.

    Science.gov (United States)

    Drayer, Sara M; Laufer, Larry R; Farrell, Maureen E

    2017-10-01

    Autoimmune progesterone dermatitis is an uncommon disease presenting with cyclical skin eruptions corresponding with the menstrual cycle luteal phase. Because symptoms are precipitated by rising progesterone levels, treatment relies on hormone suppression. A 22-year-old nulligravid woman presented with symptoms mistaken for Stevens-Johnson syndrome. A cyclic recurrence of her symptoms was noted, and the diagnosis of autoimmune progesterone dermatitis was made by an intradermal progesterone challenge. After 48 months, she remained refractory to medical management and definitive surgical treatment with bilateral oophorectomy was performed. Autoimmune progesterone dermatitis is a challenging diagnosis owing to its rarity and variety of clinical presentations. Treatment centers on suppression of endogenous progesterone and avoidance of exogenous triggers. When these modalities fail, surgical management must be undertaken.

  11. Autoimmune/inflammatory syndrome induced by adjuvants (Shoenfeld's syndrome) - An update.

    Science.gov (United States)

    Watad, A; Quaresma, M; Brown, S; Cohen Tervaert, J W; Rodríguez-Pint, I; Cervera, R; Perricone, C; Shoenfeld, Y

    2017-06-01

    Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) has been widely described in many studies conducted thus far. The syndrome incorporates five immune-mediated conditions, all associated with previous exposure to various agents such as vaccines, silicone implants and several others. The emergence of ASIA syndrome is associated with individual genetic predisposition, for instance those carrying HLA-DRB1*01 or HLA-DRB4 and results from exposure to external or endogenous factors triggering autoimmunity. Such factors have been demonstrated as able to induce autoimmunity in both animal models and humans via a variety of proposed mechanisms. In recent years, physicians have become more aware of the existence of ASIA syndrome and the relationship between adjuvants exposure and autoimmunity and more cases are being reported. Accordingly, we have created a registry that includes at present more than 300 ASIA syndrome cases that have been reported by different physicians worldwide, describing various autoimmune conditions induced by diverse adjuvants. In this review, we have summarized the updated literature on ASIA syndrome and the knowledge accumulated since 2013 in order to elucidate the association between the exposure to various adjuvant agents and its possible clinical manifestations. Furthermore, we especially referred to the relationship between ASIA syndrome and systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS).

  12. Autoimmunity in Wiskott-Aldrich Syndrome: an unsolved enigma

    Directory of Open Access Journals (Sweden)

    Marco eCatucci

    2012-07-01

    Full Text Available Wiskott-Aldrich Syndrome (WAS is a severe X-linked Primary Immunodeficiency (PID that affects 1 to 10 out of 1 million male individuals. WAS is caused by mutations in the WAS Protein (WASP expressing gene that leads to the absent or reduced expression of the protein. WASP is a cytoplasmic protein that regulates the formation of actin filaments in hematopoietic cells. WASP deficiency causes many immune cell defects both in humans and in the WAS murine model, the Was-/- mouse. Both cellular and humoral immune defects in WAS patients contribute to the onset of severe clinical manifestations, in particular microthrombocytopenia, eczema, recurrent infections and a high susceptibility to develop autoimmunity and malignancies. Autoimmune diseases affect from 22% to 72% of WAS patients and the most common manifestation is autoimmune hemolytic anemia, followed by vasculitis, arthritis, neutropenia, inflammatory bowel disease and IgA nephropathy. Many groups have widely explored immune cell functionality in WAS partially explaining how cellular defects may lead to pathology. However, the mechanisms underlying the occurrence of autoimmune manifestations have not been clearly described yet. In the present review, we report the most recent progresses in the study of immune cell function in WAS that have started to unveil the mechanisms contributing to autoimmune complications in WAS patients.

  13. Autoimmune neurological syndromes associated limbic encephalitis and paraneoplastic cerebellar degeneration.

    Science.gov (United States)

    Ayas, Zeynep Özözen; Kotan, Dilcan; Aras, Yeşim Güzey

    2016-10-06

    Autoimmune neurological syndrome is a group of disorders caused by cancer affecting nervous system by different immunological mechanisms. In this study, we aim to study the clinical symptoms, cerebrospinal fluid (CSF) findings, autoantibody tests, computed tomography (CT), magnetic resonance imaging (MRI) signs and treatment outcome of patients with autoimmune syndromes. In this study, 7 patients (4 male, 3 female) diagnosed with autoimmune neurological syndrome were retrospectively examined. Five of patients were diagnosed with limbic encephalitis, two of them were paraneoplastic cerebellar degeneration. Confusion and seizure were the most seen symptoms. Two patients had psychiatric disturbances (28,5%) followed by seizure. Headache was seen in 2 patients (% 28,5), disartria in 1 patient (% 14,2), and gait disorder in 2 patients (28,5%). The duration of symptoms was 46 (3-150) days on average. CSF abnormalities were detected in 2 patients. CT and MRI of the brain was available in all patients. Five patients had involvement of mesiotemporal region, two patients had diffuse cerebellar atrophy. One of patients had anti-GABAR B1 positivity. Tumors were detected in 2 patients while investigation for paraneoplasia screening. Remission is only possible with the detection and treatment of the malignancy. Early diagnosis and treatment are of paramount importance. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  14. Primary Biliary Cirrhosis and Type II Autoimmune Polyglandular Syndrome

    Directory of Open Access Journals (Sweden)

    Mark Ram Borgaonkar

    1999-01-01

    Full Text Available A 45-year-old female was diagnosed with Hashimoto’s thyroiditis in 1976 and Addison’s disease in 1979. At that time, her antimitochondrial antibody (AMA level was elevated at 1:32. She subsequently developed premature ovarian failure and type I diabetes mellitus. In 1996, she became jaundiced with a cholestatic enzyme pattern. AMA was positive at a titre of 1:256. A liver biopsy confirmed the diagnosis of primary biliary cirrhosis (PBC. She underwent a liver transplantation in January 1998. This is the first report of PBC in association with type II autoimmune polyglandular syndrome. The association of PBC with other organ-specific autoimmune diseases supports an immune-mediated pathogenesis and may have implications in further studies of PBC.

  15. Oral microbiota in autoimmune polyendocrine syndrome type 1

    Science.gov (United States)

    Bruserud, Øyvind; Siddiqui, Huma; Marthinussen, Mihaela Cuida; Chen, Tsute; Jonsson, Roland; Oftedal, Bergithe Eikeland; Olsen, Ingar; Husebye, Eystein Sverre; Wolff, Anette Bøe

    2018-01-01

    ABSTRACT Background: Autoimmune polyendocrine syndrome type-1 (APS-1) is a rare, childhood onset disease caused by mutations in the Autoimmune Regulator gene. The phenotypic expression is highly variable and includes disease manifestations in the oral cavity, including mucocutaneous candidiasis. Increasing evidence suggests a potential role of the skin, oral and gut microbiotas in the pathogenesis of autoimmunity. To date, no information exists regarding the oral microbiota in APS-1. Objective: To assess the bacterial microbiota of whole saliva in APS-1 patients by using high throughput sequencing. Design: Whole unstimulated saliva was collected from 10 APS-1 patients and 17 healthy controls and examined by high throughput sequencing of the hypervariable region V1-V2 of 16S rRNA using the 454 GS Junior system. Metastats (http://cbcb.umd.edu/software/metastats) was used to analyse the pyrosequencing reads. Results: A reduction in the total number of bacterial genera and species was detected in APS-1 compared to healthy controls. The proportion of the major phyla Firmicutes was higher (60% vs 41%, p = 0.002) and Bacteroidetes lower (15% vs 28%, p = 0.007) in APS-1 compared to healthy controls. On the genus level, Streptococcus and Gemella were prevalent in APS-1. Conclusion: Our findings indicate a significantly altered oral microbiota in APS-1. PMID:29503707

  16. Autoimmune polyglandular syndrome type 1 in a 12-year-old ...

    African Journals Online (AJOL)

    Autoimmune polyglandular syndrome type 1 (APS-1), also known as autoimmune polyendocrinopathy-candidiasisectodermal dystrophy syndrome, is a very rare disorder of childhood. It is mainly characterised by the presence of at least two of the following: chronic mucocutaneous candidiasis, chronic hypoparathyroidism ...

  17. Lack of evidence for post-vaccine onset of autoimmune/lymphoproliferative disorders, during a nine-month follow-up in multiply vaccinated Italian military personnel.

    Science.gov (United States)

    Ferlito, Claudia; Barnaba, Vincenzo; Abrignani, Sergio; Bombaci, Mauro; Sette, Alessandro; Sidney, John; Biselli, Roberto; Tomao, Enrico; Cattaruzza, Maria Sofia; Germano, Valentina; Biondo, Michela Ileen; Salerno, Gerardo; Lulli, Patrizia; Caporuscio, Sara; Picchianti Diamanti, Andrea; Falco, Mirella; Biselli, Valentina; Cardelli, Patrizia; Autore, Alberto; Lucertini, Elena; De Cesare, Donato Pompeo; Peragallo, Mario Stefano; Lista, Florigio; Martire, Carmela; Salemi, Simonetta; Nisini, Roberto; D'Amelio, Raffaele

    2017-08-01

    Anecdotal case reports, amplified by mass media and internet-based opinion groups, have recently indicated vaccinations as possibly responsible for autoimmunity/lymphoproliferation development. Multiply vaccinated Italian military personnel (group 1, operating in Italy, group 2, operating in Lebanon) were followed-up for nine months to monitor possible post-vaccine autoimmunity/lymphoproliferation onset. No serious adverse event was noticed in both groups. Multivariate analysis of intergroup differences only showed a significant association between lymphocyte increase and tetanus/diphtheria vaccine administration. A significant post-vaccine decrease in autoantibody positivity was observed. Autoantibodies were also studied by microarray analysis of self-proteins in subjects exposed to ≥4 concurrent vaccinations, without observing significant difference among baseline and one and nine months post-vaccine. Moreover, HLA-A2 subjects have been analyzed for the possible CD8T-cell response to apoptotic self-epitopes, without observing significant difference between baseline and one month post-vaccine. Multiple vaccinations in young adults are safe and not associated to autoimmunity/lymphoproliferation onset during a nine-month-long follow-up. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Polyglandular autoimmune syndrome type I – a novel AIRE mutation in a North American patient

    Science.gov (United States)

    Huibregtse, Kelly Egan; Wolfgram, Peter; Winer, Karen K.; Connor, Ellen L.

    2015-01-01

    Autoimmune polyglandular syndrome type 1 (APS-1), also referred to as autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), is a rare autoimmune disease that results from autosomal recessive mutations of the human autoimmune regulatory (AIRE) gene. We present the case of a 17-year-old North American girl of primarily Norwegian descent with a novel AIRE gene mutation causing APS-1. In addition to the classic triad of chronic candidiasis, hypoparathyoidism and autoimmune adrenocortical insufficiency, she also has vitiligo, intestinal malabsorption, autoimmune hepatitis, autoimmune hypothyroidism, myositis, myalgias, chronic fatigue, and failure to thrive. Genetic testing revealed heterozygosity for c.20_115de196 and c.967_979del13 mutations in the AIRE gene. The AIRE gene c.20_115de196 mutation has not been previously reported. PMID:24945421

  19. Polyglandular autoimmune syndrome type I - a novel AIRE mutation in a North American patient.

    Science.gov (United States)

    Huibregtse, Kelly Egan; Wolfgram, Peter; Winer, Karen K; Connor, Ellen L

    2014-11-01

    Autoimmune polyglandular syndrome type 1 (APS-1), also referred to as autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), is a rare autoimmune disease that results from autosomal recessive mutations of the human autoimmune regulatory (AIRE) gene. We present the case of a 17-year-old North American girl of primarily Norwegian descent with a novel AIRE gene mutation causing APS-1. In addition to the classic triad of chronic candidiasis, hypoparathyoidism and autoimmune adrenocortical insufficiency, she also has vitiligo, intestinal malabsorption, autoimmune hepatitis, autoimmune hypothyroidism, myositis, myalgias, chronic fatigue, and failure to thrive. Genetic testing revealed heterozygosity for c.20_115de196 and c.967_979del13 mutations in the AIRE gene. The AIRE gene c.20_115de196 mutation has not been previously reported.

  20. Diagnosis, progression and intervention in Sjogren's syndrome

    NARCIS (Netherlands)

    Pijpe, Justin

    2006-01-01

    Sjögren’s syndrome (SS) is a chronic inflammatory and lymphoproliferative progressive autoimmune disease. It is characterized by B cell activation and infiltration of T and B cells in the exocrine glands. Common symptoms are related to diminished lacrimal and salivary gland function. Besides

  1. Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy: known and novel aspects of the syndrome.

    Science.gov (United States)

    Kisand, Kai; Peterson, Pärt

    2011-12-01

    Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) is a monogenic autosomal recessive disease caused by mutations in the autoimmune regulator (AIRE) gene and, as a syndrome, is characterized by chronic mucocutaneous candidiasis and the presentation of various autoimmune diseases. During the last decade, research on APECED and AIRE has provided immunologists with several invaluable lessons regarding tolerance and autoimmunity. This review describes the clinical and immunological features of APECED and discusses emerging alternative models to explain the pathogenesis of the disease. © 2011 New York Academy of Sciences.

  2. Autoimmune polyendocrine syndrome type 1: case report and review of literature.

    Science.gov (United States)

    Weiler, Fernanda Guimarães; Dias-da-Silva, Magnus R; Lazaretti-Castro, Marise

    2012-02-01

    Autoimmune polyendocrine syndrome type 1 (APECED) is a rare autosomal recessive disorder characterized by autoimmune multiorgan attack. The disease is caused by mutations in the autoimmune regulator gene (AIRE), resulting in defective AIRE protein, which is essential for selftolerance. Clinical manifestations are widely variable. Although the classic triad is composed by mucocutaneous candidiasis, hypoparathyroidism and adrenal failure, many other components may develop. Treatment is based on supplementation of the various deficiencies, and patients require regular follow-up throughout their lifespan. This article describes the case of a patient with the disease, and reviews literature data on the epidemiology, clinical course, immunogenetic aspects, diagnosis and treatment of the syndrome.

  3. Evidence Refuting the Existence of Autoimmune/Autoinflammatory Syndrome Induced by Adjuvants (ASIA)

    DEFF Research Database (Denmark)

    Ameratunga, Rohan; Gillis, David; Gold, Michael

    2017-01-01

    Autoimmune/autoinflammatory syndrome induced by adjuvants (ASIA) was described in 2011. Over time the condition and its triggers have broadened to include several autoimmune disorders, the macrophagic myofasciitis syndrome, the Gulf war syndrome, the sick building syndrome, siliconosis......, and the chronic fatigue syndrome. The aluminum-containing adjuvants in the hepatitis B vaccine and the human papillomavirus vaccine in particular have been stated to be the major causes of the disorder. Here, we review the specificity of the diagnostic criteria for ASIA. We also examine relevant human data...... pharmacoepidemiological study, in contrast to case series of ASIA, patients receiving aluminum-containing allergen IT preparations were shown to have a lower incidence of autoimmune disease. In another clinical trial, there were no increases in exacerbations in a cohort of patients with systemic lupus erythematosus...

  4. Kounis Syndrome Caused by Chronic Autoimmune Urticaria: A Case Report.

    Science.gov (United States)

    Erxun, Kang; Wei, Liu; Shuying, Qi

    2016-01-01

    Coincidental occurrence of acute coronary syndrome with symptoms associated with an allergic reaction is called Kounis syndrome (KS). Although KS has been recognized for several years and has been reported in many documents, KS induced by chronic autoimmune urticaria (CAU), to the authors' knowledge, has not been reported. The patient was a 31-year-old woman who suffered from chronic urticaria for nearly 3 years. Her urticaria became more serious 1 week before this visit and was accompanied by repeated attacks of cardiac symptoms. Autologous serum skin test and serum anti-high affinity immunoglobulin E receptor antibody test were positive for CAU. Her coronary artery pathological changes were confirmed by electrocardiogram (ECG), cardiac troponin T (cTnT) value, and angiocardiography. The patient was diagnosed with KS. After being treated with cetirizine, glucocorticoids, and azathioprine, the patient did not relapse during the first year of follow-up. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: When seeing a patient with intermittent exacerbations of chronic urticaria accompanied by repeated attacks of cardiac symptoms, emergency physicians should consider the diagnosis of KS. It is important to monitor changes in the ECG and cTnT value. Angiocardiography is necessary to eliminate myocardial infarction or unstable angina. Second-generation antihistamines and glucocorticoids are effective in the treatment of CAU and also alleviate coronary spasm. Another important consideration for the emergency physician is the fact that some first-generation antihistamines have the side effect of ventricular tachycardia or fibrillation, so it is better not to use these drugs to treat urticaria if KS is suspected. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. An uncommon cause of hypoglycemia: insulin autoimmune syndrome.

    Science.gov (United States)

    Savas-Erdeve, Senay; Yılmaz Agladioglu, Sebahat; Onder, Asan; Peltek Kendirci, Havva Nur; Bas, Veysel Nijat; Sagsak, Elif; Cetinkaya, Semra; Aycan, Zehra

    2014-01-01

    Insulin autoimmune syndrome (IAS) is a condition characterized by hypoglycemia associated with the presence of autoantibodies to insulin in patients who have not been injected with insulin. A female patient (aged 16 years and 3 months) presented with the complaint of being overweight. Physical examination revealed a body weight of 78.2 kg (+2.6 SD) and a height of 167 cm (+0.73 SD). While the patient's fasting blood glucose level was found to be 40 mg/dl, blood ketone was negative and the serum insulin level was determined as 379 mIU/ml. The patient was diagnosed with hyperinsulinemic hypoglycemia. Abdominal ultrasound, pancreas MRI and endoscopic ultrasound were normal. The daily blood glucose profile revealed postprandial hyperglycemia and reactive hypoglycemia in addition to fasting hypoglycemia. The results of anti-insulin antibody measurements were as high as 41.8% (normal range 0-7%). A 1,600-calorie diet containing 40% carbohydrate and divided into 6 meals a day was given to the patient. Simple sugars were excluded from the diet. Hypoglycemic episodes were not observed, but during 2 years of observation, serum levels of insulin and anti-insulin antibodies remained elevated. In all hyperinsulinemic hypoglycemia cases, IAS should be considered in the differential diagnosis and insulin antibody measurements should be carried out. © 2014 S. Karger AG, Basel.

  6. Topical tacrolimus solution in autoimmune polyglandular syndrome-1-associated keratitis.

    Science.gov (United States)

    Shoughy, Samir S; Tabbara, Khalid F

    2017-09-01

    To evaluate the efficacy of topical tacrloimus eye drops in the treatment of keratitis associated with autoimmune polyglandular syndrome (APS)-1. This is a retrospective review of 10 patients with APS-1. The patients were treated with topical tacrolimus 0.01% solution at The Eye Center, between 1 March 2012 and 30 April 2016. The outcome measures included improvement in visual acuity, photophobia and keratitis following treatment. Clinical assessment was carried out before, during and on the last visit following initiation of therapy. A total of 10 patients were included. There were five male and five female patients. The mean age was 11 years with age range of 3-42 years. The mean duration of treatment with topical tacrolimus was 26 months (range 8-46 months). There was improvement of photophobia in 7 out of 10 patients following therapy with topical tacrolimus. In three patients, the photophobia was persistent. There was no clinically detectable improvement in the severity of keratitis in all patients. The mean best corrected visual acuity was 0.1 before and following therapy. Topical tacrolimus is effective in reducing the photophobia in patients with APS-1-associated keratitis, but showed no effects on the severity of keratitis. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  7. Myelodysplastic Syndromes (MDS) and autoimmune disorders (AD): cause or consequence?

    Science.gov (United States)

    Braun, Thorsten; Fenaux, Pierre

    2013-12-01

    Myelodysplastic Syndromes (MDS) and Chronic Myelomonocytic Leukemia (CMML) are frequently associated with clinical manifestations of autoimmune disorders (AD) and inflammatory response of the immune system. AD accompanying MDS and CMML include vasculitis, seronegative polyarthritis and neutrophilic dermatosis. Rare AD including relapsing polychondritis is strongly associated with MDS as in a high proportion of those patients MDS is diagnosed during disease course. Antinuclear antibodies (ANA) are frequently found among MDS patients without clinical manifestation of AD. In a subset of patients, MDS and resulting cytopenias appear to be the consequence of auto reactive immunologic activity and may respond to immunosuppressive treatment (IST). Increased release of inflammatory cytokines like tumor necrosis factor-(TNF)-α and interferon (IF)-γ triggers apoptosis of myeloid precursor cells leading to cytopenias. Impaired function of immune cells including cytotoxic, regulatory (Treg), helper (Th17) T cells and NK cells also appears to predict response to IST, outcome and occurrence of AD. Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. Lymphadenopathy driven by TCR-Vγ8Vδ1 T-cell expansion in FAS-related autoimmune lymphoproliferative syndrome

    NARCIS (Netherlands)

    Vavassori, Stefano; Galson, Jacob D; Trück, Johannes; van den Berg, Anke; Tamminga, Rienk Y J; Magerus-Chatinet, Aude; Pellé, Olivier; Camenisch Gross, Ulrike; Marques Maggio, Ewerton; Prader, Seraina; Opitz, Lennart; Nüesch, Ursina; Mauracher, Andrea; Volkmer, Benjamin; Speer, Oliver; Suda, Luzia; Röthlisberger, Benno; Zimmermann, Dieter Robert; Müller, Rouven; Diepstra, Arjan; Visser, Lydia; Haralambieva, Eugenia; Neven, Bénédicte; Rieux-Laucat, Frédéric; Pachlopnik Schmid, Jana

    2017-01-01

    FAS-dependent apoptosis in Vδ1 T cells makes the latter possible culprits for the lymphadenopathy observed in patients with FAS mutations.Rapamycin and methylprednisolone resistance should prompt clinicians to look for Vδ1 T cell proliferation in ALPS-FAS patients.

  9. [Auto-immune disorders as a possible cause of neuropsychiatric syndromes].

    Science.gov (United States)

    Martinez-Martinez, P; Molenaar, P C; Losen, M; Hoffmann, C; Stevens, J; de Witte, L D; van Amelsvoort, T; van Os, J; Rutten, B P F

    2015-01-01

    Changes that occur in the behaviour of voltage-gated ion channels and ligand-gated receptor channels due to gene mutations or auto-immune attack are the cause of channelopathies in the central and peripheral nervous system. Although the relation between molecular channel defects and clinical symptoms has been explained in the case of many neuromuscular channelopathies, the pathophysiology of auto-immunity in neuropsychiatric syndromes is still unclear. To review recent findings regarding neuronal auto-immune reactions in severe neuropsychiatric syndromes. Using PubMed, we consulted the literature published between 1990 and August 2014 relating to the occurrence of auto-immune antibodies in severe and persistent neuropsychiatric syndromes. Auto-antibodies have only limited access to the central nervous system, but if they do enter the system they can, in some cases, cause disease. We discuss recent findings regarding the occurrence of auto-antibodies against ligand-activated receptor channels and potassium channels in neuropsychiatric and neurological syndromes, including schizophrenia and limbic encephalitis. Although the occurrence of several auto-antibodies in schizophrenia has been confirmed, there is still no proof of a causal relationship in the syndrome. We still have no evidence of the prevalence of auto-immunity in neuropsychiatric syndromes. The discovery that an antibody against an ion channel is associated with some neuropsychiatric disorders may mean that in future it will be possible to treat patients by means of immunosuppression, which could lead to an improvement in a patient's cognitive abilities.

  10. Associations between Klinefelter's syndrome and autoimmune diseases: English national record linkage studies.

    Science.gov (United States)

    Seminog, Olena O; Seminog, Alla B; Yeates, David; Goldacre, Michael J

    2015-03-01

    There are reports suggesting that people with Klinefelter's syndrome (KS) may be at increased risk of some autoimmune diseases, but the evidence is not substantial. We wanted to add to the evidence by systematically assessing the risk of autoimmune diseases in a national cohort of people with KS. We selected records of all people with KS in a record-linked dataset of all hospital day cases and inpatient admissions in England, 1999-2011; and we followed them up by electronic record linkage to identify the occurrence of autoimmune diseases. We compared their occurrence in the KS cohort with a control cohort, studied in the same way, and expressed the results as rate ratios (RR). Of 30 autoimmune diseases studied in people with KS, there were significantly increased risks of seven-Addison's disease (RR 11.7, 95% confidence interval 2.4-34.4), diabetes mellitus type 1 (6.1, 4.4-8.3), multiple sclerosis (4.3, 1.2-11.0), acquired hypothyroidism (2.7, 1.8-4.0), rheumatoid arthritis (3.3, 2.0-5.2), Sjogren's syndrome (19.3, 4.0-57.0) and systemic lupus erythematosus (18.1, 2.2-65.6). We concluded that people with KS have increased risk of some autoimmune diseases, particularly those that are female-predominant. The increased risk of autoimmune diseases associated with the XXY karyotype may hold clues to the pathogenesis of some aspects of autoimmunity.

  11. Challenges in Management of Primary Hypoparathyroidism Associated with Autoimmune Polyglandular Syndrome Type 1

    Directory of Open Access Journals (Sweden)

    I. R. Wallace

    2011-01-01

    Full Text Available We report a case of autoimmune polyglandular syndrome type 1 (APS1 complicated by severe vascular insufficiency due to diffuse vascular calcification. APS1 is characterised clinically by multiple autoimmune conditions and development of at least two components of the triad of mucocutaneous candidiasis, hypoparathyroidism, and autoimmune adrenal insufficiency. We highlight the problems in current serum calcium monitoring methods and suggest that fluctuations in serum calcium concentrations due to difficulties treating hypoparathyroidism may have contributed to the vascular calcification seen in this case.

  12. Diagnosis and Management of the Overlap Syndromes of Autoimmune Hepatitis

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    Albert J Czaja

    2013-01-01

    Full Text Available BACKGROUND: Autoimmune hepatitis may have cholestatic features that are outside the classical phenotype and that resemble findings in other immune-mediated liver diseases. These cholestatic phenotypes have been designated ‘overlap syndromes’.

  13. Insulin autoimmune syndrome induced by methimazole in a Korean girl with Graves' disease

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    Sun Hee Lee

    2013-03-01

    Full Text Available Hypoglycemia was detected in a 15-year-old girl due to loss of consciousness. She was diagnosed with Graves' disease and was being treated with methimazole for the past 4 months. A paradoxically increased insulin levels was found when she suffered from the hypoglycemic episode. An imaging study showed no mass lesion in the pancreas, and insulin antibodies were found in the serum. She was diagnosed with insulin autoimmune syndrome. Her HLA typing was performed, and it revealed HLA-DRB1 *04:06. The patient was treated with a corticosteroid for 2 months. After discontinuing the steroid, the insulin antibody titer decreased dramatically, and she did not have any episode of hypoglycemia since. This is the first report of insulin autoimmune syndrome in a Korean girl, and we have revealed the connection between HLA type and insulin autoimmune syndrome in Korea.

  14. Airway Autoimmune Inflammatory Response (AAIR) Syndrome: An Asthma-Autoimmune Overlap Disorder?

    Science.gov (United States)

    Spencer, Chantal Y; Millman, Jennifer; Veiga, Keila; Vicencio, Alfin G

    2018-02-15

    Asthma encompasses numerous phenotypes that may require alternate approaches to diagnosis and therapy, particularly for patients whose symptoms remain poorly controlled despite escalating treatment. We describe 3 patients with apparent asthma who demonstrated unusual findings on cryobiopsy by flexible bronchoscopy and responded to therapy directed against autoimmune disease. Copyright © 2018 by the American Academy of Pediatrics.

  15. Pulmonary autoimmunity as a feature of autoimmune polyendocrine syndrome type 1 and identification of KCNRG as a bronchial autoantigen.

    Science.gov (United States)

    Alimohammadi, Mohammad; Dubois, Noémie; Sköldberg, Filip; Hallgren, Asa; Tardivel, Isabelle; Hedstrand, Håkan; Haavik, Jan; Husebye, Eystein S; Gustafsson, Jan; Rorsman, Fredrik; Meloni, Antonella; Janson, Christer; Vialettes, Bernard; Kajosaari, Merja; Egner, William; Sargur, Ravishankar; Pontén, Fredrik; Amoura, Zahir; Grimfeld, Alain; De Luca, Filippo; Betterle, Corrado; Perheentupa, Jaakko; Kämpe, Olle; Carel, Jean-Claude

    2009-03-17

    Patients with autoimmune polyendocrine syndrome type 1 (APS-1) suffer from multiple organ-specific autoimmunity with autoantibodies against target tissue-specific autoantigens. Endocrine and nonendocrine organs such as skin, hair follicles, and liver are targeted by the immune system. Despite sporadic observations of pulmonary symptoms among APS-1 patients, an autoimmune mechanism for pulmonary involvement has not been elucidated. We report here on a subset of APS-1 patients with respiratory symptoms. Eight patients with pulmonary involvement were identified. Severe airway obstruction was found in 4 patients, leading to death in 2. Immunoscreening of a cDNA library using serum samples from a patient with APS-1 and obstructive respiratory symptoms identified a putative potassium channel regulator (KCNRG) as a pulmonary autoantigen. Reactivity to recombinant KCNRG was assessed in 110 APS-1 patients by using immunoprecipitation. Autoantibodies to KCNRG were present in 7 of the 8 patients with respiratory symptoms, but in only 1 of 102 APS-1 patients without respiratory symptoms. Expression of KCNRG messenger RNA and protein was found to be predominantly restricted to the epithelial cells of terminal bronchioles. Autoantibodies to KCNRG, a protein mainly expressed in bronchial epithelium, are strongly associated with pulmonary involvement in APS-1. These findings may facilitate the recognition, diagnosis, characterization, and understanding of the pulmonary manifestations of APS-1.

  16. Transplantation of autoimmune potential. IV. Reversal of the NZB autoimmune syndrome by bone marrow transplantation

    International Nuclear Information System (INIS)

    Morton, J.I.; Siegel, B.V.

    1979-01-01

    The results of the present experiments support the concept of an etiology of autoimmune disease predicated upon innate properties of the hemopoietic stem cell and its differentiated lymphocytic progeny, independent of the host internal environment. It was concluded earlier that the NZB mouse strain possessed an enlarged compartment of cyclically active stem cells, providing an etiological basis for the development of autoimmune disease. Conceivably, a rapidly cycling stem cell population could randomly generate excessive numbers of lymphocytic progeny. Autoantibody formation would represent, then, a manifestation of the consequent hyperresponsiveness to immunological stimuli, both foreign and autologous. Alternatively, there may exist a parallel defect in the homeostatic regulation of both stem cell and immunocyte populations, attributable to either a defect in a shared regulator mechanism or to an unusually high threshold of these cells in response to negative feedback signals

  17. Autoimmune hemolytic anemia, as part of Evans' syndrome, caused by cold reactive IgG autoantibodies

    NARCIS (Netherlands)

    Jaarsma, AS; Muis, N; DeGraaf, SSN

    1996-01-01

    We describe a boy with Evans' syndrome, consisting of immune thrombocytopenic purpura at age 2 and autoimmune hemolytic anemia (AIHA) at age 4. AIHA was caused by cold Ige autoantibodies. This is unusual because AIHA is generally associated with either warm IgG antibodies or cold IgM antibodies.

  18. The immunobiology and clinical features of type 1 autoimmune polyglandular syndrome (APS-1).

    Science.gov (United States)

    Guo, Can-Jie; Leung, Patrick S C; Zhang, Weici; Ma, Xiong; Gershwin, M Eric

    2018-01-01

    Autoimmune Polyglandular Syndrome type 1 (APS-1) is a subtype of the autoimmune polyendocrine syndrome characterized by the simultaneous or sequential dysfunction of multiple endocrine or non-endocrine glands. A clinical diagnosis of APS-1 is typically based on the presence of at least two of three following criteria: chronic mucocutaneous candidiasis, hypoparathyroidism and adrenal insufficiency. The first identified causative mutated gene for APS-1 is autoimmune regulator (AIRE) encoding a critical transcription factor, which is primarily expressed in the medullary thymic epithelial cells (mTECs) for generating central immune tolerance. A wide range of chronic, debilitating complications, with no obvious correlation with genetics, makes a diagnosis of APS-1 challenging early in the disease course. Managing APS-1 is difficult due to its complexity, especially the intricate relationships within manifestations and genetic mutations. The past decades have witnessed dramatic progress in elucidating the function of AIRE and conducting large-scale cohort studies in APS-1. However, no clear evidence-based guidelines have been established in APS-1. In this review, we provide a detailed critical overview of the study history, epidemiology, clinical features, and related mechanisms of autoimmunity in APS-1, as well as currently available therapies for this autoimmune disorder. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Is disomic homozygosity at the APECED locus the cause of increased autoimmunity in Down's syndrome?

    Science.gov (United States)

    Shield, J.; Wadsworth, E.; Hassold, T.; Judis, L. A.; Jacobs, P.

    1999-01-01

    AIMS—To examine the age of onset of insulin dependent diabetes mellitus (IDDM) in children with Down's syndrome compared with non-trisomic individuals, and to assess whether differences might be related to disomic homozygosity at the autoimmune polyglandular disease type 1 (APECED) gene locus.
METHODS—Children with Down's syndrome and IDDM were identified through the Down's syndrome association newsletter and from paediatricians. DNA was extracted from mouthbrush preparations provided by the parents and patients using standard techniques. Mapping techniques were then used to identify areas of reduction to homozygosity, including a marker that overlaps the locus for APECED. The frequency of disomic homozygosity for all markers (n = 18) was compared with a control group of 99 patients with Down's syndrome and their parents. The families also answered a questionnaire concerning diabetes and related autoimmune conditions in the family. Details were compared with the British Paediatric Surveillance Group 1988diabetes study.
RESULTS—Children with Down's syndrome and IDDM were diagnosed significantly earlier than the general population (6.7 v 8.0 years) with a far higher proportion diagnosed in the first 2 years of life (22% v 7%). There was no evidence of increased disomic homozygosity in the region of the APECED locus in Down's syndrome patients with IDDM compared with simple Down's syndrome.
CONCLUSIONS—The natural history of IDDM in Down's syndrome is different from that of the general population. Although children with Down's syndrome have features similar to cases of APECED, disomic homozygosity in this region does not explain the predilection for autoimmune disease.

 PMID:10490523

  20. Immune dysregulation, Polyendocrinopathy, Enteropathy, X-linked (IPEX syndrome: a paradigm of immunodeficiency with autoimmunity

    Directory of Open Access Journals (Sweden)

    Federica eBarzaghi

    2012-07-01

    Full Text Available Immune dysregulation, Polyendocrinopathy, Enteropathy, X-linked (IPEX syndrome is a rare monogenic primary immunodeficiency (PID due to mutations of FOXP3, a key transcription factor for naturally occurring (n regulatory T (Treg cells. The dysfunction of Treg cells is the main pathogenic event leading to the multi-organ autoimmunity that characterizes IPEX syndrome, a paradigm of genetically determined PID with autoimmunity. IPEX has a severe early onset and can become rapidly fatal within the first year of life regardless of the type and site of the mutation. The initial presenting symptoms are severe enteritis and/or type 1 diabetes mellitus, alone or in combination with eczema and elevated serum IgE. Other autoimmune symptoms, such as hypothyroidism, cytopenia, hepatitis, nephropathy, arthritis, and alopecia, can develop in patients who survive the initial acute phase.The current therapeutic options for IPEX patients are limited. Supportive and replacement therapies combined with pharmacological immunosuppression are required to control symptoms at onset. However, these procedures can allow only a reduction of the clinical manifestations without a permanent control of the disease. The only known effective cure for IPEX syndrome is haematopoietic stem cell transplantation, but it is always limited by the availability of a suitable donor and the lack of specific guidelines for bone marrow transplant in the context of this disease.This review aims to summarize the clinical histories and genomic mutations of the IPEX patients described in the literature to date. We will focus on the clinical and immunological features that allow differential diagnosis of IPEX syndrome and distinguish it from other PID with autoimmunity. The efficacy of the current therapies will be reviewed, and possible innovative approaches, based on the latest highlights of the pathogenesis to treat this severe primary autoimmune disease of childhood, will be discussed.

  1. Multiple endocrinopathies (growth hormone deficiency, autoimmune hypothyroidism and diabetes mellitus in Kearns-Sayre syndrome

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    A. Berio

    2013-06-01

    Full Text Available Kearns-Sayre syndrome is characterized by onset before 20 years, chronic progressive external opthalmoplegia, pigmentary retinal degeneration, and ataxia (and/or hearth block, and/or high protein content in the cerebrospinal fluid in the presence of mtDNA rearrangements. Multiple endocrine dysfunction associated with this syndrome was rarely reported. In this paper, the Authors report on a female patient with Kearns-Sayre syndrome with large heteroplasmic mtDNA deletion, absence of cytochrome c oxidase in many muscle fibers, partial GH deficiency, hypothyroidism and subsequently insulin dependent diabetes mellitus (IDDM. Anti-thyroid peroxidase and antithyreoglobulin antibodies were present in high titer in serum while anti-islet cell antibodies were absent. The patient developed thyroiditis with Hashimoto encephalopathy. The presence of GH deficiency, autoimmune thyroiditis with hypothyroidism and IDDM distinguishes this case from others and confirms the association of Kearns-Sayre syndrome with multiple endocrine dysfunction. Hashimoto encephalopathy and anti-thyroideal antibodies suggest that in this patient, predisposed by a genetic factor (a mitochondrial deletion anti-thyroideal antibodies may have contributed to the hypothyroidism and, by interfering with cerebral mitochondrial function, may have caused the encephalopathy. GH deficiency and IDDM can be attributed to oxidative phosphorylation deficiency but the autoimmunity may also have played a role in the production of glandular insufficiencies. It seems important to search for endocrine autoimmunity in every case of KSS.

  2. Autoimmune Polyendocrine Syndrome 3 Onset with Severe Ketoacidosis in a 74-Year-Old Woman

    Directory of Open Access Journals (Sweden)

    Stefano Benedini

    2015-01-01

    Full Text Available Type 1 diabetes mellitus (T1D, autoimmune thyroid disease, and autoimmune gastritis often occur together forming the so-called autoimmune polyendocrine syndrome type 3 (APS3. We here report a clinical case of a 74-year-old woman who presented for the first time with severe hyperglycemia and ketoacidosis diagnosed as T1D. Further clinical investigations revealed concomitant severe hypothyroidism with autoimmune thyroid disease and severe cobalamin deficiency due to chronic atrophic gastritis. The diagnosis of type 1 diabetes mellitus was confirmed by the detection of autoantibodies against glutamic acid decarboxylase 65, islet cell antibodies, and anti-insulin autoantibodies. Anti-thyroperoxidase, anti-thyroglobulin, and anti-gastric parietal cell antibodies were also clearly positive. The case emphasized that new onset diabetic ketoacidosis, hypothyroidism, and cobalamin deficiency may simultaneously occur, and one disease can mask the features of the other, thereby making diagnosis difficult. It is noteworthy that an APS3 acute episode occurred in an asymptomatic elder woman for any autoimmune diseases.

  3. [Type 1 polyglandular autoimmune syndrome associated with C322fsx372 mutation].

    Science.gov (United States)

    Roncalés-Samanes, P; de Arriba Muñoz, A; Lou Francés, G M; Ferrer Lozano, M; Justa Roldán, M L; Labarta Aizpun, J I

    2015-01-01

    Polyglandular autoimmune syndromes are rare diseases based on autoimmune mechanisms in which endocrine and non-endocrine disorders coexist. In type 1 the characteristic manifestations are chronic mucocutaneous candidiasis, hypoparathyroidism and adrenal insufficiency. A case is presented of a patient with typical clinical sequence, along with other changes, and in whom a mutation in homozygosis, C322fsX372, was detected after performing a molecular analysis of autoimmunity regulator gene (AIRE). Inheritance is autosomal recessive, associated with mutations in the AIRE gene, which encodes a protein involved in autoimmunity and immunodeficiency. For diagnosis, At least two of the three major clinical manifestations are required for a diagnosis. However, only one of them is necessary in the study of relatives of affected patients. These syndromes must be diagnosed early, given their high morbidity and mortality. Every manifestation needs to be treated, in order to maintain the quality of life. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

  4. Autoimmune polyendocrine syndrome type 1 – a case report from Bangladesh

    Directory of Open Access Journals (Sweden)

    Tahniyah Haq

    2016-01-01

    Full Text Available We describe a case of a 26 years old man who presented with adrenocortical insufficiency followed by hypoparathyroidism and subsequently mucocutaneous candidiasis. He also had nail dystrophy, cataract and alopecia, but no other endocrinopathies. He was diagnosed as a case of autoimmune polyendocrine syndrome type 1(APS 1. APS1 is a rare endocrine disorder and only a few cases have been reported from Bangladesh. IMC J Med Sci 2016; 10(1: 33-35

  5. Relation between infection and autoimmunity in mixed cryoglobulinemia.

    Science.gov (United States)

    Ferri, C; Zignego, A L

    2000-01-01

    Mixed cryoglobulinemia (MC) is a systemic vasculitis of small to medium-sized vessels due to the vascular deposition of circulating immune-complexes (CIC) and complement. A leukocytoclastic vasculitis is the histologic hallmark of cutaneous manifestations of the disease, while a clonal B lymphocyte expansion in blood, bone marrow, liver, and spleen represents the underlying pathologic alteration responsible for the production of cryo-CIC and non-cryo CIC with rheumatoid factor activity. A causative role of hepatitis C virus (HCV) infection has been demonstrated in the large majority of MC patients. Hepatitis C virus is both a hepatotropic and a lymphotropic virus; due to this latter biological peculiarity, HCV may trigger a constellation of autoimmune-lymphoproliferative disorders. Besides MC, other important HCV-related diseases are porphyria cutanea tarda, autoimmune hepatitis, membranoproliferative glomerulonephritis, and B cell neoplasias. Hepatitis C virus-related MC represents a link between autoimmune and lymphoproliferative disorders; moreover, MC is an important model to study the complex relation between infections and immune system alterations in humans. During the last years many other autoimmune manifestations have been correlated with HCV infection; namely, sicca syndrome, chronic polyarthritis, polydermatomyositis, fibromyalgia, autoimmune thyroiditis, lung fibrosis, and diabetes mellitus. It is often difficult to verify whether the above associations are coincidental or a pathogenetic link actually exists. At least for particular patients' subsets and in some geographic areas, a causative role of HCV seems to be likely. The geographically heterogeneous distribution of HCV-related autoimmune diseases suggests the contribution of important environmental and genetic factors in the pathogenesis of such conditions. In clinical practice, patients with recent-onset, atypical rheumatic and autoimmune disorders should be carefully investigated for possible

  6. Immune complex-mediated autoimmunity in a patient With Smith-Magenis syndrome (del 17p11.2).

    Science.gov (United States)

    Yang, Jianying; Chandrasekharappa, Settara C; Vilboux, Thierry; Smith, Ann C M; Peterson, Erik J

    2014-08-01

    Smith-Magenis syndrome (SMS) is a sporadic congenital disorder involving multiple organ systems caused by chromosome 17p11.2 deletions. Smith-Magenis syndrome features craniofacial and skeletal anomalies, cognitive impairment, and neurobehavioral abnormalities. In addition, some SMS patients may exhibit hypogammaglobulinemia. We report the first case of SMS-associated autoimmunity in a woman who presented with adult onset of multiple autoimmune disorders, including systemic lupus erythematosus, antiphospholipid antibody syndrome, and autoimmune hepatitis. Molecular analysis using single-nucleotide polymorphism array confirmed a de novo 3.8-Mb deletion (breakpoints, chr17: 16,660,721-20,417,975), resulting in haploinsufficiency for TACI (transmembrane activator and CAML interactor). Our data are consistent with potential loss of function for the BAFF (B cell-activating factor) receptor TACI as a contributing factor to human autoimmune phenomena.

  7. Deep vein thrombosis, an unreported first manifestation of polyglandular autoimmune syndrome type III

    Directory of Open Access Journals (Sweden)

    M Horsey

    2016-07-01

    Full Text Available A 71-year-old woman with severe right lower leg pain, edema and erythema was presented to the Emergency Department and was found to have an extensive deep vein thrombosis (DVT confirmed by ultrasound. She underwent an extensive evaluation due to her prior history of malignancy and new hypercoagulable state, but no evidence of recurrent disease was detected. Further investigation revealed pernicious anemia (PA, confirmed by the presence of a macrocytic anemia (MCV=115.8fL/red cell, Hgb=9.0g/dL, decreased serum B12 levels (56pg/mL, with resultant increased methylmalonic acid (5303nmol/L and hyperhomocysteinemia (131μmol/L, the presumed etiology of the DVT. The patient also suffered from autoimmune thyroid disease (AITD, and both antithyroglobulin and anti-intrinsic factor antibodies were detected. She responded briskly to anticoagulation with heparin and coumadin and treatment of PA with intramuscular vitamin B12 injections. Our case suggests that a DVT secondary to hyperhomocystenemia may represent the first sign of polyglandular autoimmune syndrome III-B (PAS III-B, defined as the coexistent autoimmune conditions AITD and PA. It is important to recognize this clinical entity, as patients may not only require acute treatment with vitamin B12 supplementation and prolonged anticoagulation, as in this patient, but may also harbor other autoimmune diseases.

  8. Loss of enteroendocrine cells in autoimmune-polyendocrine-candidiasis-ectodermal-dystrophy (APECED) syndrome with gastrointestinal dysfunction.

    Science.gov (United States)

    Posovszky, C; Lahr, G; von Schnurbein, J; Buderus, S; Findeisen, A; Schröder, C; Schütz, C; Schulz, A; Debatin, K M; Wabitsch, M; Barth, T F

    2012-02-01

    Enteroendocrine (EE) cells are necessary for the regulation of gastrointestinal function. The lack of intestinal enteroendocrine cells in enteroendocrine cell dysgenesis causes severe malabsorptive diarrhea. Autoimmune-polyendocrinopathy-candidiasis-ectodermal-dystrophy (APECED) is often accompanied by gastrointestinal (GI) symptoms. We hypothesized that an autoimmune attack against the cells of the GI-associated diffuse endocrine system may be a specific feature of GI dysfunction in APECED disorders. Biopsies were obtained during routine diagnostic endoscopy from 35 pediatric patients with gastrointestinal symptoms as well as from five healthy controls; biopsies were immunostained for chromogranin A and serotonin. Four patients were classified as APECED syndrome on molecular and clinical grounds. Immunohistological analysis of biopsies along the GI tract (stomach, duodenum, colon) immunostained with chromogranin A and serotonin revealed a widespread reduction or complete loss of EE cells in all four patients with APECED syndrome suffering from severe diarrhea, vomiting, malabsorption, or constipation. In contrast, EE cells were present in pediatric patients with similar gastrointestinal symptoms caused by inflammatory bowel disease, celiac disease, lymphocytic colitis, and autoimmune disorders without endocrinopathy or graft vs. host disease of the gut. The reduction of EE cells is a specific and important early event in the pathogenesis of APECED with GI dysfunction. We propose a diagnostic algorithm integrating clinics, genetics and immunohistology.

  9. Genetic and immunologic aspects of autoimmune poliendocrine syndrome type I: review

    Directory of Open Access Journals (Sweden)

    Alice Rachel Bandeira de Araújo

    2016-10-01

    Full Text Available The autoimmune polyendocrinopathy syndrome type 1 (APS-1, also known as candidiasis ectodermal-autoimmune polyendocrinopathy-dystrophy (APECED, it is a rare autosomal recessive disorder caused by mutations in the autoimmune regulator gene (AIRE. Therefore, it is immunologically characterized by cell attack and / or antibodymediated generating the destruction of target organs. Furthermore, it is characterized by the pathognomonic triad chronic candidiasis, hypoparathyroidism and Addison's disease with many other endocrine and non-endocrine events. Soon, the diagnosis is made based on the presence of two of the three classic features and treatment aims to control the numerous deficiencies that patients may present. This literature review was aimed at understanding the involvement of AIRE gene in relation to immunological aspects present and, consequently, clinical manifestations of this disease. Thus, evidence of the need to broaden the discussion about this disease, in order to improve the quality of life of patients by early diagnosis and treatment and are in accordance with the clinical manifestations of each patient. Thereby, qualitative research involved scientific articles from electronic journals LILACS (Latin American and Caribbean, SCIELO (Scientific Electronic Library Online and NCBI (National Center for Biotechnology Information, between the years 2009 and 2016. Pursuant to, there is the relevance of this review, it is noted that, although the authors converge on views on this syndrome, there are still many unclear matters with regard to the mechanisms of the disease. This highlights the need to promote more discussion on this topic.

  10. Autoimmune Syndrome Induced by Adjuvants (ASIA after Silicone Breast Augmentation Surgery

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    Daniel Nunes e Silva, MD

    2017-09-01

    Full Text Available Summary:. Generally, the main complications of silicone implantation are local symptoms. However, some patients develop late-onset systemic symptoms often associated with a rare form of hyperactive immune response, as part of a syndrome known as autoimmune syndrome induced by adjuvants (ASIA. Reported cases of ASIA have shown resolution with explantation, but not with immunomodulatory therapy. In this report, we described a case of a previously healthy 23-year-old woman, who has undergone silicone breast implant augmentation, for aesthetic reasons, and developed localized cutaneous impairment 3 years postsurgery. She received a diagnosis of ASIA with a new presentation: Lupus-like manifestation through localized cutaneous impairment. This patient’s symptoms were managed without the need for surgical intervention, which has not been previously reported, because the patient did not want an explantation for aesthetic reasons. The patient was started on hydroxychloroquine, 400 mg per day, and remains asymptomatic after 2 years of treatment. The exact predisposition to ASIA is still unknown. Without implant explantation and with immunomodulatory treatment, this patient’s condition substantially improved. Based on our current understanding of this disease, it might not be prudent to indicate breast augmentation with silicone implants in patients with documented autoimmune reaction to an adjuvant, an established autoimmune condition, or genetic predisposition. However, if a patient does develop silicone-induced ASIA, explantation is no longer the only successfully reported option, as these symptoms can be managed with immune suppression.

  11. Autoimmune polyendocrine syndrome type 2 in patient with severe allergic asthma treated with omalizumab.

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    Rams, Anna; Żółciński, Marek; Zastrzeżyńska, Weronika; Polański, Stanisław; Serafin, Agnieszka; Wilańska, Joanna; Musiał, Jacek; Bazan-Socha, Stanisława

    2018-01-04

    Asthma therapy with monoclonal antibodies is a promising and effective approach for those with a severe and refractory type of disease. Although such a targeted therapy is considered to be safe, unusual complications may occur. We present a case of a 45 year-old female patient with severe allergic asthma and chronic spontaneous urticaria, who developed autoimmune polyendocrine syndrome type 2 (APS-2) after 26 months of omalizumab administration. The patient was diagnosed with primary adrenal insufficiency (Addison's disease) and Hashimoto's thyroiditis accompanied by autoimmune atrophic gastritis. According to our knowledge this is the first description of APS-2 that developed in conjunction with omalizumab treatment, although we have no evidence that the observed phenomenon indicated a cause-effect relationship to omalizumab.

  12. Uroplakin peptide-specific autoimmunity initiates interstitial cystitis/painful bladder syndrome in mice.

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    Kenan Izgi

    Full Text Available The pathophysiology of interstitial cystitis/painful bladder syndrome (IC/PBS is enigmatic. Autoimmunity and impaired urothelium might lead the underlying pathology. A major shortcoming in IC/PBS research has been the lack of an appropriate animal model. In this study, we show that the bladder specific uroplakin 3A-derived immunogenic peptide UPK3A 65-84, which contains the binding motif for IA(d MHC class II molecules expressed in BALB/c mice, is capable of inducing experimental autoimmune cystitis in female mice of that strain. A highly antigen-specific recall proliferative response of lymph node cells to UPK3A 65-84 was observed, characterized by selectively activated CD4+ T cells with a proinflammatory Th1-like phenotype, including enhanced production of interferon γ and interleukin-2. T cell infiltration of the bladder and bladder-specific increased gene expression of inflammatory cytokines were observed. Either active immunization with UPK3A 65-84 or adoptive transfer of peptide-activated CD4+ T cells induced all of the predominant IC/PBS phenotypic characteristics, including increased micturition frequency, decreased urine output per micturition, and increased pelvic pain responses to stimulation with von Frey filaments. Our study demonstrates the creation of a more specific experimental autoimmune cystitis model that is the first inducible model for IC/PBS that manifests all of the major symptoms of this debilitating condition.

  13. Non-Autoimmune Subclinical and Overt Hypothyroidism in Idiopathic Steroid-resistant Nephrotic Syndrome in Children.

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    Marimuthu, Vidhya; Krishnamurthy, Sriram; Rajappa, Medha

    2017-11-15

    To evaluate the frequency of non-autoimmune subclinical and overt hypothyroidism in children with idiopathic steroid-resistant nephrotic syndrome (SRNS). This cross-sectional study recruited 30 children (age 1-18 y) with idiopathic SRNS; and 30 healthy controls. Serum T3, T4 and TSH were performed in cases as well as controls. Anti-thyroid peroxidase and anti-thyroglobulin antibody tests were performed in all cases. Non-autoimmune subclinical or overt hypothyroidism was detected in 10 out of 30 children with idiopathic SRNS; 2 had overt hypothyroidism, while 8 patients had subclinical hypothyroidism. Children with SRNS had a mean (SD) TSH value 4.55 (4.64) mIU/L that was higher as compared to controls (1.88 (1.04) mIU/L) (Phypothyroidism (2 cases) and grade III subclinical hypothyroidism (1 case) were subsequently started on levothyroxine therapy. The prevalence of subclinical and overt hypothyroidism seems to be high in idiopathic SRNS, with almost one-third of children having overt or subclinical non-autoimmune hypothyroidism.

  14. Insulin gene polymorphisms in type 1 diabetes, Addison's disease and the polyglandular autoimmune syndrome type II

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    Hahner Stefanie

    2008-07-01

    Full Text Available Abstract Background Polymorphisms within the insulin gene can influence insulin expression in the pancreas and especially in the thymus, where self-antigens are processed, shaping the T cell repertoire into selftolerance, a process that protects from β-cell autoimmunity. Methods We investigated the role of the -2221Msp(C/T and -23HphI(A/T polymorphisms within the insulin gene in patients with a monoglandular autoimmune endocrine disease [patients with isolated type 1 diabetes (T1D, n = 317, Addison's disease (AD, n = 107 or Hashimoto's thyroiditis (HT, n = 61], those with a polyglandular autoimmune syndrome type II (combination of T1D and/or AD with HT or GD, n = 62 as well as in healthy controls (HC, n = 275. Results T1D patients carried significantly more often the homozygous genotype "CC" -2221Msp(C/T and "AA" -23HphI(A/T polymorphisms than the HC (78.5% vs. 66.2%, p = 0.0027 and 75.4% vs. 52.4%, p = 3.7 × 10-8, respectively. The distribution of insulin gene polymorphisms did not show significant differences between patients with AD, HT, or APS-II and HC. Conclusion We demonstrate that the allele "C" of the -2221Msp(C/T and "A" -23HphI(A/T insulin gene polymorphisms confer susceptibility to T1D but not to isolated AD, HT or as a part of the APS-II.

  15. Autoimmune polyglandular syndrome type 3 (APS-3) among patients with premature ovarian insufficiency (POI).

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    Szlendak-Sauer, Katarzyna; Jakubik, Daniel; Kunicki, Michał; Skórska, Jolanta; Smolarczyk, Roman

    2016-08-01

    Autoimmune polyglandular syndrome type 3 - (APS-3), is defined as the coexistence of autoimmune thyroiditis with other non-ovarian autoimmune diseases without primary adrenal insufficiency. Additionally the definition of APS-3 also includes primary ovarian insufficiency (POI) coexistence with autoimmune thyroiditis. The main goal of that study is to assess the prevalence of APS-3 defined as coexistence of autoimmune thyroiditis with POI in population of 46 XX karyotype women with primary ovarian insufficiency (POI). The second goal is to investigate hormonal profile and insulin sensitivity in women with POI and subgroups of women with APS-3 - POI/APS-3(+) and without APS 3 - POI/APS-3(-). Anthropometric measurements, coexistence of autoimmune diseases, androgens, fasting glucose and insulin, glucose and insulin at 60' and 120' of oral glucose tolerance test (OGTT) and homeostasis model for insulin resistance (HOMA-IR), were determine in 98 patients aged between 18 and 39 with spontaneous 46 XX primary ovarian insufficiency (POI), in 33 POI/APS-3(+), 65 POI/APS-3(-), and 75 healthy controls. Continuous data were summarized by the mean±standard deviation (SD), and categorical data by number (percentages). Data were checked for normality using Shapiro-Wilk test, the comparison between groups were performed using non-parametric Mann-Whitney or Kruskall-Wallis test. Pearson's correlation coefficient was used to assess the relationships between parameters. Statistical significance was defined as p values APS-3(+) and POI/APS-3(-) showed significantly lower serum androgens in comparison to controls. Additionally women with POI/APS-3(+) showed hyperinsulinemia after 1h of OGTT; No significant differences in serum fasting glucose, insulin and during 2h OGTT between groups were observed. The prevalence of APS-3 is 33.7% in patients with spontaneous 46 XX primary ovarian insufficiency. Women with POI, POI/APS-3(+) and POI/APS-3(-) feature lower testosterone, androstendione

  16. Autoimmune polyendocrine syndrome type 1 in an Indian cohort: a longitudinal study

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    Ghazala Zaidi

    2017-07-01

    Full Text Available Objective: Autoimmune polyendocrine syndrome type 1 (APS1 is a rare autosomal recessive disorder characterized by progressive organ-specific autoimmunity. There is scant information on APS1 in ethnic groups other than European Caucasians. We studied clinical aspects and autoimmune regulator (AIRE gene mutations in a cohort of Indian APS1 patients. Design: Twenty-three patients (19 families from six referral centres in India, diagnosed between 1996 and 2016, were followed for [median (range] 4 (0.2–19 years. Methods: Clinical features, mortality, organ-specific autoantibodies and AIRE gene mutations were studied. Results: Patients varied widely in their age of presentation [3.5 (0.1–17 years] and number of clinical manifestations [5 (2–11]. Despite genetic heterogeneity, the frequencies of the major APS1 components (mucocutaneous candidiasis: 96%; hypoparathyroidism: 91%; primary adrenal insufficiency: 55% were similar to reports in European series. In contrast, primary hypothyroidism (23% occurred more frequently and at an early age, while kerato-conjunctivitis, urticarial rash and autoimmune hepatitis were uncommon (9% each. Six (26% patients died at a young age [5.8 (3–23 years] due to septicaemia, hepatic failure and adrenal/hypocalcaemic crisis from non-compliance/unexplained cause. Interferon-α and/or interleukin-22 antibodies were elevated in all 19 patients tested, including an asymptomatic infant. Eleven AIRE mutations were detected, the most common being p.C322fsX372 (haplotype frequency 37%. Four mutations were novel, while six others were previously described in European Caucasians. Conclusions: Indian APS1 patients exhibited considerable genetic heterogeneity and had highly variable clinical features. While the frequency of major manifestations was similar to that of European Caucasians, other features showed significant differences. A high mortality at a young age was observed.

  17. Lambert-Eaton myasthenic syndrome (LEMS): a rare autoimmune presynaptic disorder often associated with cancer.

    Science.gov (United States)

    Schoser, Benedikt; Eymard, Bruno; Datt, Joe; Mantegazza, Renato

    2017-09-01

    Lambert-Eaton myasthenic syndrome (LEMS) is a rare autoimmune neuromuscular junction disorder that is related to the loss of functional P/Q-type voltage-gated calcium channels (VGCCs) on presynaptic nerve terminals. Up to 60% of cases occur as a paraneoplastic disorder (SCLC-LEMS), most commonly in association with small cell lung cancer. The remaining cases have an idiopathic non-tumor etiology but are associated with underlying autoimmune disease (NT-LEMS). Patients with LEMS invariably experience progressive proximal muscle weakness, often accompanied by general fatigue and autonomic symptoms. Some LEMS clinical symptoms overlap with those of other myasthenic syndromes, most commonly myasthenia gravis, which can contribute to misdiagnosis or delayed diagnosis. Prognosis is related to the presence of cancer or autoimmune disease and the severity/distribution of muscle weakness. Cause of death in patients with SCLC-LEMS is typically tumor progression, whereas NT-LEMS does not reduce life expectancy. LEMS diagnosis is supported by a threefold approach: clinical features, electromyography, and anti-VGCC antibody serology. LEMS is a clinically important early indicator of possible cancer; therefore, a LEMS diagnosis should immediately prompt rigorous oncological screening and surveillance. Symptomatic treatment of LEMS typically involves medications that improve neurotransmission (e.g., the potassium channel blocker amifampridine [3,4-diaminopyridine]), with addition of immunosuppressants/modulators (e.g., prednisone plus azathioprine) in individuals with persistent symptoms. Where a tumor is identified, oncological treatment should take priority. It should be remembered, however, that LEMS has a significant impact on a patient's quality of life and ability to perform daily activities, and therefore warrants timely diagnosis and appropriate treatment in and of itself.

  18. Unusual pediatric co-morbility: autoimmune thyroiditis and cortico-resistant nephrotic syndrome in a 6-month-old Italian patient

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    Urbano Flavia

    2012-10-01

    Full Text Available Abstract We report on a case of autoimmune thyroiditis in a 6-month-old patient with cortico-resistant nephrotic syndrome. Normal serum levels of thyroid hormons and thyroid-stimulating hormone were detected with high titers of circulant antithyroid antibodies and a dysomogeneous ultrasound appearance of the gland, typical of autoimmune thyroiditis. The research of maternal thyroid antibodies was negative. This is the first case of autoimmune thyroiditis found in such a young patient with pre-existing nephrotic syndrome ever described in literature. This association is random because nephrotic syndrome does not have an autoimmune pathogenesis and the genes involved in autoimmune thyroiditis are not related to those of nephrotic syndrome.

  19. Retrospective analysis of autoimmune hepatitis-primary biliary cirrhosis overlap syndrome in Korea: characteristics, treatments, and outcomes.

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    Park, Yoonsang; Cho, Yuri; Cho, Eun Ju; Kim, Yoon Jun

    2015-06-01

    Overlap syndrome of autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC) (AIH-PBC overlap syndrome) is a rare disease that has not been clearly characterized in Korean patients. This study investigated the clinical features of AIH-PBC overlap syndrome compared with those of AIH and PBC alone. This retrospective cohort study included 158 consecutive patients who were diagnosed as AIH (n=61), PBC (n=81), or AIH-PBC overlap syndrome (n=9) based on the Paris and the International Autoimmune Hepatitis Group (IAIHG) criteria from 2001 to 2011 in Korea. We compared the clinical features of these three groups retrospectively, including their biochemical characteristics, treatments, responses, and clinical outcomes. The AIH-PBC overlap syndrome patients exhibited biochemical characteristics of both AIH and PBC, and showed a similar response to ursodeoxycholic acid (UDCA) monotherapy as for the PBC patients. However, the response of AIH-PBC overlap syndrome patients to UDCA and steroid combination therapy was worse than the response of AIH patients to steroid-based therapy (P=0.024). Liver cirrhosis developed more rapidly in AIH-PBC overlap syndrome patients than in AIH patients group (P=0.013), but there was no difference between AIH-PBC overlap syndrome patients and PBC patients. The rates of developing hepatic decompensation did not differ significantly between the groups. The AIH-PBC overlap syndrome patients exhibited a worse response to UDCA and steroid combination therapy and a faster cirrhotic progression compared with AIH patients.

  20. A functional alternative splicing mutation in AIRE gene causes autoimmune polyendocrine syndrome type 1.

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    Junyu Zhang

    Full Text Available Autoimmune polyendocrine syndrome type 1 (APS-1 is a rare autosomal recessive disease defined by the presence of two of the three conditions: mucocutaneous candidiasis, hypoparathyroidism, and Addison's disease. Loss-of-function mutations of the autoimmune regulator (AIRE gene have been linked to APS-1. Here we report mutational analysis and functional characterization of an AIRE mutation in a consanguineous Chinese family with APS-1. All exons of the AIRE gene and adjacent exon-intron sequences were amplified by PCR and subsequently sequenced. We identified a homozygous missense AIRE mutation c.463G>A (p.Gly155Ser in two siblings with different clinical features of APS-1. In silico splice-site prediction and minigene analysis were carried out to study the potential pathological consequence. Minigene splicing analysis and subsequent cDNA sequencing revealed that the AIRE mutation potentially compromised the recognition of the splice donor of intron 3, causing alternative pre-mRNA splicing by intron 3 retention. Furthermore, the aberrant AIRE transcript was identified in a heterozygous carrier of the c.463G>A mutation. The aberrant intron 3-retaining transcript generated a truncated protein (p.G155fsX203 containing the first 154 AIRE amino acids and followed by 48 aberrant amino acids. Therefore, our study represents the first functional characterization of the alternatively spliced AIRE mutation that may explain the pathogenetic role in APS-1.

  1. [Cold autoimmune hemolytic anemia complicated with relapsed myelodysplastic syndrome after allogeneic hematopoietic cell transplantation].

    Science.gov (United States)

    Okamura, Hiroshi; Nakane, Takahiko; Fujino, Keizo; Koh, Shiro; Yoshimura, Takuro; Nishimoto, Mitsutaka; Hayashi, Yoshiki; Koh, Hideo; Nakao, Yoshitaka; Nakamae, Hirohisa; Hino, Masayuki

    2015-04-01

    Myelodysplastic syndrome (MDS) is known to often be complicated by a range of autoimmune diseases. We herein present a case with MDS complicated by cold autoimmune hemolytic anemia (cold AIHA). The patient was a 51-year-old woman. She was diagnosed with MDS (refractory cytopenia with multilineage dysplasia) in May 2009. In January 2010, she underwent unrelated allogeneic bone marrow transplantation but was re-admitted in October 2010 for treatment of relapsed MDS. Despite daily transfusions of red blood cells, her anemia failed to improve. Her laboratory examinations showed a low haptoglobin level and elevation of indirect bilirubin and LDH. The direct Coombs test was positive at a low and at room temperature and cold agglutinin was negative. After confirming the diagnosis of cold AIHA, all transfusion fluids were warmed but her anemia still failed to improve. In addition to the warmed transfusion fluids, we administered corticosteroids, immunosuppressive agents and high-dose intravenous immunoglobulin infusions. This management strategy ameliorated the patient's hemolytic anemia. To our knowledge, MDS cases complicated by cold AIHA are rare. Our patient thus provides a valuable contribution to medical knowledge.

  2. Cutaneous manifestations of autoimmune polyglandular syndrome type 1 – case report and literature review

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    Julita A. Krahel

    2016-10-01

    Full Text Available Introduction. Autoimmune polyglandular syndrome type 1 (APS-1 is a type of polyendocrinopathy, inherited in an autosomal recessive manner. Beside the classic triad of symptoms (candidiasis of the skin and mucous membranes, hypoparathyroidism and Addison’s disease, other skin and systemic diseases may be present. Objective . To present a patient with history of APS-1, in whom in addition to the classic triad of symptoms vitiligo, alopecia, and dental enamel hypoplasia and nail dystrophy were observed. Case report . A 43-year-old patient, with a history of APS-1 syndrome, was admitted to the hospital because of exacerbation of candidiasis of the mucous membranes of the mouth. Additionally, dystrophy of the nails and the dental enamel, generalized alopecia and extensive vitiligo were observed. Due to antifungal treatment partial clinical improvement was achieved. Conclusions . APS-1 is a potentially life-threatening complex set of symptoms. Consistent treatment and strict follow-up of patients with this syndrome are necessary.

  3. Severe hypoglycaemia in a person with insulin autoimmune syndrome accompanied by insulin receptor anomaly type B.

    Science.gov (United States)

    Kato, T; Itoh, M; Hanashita, J; Itoi, T; Matsumoto, T; Ono, Y; Imamura, S; Hayakawa, N; Suzuki, A; Mizutani, Y; Uchigata, Y; Oda, N

    2007-11-01

    A rare case of the insulin autoimmune syndrome (IAS) accompanied by insulin receptor anomaly is reported. Antibodies to insulin and insulin receptor were determined in the patient with severe hypoglycaemia before and after the treatment with prednisolone. Titers of antibody to insulin and insulin receptors were 73.0% and 41.5%, respectively. Drug-induced lymphocyte stimulation tests were all negative for the suspicious drugs. Her HLA-DR was DRB1*0403/04051. Following steroid therapy, the formation of antibodies was suppressed and alleviated her symptoms. Scatchard analysis yielded findings specific to polyclonal antibodies. The changes in autoantibodies resulted in alleviation of the hypoglycemic symptoms as a result of steroid therapy.

  4. Sjogren′s Syndrome: A Review

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    Rani Somani

    2011-01-01

    Full Text Available Sjogren′s syndrome, also known as "Mikulicz disease" or "Sicca syndrome" is a systemic autoimmune disease in which immune cells attack and destroy the exocrine glands that produce tears and saliva. It can exist by itself (primary Sjogren syndrome or develop in association with another disorder such as rheumatoid arthritis, systemic sclerosis, primary biliary cirrhosis or Hashimoto thyroiditis (associated Sjogren syndrome. Hallmarks are the dry mouth and dry eyes known as the Sicca syndrome. Sjogren syndrome affects t million to 4 million people in the United States- Most are over 40 years old at the time of diagnosis. As there is no known cure for Sjogren syndrome, treatment focuses on relieving symptoms and preventing complications. The most serious complication associated with primary Sjogren syndrome is the development of a lymphoproliferative disease. primarily non-Hodgkin lymphoma.

  5. Type 1 Diabetes in Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy Syndrome (APECED): A "Rare" Manifestation in a "Rare" Disease.

    Science.gov (United States)

    Fierabracci, Alessandra

    2016-07-12

    Type 1 autoimmune polyglandular syndrome (APS1) is a rare autosomal recessive disease, caused by mutations in the autoimmune regulator gene (AIRE); the encoded Aire protein plays an important role in the establishment of the immunological tolerance acting as a transcriptional regulator of the expression of organ-specific antigens within the thymus in perinatal age. While a high prevalence for this rare syndrome is reported in Finland and Scandinavia (Norway), autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome (APECED) cohorts of patients are also detected in continental Italy and Sardinia, among Iranian Jews, as well as in other countries. The syndrome is diagnosed when patients present at least two out of the three fundamental disorders including chronic mucocutaneous candidiasis, hypoparathyroidism, and Addison's disease. Among the associated conditions insulin-dependent diabetes mellitus (Type 1 diabetes) has been rarely reported in different series of patients and occurring more frequently in Finnish APECED patients. In this review, we analyze the incidence of Type 1 diabetes as a clinical manifestation of APECED in different populations highlighting the peculiar genetic and immunological features of the disease when occurring in the context of this syndrome.

  6. Increased prevalence of autoimmune disorders and autoantibodies in parents of children with opsoclonus-myoclonus syndrome (OMS).

    Science.gov (United States)

    Krasenbrink, I; Fühlhuber, V; Juhasz-Boess, I; Stolz, E; Hahn, A; Kaps, M; Hero, B; Blaes, F

    2007-06-01

    Opsoclonus-myoclonus syndrome (OMS) is a rare neurological disease in childhood which can be associated with neuroblastoma. Since autoantibodies have been detected in some patients with OMS, an autoimmune etiology is suspected. We compared the prevalence of autoimmune disorders and autoantibodies in parents of children with OMS and in a group of controls of same age and sex. Autoimmune diseases were found in 15.8% of the parents of OMS children, but only in 2.0% of the controls (pOMS parents (42.8% vs. 8.0%, pOMS parents also had significantly more autoantibodies against CNS structures than the controls (pOMS and may also hint to a genetic susceptibility for OMS.

  7. Pediatric Sjogren syndrome with distal renal tubular acidosis and autoimmune hypothyroidism: an uncommon association.

    Science.gov (United States)

    Agarwal, Amit; Kumar, Pradeep; Gupta, Nomeeta

    2015-11-01

    A 14-year-old female came with the history of sudden onset weakness; during work up, she was found to have hyperchloremic metabolic acidosis with normal anion gap and normal renal function suggesting the possibility of renal tubular acidosis (RTA). On further evaluation of RTA, she had positive antinuclear antibody, anti-Ro, and anti-La antibodies. On nuclear scan of salivary glands, her left parotid gland was nonfunctional. Her parotid biopsy revealed dilated interlobular ducts engulfed by lymphoid cells. She also had autoimmune hypothyroidism as suggested by raised TSH and positive anti-TPO antibodies. At admission, her serum potassium levels were low and she was treated with intravenous potassium chloride. After she recovered from acute hypokalemic paralysis, she was started on oral potassium citrate along with phosphate supplements, hydroxychloroquine, oral prednisolone and thyroxine supplements. Over the next 6 months, she has significant reduction in the dosage of potassium, bicarbonate and phosphate and gained 3 kg of weight and 3.5 cm of height. As primary Sjogren syndrome itself is rare in pediatric population and its association with renal tubular acidosis is even rarer, we suggest considering Sjogren syndrome as a differential diagnosis during the RTA work-up is worth trying.

  8. COEXISTENCE OF ADDISON'S DISEASE AND PERNICIOUS ANEMIA: IS THE NEW CLASSIFICATION OF AUTOIMMUNE POLYGLANDULAR SYNDROME APPROPRIATE?

    Science.gov (United States)

    Vrkljan, Ana Marija; Pašalić, Ante; Strinović, Mateja; Perić, Božidar; Kruljac, Ivan; Miroševć, Gorana

    2015-06-01

    A case of autoimmune polyglandular syndrome (APS) is presented. A 45-year-old man was admitted due to fatigue, malaise and inappetence. He had a history of primary hypothyroidism and was on levothyroxine substitution therapy. One year before, he was diagnosed with normocytic anemia and vitamin B12 deficiency, which was treated with vitamin B12 substitution therapy. Physical examination revealed hypotension and marked hyperpigmentation. Laboratory testing showed hyponatremia, hyperkaliemia and severe normocytic anemia. Endocrinological evaluation disclosed low morning cortisol and increased adrenocorticotropic hormone levels. Hence, the diagnosis of Addison's disease was established. Additional laboratory workup showed positive parietal cell antibodies. However, his vitamin B12 levels were increased due to vitamin B12 supplementation therapy, which was initiated earlier. Gastroscopy and histopathology of gastric mucosa confirmed atrophic gastritis. Based on prior low serum vitamin B12 levels, positive parietal cell antibodies and atrophic gastritis, the patient was diagnosed with pernicious anemia. Hydrocortisone supplementation therapy was administered and titrated according to urinary-free cortisol levels. Electrolyte disbalance and red blood cell count were normalized. This case report demonstrates rather unique features of pernicious anemia in a patient with Addison's disease. It also highlights the link between type II and type III APS. Not only do they share the same etiological factors, but also overlap in pathophysiological and clinical characteristics. This case report favors older classification of APS, which consolidates all endocrine and other organ-specific autoimmune diseases into one category. This is important since it might help avoid pitfalls in the diagnosis and treatment of patients with APS.

  9. Autoimmune sialadenitis

    NARCIS (Netherlands)

    Guntinas-Lichius, O.; Vissink, A.; Ihrler, S.

    Using the European-American classification criteria the diagnosis of autoimmune sialadenitis in Sjogren's syndrome can generally be easily established or excluded. In addition, sonography performed by the ENT physician is helpful in diagnosing and especially in follow-up screening for MALT

  10. Two different cytochrome P450 enzymes are the adrenal antigens in autoimmune polyendocrine syndrome type I and Addison's disease.

    OpenAIRE

    Winqvist, O; Gustafsson, J; Rorsman, F; Karlsson, F A; Kämpe, O

    1993-01-01

    Autoimmune polyendocrine syndrome type I (APS I) and idiopathic Addison's disease are both disorders with adrenal insufficiency but with differences in genetic background, clinical presentation, and extent of extraadrenal manifestations. In this study the major adrenal autoantigen identified with sera from patients with APS I was characterized by analyses using indirect immunofluorescence, Western blots of adrenal subcellular fractions and of recombinant proteins, immunoprecipitations of [35S...

  11. Classification, clinical manifestations, and immunopathological mechanisms of the epithelial variant of paraneoplastic autoimmune multiorgan syndrome: a reappraisal of paraneoplastic pemphigus.

    Science.gov (United States)

    Nguyen, V T; Ndoye, A; Bassler, K D; Shultz, L D; Shields, M C; Ruben, B S; Webber, R J; Pittelkow, M R; Lynch, P J; Grando, S A

    2001-02-01

    Recent studies suggest that paraneoplastic pemphigus (PNP) is a heterogeneous autoimmune syndrome involving several internal organs and that the pathophysiological mechanisms mediating cutaneous, mucosal, and internal lesions are not limited to autoantibodies targeting adhesion molecules. To classify the diverse mucocutaneous and respiratory presentations of PNP and characterize the effectors of humoral and cellular autoimmunity mediating epithelial tissue damage. We examined 3 patients manifesting the lichen planus pemphigoideslike subtype of PNP. A combination of standard immunohistochemical techniques, enzyme-linked immunosorbent assay with desmoglein (DSG) baculoproteins, and an immunoprecipitation assay were used to characterize effectors of humoral and cellular autoimmunity in patients with PNP and in neonatal wild-type and DSG3-knockout mice with PNP phenotype induced by passive transfer of patients' IgGs. In addition to the known "PNP antigenic complex," epithelial targets recognized by PNP antibodies included 240-, 150-, 130-, 95-, 80-, 70-, 66-, and 40/42-kd proteins but excluded DSG1 and DSG3. In addition to skin and the epithelium lining upper digestive and respiratory tract mucosa, deposits of autoantibodies were found in kidney, urinary bladder, and smooth as well as striated muscle. Autoreactive cellular cytotoxicity was mediated by CD8(+) cytotoxic T lymphocytes, CD56(+) natural killer cells, and CD68(+) monocytes/macrophages. Inducible nitric oxide synthase was visualized both in activated effectors of cellular cytotoxicity and their targets. Keratin 14-positive basal epithelial cells sloughed from the large airways and obstructed small airways. The paraneoplastic disease of epithelial adhesion known as PNP in fact represents only 1 manifestation of a heterogeneous autoimmune syndrome in which patients, in addition to small airway occlusion and deposition of autoantibodies in different organs, may display a spectrum of at least 5 different clinical

  12. Two Paraneoplastic Autoimmune Syndromes: Limbic Encephalitis and Palmar Fasciitis in a Patient with Small Cell Lung Cancer.

    Science.gov (United States)

    Lazarev, Irina; Shelef, Ilan; Refaely, Yael; Ariad, Samuel; Ifergane, Gal

    2015-09-07

    Small cell lung cancer (SCLC) is characterized by a relatively high rate of autoimmune phenomena. Paraneoplastic limbic encephalitis (PLE) is an autoimmune syndrome in which a non-neural tumor containing an antigen normally present in the nervous system precipitates an antibody attack on neural tissues. Patients with PLE usually present with rapidly progressive short-term memory deficits, confusion or even dementia. Palmar fasciitis and polyarthritis syndrome (PFPAS) is another autoimmune syndrome characterized by rheumatologic manifestations, especially involving the palms of the hands. We report a case of a 59-year old woman who presented with worsening neurological symptoms of two-week duration, and later coma. The combined clinical, serological, and imaging studies suggested a diagnosis of PLE. A chest computed tomographic scan showed a 1.2 cm-diameter mass in the upper lobe of the left lung that was surgically removed and showed SCLC. Following surgery, neurological symptoms rapidly improved, allowing the patient to receive adjuvant chemotherapy. While in remission for both SCLC and PLE, the patient developed pain, soft-tissue swelling, and stiffness in both palms, suggesting the diagnosis of PFPAS. Five months following the diagnosis of palmar fasciitis, SCLC relapsed with mediastinal and cervical lymphadenopathy. This case report underlines the continuous interaction of SCLC with the immune system, expressed by coexistence of two rare paraneoplastic diseases, PLE, and PFPAS, in a patient with SCLC. While symptoms related to PLE preceded the initial diagnosis of SCLC, other symptoms related to PFPAS preceded relapse.

  13. Two paraneoplastic autoimmune syndromes: limbic encephalitis and palmar fasciitis in a patient with small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Irina Lazarev

    2015-09-01

    Full Text Available Small cell lung cancer (SCLC is characterized by a relatively high rate of autoimmune phenomena. Paraneoplastic limbic encephalitis (PLE is an autoimmune syndrome in which a non-neural tumor containing an antigen normally present in the nervous system precipitates an antibody attack on neural tissues. Patients with PLE usually present with rapidly progressive short-term memory deficits, confusion or even dementia. Palmar fasciitis and polyarthritis syndrome (PFPAS is another autoimmune syndrome characterized by rheumatologic manifestations, especially involving the palms of the hands. We report a case of a 59-year old woman who presented with worsening neurological symptoms of two-week duration, and later coma. The combined clinical, serological, and imaging studies suggested a diagnosis of PLE. A chest computed tomographic scan showed a 1.2 cm-diameter mass in the upper lobe of the left lung that was surgically removed and showed SCLC. Following surgery, neurological symptoms rapidly improved, allowing the patient to receive adjuvant chemotherapy. While in remission for both SCLC and PLE, the patient developed pain, soft-tissue swelling, and stiffness in both palms, suggesting the diagnosis of PFPAS. Five months following the diagnosis of palmar fasciitis, SCLC relapsed with mediastinal and cervical lymphadenopathy. This case report underlines the continuous interaction of SCLC with the immune system, expressed by coexistence of two rare paraneoplastic diseases, PLE, and PFPAS, in a patient with SCLC. While symptoms related to PLE preceded the initial diagnosis of SCLC, other symptoms related to PFPAS preceded relapse.

  14. Aicardi-Goutieres syndrome, a rare neurological disease in children: a new autoimmune disorder?

    Science.gov (United States)

    Fazzi, Elisa; Cattalini, Marco; Orcesi, Simona; Tincani, Angela; Andreoli, L; Balottin, U; De Simone, M; Fredi, M; Facchetti, F; Galli, J; Giliani, S; Izzotti, A; Meini, A; Olivieri, I; Plebani, A

    2013-02-01

    Aicardi-Goutieres syndrome (AGS), described by J. Aicardi and F. Goutieres in 1984, is a rare neurological disease with onset in infancy. It is often misdiagnosed as a sequela of congenital infection or recognized later. Nowadays almost 200 cases are reported all over the world, most of them collected by the International Aicardi-Goutieres Syndrome Association (IAGSA), founded in Pavia (Italy) in 2000. AGS (MIM 225750) is a genetically-determined encephalopathy characterized by severe neurological dysfunction, acquired microcephaly associated with severe prognosis quoad valetudinem, and less frequently also quoad vitam. Some AGS children also develop some symptoms overlapping with systemic lupus erythematosus (SLE). Intracranial calcification, white matter involvement and brain atrophy revealed on MRI, lymphocytosis and elevated levels of interferon alpha (IFN-α) in the cerebrospinal fluid (CSF) are features of both AGS and congenital viral infection. No evidence of congenital infection at serological exams has ever been found. A genetic etiology was hypothesized since the first descriptions, because of the recurrence in families, and demonstrated some years ago. Nowadays five genes (AGS1-5), if mutated, can be responsible for 90% of the cases. The transmission is autosomal recessive but there are also rare "de novo" autosomal dominant cases. Even if pathogenesis is still almost unknown, it seems that responsible genes are involved in nucleic acid reparation mechanisms and consequently in a secondary activation of innate autoimmunity. The relative lack of precise information on pathogenesis and on the evolution of the disease over time has not yet allowed the creation of codified diagnostic and therapeutic models and programs. Copyright © 2012 Elsevier B.V. All rights reserved.

  15. Autoimmune pancreatitis

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    Davorin Dajčman

    2007-05-01

    Full Text Available Background: Autoimmune pancreatitis is a recently described type of pancreatitis of presumed autoimmune etiology. Autoimmune pancreatitis is often misdiagnosed as pancreatic cancer difficult, since their clinical presentations are often similar. The concept of autoimmune pancreatitis was first published in 1961. Since then, autoimmune pancreatitis has often been treated not as an independent clinical entity but rather as a manifestation of systemic disease. The overall prevalence and incidence of the disease have yet to be determined, but three series have reported the prevalence as between 5 and 6 % of all patients with chronic pancreatitis. Patient vary widely in age, but most are older than 50 years. Patients with autoimmune pancreatitis usually complain of the painless jaundice, mild abdominal pain and weight loss. There is no laboratory hallmark of the disease, even if cholestatic profiles of liver dysfunction with only mild elevation of amylase and lipase levels have been reported.Conclusions: Proposed diagnostic criteria contains: (1 radiologic imaging, diffuse enlargement of the pancreas and diffusely irregular narrowing of the main pancreatic duct, (2 laboratory data, elevated levels of serum ã-globulin and/or IgG, specially IgG4, or the presence of autoantibodies and (3 histopathologic examination, fibrotic change with dense lymphoplasmacytic infiltration in the pancreas. For correct diagnosis of autoimmune pancreatitis, criterion 1 must be present with criterion 2 and/or 3. Autoimmune pancreatitis is frequently associated with rheumatoid arthritis, Sjogren’s syndrome, inflammatory bowel disease, tubulointersticial nephritis, primary sclerosing cholangitis and idiopathic retroperitoneal fibrosis. Pancreatic biopsy using an endoscopic ultrasound-guided fine needle aspiration biopsy is the most important diagnostic method today. Treatment with corticosteroids leads to the and resolution of pancreatic inflamation, obstruction and

  16. Coagulopathy triggered autoimmunity: experimental antiphospholipid syndrome in factor V Leiden mice

    Science.gov (United States)

    2013-01-01

    Background We investigated interactions between genetically and autoimmune-mediated coagulopathies by inducing experimental antiphospholipid syndrome (eAPS) in mice carrying the factor V Leiden (FVL) mutation. Methods eAPS was induced in heterozygous and homozygous FVL transgenic mice (C57BL/6 background) by immunization with β2-glycoprotein I (β2-GPI). Autoantibody levels were measured at 1 and 5 months post-immunization. Mice were tested at 4 months post-immunization for behavior and cognitive function in the staircase, elevated plus-maze, and swim T-maze tests. Brains were removed and analyzed by immunohistochemistry for inflammatory markers and neurodegenerative processes. Results A single immunization with β2-GPI induced significantly higher and longer-lasting immune responses, and this was dependent on the number of FVL alleles. At 1 and 5 months post-immunization, levels of antibodies rose from 1.17 ± 0.07 to 1.62 ± 0.17 (optical density units; ODU) in homozygous FVL mice, compared with stable levels of 0.59 ± 0.17 and 0.48 ± 0.16 ODU in heterozygous FVL mice and a drop from 1.62 ± 0.21 to 0.61 ± 0.13 ODU in wild-type mice. Behavioral and cognitive clinical features of eAPS were also correlated with FVL allele load, as assessed by the elevated plus-maze (altered anxiety), staircase (hyperactivity and higher exploration), and swim T-maze (impaired learning) tests. Histological studies identified significant neurodegenerative changes in both grey and white matter in the eAPS-FVL brains. In spite of the potential interaction of two prothrombotic disease states, there were no ischemic lesions seen in this group. Conclusions The results indicate that genetically mediated coagulopathies increase the risk of developing coagulation-targeted autoimmune responses, and suggest the importance of antibody-mediated neurodegenerative processes in the brain in APS. PMID:23566870

  17. Association of Therapy for Autoimmune Disease With Myelodysplastic Syndromes and Acute Myeloid Leukemia.

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    Ertz-Archambault, Natalie; Kosiorek, Heidi; Taylor, Gretchen E; Kelemen, Katalin; Dueck, Amylou; Castro, Janna; Marino, Robert; Gauthier, Susanne; Finn, Laura; Sproat, Lisa Z; Palmer, Jeanne; Mesa, Ruben A; Al-Kali, Aref; Foran, James; Tibes, Raoul

    2017-07-01

    Therapy-related myeloid neoplasms are a potentially life-threatening consequence of treatment for autoimmune disease (AID) and an emerging clinical phenomenon. To query the association of cytotoxic, anti-inflammatory, and immunomodulating agents to treat patients with AID with the risk for developing myeloid neoplasm. This retrospective case-control study and medical record review included 40 011 patients with an International Classification of Diseases, Ninth Revision, coded diagnosis of primary AID who were seen at 2 centers from January 1, 2004, to December 31, 2014; of these, 311 patients had a concomitant coded diagnosis of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). Eighty-six cases met strict inclusion criteria. A case-control match was performed at a 2:1 ratio. Odds ratio (OR) assessment for AID-directed therapies. Among the 86 patients who met inclusion criteria (49 men [57%]; 37 women [43%]; mean [SD] age, 72.3 [15.6] years), 55 (64.0%) had MDS, 21 (24.4%) had de novo AML, and 10 (11.6%) had AML and a history of MDS. Rheumatoid arthritis (23 [26.7%]), psoriasis (18 [20.9%]), and systemic lupus erythematosus (12 [14.0%]) were the most common autoimmune profiles. Median time from onset of AID to diagnosis of myeloid neoplasm was 8 (interquartile range, 4-15) years. A total of 57 of 86 cases (66.3%) received a cytotoxic or an immunomodulating agent. In the comparison group of 172 controls (98 men [57.0%]; 74 women [43.0%]; mean [SD] age, 72.7 [13.8] years), 105 (61.0%) received either agent (P = .50). Azathioprine sodium use was observed more frequently in cases (odds ratio [OR], 7.05; 95% CI, 2.35- 21.13; P myeloid neoplasm. The control and case cohorts had similar systemic exposures by agent category. No association was found for anti-tumor necrosis factor agents. Finally, no timeline was found for the association of drug exposure with the incidence in development of myeloid neoplasm.

  18. Psoriasis in autoimmune polyendocrine syndrome type I: A possible complication or a non-endocrine minor component?

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    Shital Amin Poojary

    2015-01-01

    Full Text Available Introduction: Autoimmune polyendocrine syndrome type I (APS I is an autosomal recessive systemic autoimmune disorder, affecting primarily endocrine glands, in which chronic mucocutaneous candidiasis is an early and prominent manifestation. We describe the rare occurrence of unstable psoriasis (with onset of pustular lesions in a case of APS I without mucocutaneous candidiasis. A patient presenting with unstable psoriasis (with onset of pustular lesions was detected to have persistent hypocalcemia which led to the diagnosis of hypoparathyroidism. Subsequently he was found to have hypergonadotrophic hypogonadism, primary adrenal insufficiency (compensated, and coeliac disease, thus confirming the diagnosis of APS I. Psoriasis is very rarely reported in APS I, possibly due to the protective effect of antibodies to Th17 cytokines, which are responsible for the occurrence of candidiasis in this syndrome. However, psoriasis could occur in APS I patients without mucocutaneous candidiasis, who lack these antibodies. In our patient, possible factors aggravating psoriasis include hypocalcemia due to hypoparathyroidism as well as coeliac disease via anti-tissue transglutaminase antibodies. However, defining psoriasis as a possible minor component of APS I would require further studies of the autoimmune regulator (AIRE gene functions.

  19. Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome (APECED) due to AIRET16M mutation in a consanguineous Greek girl.

    Science.gov (United States)

    Kollios, Konstantinos; Tsolaki, Anastasia; Antachopoulos, Charalampos; Moix, I; Morris, Michael A; Papadopoulou, Maria; Roilides, Emmanuel

    2011-01-01

    Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome (APECED) or autoimmune polyendocrine syndrome type 1 (APS-1) is a rare autosomal recessive disease caused by mutations of the AutoImmune REgulator (AIRE) gene, an important mediator of tolerance to self-antigens. It is characterized by two out of three major components: chronic mucocutaneous candidiasis, hypoparathyroidism and Addison's disease. We present an 11-year-old girl suffering from recurrent episodes of mucocutaneous candidiasis and onychomycosis from 1 to 6 years of age, and transient alopecia at the age of 4 years. Hypoparathyroidism and dental enamel hypoplasia were diagnosed at 8 years. Autoantibodies to thyroid and adrenal glands were not detected and all other endocrine functions have remained normal. Genetic analysis revealed that the patient was homozygous for the mutation T16M in exon 1 of the AIRE gene (p.T16M, c.47C>T). This is the first APECED case reported for carrying this mutation in homozygous form. Parents were third cousins and heterozygous carriers of this mutation.

  20. Autoimmune Hepatitis

    Science.gov (United States)

    ... with type 1 autoimmune hepatitis commonly have other autoimmune disorders, such as celiac disease, an autoimmune disease in ... 2 can also have any of the above autoimmune disorders. What are the symptoms of autoimmune hepatitis? The ...

  1. Abdominal ultrasonogram of autoimmune pancreatitis: Five cases of pancreatic lesions accompanied by Sjögren syndrome.

    Science.gov (United States)

    Yoshizaki, Hideo; Takeuchi, Kazuo; Okuda, Chikao; Honjyo, Hajime; Yamamoto, Takatugu; Kora, Tetuo; Takamori, Yoriyuki

    2002-09-01

    The concept of autoimmune pancreatitis has recently been established, and ultrasonographic findings we obtained from five cases consistent with autoimmune pancreatitis are reported here. Case 1, a 77-year-old man, was admitted complaining of loss of body weight. Serum hepatobiliary enzymes and γ-globulin levels were elevated, and antinuclear antibody was positive, Abdominal ultrasonography showed dilatation of the intrahepatic bile duct, wall thickening of the common bile duct and hypoechoic swelling of the pancreatic head and body. ERCP revealed multiple stenosis of the intra-and extra-hepatic bile ducts, and diffuse irregular narrowing of the main pancreatic duct. The patient complained of thirst, and the minor salivary gland was examined histologically. Our diagnosis was Sjögren syndrome accompanied by sclerosing cholangitis and a pancreatic lesion. Obstructive jaundice also developed, and PTCD was therefore performed. Both the pancreatic swelling and multiple stenosis of the bile duct improved after steroids were administered. Case 2, a 71-year-old man, was admitted with jaundice. Abdominal ultrasonography showed hypoechoic swelling of the pancreas. ERCP showed stenosis of the common bile duct in the pancreatic head region and diffuse irregular narrowing of the main pancreatic duct. Histological examination of the minor salivary gland suggested Sjögren syndrome. Steroids were therefore administered because the presence of both hyper-γ-globulinemia and positive antinuclear antibody suggested involvement of the autoimmune mechanism. Steroid therapy improved the jaundice as well as the findings from the cholangiograms and pancreatograms. We also encountered three similar cases, all consistent with the concept of autoimmune pancreatitis. The ultrasonographic findings of the pancreatic lesion (1) showed them as homogeneous and markedly hypoechoic areas and, (2) visualized the main pancreatic duct in the lesion, which facilitated a differential diagnosis of the

  2. Cutaneous vasculitis in patients with autoimmune polyendocrine syndrome type 1: report of a case and brief review of the literature.

    Science.gov (United States)

    Improda, Nicola; Capalbo, Donatella; Cirillo, Emilia; Cerbone, Manuela; Esposito, Andrea; Pignata, Claudio; Salerno, Mariacarolina

    2014-11-01

    Autoimmune polyendocrine syndrome type 1, also known as autoimmune polyendocrinopathy-candidiasis-ectodermal-dystrophy, is a rare autosomal recessive disease due to pathogenic variants in the AIRE gene. Classic features of the syndrome are mucocutaneous candidiasis, chronic idiopathic hypoparathyroidism and Addison disease. However, other endocrine and non-endocrine components, may occur with a different prevalence. In addition to ectodermal features, which are quite common features of the disease, APS 1 patients may experience other types of skin alterations, such as vasculitic skin rash. An early diagnosis of APS 1 can be very challenging, due to the high clinical heterogeneity, and a considerable delay may occur between the appearance of symptoms and the diagnosis. We report on a girl affected by APS 1 who presented with cutaneous vasculitis when she was seven-months old, some years before the onset of the common components of the disease. Clinical picture of APS 1 may be characterized by isolated rare or atypical autoimmune or immune-mediated manifestations, even years before the onset of the classic components of the disease. Among these uncommon features, skin rashes of variable form and duration may occur, most of them being associated with histopathological features of vasculitis. Our case suggests that cutaneous vasculitis may represent a first sign of APS 1. The clinical significance of cutaneous vasculitis in the context of APS 1 is still debated. It may represent a rare, unusual, early component of the disease or a clinical manifestation secondarily related to the typical APS 1 components (i.e. autoimmune thyroid disease), which are frequently associated with rheumatologic-like signs and symptoms. Alternatively, it may be the expression of an independent disease co-occuring with APS 1. In conclusion, our case suggests that children presenting with unexplained vasculitic skin rash should be followed-up in order to early identify APS 1.

  3. Altered expression of circadian clock genes in polyglandular autoimmune syndrome type III.

    Science.gov (United States)

    Angelousi, Anna; Nasiri-Ansari, Narjes; Spilioti, Eliana; Mantzou, Emilia; Kalotyxou, Vasiliki; Chrousos, George; Kaltsas, Gregory; Kassi, Eva

    2018-01-01

    Circadian timing system is a highly conserved, ubiquitous molecular "clock" which creates internal circadian rhythmicity. Dysregulation of clock genes expression is associated with various diseases including immune dysregulation. In this study we investigated the circadian pattern of Clock-related genes in patients with polyglandular autoimmune syndrome type III (PAS type III). Nineteen patients diagnosed with PAS type III and 12 healthy controls were enrolled. mRNA and protein expression of Clock-related genes (CLOCK, BMAL1, ROR and Per-1,-2,-3), as well as the GR-a and the GILZ genes were determined by real-time quantitative PCR and western blot analysis from blood samples drawn at 8 pm and 8am. Serum cortisol and TSH, as well as plasma ACTH, were measured by chemiluminescence. There were no statistical significant differences in the metabolic profile, cortisol, ACTH and TSH levels between patients and controls. Patients with PAS type III expressed higher transcript levels of CLOCK, BMAL1 and Per-1 in the evening than in the morning (p = 0.03, p = 0.029, p = 0.013, respectively), while the ratios (R pm/am ) of GR-a, CLOCK, BMAL1, and Per-3 mRNA levels were statistically different between patients and controls. Cortisol circadian variation (F pm/am ) was positively correlated with GILZ mRNA circadian pattern (R pm/am ) in the patient group and with the GR-a mRNA (R pm/am ) in the control group. Our findings suggest that there is an aberrant circadian rhythm of Clock-related genes in patients with PAS type III. The disruption of the expression of 4 circadian Clock-related genes could indicate a possible association with the pathogenesis of the disease.

  4. The serological profile of the autoimmune hepatitis/primary biliary cirrhosis overlap syndrome.

    Science.gov (United States)

    Muratori, Paolo; Granito, Alessandro; Pappas, Georgios; Pendino, Gaspare M; Quarneti, Chiara; Cicola, Ronny; Menichella, Rita; Ferri, Silvia; Cassani, Fabio; Bianchi, Francesco B; Lenzi, Marco; Muratori, Luigi

    2009-06-01

    During the last decade patients with concomitant clinical, biochemical, immunoserological, and histological features of both autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC) were sporadically described, but definite diagnostic criteria and specific serological markers to support the diagnosis of AIH/PBC overlap syndrome (AIH/PBC OS) are still lacking. Clinical, biochemical, and histological features, autoantibody profile, and treatment response of 15 patients with coexistent hepatitic and cholestatic liver damage, all fulfilling strict diagnostic criteria for both AIH and PBC, were compared with those of 120 patients with pure PBC and 120 patients with pure AIH. At diagnosis, the AIH/PBC OS patients' median age was 51 years, similar to that of the PBC patients (52 years, P=NS), but significantly higher than that of the AIH patients (40 years, P=0.04). Anti-dsDNA antibodies were detected in 60% of AIH/PBC OS patients, but only in 4% of PBC patients and 26% of AIH patients (P<0.0001 and 0.01, respectively). Double positivity for antimitochondrial antibodies (AMA) and anti-dsDNA was present in 47% of those with AIH/PBC OS, but only in 2% of the pathological controls (P<0.0001; specificity: 98; 95% confidence interval (CI): 97-99.2; positive likelihood ratio: 28; 95% CI: 9.8-79.4). Combined therapy (ursodeoxycholic acid (UDCA) plus steroids) achieved biochemical response in 77% of AIH/PBC OS patients. Concomitant AMA/anti-dsDNA seropositivity can be considered the serological profile of AIH/PBC OS. The combination of UDCA and steroids is effective in achieving persistent biochemical amelioration in most AIH/PBC OS patients.

  5. X-Linked Lymphoproliferative Disease Presenting as Pancytopenia in a 10-Month-Old Boy

    Directory of Open Access Journals (Sweden)

    S. Nicole Chadha

    2010-01-01

    Full Text Available X-linked lymphoproliferative disease, also known as Duncan's syndrome, is a rare genetic disorder that causes exaggerated immune responses to Epstein-Barr virus (EBV infection and often leads to death. Patient presentation varies but can include signs and symptoms typical of EBV, pancytopenia, and fulminant hepatitis.

  6. [Autoimmune channelopathies].

    Science.gov (United States)

    Michaud, M; Delrieu, J; Astudillo, L

    2011-12-01

    Autoimmune channelopathies are rare neuromuscular diseases that have been characterized clinically for several decades but for which the evidence of associated antibodies has only been recently demonstrated. Ion channels have an important role of activation, inhibition and regulation in neuromuscular transmission. Myasthenia gravis, generally associated with the presence of anti-acetylcholine receptor antibody, is the best-known channelopathy. Other anti-channel antibodies, including voltage-dependent, are associated with several neurological diseases, as illustrated by anti-voltage-gated calcium channels found in Lambert-Eaton myasthenic syndrome and paraneoplastic cerebellar ataxia, and anti-voltage-gated potassium channels found in neuromyotonia, Morvan's syndrome and limbic encephalitis. The treatment of autoimmune channelopathies is logically based on corticosteroids, immunosuppressant drugs, intravenous immunoglobulins and plasmapheresis. Copyright © 2011 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  7. Autoimmune myelofibrosis accompanied by Sjögren's syndrome in a 47, XXX/46, XX mosaic woman.

    Science.gov (United States)

    Takahashi, Tohru

    2014-01-01

    This report describes a patient with autoimmune myelofibrosis accompanied by Sjögren's syndrome (SS). A 36-year-old woman was admitted due to petechiae, purpura, gingival bleeding, dyspnea on exertion, and a lack of concentration. She had pancytopenia and was diagnosed with SS. A bone marrow study showed hypercellular marrow with reticulin fibrosis. Lymphocytic infiltrates and aggregates composed of a mixture of T and B cells in the marrow were also observed. A chromosomal analysis of the marrow cells showed 47, XXX and an analysis of peripheral lymphocytes revealed 47, XXX/46, XX mosaic results. The patient's cytopenia resolved following treatment with oral prednisolone.

  8. A strange case of Evans syndrome

    Directory of Open Access Journals (Sweden)

    Manuel Monti

    2013-12-01

    Full Text Available Evans syndrome is a rare autoimmune disease presenting hemolytic anemia, thrombocytopenia and/or neutropenia. It may be associated with other autoimmune or lymphoproliferative diseases. It can have an extremely serious disease course and, in rare cases, this can even be life-threatening. First-line treatment consists of steroids and/or immunoglobulin. Further therapy with rituximab, vincristine, cyclophosphamide and other immunosuppressive drugs can be considered in unresponsive patients. We report a case of Evans syndrome in a 54-year old woman admitted to the Emergency Department (ED for asthenia. Etiopathogenic, clinical, therapeutic and evolutive aspects are discussed. In contrast to many cases described in the literature, our patient had a satisfactory response to corticoids. We also discuss how to make a specific diagnosis, even in a suburban ED with limited resources, in order to admit patients to the appropriate hospital department and allow the correct therapy to be started as early as possible.

  9. Melkersson-Rosenthal syndrome with Hashimoto thyroiditis in a 9-year-old girl: an autoimmune disorder.

    Science.gov (United States)

    Lee, Yun-Jin; Cheon, Chong Kun; Yeon, Gyu Min; Kim, Young Mi; Nam, Sang Ook

    2014-05-01

    Melkersson-Rosenthal syndrome (MRS) is a rare disorder of unknown cause. The classical triad of MRS is orofacial edema, recurrent facial paralysis, and a fissured tongue. We present a 9-year-old girl with a recurrent peripheral facial paralysis. She experienced the first episode of a peripheral facial paralysis on the same side without orofacial swelling and lingua plicata 1 year ago. She was diagnosed with Hashimoto thyroiditis 9 months earlier, as confirmed by an endocrinologic investigation. While the patient was hospitalized with recurrent facial paralysis, we found that serum levels of free thyroxine (1.3 ng/dL) and thyrotropin (0.4 uIU/mL) were within normal range, but the level of antithyroperoxidase antibodies (772.0 IU/mL) was very increased. She had been taking an oral prednisolone orally for 2 weeks. At the 1-month follow-up, the patient's symptoms had completely disappeared. The possible correlation between MRS and autoimmune disorders has been documented in only one report, which described an adult with autoimmune thyroiditis (Hashimoto thyroiditis) and MRS. We suggest that the co-occurrence of MRS and Hashimoto thyroiditis is not coincidental but linked to autoimmunity. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Towards a further understanding of prenatal thyroid theory of homosexuality: Autoimmune thyroiditis, polycystic ovary syndrome, autism and low birth weight

    Directory of Open Access Journals (Sweden)

    Osman Sabuncuoglu

    2017-10-01

    Full Text Available Research into the neurobiological origins of same-sex attraction is inconclusive. A recent theory of homosexuality posited that maternal thyroid dysfunction during pregnancy is associated with an increased rate of homosexual orientation in offspring. Relevant studies from the prenatal thyroid model perspective were reviewed, the major findings of which are as follows: i An increased prevalence of Hashimoto’s disease in lesbian women suggests a maternal and even familial presence of the same autoimmune thyroid disease. Female-tomale transsexuals and lesbian women were also reported to have higher rates of polycystic ovary syndrome (PCOS. Over the last several years, reports suggesting a strong link between PCOS and thyroid autoimmunity have accumulated. ii The increased risk of autism spectrum disorders (ASD in the offspring of mothers with thyroid autoimmunity in pregnancy and the association between ASD and gender dysphoria indicate a link between maternal thyroid dysfunction and gender dysphoria/same-sex attraction in the offspring. iii The high risk of miscarriage and retarded fetal growth in pregnancies of mothers who give birth to homosexual offspring can be explained by the impact of maternal thyroid dysfunction during pregnancy. This perspective review highlights relevant research findings and integrates them into the prenatal thyroid model of homosexuality. A better understanding of the mechanisms involved in the generation of same-sex orientation will contribute to the betterment of individual lives, as well as of society.

  11. A Case of Autoimmune Polyglandular Syndrome (APS) Type II with Hypothyroidism, Hypoadrenalism, and Celiac Disease - A Rare Combination.

    Science.gov (United States)

    Lakhotia, Manoj; Pahadia, Hans Raj; Kumar, Harish; Singh, Jagdish; Tak, Sandeep

    2015-04-01

    Autoimmune Polyglandular syndrome (APS) are rare condition characterised by presence of immune dysfunction of two or more endocrine glands and other non-endocrine organs. APS is divided into 2 major subtypes based on age of presentation, pattern of disease combinations and mode of inheritance. APS 1(juvenile) usually manifest in early adolescence or in infancy. It is characterised by multiple endocrinal deficiency with mucocutaneous candidiasis and ectodermal dystrophy. Of the endocrine diseases, hypoparathyroidism form an important component followed by Addison's disease, type 1A diabetes, hypogonadism and thyroid disease. On the other hand APS II usually manifest in 3rd or 4th decade of life with female preponderance. Endocrine diseases commonly include autoimmune thyroid disease (graves or autoimmune thyroiditis), type 1A diabetes, and Addison's disease. Hypoparathyroidism is of rare occurrence and there is no mucocutaneous candidiasis. We report here a case of APS type II in a 29-year-old male who initially presented with hypothyroidism, which was soon followed by Addison's disease. The involvement of thyroid gland preceding the involvement of adrenal is of rare occurrence. The patient also had celiac disease which makes the combination further uncommon.

  12. Is chronic fatigue syndrome an autoimmune disorder of endogenous neuropeptides, exogenous infection and molecular mimicry?

    Science.gov (United States)

    Staines, Donald R

    2004-01-01

    Chronic fatigue syndrome is a disorder characterised by prolonged fatigue and debility and is mostly associated with post-infection sequelae although ongoing infection is unproven. Immunological aberration is likely and this may prove to be associated with an expanding group of vasoactive neuropeptides in the context of molecular mimicry and inappropriate immunological memory. Vasoactive neuropeptides including vasoactive intestinal peptide (VIP) and pituitary adenylate activating polypeptide (PACAP) belong to the secretin/glucagon superfamily and act as hormones, neurotransmitters, immune modulators and neurotrophes. They are readily catalysed to smaller peptide fragments by antibody hydrolysis. They and their binding sites are immunogenic and are known to be associated with a range of autoimmune conditions. Vasoactive neuropeptides are widely distributed in the body particularly in the central, autonomic and peripheral nervous systems and have been identified in the gut, adrenal gland, reproductive organs, vasculature, blood cells and other tissues. They have a vital role in maintaining vascular flow in organs, and in thermoregulation, memory and concentration. They are co-transmitters for acetylcholine, nitric oxide, endogenous opioids and insulin, are potent immune regulators with primarily anti-inflammatory activity, and have a significant role in protection of the nervous system to toxic assault, promotion of neural development and the maintenance of homeostasis. This paper describes a biologically plausible mechanism for the development of CFS based on loss of immunological tolerance to the vasoactive neuropeptides following infection, significant physical exercise or de novo. It is proposed that release of these substances is accompanied by a loss of tolerance either to them or their receptor binding sites in CFS. Such an occurrence would have predictably serious consequences resulting from compromised function of the key roles these substances perform. All

  13. [Thymoma and autoimmune diseases].

    Science.gov (United States)

    Jamilloux, Y; Frih, H; Bernard, C; Broussolle, C; Petiot, P; Girard, N; Sève, P

    2018-01-01

    The association between thymoma and autoimmunity is well known. Besides myasthenia gravis, which is found in 15 to 20% of patients with thymoma, other autoimmune diseases have been reported: erythroblastopenia, systemic lupus erythematosus, inflammatory myopathies, thyroid disorders, Isaac's syndrome or Good's syndrome. More anecdotally, Morvan's syndrome, limbic encephalitis, other autoimmune cytopenias, autoimmune hepatitis, and bullous skin diseases (pemphigus, lichen) have been reported. Autoimmune diseases occur most often before thymectomy, but they can be discovered at the time of surgery or later. Two situations require the systematic investigation of a thymoma: the occurrence of myasthenia gravis or autoimmune erythroblastopenia. Nevertheless, the late onset of systemic lupus erythematosus or the association of several autoimmune manifestations should lead to look for a thymoma. Neither the characteristics of the patients nor the pathological data can predict the occurrence of an autoimmune disease after thymectomy. Thus, thymectomy usefulness in the course of the autoimmune disease, except myasthenia gravis, has not been demonstrated. This seems to indicate the preponderant role of self-reactive T lymphocytes distributed in the peripheral immune system prior to surgery. Given the high infectious morbidity in patients with thymoma, immunoglobulin replacement therapy should be considered in patients with hypogammaglobulinemia who receive immunosuppressive therapy, even in the absence of prior infection. Copyright © 2017 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  14. Clinical heterogeneity and diagnostic delay of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome.

    Science.gov (United States)

    Mazza, Cinzia; Buzi, Fabio; Ortolani, Federica; Vitali, Alberto; Notarangelo, Lucia D; Weber, Giovanna; Bacchetta, Rosa; Soresina, Annarosa; Lougaris, Vassilios; Greggio, Nella A; Taddio, Andrea; Pasic, Srdjan; de Vroede, Monique; Pac, Malgorzata; Kilic, Sara Sebnem; Ozden, Sanal; Rusconi, Roberto; Martino, Silvana; Capalbo, Donatella; Salerno, Mariacarolina; Pignata, Claudio; Radetti, Giorgio; Maggiore, Giuseppe; Plebani, Alessandro; Notarangelo, Luigi D; Badolato, Raffaele

    2011-04-01

    Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare autosomal recessive organ-specific autoimmune disorder that is characterized by a variable combination of (i) chronic mucocutaneous candidiasis, (ii) polyendocrinopathy and/or hepatitis and (iii) dystrophy of the dental enamel and nails. We analyzed the AIRE (autoimmune regulator) gene in subjects who presented any symptom that has been associated with APECED, including candidiasis and autoimmune endocrinopathy. We observed that 83.3% of patients presented at least two of the three typical manifestations of APECED, while the remaining 16.7% of patients showed other signs of the disease. Analysis of the genetic diagnosis of these subjects revealed that a considerable delay occurs in the majority of patients between the appearance of symptoms and the diagnosis. Overall, the mean diagnostic delay in our patients was 10.2 years. These results suggest that molecular analysis of AIRE should be performed in patients with relapsing mucocutaneous candidiasis for early identification of APECED. Copyright © 2010 Elsevier Inc. All rights reserved.

  15. Primary biliary cirrhosis-autoimmune hepatitis overlap syndrome: simplified criteria may be effective in the diagnosis in Chinese patients.

    Science.gov (United States)

    Liu, Fang; Pan, Zhen Guo; Ye, Jin; Xu, Dong; Guo, Hui; Li, Gang Ping; Xu, Ke Shu; Hou, Xiao Hua; Song, Yu Hu

    2014-12-01

    To evaluate the Paris criteria, the revised diagnostic criteria and the simplified diagnostic scoring system in the diagnosis of primary biliary cirrhosis (PBC)-autoimmune hepatitis (AIH) overlap syndrome in Chinese patients. Medical records of the patients who were diagnosed with PBC at the Union Hospital and Tongji Hospital, Tongji Medical University, Huazhong University of Science and Technology (Wuhan, Hubei Province, China) from 2003 to 2012 were retrospectively reviewed. The overlap syndrome was diagnosed based on the Paris criteria, the revised criteria and the simplified criteria, respectively. Patients' clinical characteristics, laboratory examination results and histological findings were collected. The sensitivity and specificity of the three criteria for diagnosing PBC-AIH overlap syndrome were calculated. PBC-AIH overlap syndrome was diagnosed in 2, 13 and 10 patients with PBC based on the Paris, the revised and the simplified criteria, respectively. The sensitivity and specificity of the simplified criteria in diagnosing the overlap syndrome was 90.0% and 98.2%, which were the highest among the three criteria, followed by the revised criteria. The Paris criteria showed a high specificity (100%) but a relatively low sensitivity (20.0%). In addition, some patients who did not fulfil the Paris criteria still benefited from the immunosuppressive agents. For Chinese patients with the PBC-AIH overlap syndrome, the simplified criteria appear to be the most efficacious compared with the Paris criteria and the revised criteria. Further studies should be performed to confirm these observations with respect to long-term outcomes and therapeutic implications. © 2014 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

  16. Chronic fatigue syndrome and fibromyalgia following immunization with the hepatitis B vaccine: another angle of the 'autoimmune (auto-inflammatory) syndrome induced by adjuvants' (ASIA).

    Science.gov (United States)

    Agmon-Levin, Nancy; Zafrir, Yaron; Kivity, Shaye; Balofsky, Ari; Amital, Howard; Shoenfeld, Yehuda

    2014-12-01

    The objectives of this study were to gather information regarding demographic and clinical characteristics of patients diagnosed with either fibromyalgia (FM) or chronic fatigue (CFS) following hepatitis B vaccination (HBVv) and furthermore to apply the recently suggested criteria of autoimmune (auto-inflammatory) syndromes induced by adjuvants (ASIA), in the aim of identifying common characteristics that may suggest an association between fibromyalgia, chronic fatigue and HBV vaccination. Medical records of 19 patients with CFS and/or fibromyalgia following HBVv immunization were analyzed. All of which were immunized during 1990-2008 in different centers in the USA. All medical records were evaluated for demographics, medical history, the number of vaccine doses, as well as immediate and long term post-immunization adverse events and clinical manifestations. In addition, available blood tests, imaging results, treatments and outcomes were analyzed. ASIA criteria were applied to all patients. The mean age of patients was 28.6 ± 11 years, of which 68.4 % were females. 21.05 % had either personal or familial background of autoimmune disease. The mean latency period from the last dose of HBVv to onset of symptoms was 38.6 ± 79.4 days, ranging from days to a year. Eight (42.1 %) patients continued with the immunization program despite experiencing adverse events. Manifestations that were commonly reported included neurological manifestations (84.2 %), musculoskeletal (78.9 %), psychiatric (63.1 %), fatigue (63.1 %), gastrointestinal complains (58 %) and mucocutaneous manifestations (36.8 %). Autoantibodies were detected in 71 % of patients tested. All patients fulfilled the ASIA criteria. This study suggests that in some cases CFS and FM can be temporally related to immunization, as part of ASIA syndrome. The appearance of adverse event during immunization, the presence of autoimmune susceptibility and higher titers of autoantibodies all can be suggested as risk

  17. Membranoproliferative glomerulonephritis in the setting of multicentric angiofollicular lymph node hyperplasia (Castleman's disease) complicated by Evan's syndrome.

    Science.gov (United States)

    Gakiopoulou, Hariklia; Korkolopoulou, Penelope; Paraskevakou, Helen; Marinaki, Smaragdi; Voulgarelis, Michael; Stofas, Anastasios; Lelouda, Maria; Lazaris, Andreas C; Boletis, John; Patsouris, Efstratios

    2010-06-01

    Systemic Castleman's disease is a lymphoproliferative disorder with various clinical presentations and incompletely understood aetiology. The authors report on a rare case of the plasma cell variant of Castleman's disease associated with autoimmune haemolytic anaemia and autoimmune thrombocytopenia (Evan's syndrome) and complicated by mixed nephrotic-nephritic syndrome and acute renal failure due to an underlying glomerulopathy with microscopic and immunofluorescence findings suggestive of membranoproliferative glomerulonephritis (MPGN) type I. Immunocomplexed glomerulonephritis is rare in Castleman's disease, while, to the best of our knowledge, constellation of all these autoimmune phenomena is reported for the first time suggesting that apart from the putative role of VEGF and IL-6 in the pathogenesis of the disease, a more generalised immunological disturbance occurs, probably through autoantibodies induced by active polyclonal B cells raised from Castleman's disease tumour.

  18. Development of central nervous system autoimmunity is impaired in the absence of Wiskott-Aldrich syndrome protein.

    Directory of Open Access Journals (Sweden)

    Marita Bosticardo

    Full Text Available Wiskott-Aldrich Syndrome protein (WASP is a key regulator of the actin cytoskeleton in hematopoietic cells. Defective expression of WASP leads to multiple abnormalities in different hematopoietic cells. Despite severe impairment of T cell function, WAS patients exhibit a high prevalence of autoimmune disorders. We attempted to induce EAE, an animal model of organ-specific autoimmunity affecting the CNS that mimics human MS, in Was(-/- mice. We describe here that Was(-/- mice are markedly resistant against EAE, showing lower incidence and milder score, reduced CNS inflammation and demyelination as compared to WT mice. Microglia was only poorly activated in Was(-/- mice. Antigen-induced T-cell proliferation, Th-1 and -17 cytokine production and integrin-dependent adhesion were increased in Was(-/- mice. However, adoptive transfer of MOG-activated T cells from Was(-/- mice in WT mice failed to induce EAE. Was(-/- mice were resistant against EAE also when induced by adoptive transfer of MOG-activated T cells from WT mice. Was(+/- heterozygous mice developed an intermediate clinical phenotype between WT and Was(-/- mice, and they displayed a mixed population of WASP-positive and -negative T cells in the periphery but not in their CNS parenchyma, where the large majority of inflammatory cells expressed WASP. In conclusion, in absence of WASP, T-cell responses against a CNS autoantigen are increased, but the ability of autoreactive T cells to induce CNS autoimmunity is impaired, most probably because of an inefficient T-cell transmigration into the CNS and defective CNS resident microglial function.

  19. A novel heterozygous mutation of the AIRE gene in a patient with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome (APECED).

    Science.gov (United States)

    Fierabracci, Alessandra; Bizzarri, Carla; Palma, Alessia; Milillo, Annamaria; Bellacchio, Emanuele; Cappa, Marco

    2012-12-10

    Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome (APECED) is an autosomal recessive disease due to mutations of the autoimmune regulator (AIRE) gene. Typical manifestations include candidiasis, Addison's disease, and hypoparathyroidism. Type 1 diabetes, alopecia, vitiligo, ectodermal dystrophy, celiac disease and other intestinal dysfunctions, chronic atrophic gastritis, chronic active hepatitis, autoimmune thyroid disorders, pernicious anemia and premature ovarian failure are other rare associated diseases although other conditions have been associated with APECED. What follows is the clinical, endocrinological and molecular data of a female APECED patient coming from Lithuania. The patient was affected by chronic mucocutaneous candidiasis, hypoparathyroidism and pre-clinical Addison's disease. Using direct sequencing of all the 14 exons of the AIRE gene in the patient's DNA, we identified in exon 6 the known mutation c.769 C>T (p.Arg257X) in compound heterozygosity with the newly discovered mutation c.1214delC (p.Pro405fs) in exon 10. The novel mutation results in a frameshift that is predicted to alter the sequence of the protein starting from amino acid 405 as well as to cause its premature truncation, therefore a non-functional Aire protein. A novel mutation has been described in a patient with APECED with classical clinical components, found in compound heterozygosity with the c.769 C>T variation. Expanded epidemiological investigations based on AIRE gene sequencing are necessary to verify the relevancy of the novel mutation to APECED etiopathogenesis in the Lithuanian population and to prove its diagnostic efficacy in association with clinical and immunological findings. Copyright © 2012 Elsevier B.V. All rights reserved.

  20. Analysis of PTPN22, ZFAT and MYO9B polymorphisms in Turner Syndrome and risk of autoimmune disease.

    Science.gov (United States)

    Villanueva-Ortega, E; Ahedo, B; Fonseca-Sánchez, M A; Pérez-Durán, J; Garibay-Nieto, N; Macías-Galavíz, M T; Trujillo-Cabrera, Y; García-Latorre, E; Queipo, G

    2017-08-01

    Turner syndrome (TS) is one of the most common sexual chromosome abnormalities and is clearly associated with an increased risk of autoimmune diseases, particularly thyroid disease and coeliac disease (CD). Single-nucleotide polymorphism analyses have been shown to provide correlative evidence that specific genes are associated with autoimmune disease. Our aim was to study the functional polymorphic variants of PTPN22 and ZFAT in relation to thyroid disease and those of MYO9B in relation to CD. A cross-sectional comparative analysis was performed on Mexican mestizo patients with TS and age-matched healthy females. Our data showed that PTPN22 C1858T (considered a risk variant) is not associated with TS (X 2  = 3.50, p = .61, and OR = 0.33 [95% CI = 0.10-1.10]). Also, ZFAT was not associated with TS (X 2  = 1.2, p = .28, and OR = 1.22 [95% CI = 0.84-1.79]). However, for the first time, rs2305767 MYO9B was revealed to have a strong association with TS (X 2  = 58.6, p = .0001, and OR = 10.44 [95% C = 5.51-19.80]), supporting a high level of predisposition to CD among TS patients. This report addresses additional data regarding the polymorphic variants associated with autoimmune disease, one of the most common complications in TS. © 2017 John Wiley & Sons Ltd.

  1. Síndrome linfoproliferativo ligado al cromosoma X, infección por el virus EBV y defectos en la regulación de la citotoxicidad linfocitaria X-linked lymphoproliferative syndrome, EBV infection and impaired regulation of cell-mediated cytotoxicity

    Directory of Open Access Journals (Sweden)

    A. Malbrán

    2003-01-01

    Full Text Available La deficiencia del gen SH2D1A que codifica para la proteína reguladora SAP trae aparejada la activación incontrolada de la vía de activación linfocitaria señalizada por SLAM (molécula señaladora de la activación linfocitaria. Es una inmunodeficiencia ligada al cromosoma X (XLP que se pone en evidencia cuando los pacientes portadores de mutaciones en el gen se enfrentan con el virus de Epstein Barr, desarrollando una mononucleosis infecciosa fulminante. Algunos pacientes desarrollan un síndrome linfoproliferativo fatal; los que sobreviven pueden presentar hipogammaglobulinemia severa y mayor frecuencia de neoplasia hematológica que la población normal. En esta revisión se discuten los mecanismos inmuno-regulatorios involucrados en el desarrollo de la patología mencionada, así como la participación de diferentes células efectoras de la respuesta inmune (linfocitos CD8 citotóxicos, células NK.Mutations in SH2D1A, a gene that codifies for the regulatory protein SAP, result in uncontrolled activation of the SLAM (signaling lymphocyte-activation molecule pathway. This X-linked immunodeficiency becomes evident when the patients are infected with Epstein Barr virus (EBV and develop a fulminant form of infectious mononucleosis leading to a lymphoproliferative syndrome that is often fatal (X-linked lymphoproliferative syndrome, XLP. In those who survive, hypogammaglobulinemia and oncohematologic diseases are frequently observed. In this revision, the immuno-regulatory mechanisms involved in XLP immunopathology and the role of different effector cells (CD8 T lymphocytes, NK cells are discussed.

  2. AIRE variations in Addison's disease and autoimmune polyendocrine syndromes (APS): partial gene deletions contribute to APS I.

    Science.gov (United States)

    Bøe Wolff, A S; Oftedal, B; Johansson, S; Bruland, O; Løvås, K; Meager, A; Pedersen, C; Husebye, E S; Knappskog, P M

    2008-03-01

    Autoimmune Addison's disease (AAD) is often associated with other components in autoimmune polyendocrine syndromes (APS). Whereas APS I is caused by mutations in the AIRE gene, the susceptibility genes for AAD and APS II are unclear. In the present study, we investigated whether polymorphisms or copy number variations in the AIRE gene were associated with AAD and APS II. First, nine SNPs in the AIRE gene were analyzed in 311 patients with AAD and APS II and 521 healthy controls, identifying no associated risk. Second, in a subgroup of 25 of these patients, AIRE sequencing revealed three novel polymorphisms. Finally, the AIRE copy number was determined by duplex quantitative PCR in 14 patients with APS I, 161 patients with AAD and APS II and in 39 healthy subjects. In two Scandinavian APS I patients previously reported to be homozygous for common AIRE mutations, we identified large deletions of the AIRE gene covering at least exon 2 to exon 8. We conclude that polymorphisms in the AIRE gene are not associated with AAD and APS II. We further suggest that DNA analysis of the parents of patients found to be homozygous for mutations in AIRE, always should be performed.

  3. Rapidly progressive post-transplant lymphoproliferative disease ...

    African Journals Online (AJOL)

    of patients, and just over half of these affect only the brain.1,2. Presentation is often late, with mortality rates in excess of 60%.2. PTLD comprises a heterogeneous group of lymphoproliferative diseases, ranging from the early indolent disorders that resemble infectious mononucleosis, through to polymorphic PTLD and onto.

  4. Type 1 Diabetes in Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy Syndrome (APECED): A “Rare” Manifestation in a “Rare” Disease

    Science.gov (United States)

    Fierabracci, Alessandra

    2016-01-01

    Type 1 autoimmune polyglandular syndrome (APS1) is a rare autosomal recessive disease, caused by mutations in the autoimmune regulator gene (AIRE); the encoded Aire protein plays an important role in the establishment of the immunological tolerance acting as a transcriptional regulator of the expression of organ-specific antigens within the thymus in perinatal age. While a high prevalence for this rare syndrome is reported in Finland and Scandinavia (Norway), autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome (APECED) cohorts of patients are also detected in continental Italy and Sardinia, among Iranian Jews, as well as in other countries. The syndrome is diagnosed when patients present at least two out of the three fundamental disorders including chronic mucocutaneous candidiasis, hypoparathyroidism, and Addison’s disease. Among the associated conditions insulin-dependent diabetes mellitus (Type 1 diabetes) has been rarely reported in different series of patients and occurring more frequently in Finnish APECED patients. In this review, we analyze the incidence of Type 1 diabetes as a clinical manifestation of APECED in different populations highlighting the peculiar genetic and immunological features of the disease when occurring in the context of this syndrome. PMID:27420045

  5. Type 1 Diabetes in Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy Syndrome (APECED: A “Rare” Manifestation in a “Rare” Disease

    Directory of Open Access Journals (Sweden)

    Alessandra Fierabracci

    2016-07-01

    Full Text Available Type 1 autoimmune polyglandular syndrome (APS1 is a rare autosomal recessive disease, caused by mutations in the autoimmune regulator gene (AIRE; the encoded Aire protein plays an important role in the establishment of the immunological tolerance acting as a transcriptional regulator of the expression of organ-specific antigens within the thymus in perinatal age. While a high prevalence for this rare syndrome is reported in Finland and Scandinavia (Norway, autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome (APECED cohorts of patients are also detected in continental Italy and Sardinia, among Iranian Jews, as well as in other countries. The syndrome is diagnosed when patients present at least two out of the three fundamental disorders including chronic mucocutaneous candidiasis, hypoparathyroidism, and Addison’s disease. Among the associated conditions insulin-dependent diabetes mellitus (Type 1 diabetes has been rarely reported in different series of patients and occurring more frequently in Finnish APECED patients. In this review, we analyze the incidence of Type 1 diabetes as a clinical manifestation of APECED in different populations highlighting the peculiar genetic and immunological features of the disease when occurring in the context of this syndrome.

  6. Hodgkin’s lymphoma presenting as autoimmune hemolytic anemia

    Directory of Open Access Journals (Sweden)

    Sohaila Fatima

    2017-01-01

    Full Text Available Hodgkin’s lymphoma is a B-cell neoplasm, which usually presents with painless lymphadenopathy. Its presentation with autoimmune hemolytic anemia (AIHA is rare, although the association of AIHA with other lymphoproliferative disorders is well known. Here, we report a case of a patient with warm AIHA who presented in a critical condition to hospital and was diagnosed with HL.

  7. [Autoimmune disorder secondary to DiGeorge syndrome: a long-term follow-up case report and literature review].

    Science.gov (United States)

    Xie, Y; Guo, J Q; Hua, Y; Zhao, W H; Sun, Q; Lu, X T

    2016-12-18

    DiGeorge syndrome is the most common chromosome microdeletion disease. The classical complications include congenital heart disease, hypothyroidism, immunodeficiency, facial abnormalities, and hypocalcemia. According to whether there is an absence or hypoplasia of the thymus, DiGeorge syndrome can be divided into two types, complete DiGeorge syndrome and partial DiGeorge syndrome. The patient was a female born with congenital heart disease, facial abnormalities and cleft palate. When the patient went to school, she had learning difficulty and had problems in communication and personal social behavior. Breath-holding occurred when she was 6 years old. She got infections about 2-3 times a year, which was easy to be cured each time. Chromosome microdeletion test of peripheral blood showed the classical 22q11.2 microdeletion, and no evidence showed that she has thymus absence, thus her disease was diagnosed as partial DiGeorge syndrome. When the patient was 6 years old, the blood routine test showed slight thrombocytopenia, and reexaminations after that indicated the similar result. When 9 years old, she was found with anemia and severe thrombocytopenia. At the age of 10, the patient was admitted to our hospital, complaining of petechia in the body and mucous of mouth. According to the various examinations results, doctors eventually considered the situation as an autoimmune disorder phenomenon. After being treated by pulse-dose methylprednisolone for three days, the bleeding ceased. Then the patient orally took prednisone acetate and pulse-dose cyclophosphamide, however the thrombocyte and hemoglobin levels had not been back to a normal range. But when the dose of prednisone acetate was reduced, the blood platelet count declined again while the hemoglobin kept normal. The long-term follow-up of this case lasted for more than 20 years. Until now, the patient is taking orally prednisone acetate as a maintainance treatment, and the anemia has been improved since, but

  8. [Autoimmune thyroid disease and other non-endocrine autoimmune diseases].

    Science.gov (United States)

    Dilas, Ljiljana Todorović; Icin, Tijana; Paro, Jovanka Novaković; Bajkin, Ivana

    2011-01-01

    Autoimmune diseases are chronic conditions initiated by the loss of immunological tolerance to self-antigens. They constitute heterogeneous group of disorders, in which multiple alterations in the immune system result in a spectrum of syndromes that either target specific organs or affect the body systematically. Recent epidemiological studies have shown a possible shift of one autoimmune disease to another or the fact that more than one autoimmune disease may coexist in a single patient or in the same family. Numerous autoimmune diseases have been shown to coexist frequently with thyroid autoimmune diseases. AUTOIMMNUNE THYROID DISEASE AND OTHER ORGAN SPECIFIC NON-ENDOCRINE AUTOIMMUNE DISEASES: This part of the study reviews the prevalence of autoimmune thyroid disease coexisting with: pernicious anaemia, vitiligo, celiac disease, autoimmune liver disease, miastenia gravis, alopecia areata and sclerosis multiplex, and several recommendations for screening have been given. AUTOIMMUNE THYROID DISEASE AND OTHER ORGAN NON-SPECIFIC NON-ENDOCRINE AUTOIMMUNE DISEASES: Special attention is given to the correlation between autoimmune thyroid disease and rheumatoid arthritis, systemic lupus erythematosus, syndrome Sjögren, systemic sclerosis and mixed connective tissue disease. Screening for autoimmune thyroid diseases should be recommended in everyday clinical practice, in patients with primary organ-specific or organ non-specific autoimmune disease. Otherwise, in patients with primary thyroid autoimmune disease, there is no good reason of seeking for all other autoimmune diseases, although these patients have a greater risk of developing other autoimmune disease. Economic aspects of medicine require further analyzing of these data, from cost/benefit point of view to justified either mandatory screening or medical practitioner judgment.

  9. Posttransplant lymphoproliferative disorder: a pictorial review

    International Nuclear Information System (INIS)

    Burney, K.; Bradley, M.; Lyburn, I.; Hopkins, R.; Buckley, A.; Rye, A.

    2006-01-01

    Posttransplant lymphoproliferative disorder (PTLD) is a serious and potentially fatal complication after solid organ and haemopoietic stem cell transplantation. The frequency of PTLD varies with the type of organ transplant but overall it affects 2-10% of all solid organ transplant recipients. Most cases develop within 1 year after the transplant, although occasional cases present 5-10 years later. Posttransplant lymphoproliferative disorder is clinically and pathologically heterogeneous - the majority are of the non-Hodgkin's lymphoma type, whereas Hodgkin's lymphoma arising after transplantation is rare. We have retrospectively reviewed patients with a histological diagnosis of PTLD after a solid organ transplant. We present the imaging features and a clinical review of this condition. Early diagnosis of PTLD may alter the management and outcome of the disease. The radiologist can play a vital role in establishing the diagnosis by imaging features supplemented with percutaneous biopsy and also in monitoring the disease response to treatment

  10. Altered Immune Activation and IL-23 Signaling in Response to Candida albicans in Autoimmune Polyendocrine Syndrome Type 1

    Directory of Open Access Journals (Sweden)

    Øyvind Bruserud

    2017-09-01

    Full Text Available ObjectiveAutoimmune polyendocrine syndrome type 1 (APS-1 is a rare, childhood onset disease caused by mutations in the autoimmune regulator (AIRE gene. Chronic mucocutaneous candidiasis (CMC is one of the three major disease components and is, to date, mainly explained by the presence of neutralizing auto-antibodies against cytokines [interleukin (IL-17A, IL-17F, and IL-22] from T helper 17 cells, which are critical for the protection against fungal infections. However, patients without current auto-antibodies also present CMC and we, therefore, hypothesized that other immune mechanisms contribute to CMC in APS-1.MethodsWhole blood was stimulated with Candida albicans (C. albicans in a standardized assay, and immune activation was investigated by analyzing 46 secreted immune mediators. Then, peripheral blood mononuclear cells were stimulated with curdlan, a Dectin-1 agonist and IL-23 inducer, and the IL-23p19 response in monocytes was analyzed by flow cytometry.ResultsWe found an altered immune response in APS-1 patients compared with healthy controls. Patients fail to increase the essential ILs, such as IL-2, IL-17A, IL-22, and IL-23, when stimulating whole blood with C. albicans. A significantly altered IL-23p19 response was detected in patients’ monocytes upon stimulation with curdlan.ConclusionAPS-1 patients have an altered immune response to C. albicans including a dysregulation of IL-23p19 production in monocytes. This probably contributes to the selective susceptibility to CMC found in the majority of patients.

  11. Mutlifocal osseous posttransplantation lymphoproliferative disorder: case report

    Energy Technology Data Exchange (ETDEWEB)

    Lo, Ryan [University of Chicago, Department of Radiology, Chicago, IL (United States); Michalicek, Zachary [Northshore University Healthsystems, Department of Pathology, Evanston, IL (United States); Lazarus, Martin [Northshore University Healthsystems, Department of Radiology, Evanston, IL (United States)

    2015-02-14

    Posttransplant lymphoproliferative disorder (PTLD) is a known complication of organ transplantation, but musculoskeletal involvement of PTLD remains very rare. We present a case of recurrent PTLD of the bone in a heart transplant patient that was misdiagnosed as gout for several years. There are only a few cases of osseous PTLD in the literature, and we hope to better characterize its imaging findings on multiple imaging modalities. (orig.)

  12. In myalgic encephalomyelitis/chronic fatigue syndrome, increased autoimmune activity against 5-HT is associated with immuno-inflammatory pathways and bacterial translocation.

    Science.gov (United States)

    Maes, Michael; Ringel, Karl; Kubera, Marta; Anderson, George; Morris, Gerwyn; Galecki, Piotr; Geffard, Michel

    2013-09-05

    Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is accompanied by activation of immuno-inflammatory pathways, increased bacterial translocation and autoimmune responses to serotonin (5-HT). Inflammation is known to damage 5-HT neurons while bacterial translocation may drive autoimmune responses. This study has been carried out to examine the autoimmune responses to 5-HT in ME/CFS in relation to inflammation and bacterial translocation. We examined 5-HT antibodies in 117 patients with ME/CFS (diagnosed according to the centers for disease control and prevention criteria, CDC) as compared with 43 patients suffering from chronic fatigue (CF) but not fulfilling the CDC criteria and 35 normal controls. Plasma interleukin-1 (IL-1), tumor necrosis factor (TNF)α, neopterin and the IgA responses to Gram-negative bacteria were measured. Severity of physio-somatic symptoms was measured using the fibromyalgia and chronic fatigue syndrome rating scale (FF scale). The incidence of positive autoimmune activity against 5-HT was significantly higher (pimmune disorder. Copyright © 2013 Elsevier B.V. All rights reserved.

  13. Medical comorbidity in polycystic ovary syndrome with special focus on cardiometabolic, autoimmune, hepatic and cancer diseases

    DEFF Research Database (Denmark)

    Glintborg, Dorte; Andersen, Marianne

    2017-01-01

    PURPOSE OF REVIEW: Polycystic ovary syndrome (PCOS) is defined by hyperandrogenism, irregular menses and polycystic ovaries when other causes are excluded. The possible implication of increased morbidity in PCOS for screening and follow-up is uncertain and is reviewed in this article. RECENT...

  14. Aquaporin-4 IgG autoimmune syndrome and immunoreactivity associated with thyroid cancer

    DEFF Research Database (Denmark)

    Soelberg, Kerstin; Larsen, Stine Rosenkilde; Mørch, Marlene

    2016-01-01

    Tumor cells can express so-called onconeural antigens, which are normally restricted to mature neurons and glial cells in the CNS.1 The detection of neural-reactive immunoglobulin G (IgG) aids the diagnosis of paraneoplastic neurologic syndromes (PNS)1; however, the diagnostic utility and potenti...

  15. Update in endocrine autoimmunity.

    Science.gov (United States)

    Anderson, Mark S

    2008-10-01

    The endocrine system is a common target in pathogenic autoimmune responses, and there has been recent progress in our understanding, diagnosis, and treatment of autoimmune endocrine diseases. Rapid progress has recently been made in our understanding of the genetic factors involved in endocrine autoimmune diseases. Studies on monogenic autoimmune diseases that include endocrine phenotypes like autoimmune polyglandular syndrome type 1 and immune dysregulation, polyendocrinopathy, enteropathy, X-linked have helped reveal the role of key regulators in the maintenance of immune tolerance. Highly powered genetic studies have found and confirmed many new genes outside of the established role of the human leukocyte antigen locus with these diseases, and indicate an essential role of immune response pathways in these diseases. Progress has also been made in identifying new autoantigens and the development of new animal models for the study of endocrine autoimmunity. Finally, although hormone replacement therapy is still likely to be a mainstay of treatment in these disorders, there are new agents being tested for potentially treating and reversing the underlying autoimmune process. Although autoimmune endocrine disorders are complex in etiology, these recent advances should help contribute to improved outcomes for patients with, or at risk for, these disorders.

  16. Autoimmune predisposition in Down syndrome may result from a partial central tolerance failure due to insufficient intrathymic expression of AIRE and peripheral antigens.

    Science.gov (United States)

    Giménez-Barcons, Mireia; Casteràs, Anna; Armengol, Maria del Pilar; Porta, Eduard; Correa, Paula A; Marín, Ana; Pujol-Borrell, Ricardo; Colobran, Roger

    2014-10-15

    Down syndrome (DS), or trisomy of chromosome 21, is the most common genetic disorder associated with autoimmune diseases. Autoimmune regulator protein (AIRE), a transcription factor located on chromosome 21, plays a crucial role in autoimmunity by regulating promiscuous gene expression (pGE). To investigate if autoimmunity in DS is promoted by the reduction of pGE owing to dysregulation of AIRE, we assessed the expression of AIRE and of several peripheral tissue-restricted Ag genes by quantitative PCR in thymus samples from 19 DS subjects and 21 euploid controls. Strikingly, despite the 21 trisomy, AIRE expression was significantly reduced by 2-fold in DS thymuses compared with controls, which was also confirmed by fluorescent microscopy. Allele-specific quantification of intrathymic AIRE showed that despite its lower expression, the three copies are expressed. More importantly, decreased expression of AIRE was accompanied by a reduction of pGE because expression of tissue-restricted Ags, CHRNA1, GAD1, PLP1, KLK3, SAG, TG, and TSHR, was reduced. Of interest, thyroid dysfunction (10 cases of hypothyroidism and 1 of Graves disease) developed in 11 of 19 (57.9%) of the DS individuals and in none of the 21 controls. The thymuses of these DS individuals contained significantly lower levels of AIRE and thyroglobulin, to which tolerance is typically lost in autoimmune thyroiditis leading to hypothyroidism. Our findings provide strong evidence for the fundamental role of AIRE and pGE, namely, central tolerance, in the predisposition to autoimmunity of DS individuals. Copyright © 2014 by The American Association of Immunologists, Inc.

  17. Giant Splenorenal Shunt in a Young Patient with Autoimmune Hepatitis/Primary Biliary Cholangitis Overlap Syndrome and Portal Vein Thrombosis

    Directory of Open Access Journals (Sweden)

    F. Chegai

    2017-01-01

    Full Text Available We present a case of giant Splenorenal Shunt (SRS associated with portal vein thrombosis in a 37-year-old woman with a twelve-year history of autoimmune hepatitis/primary biliary cholangitis overlap syndrome. At the moment of the CT examination laboratory tests showed creatinine 1.5 mg/dl, bilirubin 1.5 mg/dl, INR 3, and Na 145 mmol/l and the Model End-Stage Liver Disease score was 24. Extensive calcified thrombosis causing complete occlusion of the portal vein lumen and partially occluding the origin of the superior mesenteric vein was present and a small calcified thrombus in the Splenic Vein lumen was also evident. SRS was located among the spleen hilum and the left kidney with a maximum diameter of 3.25 cm and was associated with dilatation of left renal vein and inferior vena cava. After a multidisciplinary evaluation the patient was put on the Regional Liver Transplant waiting list and liver transplantation was performed successfully. Although portal vein thrombosis and SRS are common occurrences in cirrhotic patients, the impact in the natural history of the disease is still unclear. Careful management and accurate imaging protocols are essential in the evaluation of those patients.

  18. An Immunogenic Peptide, T2 Induces Interstitial Cystitis/Painful Bladder Syndrome: an Autoimmune Mouse Model for Interstitial Cystitis/Painful Bladder Syndrome.

    Science.gov (United States)

    Zhang, Li; Ihsan, Awais Ullah; Cao, Yanfang; Khan, Farhan Ullah; Cheng, Yijie; Han, Lei; Zhou, Xiaohui

    2017-12-01

    The exact pathophysiology of interstitial cystitis/painful bladder syndrome is unknown; however, autoimmunity is a valid theory. We developed an autoimmune chronic cystitis model by administration of the medium dose of immunogenic peptide T2. Sixty female C57BL/6 mice were divided into six groups. The control group was not treated with any reagent. CFA group was injected with CFA + normal saline, homogenate group with bladder homogenate + CFA, low-dose group with low dose of T2 peptide + CFA, medium dose group with the medium dose of T2 peptide + CFA, and high-dose group with the high dose of T2 peptide + CFA. Micturition habits, withdrawal frequencies of mice, and bladders weight were measured for each group. Hematoxylin and eosin staining and toluidine blue staining were used to investigate bladder inflammation and mast cells accumulation, respectively. T cells infiltration in the bladder tissues and serum TNF-α level were measured by using immunohistochemistry and ELISA, respectively. Mice immunized with the medium dose of T2 peptide (0.225 mg/ml) were extremely sensitive to the applied force, showed greater urine frequencies, and higher bladder weights. Histologic examination revealed severe edema and inflammation in bladder tissues of medium-dose group. Extensive infiltration of T cells in bladder tissues, elevated TNF-α, and increased mast cells accumulation were observed in medium-dose group as compared to that in other groups. EAC mice model established by injecting the medium dose of T2 (0.225 mg/ml) mimics all the symptoms and pathophysiologic characteristics of IC/PBS. We believe that this model can help us to investigate the pathogenesis of IC/PBS.

  19. [Treatment of autoimmune hepatic diseases].

    Science.gov (United States)

    Bueverov, A O

    2004-01-01

    The immunosuppresive drugs, primarily glucocorticosteroids, serve as the basis for the pathogenetic treatment of autoimmune diseases of the liver. In autoimmune hepatitis, immunosuppressive therapy induces and maintains persistent remission in most patients while in primary biliary cirrhosis and primary sclerosing cholangitis, its capacities are substantially limited. Ursodeoxycholic acid is used as the basic drug in predominantly occurring intrahepatic cholestasis. The treatment of cross autoimmune syndromes generally requires the choice of a combination of drugs.

  20. Autoimmune polyendocrine syndrome type 1: Utility of KCNRG autoantibodies as a marker of active pulmonary disease and successful treatment with rituximab.

    Science.gov (United States)

    Popler, Jonathan; Alimohammadi, Mohammad; Kämpe, Olle; Dalin, Frida; Dishop, Megan K; Barker, Jennifer M; Moriarty-Kelsey, Margaret; Soep, Jennifer B; Deterding, Robin R

    2012-01-01

    Autoimmune polyendocrine syndrome type 1 (APS-1), also known as Autoimmune Polyendocrinopathy Candidiasis and Ectodermal Dysplasia (APECD) is a disorder caused by mutations in the autoimmune regulator (AIRE) gene. In some APS-1 patients, significant pulmonary disease is observed. Autoantibodies directed against the potassium channel regulatory protein (KCNRG), found in epithelial cells of terminal bronchioles, have been suggested as a marker for pulmonary disease in APS-1 patients. We report two patients with APS-1; one with and one without lung disease. Patient 1 had multiple admissions for pneumonia and respiratory insufficiency, required non-invasive ventilation, and had findings of bronchiectasis on thoracic imaging and significant lymphocytic infiltrates of the airways on lung biopsy. To verify the autoimmune cause of pulmonary symptoms APS-1 patients, both were tested in a blinded manner for the presence of autoantibodies to KCNRG in serum. We found that only Patient 1 had autoantibodies present. Additionally, Patient 1 had progressive disease despite treatment with several immunomodulating agents, including corticosteroids, azathioprine, and mycophenolate. Patient 1 had a lung biopsy performed which was consistent with B cell lymphocytic aggregates. Rituximab treatment was initiated with apparent good response. This report illustrates the practical use of KCNRG autoantibodies to identify APS-1 patients with pulmonary risk and the successful use of the monoclonal antibody, Rituximab, to treat pulmonary disease in APS-1 patients. Copyright © 2011 Wiley Periodicals, Inc.

  1. Lacrimal sac lymphoproliferative lesion: case report.

    Science.gov (United States)

    Coloma-González, I; Ruíz-García, L; Ceriotto, A; Corredor-Casas, S; Salcedo-Casillas, G

    2015-03-01

    The case is presented of a 51 year-old woman with a firm mass at the medial canthus of the right eye of five years onset. A low-grade lymphoproliferative lesion (reactive lymphoid hyperplasia) was diagnosed from an excisional biopsy Lacrimal sac tumors are rare, with a peak incidence in the fifth decade of life. The initial clinical features are epiphora and medial canthus swelling. As it mimics nasolacrimal duct obstruction, up to 40% of these tumors are misdiagnosed until undergoing surgery. Copyright © 2013 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.

  2. The Janus faces of acquired angioedema: C1-inhibitor deficiency, lymphoproliferation and autoimmunity.

    Science.gov (United States)

    Wu, Maddalena Alessandra; Castelli, Roberto

    2016-02-01

    Several clinical and biological features of lymphoproliferative diseases have been associated with an increased risk of developing autoimmune manifestations. Acquired deficiency of C1-inhibitor (C1-INH) (AAE) is a rare syndrome clinically similar to hereditary angioedema (HAE) characterized by local increase in vascular permeability (angioedema) of the skin and the gastrointestinal and oro-pharyngo-laryngeal mucosa. Bradykinin, a potent vasoactive peptide, released from high molecular weight kininogen when it is cleaved by plasma kallikrein (a serine protease controlled by C1-INH), is the mediator of symptoms. In total 46% of AAE patients carry an underlying hematological disorder including monoclonal gammopathy of uncertain significance (MGUS) or B cell malignancies. However, 74% of AAE patients have anti-C1-INH autoantibodies without hematological, clinical or instrumental evidence of lymphoproliferative disease. Unlike HAE patients, AAE patients usually have late-onset symptoms, do not have a family history of angioedema and present variable response to treatment due to the hypercatabolism of C1-INH. Experiments show that C1-INH and/or the classical complement pathway were consumed by the neoplastic lymphatic tissues and/or anti-C1-INH neutralizing autoantibodies. Therapy of AAE follows two directions: 1) prevention/reversal of the symptoms of angioedema; and 2) treatment of the associated disease. Different forms of B cell disorders coexist and/or evolve into each other in AAE and seem to be dominated by an altered control of B cell proliferation, thus AAE represents an example of the strict link between autoimmunity and lymphoproliferation.

  3. Autoimmune disorders

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/000816.htm Autoimmune disorders To use the sharing features on this page, please enable JavaScript. An autoimmune disorder occurs when the body's immune system attacks and ...

  4. Agranulocytosis and mixed-type autoimmune hemolytic anemia in primary sjögren's syndrome: a case report and review of the literature.

    Science.gov (United States)

    Qiao, Lin; Chen, Jing; Leng, Xiao-Mei; Zhang, Wen; Han, Bing; Zhao, Yan; Zeng, Xiao-Feng

    2016-12-01

    Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease that presents with sicca symptoms of the main mucosal surfaces. Patients with pSS have a broad spectrum of laboratory features, such as cytopenias and hypergammaglobulinemia. Although hematological abnormalities are usually seen in pSS patients, agranulocytosis and autoimmune hemolytic anemia (AIHA) are rare. Here we describe a 40-year-old woman with pSS who developed both agranulocytosis and mixed-type AIHA. An increased risk of malignancies has also been reported in pSS patients with hematological changes. Although there is no evidence of malignancies, this patient should be closely followed up in case of developing lymphoma. © 2015 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

  5. Atypical Manifestation of LPS-Responsive Beige-Like Anchor Deficiency Syndrome as an Autoimmune Endocrine Disorder without Enteropathy and Immunodeficiency.

    Science.gov (United States)

    Bakhtiar, Shahrzad; Ruemmele, Frank; Charbit-Henrion, Fabienne; Lévy, Eva; Rieux-Laucat, Frédéric; Cerf-Bensussan, Nadine; Bader, Peter; Paetow, Ulrich

    2016-01-01

    Monogenic primary immunodeficiency syndromes can affect one or more endocrine organs by autoimmunity during childhood. Clinical manifestations include type 1 diabetes mellitus, hypothyroidism, adrenal insufficiency, and vitiligo. Lipopolysaccharide (LPS)-responsive beige-like anchor protein (LRBA) deficiency was described in 2012 as a novel primary immunodeficiency, predominantly causing immune dysregulation and early onset enteropathy. We describe the heterogeneous clinical course of LRBA deficiency in two siblings, mimicking an autoimmune polyendocrine disorder in one of them in presence of the same underlying genetic mutation. The third child of consanguineous Egyptian parents (Patient 1) presented at 6 months of age with intractable enteropathy and failure to thrive. Later on, he developed symptoms of adrenal insufficiency, autoimmune hemolytic anemia, thrombocytopenia, and infectious complications due to immunosuppressive treatment. The severe enteropathy was non-responsive to the standard treatment and led to death at the age of 22 years. His younger sister (Patient 2) presented at the age of 12 to the endocrinology department with decompensated hypothyroidism, perioral vitiligo, delayed pubertal development, and growth failure without enteropathy and immunodeficiency. Using whole exome sequencing, we identified a homozygous frameshift mutation (c.6862delT, p.Y2288MfsX29) in the LRBA gene in both siblings. To our knowledge, our patient (Patient 2) is the first case of LRBA deficiency described with predominant endocrine phenotype without immunodeficiency and enteropathy. LRBA deficiency should be considered as underlying disease in pediatric patients presenting with autoimmune endocrine symptoms. The same genetic mutation can manifest with a broad phenotypic spectrum without genotype-phenotype correlation. The awareness for disease symptoms among non-immunologists might be a key to early diagnosis. Further functional studies in LRBA deficiency are

  6. Vaccines, adjuvants and autoimmunity.

    Science.gov (United States)

    Guimarães, Luísa Eça; Baker, Britain; Perricone, Carlo; Shoenfeld, Yehuda

    2015-10-01

    Vaccines and autoimmunity are linked fields. Vaccine efficacy is based on whether host immune response against an antigen can elicit a memory T-cell response over time. Although the described side effects thus far have been mostly transient and acute, vaccines are able to elicit the immune system towards an autoimmune reaction. The diagnosis of a definite autoimmune disease and the occurrence of fatal outcome post-vaccination have been less frequently reported. Since vaccines are given to previously healthy hosts, who may have never developed the disease had they not been immunized, adverse events should be carefully accessed and evaluated even if they represent a limited number of occurrences. In this review of the literature, there is evidence of vaccine-induced autoimmunity and adjuvant-induced autoimmunity in both experimental models as well as human patients. Adjuvants and infectious agents may exert their immune-enhancing effects through various functional activities, encompassed by the adjuvant effect. These mechanisms are shared by different conditions triggered by adjuvants leading to the autoimmune/inflammatory syndrome induced by adjuvants (ASIA syndrome). In conclusion, there are several case reports of autoimmune diseases following vaccines, however, due to the limited number of cases, the different classifications of symptoms and the long latency period of the diseases, every attempt for an epidemiological study has so far failed to deliver a connection. Despite this, efforts to unveil the connection between the triggering of the immune system by adjuvants and the development of autoimmune conditions should be undertaken. Vaccinomics is a field that may bring to light novel customized, personalized treatment approaches in the future. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Fatigue and psychosocial variables in autoimmune rheumatic disease and chronic fatigue syndrome: A cross-sectional comparison.

    Science.gov (United States)

    Ali, Sheila; Matcham, Faith; Irving, Katherine; Chalder, Trudie

    2017-01-01

    Fatigue is common in autoimmune rheumatic diseases (ARD). This study compared symptom-related cognitions, beliefs, behaviours, quality of sleep, lack of acceptance and distress in participants with ARD such as rheumatoid arthritis (RA), seronegative spondyloarthropathy (SpA), and connective tissue disease (CTD), and participants with chronic fatigue syndrome (CFS). 303 participants with RA, SpA, CTD and CFS completed questionnaire measures of fatigue, social adjustment, cognitive-behavioural responses, lack of acceptance, distress and quality of sleep. The RA, SpA and CTD groups were first compared with each other. They were then combined into one group and compared with the CFS group. There were no statistically significant differences between the RA, SpA or CTD groups for any of the measures. The CFS group was more fatigued, reported more distress and sleep disturbance and had worse social adjustment than the ARD group after adjustment for age and illness duration. After adjustment for fatigue, age, and illness duration, the CFS group scored more highly on lack of acceptance and avoidance/resting behaviour while the ARD group showed significantly higher levels of catastrophizing, damage beliefs, and symptom focusing than the CFS group. Fatigue in rheumatic diseases may be perpetuated by similar underlying transdiagnostic processes. The ARD and CFS groups showed similarities but also key differences in their responses to symptoms. Specific aspects of treatment may need to be tailored towards each group. For example, lack of acceptance and avoidance behaviour may be particularly important in perpetuating fatigue in CFS. Copyright © 2016. Published by Elsevier Inc.

  8. Four Cases of Atopic Dermatitis Complicated by Sjogren's Syndrome: Link between Dry Skin and Autoimmune Anhidrosis

    Directory of Open Access Journals (Sweden)

    Shun Kitaba

    2011-01-01

    Full Text Available We report four adult cases of atopic dermatitis (AD complicated by Sjogren's syndrome (SS. The patients fulfilled diagnostic criteria for AD and SS. All cases showed persistent itchy dry skin and eczematous lesions complicated by sicca symptoms including dry eyes and dry mouth with moderate joint pain. One case manifested annular erythema and another manifested widespread discoid erythema. To investigate the underlying cause of dry skin in these cases, sweating function was evaluated using a quantitative sudomotor axon reflex test (QSART in which the axon reflex is stimulated by acetylcholine iontophoresis. The sweating latency time was significantly prolonged in eczematous skin of AD and AD/SS compared to normal controls. Axon reflex (AXR sweat volume was also significantly reduced in AD (normal and eczematous skin and AD/SS (normal and eczema compared to normal control. In contrast, the direct sweat volume of lesional or non-lesional AD skin induced by direct stimulation with acetylcholine was only slightly reduced compared to that in normal controls, but not in SS and lesional skin of AD/SS patients. These results suggest that the impaired sweat response in AD is attributable to an abnormal sudomotor axon reflex, which is accelerated and modulated when complicated by SS resulting in dry skin in the present cases.

  9. Attenuation of autoimmune responses to oxidative specific epitopes, but not nitroso-adducts, is associated with a better clinical outcome in Myalgic Encephalomyelitis/chronic fatigue syndrome.

    Science.gov (United States)

    Maes, Michael; Leunis, Jean-Claude

    2014-01-01

    There is evidence that inflammatory, oxidative and nitrosative stress (IO&NS) pathways participate in the pathophysiology of a subgroup of patients with Myalgic Encephalomyelitis/chronic fatigue syndrome (ME/CFS). Increased IgM-related autoimmune responses to oxidative specific epitopes (OSEs), including malondialdehyde (MDA), oleic acid and phosphatidyl inositol (Pi), and nitroso-(NO)-adducts, including NO-tryptophan (NOW), NO-arginine and NO-cysteinyl, are frequently observed in ME/CFS. Autoimmune responses in ME/CFS may be driven by increased bacterial translocation as measured by IgM and IgA responses to LPS of gram negative bacteria. The aim of this study is to examine whether IgM responses to OSEs and NO-adducts are related to a better outcome as measured by the Fibromyalgia and Fatigue Rating Scale (FF). 76 ME/CFS patients with initially abnormal autoimmune responses were treated with care-as-usual, including nutraceuticals with anti-IO&NS effects (NAIOS), such as L-carnitine, coenzyme Q10, taurine + lipoic acid, with or without curcumine + quercitine or N-acetyl-cysteine, zinc + glutamine. We found that use of these NAIOS was associated with highly significant reductions in initially increased IgM-mediated autoimmune responses to OSEs and NO-adducts. A greater reduction in autoimmune responses to OSEs during intake of these NAIOS was associated with a lower FF score. Reductions in IgM responses to oleic acid, MDA and Pi, but not in any of the NO-adducts, were associated with reductions in severity of illness. These associations remained significant after adjusting for possible effects of increased bacterial translocation (leaky gut). Our results show that autoimmune responses to OSEs are involved in the pathophysiology of ME/CFS and that these pathways are a new drug target in a subgroup of ME/CFS patients. Although hypernitrosylation and nitrosative stress play a role in ME/CFS, reductions in these pathways are not associated with lowered severity of

  10. Autoimmune liver disease and concomitant extrahepatic autoimmune disease.

    Science.gov (United States)

    Muratori, Paolo; Fabbri, Angela; Lalanne, Claudine; Lenzi, Marco; Muratori, Luigi

    2015-10-01

    To assess the frequency and clinical impact of associated extrahepatic autoimmune diseases (EAD) on autoimmune liver diseases (ALD). We investigated 608 patients with ALD (327 autoimmune hepatitis - AIH and 281 primary biliary cirrhosis - PBC) for concomitant EAD. In both AIH and PBC, we observed a high prevalence of EAD (29.9 and 42.3%, respectively); both diseases showed a significant association with autoimmune thyroid disease, followed by autoimmune skin disease, celiac disease, and vasculitis in AIH patients and sicca syndrome, CREST syndrome, and celiac disease in PBC patients. At diagnosis, AIH patients with concurrent EAD were more often asymptomatic than patients with isolated AIH (Pautoimmune thyroid disease. In the light of our results, all patients with an EAD should be assessed for the concomitant presence of an asymptomatic ALD.

  11. Recalcitrant hypocalcaemia in autoimmune enteropathy.

    Science.gov (United States)

    Geyer, Myfanwy; Fairchild, Jan; Moore, David; Moore, Lynette; Henning, Paul; Tham, Elaine

    2014-12-01

    Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy syndrome is a monogenic disorder associated with autoimmune destruction of both endocrine and nonendocrine tissues. The classic triad includes candidiasis, hypoparathyroidism, and Addison disease. Up to 25% of patients with autoimmune polyendocrinopathy candidiasis ectodermal dystrophy syndrome also have gastrointestinal manifestations, which can have an impact on the management of other aspects of the disease. The management of the case discussed was challenging because of the complex interplay between the manifestations and treatment of his hypoparathyroidism, Addison disease, and autoimmune enteropathy. Attempts at management of hypocalcemia were largely unsuccessful until the introduction of immunosuppressive therapy for autoimmune enteropathy. This case supports early consideration of immunosuppression in this condition. Copyright © 2014 by the American Academy of Pediatrics.

  12. Role of Respirable Saudi Arabian Sand and Pyridostigmine in the Gulf War syndrome: An Autoimmune Adjuvant Disease

    National Research Council Canada - National Science Library

    Sopori, Mohan

    2002-01-01

    In the Lewis rat, inhalation of silica (SL) in realistic doses for 6 wk exacerbated the Mycobacterium- induced autoimmune adjuvant disease and impaired the humoral as well as cellular immune responses...

  13. Lymphoproliferative disorders in Oxford renal transplant recipients.

    Science.gov (United States)

    Bates, W D; Gray, D W R; Dada, M A; Chetty, R; Gatter, K C; Davies, D R; Morris, P J

    2003-06-01

    Increased cancer incidence, particularly lymphoproliferative disease, is a complication of immunosuppression in organ transplantation. Non-Hodgkin's lymphomas (NHLs) occur frequently during the first year after transplantation, more so in North America than in Europe. This study audited and correlated the demographic, clinical, pathological, and outcome features of post-transplant lymphoproliferative disorders (PTLDs) in a large centre in Oxford, and assessed whether the time of onset fitted more with the European or North American pattern. There were 1383 renal transplants in the study period and 27 patients developed lymphoma: 26 NHLs and one Hodgkin's disease (1.95%). Four of the patients never received cyclosporin. The mean time of diagnosis after transplant was 46 months. Most tumours (21/27) presented extranodally. Management included reduction of immunosuppression, surgical excision, antiviral treatment, radiotherapy, and chemotherapy. Three patients presented in the first post-transplant year-0.34% of cyclosporin managed patients-similar to the North American incidence, although the incidence of extranodal late PTLDs was also high (mean onset, 36 months v 15 months international mean). Post-transplant lymphomas were the most common malignancy associated with death in transplant patients. PTLDs occurred in 2% of renal transplant patients, presenting both in the first year in association with cyclosporin use, as in North America, but also in subsequent years, giving an overall presentation time later than the international mean. The disease usually presented extranodally, accounting for the wide range of symptoms and signs. Despite awareness and active management, the disease contributed to death in more that 50% of patients with PTLDs.

  14. [An evaluation of HLA class 2 alleles and anti-islet antibodies as evidence for non-autoimmune diabetes in Wolfram syndrome].

    Science.gov (United States)

    Zmysłowska, Agnieszka; Borowiec, Maciej; Antosik, Karolina; Wyka, Krystyna; Cieślik-Heinrich, Agnieszka; Klich, Izabela; Młynarski, Wojciech

    2010-01-01

    A clinical criterion of the Wolfram syndrome is the coexistence of diabetes and optic atrophy recognized before the age of 15. Diabetes present in Wolfram syndrome is a result of the selective β cell loss and failed insulin secretion which is probably associated with non-autoimmune pathogenesis. The aim of the study was an evaluation of HLA subtypes and presence of β-cell autoantibodies in patients with molecularly confirmed Wolfram syndrome. 9 patients with Wolfram syndrome aged 10-24 years were examined. We also studied 218 patients with type 1 diabetes as a reference group. A control group of 176 healthy individuals was included in the study. Besides the clinical assessment the HLA typing by PCR-SSO was performed. Islet cell antibodies (ICA), antibodies to glutamic acid decarboxylase (GADA), thyrosine phosphatase antibodies (IA2A) and insulin antibodies (IAA) were also detected. In all nine patients the coexistence of diabetes with optic atrophy was observed and in 8/9 individuals additional symptoms were recognized. In patients with Wolfram syndrome a significantly lower age of diagnosis of diabetes (Me=5.0 years) than in type 1 diabetic children (Me=10.4; p=0.002) was observed. Studies of HLA subtypes demonstrated an increased prevalence of HLA-DQw1, DRB1⋅03 and/or 04 and DR2. A comparison of the frequency of the HLA alleles in patients with Wolfram syndrome with type 1 diabetic children showed a more frequent presence of the DRB1⋅1501 (p=0.03; OR=13.28 (2.44-72.12)) and DQB1⋅06 (p=0.016; OR=10.15 (2.49-41.35)) alleles in patients with Wolfram syndrome. Polish patients with Wolfram syndrome have a different profile of the HLA antigens with the presence of DR2, DQw1 and DRB3/4 allele and are negative for diabetes-related autoantibodies, which may confirm non-autoimmune β-cell destruction in this syndrome.

  15. Successful Management of Insulin Allergy and Autoimmune Polyendocrine Syndrome Type 4 with Desensitization Therapy and Glucocorticoid Treatment: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Joselyn Rojas

    2014-01-01

    Full Text Available Introduction. Insulin allergy is a rare complication of insulin therapy, especially in type 1 diabetes mellitus (T1DM. Key manifestations are hypersensitivity-related symptoms and poor metabolic control. T1DM, as well as insulin allergy, may develop in the context of autoimmune polyendocrine syndrome (APS, further complicating management. Case Report. A 17-year-old male patient, diagnosed with T1DM, was treated with various insulin therapy schemes over several months, which resulted in recurrent anaphylactoid reactions and poor glycemic control, after which he was referred to our Endocrinology and Immunology Department. A prick test was carried out for all commercially available insulin presentations and another insulin scheme was designed but proved unsuccessful. A desensitization protocol was started with Glargine alongside administration of Prednisone, which successfully induced tolerance. Observation of skin lesions typical of vitiligo prompted laboratory workup for other autoimmune disorders, which returned positive for autoimmune gastritis/pernicious anemia. These findings are compatible with APS type 4. Discussion. To our knowledge, this is the first documented case of insulin allergy in type 4 APS, as well as this particular combination in APS. Etiopathogenic components shared by insulin allergy and APS beg for further research in immunogenetics to further comprehend pathophysiologic aspects of these diseases.

  16. Eosinophils in Autoimmune Diseases.

    Science.gov (United States)

    Diny, Nicola L; Rose, Noel R; Čiháková, Daniela

    2017-01-01

    Eosinophils are multifunctional granulocytes that contribute to initiation and modulation of inflammation. Their role in asthma and parasitic infections has long been recognized. Growing evidence now reveals a role for eosinophils in autoimmune diseases. In this review, we summarize the function of eosinophils in inflammatory bowel diseases, neuromyelitis optica, bullous pemphigoid, autoimmune myocarditis, primary biliary cirrhosis, eosinophilic granulomatosis with polyangiitis, and other autoimmune diseases. Clinical studies, eosinophil-targeted therapies, and experimental models have contributed to our understanding of the regulation and function of eosinophils in these diseases. By examining the role of eosinophils in autoimmune diseases of different organs, we can identify common pathogenic mechanisms. These include degranulation of cytotoxic granule proteins, induction of antibody-dependent cell-mediated cytotoxicity, release of proteases degrading extracellular matrix, immune modulation through cytokines, antigen presentation, and prothrombotic functions. The association of eosinophilic diseases with autoimmune diseases is also examined, showing a possible increase in autoimmune diseases in patients with eosinophilic esophagitis, hypereosinophilic syndrome, and non-allergic asthma. Finally, we summarize key future research needs.

  17. Eosinophils in Autoimmune Diseases

    Directory of Open Access Journals (Sweden)

    Daniela Čiháková

    2017-04-01

    Full Text Available Eosinophils are multifunctional granulocytes that contribute to initiation and modulation of inflammation. Their role in asthma and parasitic infections has long been recognized. Growing evidence now reveals a role for eosinophils in autoimmune diseases. In this review, we summarize the function of eosinophils in inflammatory bowel diseases, neuromyelitis optica, bullous pemphigoid, autoimmune myocarditis, primary biliary cirrhosis, eosinophilic granulomatosis with polyangiitis, and other autoimmune diseases. Clinical studies, eosinophil-targeted therapies, and experimental models have contributed to our understanding of the regulation and function of eosinophils in these diseases. By examining the role of eosinophils in autoimmune diseases of different organs, we can identify common pathogenic mechanisms. These include degranulation of cytotoxic granule proteins, induction of antibody-dependent cell-mediated cytotoxicity, release of proteases degrading extracellular matrix, immune modulation through cytokines, antigen presentation, and prothrombotic functions. The association of eosinophilic diseases with autoimmune diseases is also examined, showing a possible increase in autoimmune diseases in patients with eosinophilic esophagitis, hypereosinophilic syndrome, and non-allergic asthma. Finally, we summarize key future research needs.

  18. The comorbidity of bipolar disorder, diabetes mellitus, and autoimmune hypothyroidism in an adult woman with Turner’s syndrome: a case report

    Directory of Open Access Journals (Sweden)

    Li J

    2017-09-01

    Full Text Available Jinling Li, Xiaohong Hong, Haiyun Xu The Mental Health Center, Shantou University Medical College, Shantou, Guangdong, People’s Republic of China Abstract: Turner’s syndrome (TS is the most common sex chromosome abnormality in females and characterized with short stature and ovarian dysgenesis. Patients with TS may also present many other physical diseases and mental disorders. In this case report, we present a 49-year-old woman with TS, who also met criteria for bipolar disorder, type 2 diabetes mellitus, and autoimmune hypothyroidism. The patient was admitted to the mental health center for depressive symptoms in 1991 and was misdiagnosed as hypopituitarism, which was not corrected until 2005 when her karyotype of 45, X/46, X, i(Xq was identified. Due to the misdiagnosis and other specific reasons, the patient missed the optimal time for hormone replacement therapy. Keywords: Turner’s syndrome, bipolar disorder, karyotype, comorbidity

  19. Involvement of nuclear factor-kappaB in a murine model for the acute form of autoimmune-like toxic oil syndrome.

    Science.gov (United States)

    Bell, S A; Page, S; Baumgartner, B; Berking, C; Haas, M; Eisele, T; Neumeier, D; Brand, K

    1999-06-15

    The toxic oil syndrome (TOS) represents an exogenously induced autoimmune disease with acute or chronic symptoms similar to systemic lupus erythematosus or scleroderma. When genetically different mouse strains were exposed to oleic acid anilide (OAA), it was possible to mimic the different syndrome manifestations. The aim of the present study was to examine the role of NF-kappaB/Rel transcription factors in the development of the severe acute wasting disease observed in A/J mice. Within a week of OAA exposure, the A/J, but not B10.S strain, displayed weight loss, cachexia, apathy, reduced activity, and breathing difficulties. In affected A/J mice we observed a marked increase in NF-kappaB activation (p50/p65 dimers) both in splenic T cells and peritoneal macrophages as well as in tissue from aorta and gut. Incubation of splenocytes with OAA in vitro induced a dose-dependent removal of IkappaB-alpha, accompanied by NF-kappaB activation, whereas Sp-1 binding was not affected. Furthermore, we demonstrated the increased expression of the two NF-kappaB target genes IL-6 and IL-1beta in OAA-exposed mice and a transient OAA-induced accumulation of TNFalpha in vitro. This is the first report which implicates NF-kappaB/Rel in acute forms of chemically induced autoimmune-like disease and may serve as a paradigm for the involvement of this transcriptional system in acute processes associated with autoimmunity, suggesting possible avenues of therapeutic intervention. Copyright 1999 Academic Press.

  20. [Therapeutic options for autoimmune encephalomyelitis].

    Science.gov (United States)

    Borisow, N; Prüss, H; Paul, F

    2013-04-01

    Autoantibodies to neuronal tissue are becoming increasingly more important in the evaluation and classification of several neurological diseases, e.g. neuromyelitis optica, paraneoplastic syndromes of the central nervous system (CNS), stiff person syndrome or autoimmune epilepsy. As these disorders are rare, no evidence-based recommendations for therapy are available. Currently, immunomodulating or immunosuppressive drugs are administered in most cases. In paraneoplastic syndromes treatment of the underlying cancer is of considerable importance. This overview summarizes current experiences and recommendations in the treatment of autoimmune neurological disorders.

  1. A sudden onset of a pseudo-neurological syndrome after HPV-16/18 AS04-adjuvated vaccine: might it be an autoimmune/inflammatory syndrome induced by adjuvants (ASIA) presenting as a somatoform disorder?

    Science.gov (United States)

    Poddighe, Dimitri; Castelli, Lucia; Marseglia, Gian Luigi; Bruni, Paola

    2014-12-01

    In last centuries, vaccines reduced the incidence of several infectious diseases. In last decades, some vaccines aimed at preventing also some cancers, where viruses play a causative role. However, several adverse events have been described after vaccines, but a causal relationship has been established only in a minority of cases. Here, we describe a pseudo-neurological syndrome occurred shortly after the administration of the bivalent HPV vaccine. Some autoimmune disorders, including neurological demyelinating diseases, have been reported after HPV vaccines, but the patient showed no organic lesions. The patient was diagnosed as having a functional somatoform syndrome, which was supposed to be autoimmune/inflammatory syndrome induced by adjuvants (ASIA), seen the temporal link with vaccination and the presence of anti-phospholipid autoantibodies. Immunological mechanisms of vaccines-and of adjuvants-have not been completely elucidated yet, and although there is no evidence of statistical association with many post-vaccination events, a causal link with vaccine cannot be excluded in some individuals.

  2. Management of autoimmune hemolytic anemia in children and adolescents: A single center experience

    Directory of Open Access Journals (Sweden)

    Nazan Sarper

    2011-09-01

    Full Text Available Objective: To present and discuss the treatment of autoimmune hemolytic anemia (AIHA. Materials and Methods: The medical records of all patients (n=19 diagnosed in a tertiary hematology center between 1999 and 2010 were retrospectively reviewed.Results: Median age at diagnosis of AIHA was 5 years (range: 4 months-17 years. In all, 13 patients had primary (idiopathic AIHA, whereas 2 had primary Evans Syndrome (ES, 2 had autoimmune lymphoproliferative syndrome (ALPS+ES, and 1 had Wiskott-Aldrich syndrome (WAS+AIHA. Among the 13 primary idiopathic AIHA patients, 9 recovered following a 4-8-week course of prednisolone treatment without relapses, whereas 3 patients required a longer course of prednisolone. One AIHA patient that was very resistant to prednisolone recovered after cyclosporine A was added to the treatment. All patients with primary idiopathic AIHA were in remission for a median of 3 years (range: 4 months-10 years at the time this manuscript was written. Among the patients with primary ES, 2 had relapses similar to the ALPS patients. Splenectomy was performed in 1 primary ES patient, who at the time this report was written was also in remission. One ALPS patient required the addition of mycophenolate mofetil due to prednisolone resistance. The WAS patient was treatment resistant and died due to septicemia.Conclusions: Primary AIHA in pediatric patients generally has an acute onset and good response to corticosteroids. Primary or secondary ES has a chronic or relapsing course, and treatment may require other immunosuppressive agents in addition to corticosteroids. Complications of splenectomy must not be underestimated in patients with underlying immunodeficiency. AIHA often causes considerable morbidity and mortality in WAS.

  3. Autoimmune gastritis.

    Science.gov (United States)

    Kulnigg-Dabsch, Stefanie

    2016-10-01

    Autoimmune gastritis is a chronic inflammatory disease with destruction of parietal cells of the corpus and fundus of the stomach. The known consequence is vitamin B12 deficiency and, consequently, pernicious anemia. However, loss of parietal cells reduces secretion of gastric acid which is also required for absorption of inorganic iron; thus, iron deficiency is commonly found in patients with autoimmune gastritis. This usually precedes vitamin B12 deficiency and is found mainly in young women. Patients with chronic iron deficiency, especially those refractory to oral iron therapy, should therefore be evaluated for the presence of autoimmune gastritis.

  4. Living with the unexplained: coping, distress, and depression among women with chronic fatigue syndrome and/or fibromyalgia compared to an autoimmune disorder.

    Science.gov (United States)

    McInnis, Opal A; Matheson, Kimberly; Anisman, Hymie

    2014-01-01

    Chronic fatigue syndrome (CFS) and fibromyalgia are disabling conditions without objective diagnostic tests, clear-cut treatments, or established etiologies. Those with the disorders are viewed suspiciously, and claims of malingering are common, thus promoting further distress. It was hypothesized in the current study that levels of unsupportive social interactions and the coping styles used among those with CFS/fibromyalgia would be associated with perceived distress and depressive symptoms. Women with CFS/fibromyalgia (n=39), in fact, reported higher depression scores, greater perceived distress and more frequent unsupportive relationships than healthy women (n=55), whereas those with a chronic, but medically accepted illness comprising an autoimmune disorder (lupus erythematosus, multiple sclerosis, rheumatoid arthritis; n=28), displayed intermediate scores. High problem-focused coping was associated with low levels of depression and perceived distress in those with an autoimmune condition. In contrast, although CFS/fibromyalgia was also accompanied by higher depression scores and higher perceived distress, this occurred irrespective of problem-focused coping. It is suggested that because the veracity of ambiguous illnesses is often questioned, this might represent a potent stressor in women with such illnesses, and even coping methods typically thought to be useful in other conditions, are not associated with diminished distress among those with CFS/fibromyalgia.

  5. Thymoma-associated multi-organ autoimmunity: A case of graft-versus-host disease-like erythroderma complicated by Good syndrome successfully treated by thymectomy.

    Science.gov (United States)

    Fukushima, Ayano; Ichimura, Yoshiko; Obata, Shoko; Kinoshita-Ise, Misaki; Fujio, Yumi; Takeno, Mitsuhiro; Konohana, Izumi

    2017-07-01

    Thymoma-associated multi-organ autoimmunity disease (TAMA) is a rare paraneoplastic disorder, clinicopathologically similar to graft-versus-host disease (GVHD). Many reported cases follow a difficult course; half of them die from serious infectious diseases subsequent to immunosuppression induced by chemotherapy for unresectable thymoma, or intensive therapies including systemic steroids for complicating autoimmune diseases and GVHD-like symptoms. We report a patient whose skin symptoms were improved subsequently to total thymectomy. The patient also presented with hypogammaglobulinemia, which led to the diagnosis of complicated Good syndrome. Taking account of her immunodeficient condition, antibiotics and i.v. immunoglobulin were administrated promptly on onset of bacterial pneumonia, which was successfully treated. According to a review of the published work, treatments with systemic steroids for skin symptoms have limited effects and may contribute to serious infection. Our case indicates that successful treatment of thymoma itself may lead to the amelioration of the disease. The management priority should be given to the treatment of thymoma and the control of subsequent immune abnormality other than GVHD-like erythroderma. © 2017 Japanese Dermatological Association.

  6. Postural Orthostatic Tachycardia With Chronic Fatigue After HPV Vaccination as Part of the “Autoimmune/Auto-inflammatory Syndrome Induced by Adjuvants”

    Directory of Open Access Journals (Sweden)

    Lucija Tomljenovic PhD

    2014-03-01

    Full Text Available We report the case of a 14-year-old girl who developed postural orthostatic tachycardia syndrome (POTS with chronic fatigue 2 months following Gardasil vaccination. The patient suffered from persistent headaches, dizziness, recurrent syncope, poor motor coordination, weakness, fatigue, myalgias, numbness, tachycardia, dyspnea, visual disturbances, phonophobia, cognitive impairment, insomnia, gastrointestinal disturbances, and a weight loss of 20 pounds. The psychiatric evaluation ruled out the possibility that her symptoms were psychogenic or related to anxiety disorders. Furthermore, the patient tested positive for ANA (1:1280, lupus anticoagulant, and antiphospholipid. On clinical examination she presented livedo reticularis and was diagnosed with Raynaud’s syndrome. This case fulfills the criteria for the autoimmune/auto-inflammatory syndrome induced by adjuvants (ASIA. Because human papillomavirus vaccination is universally recommended to teenagers and because POTS frequently results in long-term disabilities (as was the case in our patient, a thorough follow-up of patients who present with relevant complaints after vaccination is strongly recommended.

  7. Alopecia universalis, hypothyroidism and pituitary hyperplasia: polyglandular autoimmune syndrome III in a patient in remission from treated Hodgkin lymphoma.

    LENUS (Irish Health Repository)

    Quintyne, K I

    2010-10-01

    We herein report a case of a 33-year-old man in remission from Hodgkin lymphoma, who presented with reduced potency and hair loss. Initial endocrine tests revealed autoimmune hypothyroidism. An MRI of his pituitary gland at onset revealed hyperplasia. He tolerated replacement endocrine therapy with good response, but with no improvement in his alopecia universalis. A repeat MRI, 6 months after his initial endocrine manipulation, showed resolution of his pituitary hyperplasia.

  8. Hyposalivation in autoimmune diseases

    OpenAIRE

    Maeshima, Etsuko; Furukawa, Kanako; Maeshima, Shinichiro; Koshiba, Hiroya; Sakamoto, Wataru

    2012-01-01

    We have investigated the prevalence of dry mouth among patients with autoimmune diseases other than Sj?gren?s syndrome. One hundred and forty-four patients, excluding patients with primary Sj?gren?s syndrome, were enrolled in this study. The volume of saliva secreted was measured with the screening technique for estimation of salivary flow, which uses a filter paper for diagnosing dry mouth. Disturbed salivary secretion was observed in 84 (58.3?%) of the 144 patients. In the case of patients ...

  9. Prolonged extracorporeal membrane oxygenation therapy for severe acute respiratory distress syndrome in a child affected by rituximab-resistant autoimmune hemolytic anemia: a case report

    Directory of Open Access Journals (Sweden)

    Beretta Chiara

    2009-04-01

    Full Text Available Abstract Introduction Autoimmune hemolytic anemia in children younger than 2 years of age is usually characterized by a severe course, with a mortality rate of approximately 10%. The prolonged immunosuppression following specific treatment may be associated with a high risk of developing severe infections. Recently, the use of monoclonal antibodies (rituximab has allowed sustained remissions to be obtained in the majority of pediatric patients with refractory autoimmune hemolytic anemia. Case presentation We describe the case of an 8-month-old Caucasian girl affected by a severe form of autoimmune hemolytic anemia, which required continuous steroid treatment for 16 months. Thereafter, she received 4 weekly doses of rituximab (375 mg/m2/dose associated with steroid therapy, which was then tapered over the subsequent 2 weeks. One month after the last dose of rrituximab, she presented with recurrence of severe hemolysis and received two more doses of rrituximab. The patient remained in clinical remission for 7 months, before presenting with a further relapse. An alternative heavy immunosuppressive therapy was administered combining cyclophosphamide 10 mg/kg/day for 10 days with methylprednisolone 40 mg/kg/day for 5 days, which was then tapered down over 3 weeks. While still on steroid therapy, the patient developed an interstitial pneumonia with Acute Respiratory Distress Syndrome, which required immediate admission to the intensive care unit where extracorporeal membrane oxygenation therapy was administered continuously for 37 days. At 16-month follow-up, the patient is alive and in good clinical condition, with no organ dysfunction, free from any immunosuppressive treatment and with a normal Hb level. Conclusions This case shows that aggressive combined immunosuppressive therapy may lead to a sustained complete remission in children with refractory autoimmune hemolytic anemia. However, the severe life-threatening complication presented by our

  10. Bell's palsy and autoimmunity.

    Science.gov (United States)

    Greco, A; Gallo, A; Fusconi, M; Marinelli, C; Macri, G F; de Vincentiis, M

    2012-12-01

    To review our current knowledge of the etiopathogenesis of Bell's palsy, including viral infection or autoimmunity, and to discuss disease pathogenesis with respect to pharmacotherapy. Relevant publications on the etiopathogenesis, clinical presentation, diagnosis and histopathology of Bell's palsy from 1975 to 2012 were analysed. Bell's palsy is an idiopathic peripheral nerve palsy involving the facial nerve. It accounts for 60 to 75% of all cases of unilateral facial paralysis. The annual incidence of Bell's palsy is 15 to 30 per 100,000 people. The peak incidence occurs between the second and fourth decades (15 to 45 years). The aetiology of Bell's palsy is unknown but viral infection or autoimmune disease has been postulated as possible pathomechanisms. Bell's palsy may be caused when latent herpes viruses (herpes simplex, herpes zoster) are reactivated from cranial nerve ganglia. A cell-mediated autoimmune mechanism against a myelin basic protein has been suggested for the pathogenesis of Bell's palsy. Bell's palsy may be an autoimmune demyelinating cranial neuritis, and in most cases, it is a mononeuritic variant of Guillain-Barré syndrome, a neurologic disorder with recognised cell-mediated immunity against peripheral nerve myelin antigens. In Bell's palsy and GBS, a viral infection or the reactivation of a latent virus may provoke an autoimmune reaction against peripheral nerve myelin components, leading to the demyelination of cranial nerves, especially the facial nerve. Given the safety profile of acyclovir, valacyclovir, and short-course oral corticosteroids, patients who present within three days of the onset of symptoms should be offered combination therapy. However it seems logical that in fact, steroids exert their beneficial effect via immunosuppressive action, as is the case in some other autoimmune disorders. It is to be hoped that (monoclonal) antibodies and/or T-cell immunotherapy might provide more specific treatment guidelines in the

  11. AIRE-mutations and autoimmune disease.

    Science.gov (United States)

    Bruserud, Øyvind; Oftedal, Bergithe E; Wolff, Anette B; Husebye, Eystein S

    2016-12-01

    The gene causing the severe organ-specific autoimmune disease autoimmune polyendocrine syndrome type-1 (APS-1) was identified in 1997 and named autoimmune regulator (AIRE). AIRE plays a key role in shaping central immunological tolerance by facilitating negative selection of T cells in the thymus, building the thymic microarchitecture, and inducing a specific subset of regulatory T cells. So far, about 100 mutations have been identified. Recent advances suggest that certain mutations located in the SAND and PHD1 domains exert a dominant negative effect on wild type AIRE resulting in milder seemingly common forms of autoimmune diseases, including pernicious anemia, vitiligo and autoimmune thyroid disease. These findings indicate that AIRE also contribute to autoimmunity in more common organ-specific autoimmune disorders. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Severe autoimmune hemolytic anemia with renal neoplasm.

    Science.gov (United States)

    Rhodes, Emily C; Parikh, Sahil P; Bhattacharyya, Nishith

    2014-02-01

    Autoimmune hemolytic anemia is a type of hemolytic anemia characterized by autoantibodies directed against red blood cells shortening their survival. When autoimmune hemolytic anemia is secondary to a paraneoplastic process, severe anemia can occur leading to significant morbidity and even mortality. Here we discuss the literature and present the case of a child with autoimmune hemolytic anemia from a paraneoplastic syndrome secondary to a renal tumor.

  13. Role of Complement in Autoimmune Hemolytic Anemia

    OpenAIRE

    Berentsen, Sigbj?rn

    2015-01-01

    Summary The classification of autoimmune hemolytic anemias and the complement system are reviewed. In autoimmune hemolytic anemia of the warm antibody type, complement-mediated cell lysis is clinically relevant in a proportion of the patients but is hardly essential for hemolysis in most patients. Cold antibody-mediated autoimmune hemolytic anemias (primary cold agglutinin disease, secondary cold agglutinin syndrome and paroxysmal cold hemoglobinuria) are entirely complement-mediated disorder...

  14. EBV-Associated Lymphoproliferative Disorder and Hemophagocytic Lymphohistiocytosis in a Patient with Severe Celiac Disease

    Directory of Open Access Journals (Sweden)

    John Jacob Kinross-Wright

    2018-01-01

    Full Text Available Background. Epstein-Barr virus- (EBV- associated lymphoproliferative disease (LPD is a rare condition, usually occurring in immunocompromised patients. We report a case of EBV-associated LPD in a patient with severe celiac disease, the first report to describe this syndrome in a patient with this diagnosis. Case Summary. A 69-year-old Caucasian woman with recent diagnosis of celiac sprue presented to our hospital with persistent diarrhea, abdominal pain, weight loss, and fatigue despite adherence to gluten-free diet for a number of weeks prior to presentation. She underwent evaluation for occult malignancy and was found to have diffuse intra-abdominal mesenteric lymphadenopathy on CT scan. Biopsy of mesenteric nodes revealed an EBV positive, CD20 positive mixed lymphoproliferative process with T-cell predominance, but without a monoclonal cell population felt to be consistent with EBV-associated LPD. Bone marrow biopsy revealed hemophagocytic lymphohistiocytosis, complicating her course. She was treated with steroids and rituximab but continued to decline, eventually developing MSSA bacteremia and succumbing to her disease. Conclusion. To our knowledge, this is the first report of the constellation of celiac sprue, EBV-associated LPD, and hemophagocytic lymphohistiocytosis. Providers caring for patients with severe, uncontrolled celiac disease and adenopathy should consider EBV-associated LPD.

  15. Scleritis and multiple systemic autoimmune manifestations in chronic natural killer cell lymphocytosis associated with elevated TCR alpha/beta+ CD3+CD4−CD8− double-negative T cells

    Science.gov (United States)

    Yeh, Steven; Li, Zhuqing; Sen, H. Nida; Lim, Wee-Kiak; Gill, Fred; Perkins, Katie; Rao, V. Koneti; Nussenblatt, Robert B.

    2011-01-01

    Background/Aims Chronic natural killer lymphocytosis (CNKL) has been associated with systemic autoimmunity, but its association with scleritis or ocular autoimmunity has not been characterized. We evaluated the natural kill cell (NK) function and immunophenotype of a patient with CNKL who developed bilateral scleritis and multiple systemic autoimmune findings. Methods The ophthalmic records of a patient with CNKL and scleritis were reviewed over a 6-year period. Flow cytometry was performed to evaluate T-cell, NK, and B-cell populations. NK cellular functions (i.e. NK cytotoxicity and cytokine/chemokine production following IL-2 stimulation) were evaluated. Results A 56-year-old female with vitiligo, psoriatic arthritis, thyroiditis, erythema nodosum, bilateral anterior scleritis and Sjogren syndrome was managed with multiple immunosuppressive medications including prednisone, mycophenolate mofetil and methotrexate. Flow cytometry showed a persistent elevation of CD56+CD3− NK cells greater than 40%, which was consistent with CNKL. NK cell cytotoxicity assay identified a deficiency of K562 cell lysis in the patient (1.46 mean-fold greater in control vs. patient). NK cytokine/chemokine production following IL-2 stimulation was also deficient (2.5–32.5 fold greater in control). Cytokines/chemokines assessed included pro-inflammatory (IFN-γ, TNF-α, IL-1, MCP-1) and immunoregulatory cytokines (IL-4, IL-5 and IL-10). An abnormal elevation of TCRα/β+ CD3+CD4−CD8− T-cells suggestive of autoimmune lymphoproliferative syndrome was observed but apoptosis dysfunction was not found. Conclusion The association of increased but dysfunctional NK cells in the context of multiple systemic and ocular manifestations suggests a role of NK cells in the pathogenesis of our patient’s disease. Further studies regarding NK cell dysfunction and ocular autoimmunity are needed. PMID:20508050

  16. Understanding Autoimmune Diseases

    Science.gov (United States)

    ... What are they? Points To Remember About Autoimmune Diseases Autoimmune diseases refer to problems with the immune system, ... Infectious Diseases Website: https://www.niaid.nih.gov/diseases-conditions/autoimmune-diseases American Autoimmune Related Diseases Association Website: https:// ...

  17. Development of mixed-type autoimmune hemolytic anemia and Evans' syndrome following chicken pox infection in a case of low-titer cold agglutinin disease.

    Science.gov (United States)

    Tanaka, Yumi; Masuya, Masahiro; Katayama, Naoyuki; Miyata, Eri; Sugimoto, Yuka; Shibasaki, Tetsunori; Yamamura, Kentaro; Ohishi, Kohshi; Minami, Nobuyuki; Shiku, Hiroshi; Nobori, Tsutomu

    2006-10-01

    We describe a patient with low-titer cold agglutinin disease (CAD) who developed mixed-type autoimmune hemolytic anemia (AIHA) and idiopathic thrombocytopenia following chicken pox infection. At least 1 year before admission to hospital, the patient had mild hemolytic anemia associated with low-titer cold agglutinins. A severe hemolytic crisis and thrombocytopenia (Evans' syndrome) occurred several days after infection with chicken pox, and the patient was referred to our hospital. Serological findings revealed the presence of both cold agglutinins and warm-reactive autoantibodies against erythrocytes, and the diagnosis was mixed-type AIHA. Following steroid therapy, the hemoglobin (Hb) level and platelet count improved. The patient was closely followed over a 10-year period with recurrent documented hemolysis after viral or bacterial infections. Warm-reactive autoantibodies have not been detected in the last 2 years, and only the immunoglobulin M anti-I cold agglutinins with a low titer and wide thermal amplitude have remained unchanged. Therefore, the patient has received at least 10 mg prednisolone daily to maintain a Hb level of 10 g/dL. To the best of our knowledge, no adult case of low-titer CAD that has evolved into mixed-type AIHA and Evans' syndrome after chicken pox infection has been previously reported in the literature.

  18. Frequent hypermethylation of DBC1 in malignant lymphoproliferative neoplasms

    DEFF Research Database (Denmark)

    Grønbæk, Karin Elmegård; Ralfkiaer, U.; Dahl, C.

    2008-01-01

    Allelic loss at chromosome 9q31-34 is a frequent event in many lymphoproliferative malignancies. Here, we examined DBC1 at 9q33.1 as a potential target in lymphomagenesis. DBC1 is a putative tumor suppressor that has been shown to be involved in the regulation of cell growth and programmed cell d...

  19. Autoimmun hypophysitis

    DEFF Research Database (Denmark)

    Krarup, Therese; Hagen, Claus

    2010-01-01

    during pregnancy or postpartum, but also occurs in males and children. AH is often associated with other autoimmune diseases, most frequently with Hashimoto's thyroiditis. The symptoms are caused by enlargement of the pituitary gland and disturbances of the hormone function. Treatment is either......Autoimmune hypophysitis (AH) - often referred to as lymphocytic hypophysitis - is a rare disease that affects the pituitary gland and causes inflammation. The disease enlarges the pituitary gland and the clinical presentations are lack of pituitary function and headaches. AH is mostly seen in women...

  20. Autoimmun hypophysitis

    DEFF Research Database (Denmark)

    Krarup, Therese; Hagen, Claus

    2010-01-01

    during pregnancy or postpartum, but also occurs in males and children. AH is often associated with other autoimmune diseases, most frequently with Hashimoto's thyroiditis. The symptoms are caused by enlargement of the pituitary gland and disturbances of the hormone function. Treatment is either......Autoimmune hypophysitis (AH) - often referred to as lymphocytic hypophysitis - is a rare disease that affects the pituitary gland and causes inflammation. The disease enlarges the pituitary gland and the clinical presentations are lack of pituitary function and headaches. AH is mostly seen in women...... immunosuppressive treatment or surgery....

  1. X Chromosome Dose and Sex Bias in Autoimmune Diseases: Increased 47,XXX in Systemic Lupus Erythematosus and Sjögren’s Syndrome

    Science.gov (United States)

    Liu, Ke; Kurien, Biji T.; Zimmerman, Sarah L.; Kaufman, Kenneth M.; Taft, Diana H.; Kottyan, Leah C.; Lazaro, Sara; Weaver, Carrie A.; Ice, John A.; Adler, Adam J.; Chodosh, James; Radfar, Lida; Rasmussen, Astrid; Stone, Donald U.; Lewis, David M.; Li, Shibo; Koelsch, Kristi A.; Igoe, Ann; Talsania, Mitali; Kumar, Jay; Maier-Moore, Jacen S.; Harris, Valerie M.; Gopalakrishnan, Rajaram; Jonsson, Roland; Lessard, James A.; Lu, Xianglan; Gottenberg, Jacques-Eric; Anaya, Juan-Manuel; Cunninghame-Graham, Deborah S.; Huang, Andrew J. W.; Brennan, Michael T.; Hughes, Pamela; Illei, Gabor G.; Miceli-Richard, Corinne; Keystone, Edward C.; Bykerk, Vivian P.; Hirschfield, Gideon; Xie, Gang; Ng, Wan-Fai; Nordmark, Gunnel; Eriksson, Per; Omdal, Roald; Rhodus, Nelson L.; Rischmueller, Maureen; Rohrer, Michael; Segal, Barbara M.; Vyse, Timothy J.; Wahren-Herlenius, Marie; Witte, Torsten; Pons-Estel, Bernardo; Alarcon-Riquelme, Marta E.; Guthridge, Joel M.; James, Judith A.; Lessard, Christopher J.; Kelly, Jennifer A.; Thompson, Susan D.; Gaffney, Patrick M.; Montgomery, Courtney G.; Edberg, Jeffrey C; Kimberly, Robert P; Alarcón, Graciela S.; Langefeld, Carl L.; Gilkeson, Gary S.; Kamen, Diane L.; Tsao, Betty P.; McCune, W. Joseph; Salmon, Jane E.; Merrill, Joan T.; Weisman, Michael H; Wallace, Daniel J; Utset, Tammy O; Bottinger, Erwin P.; Amos, Christopher I.; Siminovitch, Katherine A.; Mariette, Xavier; Sivils, Kathy L.

    2016-01-01

    Objective More than 80% of autoimmune disease is female dominant, but the mechanism for this female bias is poorly understood. We suspected an X chromosome dose effect and hypothesized that trisomy X (47,XXX , 1 in ~1,000 live female births) would be increased in female predominant diseases (e.g. systemic lupus erythematosus [SLE], primary Sjögren’s syndrome [SS], primary biliary cirrhosis [PBC] and rheumatoid arthritis [RA]) compared to diseases without female predominance (sarcoidosis) and controls. Methods We identified 47,XXX subjects using aggregate data from single nucleotide polymorphism (SNP) arrays and confirmed, when possible, by fluorescent in situ hybridization (FISH) or quantitative polymerase chain reaction (q-PCR). Results We found 47,XXX in seven of 2,826 SLE and three of 1,033 SS female patients, but only in two of the 7,074 female controls (p=0.003, OR=8.78, 95% CI: 1.67-86.79 and p=0.02, OR=10.29, 95% CI: 1.18-123.47; respectively). One 47,XXX subject was present for ~404 SLE women and ~344 SS women. 47,XXX was present in excess among SLE and SS subjects. Conclusion The estimated prevalence of SLE and SS in women with 47,XXX was respectively ~2.5 and ~2.9 times higher than in 46,XX women and ~25 and ~41 times higher than in 46,XY men. No statistically significant increase of 47,XXX was observed in other female-biased diseases (PBC or RA), supporting the idea of multiple pathways to sex bias in autoimmunity. PMID:26713507

  2. X Chromosome Dose and Sex Bias in Autoimmune Diseases: Increased Prevalence of 47,XXX in Systemic Lupus Erythematosus and Sjögren's Syndrome.

    Science.gov (United States)

    Liu, Ke; Kurien, Biji T; Zimmerman, Sarah L; Kaufman, Kenneth M; Taft, Diana H; Kottyan, Leah C; Lazaro, Sara; Weaver, Carrie A; Ice, John A; Adler, Adam J; Chodosh, James; Radfar, Lida; Rasmussen, Astrid; Stone, Donald U; Lewis, David M; Li, Shibo; Koelsch, Kristi A; Igoe, Ann; Talsania, Mitali; Kumar, Jay; Maier-Moore, Jacen S; Harris, Valerie M; Gopalakrishnan, Rajaram; Jonsson, Roland; Lessard, James A; Lu, Xianglan; Gottenberg, Jacques-Eric; Anaya, Juan-Manuel; Cunninghame-Graham, Deborah S; Huang, Andrew J W; Brennan, Michael T; Hughes, Pamela; Illei, Gabor G; Miceli-Richard, Corinne; Keystone, Edward C; Bykerk, Vivian P; Hirschfield, Gideon; Xie, Gang; Ng, Wan-Fai; Nordmark, Gunnel; Eriksson, Per; Omdal, Roald; Rhodus, Nelson L; Rischmueller, Maureen; Rohrer, Michael; Segal, Barbara M; Vyse, Timothy J; Wahren-Herlenius, Marie; Witte, Torsten; Pons-Estel, Bernardo; Alarcon-Riquelme, Marta E; Guthridge, Joel M; James, Judith A; Lessard, Christopher J; Kelly, Jennifer A; Thompson, Susan D; Gaffney, Patrick M; Montgomery, Courtney G; Edberg, Jeffrey C; Kimberly, Robert P; Alarcón, Graciela S; Langefeld, Carl L; Gilkeson, Gary S; Kamen, Diane L; Tsao, Betty P; McCune, W Joseph; Salmon, Jane E; Merrill, Joan T; Weisman, Michael H; Wallace, Daniel J; Utset, Tammy O; Bottinger, Erwin P; Amos, Christopher I; Siminovitch, Katherine A; Mariette, Xavier; Sivils, Kathy L; Harley, John B; Scofield, R Hal

    2016-05-01

    More than 80% of autoimmune disease predominantly affects females, but the mechanism for this female bias is poorly understood. We suspected that an X chromosome dose effect accounts for this, and we undertook this study to test our hypothesis that trisomy X (47,XXX; occurring in ∼1 in 1,000 live female births) would be increased in patients with female-predominant diseases (systemic lupus erythematosus [SLE], primary Sjögren's syndrome [SS], primary biliary cirrhosis, and rheumatoid arthritis [RA]) compared to patients with diseases without female predominance (sarcoidosis) and compared to controls. All subjects in this study were female. We identified subjects with 47,XXX using aggregate data from single-nucleotide polymorphism arrays, and, when possible, we confirmed the presence of 47,XXX using fluorescence in situ hybridization or quantitative polymerase chain reaction. We found 47,XXX in 7 of 2,826 SLE patients and in 3 of 1,033 SS patients, but in only 2 of 7,074 controls (odds ratio in the SLE and primary SS groups 8.78 [95% confidence interval 1.67-86.79], P = 0.003 and odds ratio 10.29 [95% confidence interval 1.18-123.47], P = 0.02, respectively). One in 404 women with SLE and 1 in 344 women with SS had 47,XXX. There was an excess of 47,XXX among SLE and SS patients. The estimated prevalence of SLE and SS in women with 47,XXX was ∼2.5 and ∼2.9 times higher, respectively, than that in women with 46,XX and ∼25 and ∼41 times higher, respectively, than that in men with 46,XY. No statistically significant increase of 47,XXX was observed in other female-biased diseases (primary biliary cirrhosis or RA), supporting the idea of multiple pathways to sex bias in autoimmunity. © 2016, American College of Rheumatology.

  3. Autoimmun hypophysitis

    DEFF Research Database (Denmark)

    Krarup, Therese; Hagen, Claus

    2010-01-01

    during pregnancy or postpartum, but also occurs in males and children. AH is often associated with other autoimmune diseases, most frequently with Hashimoto's thyroiditis. The symptoms are caused by enlargement of the pituitary gland and disturbances of the hormone function. Treatment is either...

  4. Epigenetics as biomarkers in autoimmune diseases.

    Science.gov (United States)

    Wu, Haijing; Liao, Jieyue; Li, Qianwen; Yang, Ming; Zhao, Ming; Lu, Qianjin

    2018-03-21

    Autoimmune diseases are immune system disorders in which immune cells cannot distinguish self-antigens from foreign ones. The current criteria for autoimmune disease diagnosis are based on clinical manifestations and laboratory tests. However, none of these markers shows both high sensitivity and specificity. In addition, some autoimmune diseases, for example, systemic lupus erythematosus (SLE), are highly heterogeneous and often exhibit various manifestations. On the other hand, certain autoimmune diseases, such as Sjogren's syndrome versus SLE, share similar symptoms and autoantibodies, which also causes difficulties in diagnosis. Therefore, biomarkers that have both high sensitivity and high specificity for diagnosis, reflect disease activity and predict drug response are necessary. An increasing number of publications have proposed the abnormal epigenetic modifications as biomarkers of autoimmune diseases. Therefore, this review will comprehensively summarize the epigenetic progress in the pathogenesis of autoimmune disorders and unearth potential biomarkers that might be appropriate for disease diagnosis and prediction. Copyright © 2018. Published by Elsevier Inc.

  5. Cutaneous and Mucosal Manifestations of Sjögren's Syndrome.

    Science.gov (United States)

    Generali, Elena; Costanzo, Antonio; Mainetti, Carlo; Selmi, Carlo

    2017-12-01

    Sjögren's syndrome is currently considered an "autoimmune epithelitis," as exocrine glands, especially salivary and lacrimal, are progressively destructed by an immune-mediated process associated with specific serum autoantibodies and local lymphocyte infiltrate. Xerostomia remains a key complain in patients with Sjögren's syndrome but should be evaluated also for other causes such as xerogenic medications, followed by radiation and chemotherapy for head and neck cancers, hormone disorders, infections, or other connective tissue diseases. Further, xerophtalmia (also known as dry eye) frequently associated with keratoconjunctivitis sicca cumulatively affects approximately 10-30% of the general population with increasing incidence with age and is more frequently secondary to non-autoimmune diseases. On the other hand, numerous patients with Sjögren's syndrome manifest signs of systemic dryness involving the nose, the trachea, the vagina, and the skin, suggesting that other glands are also affected beyond the exocrine epithelia. Skin involvement in Sjögren's syndrome is relatively common, and various manifestations may be present, in particular xeroderma, eyelid dermatitis, annular erythema, and cutaneous vasculitis. Additional skin non-vasculitic manifestations include livedo reticularis which may occur in the absence of vasculitis, and localized nodular cutaneous amyloidosis possibly representing lymphoproliferative diseases related to Sjögren's syndrome. The treatment of skin and mucosal manifestations in Sjögren's syndrome is similar regardless of the cause, starting from patient education to avoid alcohol and tobacco smoking and to pursue dental hygiene. In conclusion, a strict collaboration between the dermatologist and the rheumatologist is essential in the adequate management of Sjögren's syndrome skin and mucosal manifestations.

  6. Autoimmun pankreatitis

    DEFF Research Database (Denmark)

    Fjordside, Eva; Novovic, Srdan; Schmidt, Palle Nordblad

    2015-01-01

    Autoimmune pancreatitis (AIP) is a rare inflammatory disease. AIP has characteristic histology, serology and imaging findings. Two types of AIP exist, type 1, which is a part of the systemic immunoglobulin G4-related disease, and type 2, which is only localized to the pancreas. Patients with type...... are predominantly older men, have involvement of other organs and more often experience relapse than patients with type 2. Both types respond well to steroid treatment. The most important differential diagnose is pancreatic cancer....

  7. Autoimmune liver disease 2007.

    Science.gov (United States)

    Muratori, Paolo; Granito, Alessandro; Pappas, Georgios; Muratori, Luigi; Lenzi, Marco; Bianchi, Francesco B

    2008-01-01

    Autoimmune liver disease (ALD) includes a spectrum of diseases which comprises both cholestatic and hepatitic forms: autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC) and the so called "overlap" syndromes where hepatitic and cholestatic damage coexists. All these diseases are characterized by an extremely high heterogeneity of presentation, varying from asymptomatic, acute (as in a subset of AIH) or chronic (with aspecific symptoms such as fatigue and myalgia in AIH or fatigue and pruritus in PBC and PSC). The detection and characterization of non organ specific autoantibodies plays a major role in the diagnostic approach of autoimmune liver disease; anti nuclear reactivities (ANA) and anti smooth muscle antibodies (SMA) mark type 1 AIH, liver kidney microsomal antibody type 1 (LKM1) and liver cytosol type 1 (LC1) are the serological markers of type 2 AIH; antimitochondrial antibodies (AMA) are associated with PBC, while no specific marker is found in PSC, since anticytoplasmic neutrophil antibodies with perinuclear pattern (atypical p-ANCA or p-ANNA) are also detected in a substantial proportion of type 1 AIH cases. Treatment options rely on immunosoppressive therapy (steroids and azathioprine) in AIH and on ursodeoxycholic acid in cholestatic conditions; in all these diseases liver transplantation remains the only therapeutical approach for the end stage of liver disease.

  8. Hepatitis C virus-related lymphoproliferative disorders: An overview

    OpenAIRE

    Zignego, Anna Linda; Giannini, Carlo; Ferri, Clodoveo

    2007-01-01

    Hepatitis C virus (HCV) is a global health problem affecting 3% of the world's population (about 180 million) and a cause of both hepatic and extrahepatic diseases. B-cell lymphoproliferative disorders, whose prototype is mixed cryoglobulinemia, represent the most closely related as well as the most investigated HCV-related extrahepatic disorder. The association between extrahepatic (lymphoma) as well as hepatic malignancies (hepatocellular carcinoma) has justified the inclusion of HCV among ...

  9. Marginal zone B-cell lymphoma with multiple extranodal locations in a patient with Sjögren’s syndrome – a diagnostic problem

    Directory of Open Access Journals (Sweden)

    Marta Domżalska

    2014-09-01

    Full Text Available Sjögren’s syndrome is a chronic autoimmune disease characterized by the presence of lymphocytic infiltrates in exocrine glands, mainly salivary and lacrimal glands, which result in xerophthalmia and xerostomia. About half of the patients develop systemic complications, including lymphoproliferative disorders. We report a case of a 27-year-old woman with a diagnosis of Sjögren’s syndrome and a suspicion of respiratory system involvement in the course of granulomatosis with polyangiitis. Histopathological examination of a skin lesion suggested marginal zone B-cell lymphoma. After pathological and immunohistochemical evaluation of all available previous biopsy samples and the medical documentation the diagnosis of extranodal marginal zone B-cell lymphoma stage IV according to the Ann Arbor classification was rendered. The patient was referred to the Department of Haematology and was treated with R-CVP (cyclophosphamide, vincristine, prednisone, rituximab.

  10. Reversible lacrimal gland-protective regulatory T-cell dysfunction underlies male-specific autoimmune dacryoadenitis in the non-obese diabetic mouse model of Sjögren syndrome

    Science.gov (United States)

    Lieberman, Scott M; Kreiger, Portia A; Koretzky, Gary A

    2015-01-01

    CD4+ CD25+ Foxp3+ regulatory T (Treg) cells are required to maintain immunological tolerance; however, defects in specific organ-protective Treg cell functions have not been demonstrated in organ-specific autoimmunity. Non-obese diabetic (NOD) mice spontaneously develop lacrimal and salivary gland autoimmunity and are a well-characterized model of Sjögren syndrome. Lacrimal gland disease in NOD mice is male-specific, but the role of Treg cells in this sex-specificity is not known. This study aimed to determine if male-specific autoimmune dacryoadenitis in the NOD mouse model of Sjögren syndrome is the result of lacrimal gland-protective Treg cell dysfunction. An adoptive transfer model of Sjögren syndrome was developed by transferring cells from the lacrimal gland-draining cervical lymph nodes of NOD mice to lymphocyte-deficient NOD-SCID mice. Transfer of bulk cervical lymph node cells modelled the male-specific dacryoadenitis that spontaneously develops in NOD mice. Female to female transfers resulted in dacryoadenitis if the CD4+ CD25+ Treg-enriched population was depleted before transfer; however, male to male transfers resulted in comparable dacryoadenitis regardless of the presence or absence of Treg cells within the donor cell population. Hormone manipulation studies suggested that this Treg cell dysfunction was mediated at least in part by androgens. Surprisingly, male Treg cells were capable of preventing the transfer of dacryoadenitis to female recipients. These data suggest that male-specific factors promote reversible dysfunction of lacrimal gland-protective Treg cells and, to our knowledge, form the first evidence for reversible organ-protective Treg cell dysfunction in organ-specific autoimmunity. PMID:25581706

  11. Establishment of a Novel Autoimmune Experimental Model of Bladder Pain Syndrome/Interstitial Cystitis in C57BL/6 Mice.

    Science.gov (United States)

    Jin, Xing-Wei; Liu, Bo-Ke; Zhang, Xiang; Zhao, Zhong-Hua; Shao, Yuan

    2017-06-01

    The aim of this study is to identify whether vaccinating twice with bladder homogenate can establish a new model of experimental autoimmune cystitis (EAC) in C57BL/6 strain mice. C57BL/6 mice were vaccinated with bladder homogenate in complete Freund's adjuvant (CFA) and boost immunized with bladder homogenate in incomplete Freund's adjuvant (IFA) after 2 weeks were used as the EAC model. Mice immunized with phosphate-buffered saline (PBS) in CFA or IFA were used as the control. Micturition habits and suprapubic-pelvic pain threshold were measured 4 weeks after primary immunization. Bladder to body weight ratios and expression of inflammatory cytokines and neurokinin 1 receptor (NK1R) were then examined. Histologic and immunohistochemical examination of the bladder was carried out, and IL-1β, IFN-γ, and TNF-α production by the kidneys, liver, and lungs was also tested. Double-immunized mice were extensively sensitive to pressure applied on the pelvic area (P < 0.001). Compared to single-immunized mice or controls, double-immunized mice showed more micturition frequency, lower urine output per micturition, higher bladder to body weight ratio, and significant elevation in the expression of inflammatory cytokines, including IL-1β, IL-4, IL-6, IL-10, IFN-γ, and TNF-α (all P < 0.05). NK1R gene expression was significantly increased in double-immunized mice compared to the other three groups (P < 0.001). A nonspecific immune response occurred in the liver but was much weaker than bladder inflammation. Our dual immunization EAC model in C57BL/6 mice can effectively mimic the symptoms and pathophysiologic characteristics of BPS/IC and thus can be widely used to investigate the pathogenesis and therapeutic strategies of BPS/IC.

  12. Autoimmune hemolytic anemia as an initial manifestation of Hodgkin’s Disease: Case report

    Directory of Open Access Journals (Sweden)

    José Augusto Urrego-Díaz

    2016-07-01

    Through this paper, the authors intend to remind the medical community about the importance of a prompt and deep study of all autoimmune hemolytic anemia cases found in pediatric patients, without overlooking possible malignant causes related to this condition such as a lymphoproliferative disorder. Thus, before diagnosing a hemolytic anemia as idiopathic, the practitioner must be certain that the condition is not a clinical manifestation of an underlying disease.

  13. Kaleidoscope of autoimmune diseases in HIV infection.

    Science.gov (United States)

    Roszkiewicz, Justyna; Smolewska, Elzbieta

    2016-11-01

    Within the last 30 years, the human immunodeficiency virus (HIV) infection has changed its status from inevitably fatal to chronic disorder with limited impact on life span. However, this breakthrough was mainly the effect of introduction of the aggressive antiviral treatment, which has led to the clinically significant increase in CD4+ cell count, resulting in fewer cases of the acquired immunodeficiency syndrome (AIDS) and improved management of opportunistic infections occurring in the course of the disease. The occurrence of a particular autoimmune disease depends on degree of immunosuppression of the HIV-positive patient. In 2002, four stages of autoimmunity were proposed in patients infected by HIV, based on the absolute CD4+ cell count, feature of AIDS as well as on the presence of autoimmune diseases. Spectrum of autoimmune diseases associated with HIV infection seems to be unexpectedly wide, involving several organs, such as lungs (sarcoidosis), thyroid gland (Graves' disease), liver (autoimmune hepatitis), connective tissue (systemic lupus erythematosus, rheumatoid arthritis, polyarteritis nodosa and other types of vasculitis, antiphospholipid syndrome) or hematopoietic system (autoimmune cytopenias). This paper contains the state of art on possible coincidences between HIV infection and a differential types of autoimmune diseases, including the potential mechanisms of this phenomenon. As the clinical manifestations of autoimmunization often mimic those inscribed in the course of HIV infection, health care providers should be aware of this rare but potentially deadly association and actively seek for its symptoms in their patients.

  14. AUTOIMMUNE HEPATITIS

    Directory of Open Access Journals (Sweden)

    Yusri Dianne Jurnalis

    2010-05-01

    Full Text Available AbstrakHepatitis autoimun merupakan penyakit inflamasi hati yang berat dengan penyebab pasti yang tidak diketahui yang mengakibatkan morbiditas dan mortalitas yang tinggi. Semua usia dan jenis kelamin dapat dikenai dengan insiden tertinggi pada anak perempuan usia prepubertas, meskipun dapat didiagnosis pada usia 6 bulan. Hepatitis autoimun dapat diklasifikasikan menjadi 2 bagian berdasarkan adanya antibodi spesifik: Smooth Muscle Antibody (SMA dengan anti-actin specificity dan/atau Anti Nuclear Antibody (ANA pada tipe 1 dan Liver-Kidney Microsome antibody (LKM1 dan/atau anti-liver cytosol pada tipe 2. Gambaran histologisnya berupa “interface hepatitis”, dengan infiltrasi sel mononuklear pada saluran portal, berbagai tingkat nekrosis, dan fibrosis yang progresf. Penyakit berjalan secara kronik tetapi keadaan yang berat biasanya menjadi sirosis dan gagal hati.Tipe onset yang paling sering sama dengan hepatitis virus akut dengan gagal hati akut pada beberapa pasien; sekitar sepertiga pasien dengan onset tersembunyi dengan kelemahan dan ikterik progresif ketika 10-15% asimptomatik dan mendadak ditemukan hepatomegali dan/atau peningkatan kadar aminotransferase serum. Adanya predominasi perempuan pada kedua tipe. Pasien LKM1 positif menunjukkan keadaan lebih akut, pada usia yang lebih muda, dan biasanya dengan defisiensi Immunoglobulin A (IgA, dengan durasi gejala sebelum diagnosis, tanda klinis, riwayat penyakit autoimun pada keluarga, adanya kaitan dengan gangguan autoimun, respon pengobatan dan prognosis jangka panjang sama pada kedua tipe.Kortikosteroid yang digunakan secara tunggal atau kombinasi azathioprine merupakan terapi pilihan yang dapat menimbulkan remisi pada lebih dari 90% kasus. Strategi terapi alternatif adalah cyclosporine. Penurunan imunosupresi dikaitkan dengan tingginya relap. Transplantasi hati dianjurkan pada penyakit hati dekom-pensata yang tidak respon dengan pengobatan medis lainnya.Kata kunci : hepatitis Autoimmune

  15. Associated Autoimmune Diseases

    Science.gov (United States)

    ... celiac disease are type 1 diabetes and autoimmune thyroid disease. The tendency to develop autoimmune diseases is believed ... confusion, weight loss, and coma (if left untreated). Thyroid Disease There are two common forms of autoimmune thyroid ...

  16. Autoimmune liver disease panel

    Science.gov (United States)

    Liver disease test panel - autoimmune ... Autoimmune disorders are a possible cause of liver disease. The most common of these diseases are autoimmune hepatitis and primary biliary cholangitis (formerly called primary biliary cirrhosis). This group of tests ...

  17. Endocrine autoimmune disease: genetics become complex.

    Science.gov (United States)

    Wiebolt, Janneke; Koeleman, Bobby P C; van Haeften, Timon W

    2010-12-01

    The endocrine system is a frequent target in pathogenic autoimmune responses. Type 1 diabetes and autoimmune thyroid disease are the prevailing examples. When several diseases cluster together in one individual, the phenomenon is called autoimmune polyglandular syndrome. Progress has been made in understanding the genetic factors involved in endocrine autoimmune diseases. Studies on monogenic autoimmune diseases such as autoimmune polyglandular syndrome type 1, immunodysregulation, polyendocrinopathy, enteropathy, X-linked and primary immune deficiencies helped uncover the role of key regulators in the preservation of immune tolerance. Alleles of the major histocompatibility complex have been known to contribute to the susceptibility to most forms of autoimmunity for more than 3 decades. Furthermore, sequencing studies revealed three non-major histocompatibility complex loci and some disease specific loci, which control T lymphocyte activation or signalling. Recent genome-wide association studies (GWAS) have enabled acceleration in the identification of novel (non-HLA) loci and hence other relevant immune response pathways. Interestingly, several loci are shared between autoimmune diseases, and surprisingly some work in opposite direction. This means that the same allele which predisposes to a certain autoimmune disease can be protective in another. Well powered GWAS in type 1 diabetes has led to the uncovering of a significant number of risk variants with modest effect. These studies showed that the innate immune system may also play a role in addition to the adaptive immune system. It is anticipated that next generation sequencing techniques will uncover other (rare) variants. For other autoimmune disease (such as autoimmune thyroid disease) GWAS are clearly needed. © 2010 The Authors. European Journal of Clinical Investigation © 2010 Stichting European Society for Clinical Investigation Journal Foundation.

  18. Update in Endocrine Autoimmunity

    OpenAIRE

    Anderson, Mark S.

    2008-01-01

    Context: The endocrine system is a common target in pathogenic autoimmune responses, and there has been recent progress in our understanding, diagnosis, and treatment of autoimmune endocrine diseases.

  19. Gangliosides and autoimmune diabetes.

    Science.gov (United States)

    Misasi, R; Dionisi, S; Farilla, L; Carabba, B; Lenti, L; Di Mario, U; Dotta, F

    1997-09-01

    Gangliosides are sialic acid-containing glycolipids which are formed by a hydrophobic portion, the ceramide, and a hydrophilic part, i.e. the oligosaccharide chain. First described in neural tissue, several studies have shown that gangliosides are almost ubiquitous molecules expressed in all vertebrate tissues. Within cells, gangliosides are usually associated with plasma membranes, where they can act as receptors for a variety of molecules and have been shown to take part in cell-to-cell interaction and in signal transduction. In addition, gangliosides are expressed in cytosol membranes like those of secretory granules of some endocrine cells (adrenal medulla, pancreatic islets). As far as the role of gangliosides in diseases is concerned, there are some cases in which an aberrant ganglioside expression plays a crucial role in the disease pathogenetic process. These diseases include two major forms of ganglioside storage, namely GM2-gangliosidosis (Tay-Sachs and its beta-hexosaminidase deficiency) and GM1-gangliosidosis (beta-galactosidase deficiency), where the most prominent pathological characteristic is the lysosomal ganglioside accumulation in neurons. Other inflammatory or degenerative diseases both within and outside the nervous system have been shown to be associated with an altered pattern of ganglioside expression in the target organ. Since monoclonal antibodies have been discovered and used in immunology, a large variety of ganglioside antigens has been described both as blood group antigens and as tumour-related antigens. Several studies have also indicated that gangliosides can act not only as antigens, but also as autoantigens. As a matter of fact, auto-antibodies to gangliosides, detected by immunostaining methods performed directly on TLC plates or by ELISA, have been described in several autoimmune disorders such as Guillain-Barré syndrome, multiple sclerosis, lupus erythematosus, Hashimoto's thyroiditis and, last but not least, insulin

  20. Anticuerpos anti 21 hidroxilasa séricos en pacientes con anticuerpos antifracción microsomal: Síndrome poliendocrino autoinmune Seric 21- hydroxilase antibodies in patients with anti-microsomal fraction antibodies: Autoimmune polyendocrine syndrome

    Directory of Open Access Journals (Sweden)

    Silvia Botta

    2007-04-01

    Full Text Available El síndrome poliendocrino autoinmune (SPA es la asociación de enfermedades endocrinas autoinmunes con otros desórdenes autoinmunes no endocrinos. Los tipos 1, 2 y 4 presentan adrenalitis autoinmune, esto indica la presencia de autoanticuerpos, y su marcador serológico específico es el anti 21 hidroxilasa (a21-OH. El SPA tipo 2 es la asociación de adrenalitis, enfermedad tiroidea y/o diabetes mellitus inducidas por autoanticuerpos. Como componentes menores, pueden estar asociados entre otros, vitiligo, alopecia y miastenia. Nuestros objetivos fueron: establecer la prevalencia de a21-OH séricos en pacientes con anticuerpos anti fracción microsomal (AFM positivos, enfermedad tiroidea autoinmune y/o afecciones endocrinas y no endocrinas autoinmunes; diagnosticar formas incompletas de SPA y estudiar individuos con probable riesgo de progresión a un SPA completo. Estudiamos 72 pacientes AFM positivos y 60 sujetos tomados como grupo control, AFM negativos. Hallamos a21-OH elevados en dos pacientes: A= 47 U/ml, hipotiroidismo autoinmune y miastenia; y B= 8.75 U/ml, hipotiroidismo autoinmune y vitiligo; ambos con ausencia de insuficiencia adrenal. La prevalencia de a21-OH encontrada fue del 2.8%. Las pacientes A y B corresponden a un SPA tipo 2 incompleto y latente en relación al componente adrenal. Considerando a los a21-OH marcadores de enfermedad autoinmune latente, el eventual riesgo de evolución hacia la afección clínica sugiere la necesidad de estrechos controles clínicos y bioquímicos periódicos.Autoimmune polyendocrine syndrome (APS is the association of autoimmune endocrine diseases, with other autoimmune nonendocrine disorders. APS types 1, 2 and 4 include autoimmune adrenalitis; this suggests the presence of autoantibodies. A specific serological marker for these is the anti 21- hydroxilase autoantibody (a21-OH. APS type 2 is the association of autoimmune adrenalitis, to autoimmune thyroid disease and/or diabetes mellitus, all

  1. Monogenic autoimmune diseases of the endocrine system.

    Science.gov (United States)

    Johnson, Matthew B; Hattersley, Andrew T; Flanagan, Sarah E

    2016-10-01

    The most common endocrine diseases, type 1 diabetes, hyperthyroidism, and hypothyroidism, are the result of autoimmunity. Clustering of autoimmune endocrinopathies can result from polygenic predisposition, or more rarely, may present as part of a wider syndrome due to a mutation within one of seven genes. These monogenic autoimmune diseases show highly variable phenotypes both within and between families with the same mutations. The average age of onset of the monogenic forms of autoimmune endocrine disease is younger than that of the common polygenic forms, and this feature combined with the manifestation of other autoimmune diseases, specific hallmark features, or both, can inform clinicians as to the relevance of genetic testing. A genetic diagnosis can guide medical management, give an insight into prognosis, inform families of recurrence risk, and facilitate prenatal diagnoses. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Four cases of atopic dermatitis complicated by Sjögren's syndrome: link between dry skin and autoimmune anhidrosis.

    Science.gov (United States)

    Kitaba, Shun; Matsui, Saki; Iimuro, Eriko; Nishioka, Megumi; Kijima, Akiko; Umegaki, Noriko; Murota, Hiroyuki; Katayama, Ichiro

    2011-09-01

    We report four adult cases of atopic dermatitis (AD) complicated by Sjögren's syndrome (SS). The patients fulfilled diagnostic criteria for AD and SS. All cases showed persistent itchy dry skin and eczematous lesions complicated by sicca symptoms including dry eyes and dry mouth with moderate joint pain. One case manifested annular erythema and another manifested widespread discoid erythema. To investigate the underlying cause of dry skin in these cases, sweating function was evaluated using a quantitative sudomotor axon reflex test (QSART) in which the axon reflex is stimulated by acetylcholine iontophoresis. The sweating latency time was significantly prolonged in eczematous skin of AD and AD/SS compared to normal controls. Axon reflex (AXR) sweat volume was also significantly reduced in AD (normal and eczematous skin) and AD/SS (normal and eczema) compared to normal control. In contrast, the direct sweat volume of lesional or non-lesional AD skin induced by direct stimulation with acetylcholine was only slightly reduced compared to that in normal controls, but not in SS and lesional skin of AD/SS patients. These results suggest that the impaired sweat response in AD is attributable to an abnormal sudomotor axon reflex, which is accelerated and modulated when complicated by SS resulting in dry skin in the present cases.

  3. Role of Complement in Autoimmune Hemolytic Anemia

    Science.gov (United States)

    Berentsen, Sigbjørn

    2015-01-01

    Summary The classification of autoimmune hemolytic anemias and the complement system are reviewed. In autoimmune hemolytic anemia of the warm antibody type, complement-mediated cell lysis is clinically relevant in a proportion of the patients but is hardly essential for hemolysis in most patients. Cold antibody-mediated autoimmune hemolytic anemias (primary cold agglutinin disease, secondary cold agglutinin syndrome and paroxysmal cold hemoglobinuria) are entirely complement-mediated disorders. In cold agglutinin disease, efficient therapies have been developed in order to target the pathogenic B-cell clone, but complement modulation remains promising in some clinical situations. No established therapy exists for secondary cold agglutinin syndrome and paroxysmal cold hemoglobinuria, and the possibility of therapeutic complement inhibition is interesting. Currently, complement modulation is not clinically documented in any autoimmune hemolytic anemia. The most relevant candidate drugs and possible target levels of action are discussed. PMID:26696798

  4. Role of Complement in Autoimmune Hemolytic Anemia.

    Science.gov (United States)

    Berentsen, Sigbjørn

    2015-09-01

    The classification of autoimmune hemolytic anemias and the complement system are reviewed. In autoimmune hemolytic anemia of the warm antibody type, complement-mediated cell lysis is clinically relevant in a proportion of the patients but is hardly essential for hemolysis in most patients. Cold antibody-mediated autoimmune hemolytic anemias (primary cold agglutinin disease, secondary cold agglutinin syndrome and paroxysmal cold hemoglobinuria) are entirely complement-mediated disorders. In cold agglutinin disease, efficient therapies have been developed in order to target the pathogenic B-cell clone, but complement modulation remains promising in some clinical situations. No established therapy exists for secondary cold agglutinin syndrome and paroxysmal cold hemoglobinuria, and the possibility of therapeutic complement inhibition is interesting. Currently, complement modulation is not clinically documented in any autoimmune hemolytic anemia. The most relevant candidate drugs and possible target levels of action are discussed.

  5. Autoimmune encephalitis and sleep disorders

    Directory of Open Access Journals (Sweden)

    Yan HUANG

    2017-10-01

    Full Text Available Research shows that autoimmune encephalitis is associated with sleep disorders. Paraneoplastic neurological syndrome (PNS with Ma2 antibodies can cause sleep disorders, particularly narcolepsy and rapid eye movement sleep behavior disorder (RBD. Limbic encephalitis (LE and Morvan syndrome, associated with voltage - gated potassium channel (VGKC-complex antibodies, which include leucine-rich glioma-inactivated 1 (LGI1 antibody and contactin-associated protein 2 (Caspr2, can result in profound insomnia and other sleep disorders. Central neurogenic hypoventilation are found in patients with anti-N-methyl-D-aspartate (NMDA receptor encephalitis, whereas obstructive sleep apnea (OSA, stridor and parasomnia are prominent features of encephalopathy associated with IgLON5 antibodies. Sleep disorders are cardinal manifestations in patients with autoimmune encephalitis. Immunotherapy possiblely can improve clinical symptoms and prognosis in a positive way. DOI: 10.3969/j.issn.1672-6731.2017.10.004

  6. Post-kidney transplant large bowel lymphoproliferative disorder

    Directory of Open Access Journals (Sweden)

    Neeraj Singh

    2014-01-01

    Full Text Available Epstein-Barr virus (EBV-associated post-transplant lymphoproliferative disorder (PTLD is a serious complication of organ transplantation. The gastrointestinal (GI tract is a common site involved, but non-specific signs and symptoms often delay the diagnosis. We report a case of EBV-associated GI-PTLD in a 68-year-old kidney transplant patient who received the kidney ten months earlier. He presented with chronic diarrhea and developed massive pneumo-peritoneum secondary to multiple colonic perforations.

  7. Thymic Hyperplasia after Lung Transplantation Imitating Posttransplant Lymphoproliferative Disorder

    Science.gov (United States)

    Steger, Christina Maria; Semsroth, Severin; Hager, Thomas; Rieker, Ralf; Müller, Ludwig

    2011-01-01

    Thymic hyperplasia is usually associated with the treatment of malignant tumours and is sometimes linked with endocrine diseases. For the first time, we report a case of thymic hyperplasia in a patient 2 years after bilateral lung transplantation. Contrast-enhanced chest CT scan was highly suspicious for a posttransplant lymphoma or thymoma. Therefore, the patient received total thymectomy. Excised specimens were sent to the Department of Pathology. Unexpectedly, the histological examination revealed hyperplastic thymic tissue without evidence for a posttransplant lymphoproliferative disorder or malignancy. PMID:23213605

  8. Post-transplant lymphoproliferative disorder following kidney transplantation

    DEFF Research Database (Denmark)

    Maksten, Eva Futtrup; Vase, Maja Ølholm; Kampmann, Jan

    2016-01-01

    Post-transplant lymphoproliferative disorder (PTLD) incidence is difficult to determine, mainly because both early and other lesions may go unrecognized and unregistered. Few studies have included systematic pathology review to maximize case identification and decide more accurately PTLD frequency...... after long-term post-transplantation follow-up. A retrospective population-based cohort study including all kidney transplant recipients at two Danish centres (1990-2011; population covered 3.1 million; 2175 transplantations in 1906 patients). Pathology reports were reviewed for all patient biopsies...

  9. Thymic Hyperplasia after Lung Transplantation Imitating Posttransplant Lymphoproliferative Disorder

    Directory of Open Access Journals (Sweden)

    Christina Maria Steger

    2011-01-01

    Full Text Available Thymic hyperplasia is usually associated with the treatment of malignant tumours and is sometimes linked with endocrine diseases. For the first time, we report a case of thymic hyperplasia in a patient 2 years after bilateral lung transplantation. Contrast-enhanced chest CT scan was highly suspicious for a posttransplant lymphoma or thymoma. Therefore, the patient received total thymectomy. Excised specimens were sent to the Department of Pathology. Unexpectedly, the histological examination revealed hyperplastic thymic tissue without evidence for a posttransplant lymphoproliferative disorder or malignancy.

  10. Primary immune deficiency disorders presenting as autoimmune diseases: IPEX and APECED.

    Science.gov (United States)

    Moraes-Vasconcelos, D; Costa-Carvalho, B T; Torgerson, T R; Ochs, H D

    2008-05-01

    Several primary immune deficiency disorders are associated with autoimmunity and malignancy, suggesting a state of immune dysregulation. The concept of immune dysregulation as a direct cause of autoimmunity in primary immune deficiency disorders (PIDDs) has been strengthened by the recent discovery of distinct clinical entities linked to single-gene defects resulting in multiple autoimmune phenomena including immune dysregulation, polyendocrinopathy, enteropathy and X-linked (IPEX) syndrome, and autoimmune polyendocrinopathy, candidiasis and ectodermal dystrophy (APECED) syndrome. Reviewing recent advances in our understanding of the small subgroup of PIDD patients with defined causes for autoimmunity may lead to the development of more effective treatment strategies for idiopathic human autoimmune diseases.

  11. A Rare Presentation of Isolated CNS Posttransplantation Lymphoproliferative Disorder

    Directory of Open Access Journals (Sweden)

    Jaime Morris

    2017-01-01

    Full Text Available Posttransplantation lymphoproliferative disorder (PTLD is a recognized and extremely morbid complication of solid organ transplantation, but central nervous system involvement, particularly in isolation, is rare. There are no standardized treatment strategies for PTLD, though commonly used strategies include reduction of immunosuppression, chemotherapy, rituximab, radiation, and surgery. We present a case of an unusual morphologic variant of primary central nervous system PTLD with successful response to rituximab and cranial radiation. A 69-year-old Asian male, who underwent postrenal transplant nine years earlier, presented with a one-month history of new onset seizure activity. His evaluation revealed multiple brain lesions on magnetic resonance imaging (MRI, as well as serologic and cerebrospinal fluid studies which were positive for Epstein-Barr Virus (EBV infection. Ultimately, he underwent craniotomy with tissue biopsy with the final pathology report showing posttransplant lymphoproliferative disorder, polymorphic type. The patient was managed with reduction in immunosuppression, rituximab therapy, and cranial radiation treatments. He had demonstrated marked improvement in his neurologic function and was ultimately discharged to inpatient rehabilitation facility.

  12. Hemophagocytosis in Cutaneous Autoimmune Disease.

    Science.gov (United States)

    Kerl, Katrin; Wolf, Ingrid H; Cerroni, Lorenzo; Wolf, Peter; French, Lars E; Kerl, Helmut

    2015-07-01

    The significance of the histological visualization of hemophagocytosis in tissues depends on the context, varying from a nonspecific phenomenon to a characteristic or diagnostic feature for certain disease entities. Hemophagocytosis is also one of the key features of macrophage activation syndrome (MAS) (hemophagocytic syndrome) a potentially life-threatening complication of underlying conditions such as infections, malignancy, and autoimmune disorders. Clinical manifestations of MAS are high fever, pancytopenia, liver dysfunction, and coagulopathy. These clinical symptoms are due to an abnormal activation of the immune system in a strong association with the cytokine milieu. The diagnosis of MAS may be easily missed; it is usually detected in the bone marrow, lymph node, liver, and spleen. Only few reports exist in the literature with histological description of cutaneous hemophagocytosis as a sign for MAS in patients with lymphoma and infection. In this report, the authors present the clinicopathological and immunohistochemical features of 3 patients with cutaneous hemophagocytosis, specifically erythrophagocytosis, associated with autoimmune disease, and discuss the relevance of these findings. The authors report 3 patients who developed cutaneous hemophagocytosis during the course of an underlying autoimmune disorder. One patient suffered from dermatomyositis, the other 2 patients from systemic lupus erythematosus, whereby one of them was a 3-month old girl with neonatal lupus erythematosus. The patient with dermatomyositis developed MAS according to the current diagnostic criteria. Although the 2 other patients had an acute flare of their autoimmune disease with histological signs of cutaneous hemophagocytosis, they did not fulfill the complete criteria for a diagnosis of MAS. Histiocyte proliferation and activation with increase of cytokines could be demonstrated by immunohistology. This report is the first to describe hemophagocytosis in cutaneous biopsies

  13. Autoimmune Pancreatitis.

    Science.gov (United States)

    Majumder, Shounak; Takahashi, Naoki; Chari, Suresh T

    2017-07-01

    Autoimmune pancreatitis (AIP) is a chronic fibroinflammatory disease of the pancreas that belongs to the spectrum of immunoglobulin G-subclass4-related diseases (IgG4-RD) and typically presents with obstructive jaundice. Idiopathic duct-centric pancreatitis (IDCP) is a closely related but distinct disease that mimics AIP radiologically but manifests clinically most commonly as recurrent acute pancreatitis in young individuals with concurrent inflammatory bowel disease. IgG4 levels are often elevated in AIP and normal in IDCP. Histologically, lymphoplasmacytic acinar inflammation and storiform fibrosis are seen in both. In addition, the histologic hallmark of IDCP is the granulocyte epithelial lesion: intraluminal and intraepithelial neutrophils in medium-sized and small ducts with or without granulocytic acinar inflammation often associated with destruction of ductal architecture. Initial treatment of both AIP and IDCP is with oral corticosteroids for duration of 4 weeks followed by a gradual taper. Relapses are common in AIP and relatively uncommon in IDCP, a relatively rare disease for which the natural history is not well understood. For patients with relapsing AIP, treatment with immunomodulators and more recently rituximab has been recommended. Although rare instances of pancreaticobiliary malignancy has been reported in patients with AIP, overall the lifetime risk of developing pancreatic cancer does not appear to be elevated.

  14. Sjogren's Syndrome Information Page

    Science.gov (United States)

    ... Trials Organizations Publications Definition Sjögren's syndrome is an autoimmune disorder in which immune cells attack and destroy the ... syndrome than men. × Definition Sjögren's syndrome is an autoimmune disorder in which immune cells attack and destroy the ...

  15. Controversies on Rituximab Therapy in Sjögren Syndrome-Associated Lymphoproliferation

    Directory of Open Access Journals (Sweden)

    Luca Quartuccio

    2009-01-01

    Full Text Available Sjögren's syndrome (SS is a systemic autoimmune disease characterized by chronic inflammation of salivary and lachrymal glands, and frequently accompanied by systemic symptoms. A subgroup of SS patients develops malignant B cell non-Hodgkin's lymphoma (NHL, usually of the mucosa-associated lymphoid tissue (MALT type and very often located in the major salivary glands. Currently, there is a lack of evidence-based intervention therapy which may influence SS-related chronic inflammation and lymphoproliferation. B cells are involved in the pathogenesis of SS, and B cell downregulation may lead to a decrease of disease activity. Rituximab (RTX, a chimeric monoclonal antibody targeting the CD20 antigen on the B cell surface, has been successfully investigated in other autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, ANCA-associated vasculitis, and mixed cryoglobulinemic syndrome. Preliminary experiences of RTX therapy in SS patients with or without a lymphoproliferative disorder suggest that SS patients with more residual exocrine gland function might better benefit from RTX. Efficacy of RTX in SS-associated B-cell lymphoma, mainly in low-grade salivary gland lymphomas, remains an open issue.

  16. Autoimmunity and Gastric Cancer

    Science.gov (United States)

    Bizzaro, Nicola; Antico, Antonio; Villalta, Danilo

    2018-01-01

    Alterations in the immune response of patients with autoimmune diseases may predispose to malignancies, and a link between chronic autoimmune gastritis and gastric cancer has been reported in many studies. Intestinal metaplasia with dysplasia of the gastric corpus-fundus mucosa and hyperplasia of chromaffin cells, which are typical features of late-stage autoimmune gastritis, are considered precursor lesions. Autoimmune gastritis has been associated with the development of two types of gastric neoplasms: intestinal type and type I gastric carcinoid. Here, we review the association of autoimmune gastritis with gastric cancer and other autoimmune features present in gastric neoplasms. PMID:29373557

  17. Autoimmunity and Gastric Cancer

    Directory of Open Access Journals (Sweden)

    Nicola Bizzaro

    2018-01-01

    Full Text Available Alterations in the immune response of patients with autoimmune diseases may predispose to malignancies, and a link between chronic autoimmune gastritis and gastric cancer has been reported in many studies. Intestinal metaplasia with dysplasia of the gastric corpus-fundus mucosa and hyperplasia of chromaffin cells, which are typical features of late-stage autoimmune gastritis, are considered precursor lesions. Autoimmune gastritis has been associated with the development of two types of gastric neoplasms: intestinal type and type I gastric carcinoid. Here, we review the association of autoimmune gastritis with gastric cancer and other autoimmune features present in gastric neoplasms.

  18. Autoimmunity and primary immunodeficiency: two sides of the same coin?

    Science.gov (United States)

    Schmidt, Reinhold E; Grimbacher, Bodo; Witte, Torsten

    2017-12-19

    Autoimmunity and immunodeficiency were previously considered to be mutually exclusive conditions; however, increased understanding of the complex immune regulatory and signalling mechanisms involved, coupled with the application of genetic analysis, is revealing the complex relationships between primary immunodeficiency syndromes and autoimmune diseases. Single-gene defects can cause rare diseases that predominantly present with autoimmune symptoms. Such genetic defects also predispose individuals to recurrent infections (a hallmark of immunodeficiency) and can cause primary immunodeficiencies, which can also lead to immune dysregulation and autoimmunity. Moreover, risk factors for polygenic rheumatic diseases often exist in the same genes as the mutations that give rise to primary immunodeficiency syndromes. In this Review, various primary immunodeficiency syndromes are presented, along with their pathogenetic mechanisms and relationship to autoimmune diseases, in an effort to increase awareness of immunodeficiencies that occur concurrently with autoimmune diseases and to highlight the need to initiate appropriate genetic tests. The growing knowledge of various genetically determined pathologic mechanisms in patients with immunodeficiencies who have autoimmune symptoms opens up new avenues for personalized molecular therapies that could potentially treat immunodeficiency and autoimmunity at the same time, and that could be further explored in the context of autoimmune rheumatic diseases.

  19. A typical aspects of intrathoracic posttransplantation lymphoproliferative disorders

    Energy Technology Data Exchange (ETDEWEB)

    Beigelman, C. [Dept. of Radiology, Hopital Pitie-Salpetriere, 75 Paris (France); Leblond, V. [Dept. of Hematology, Hopital Pitie-Salpetriere, 75 Paris (France); Suberbielle, C. [Dept. of Hematology, Hopital Pitie-Salpetriere, 75 Paris (France); Lenoir, S. [Dept. of Radiology, Hopital Pitie-Salpetriere, 75 Paris (France); Dorent, R. [Dept. of Thoracic Surgery, Hopital Pitie-Salpetriere, 75 Paris (France); Grenier, P. [Dept. of Radiology, Hopital Pitie-Salpetriere, 75 Paris (France)

    1995-11-01

    Posttransplant lymphoproliferative disorders (PTLD), developing after immunosuppressive therapy in human organ-graft recipients, are, for the most part, Epstein-Barr virus-induced. The earlier the diagnosis is made, the greater the potential for reversibility. The chest radiographs and CT scans of 10 patients with thoracic locations of PTLD were reviewed. Mediastinal and hilar adenopathy, pulmonary nodules, and pleural thickening or effusion were encountered. The incidence of partial resolution with clinical remission appears to be noteworthy, and in all likelihood is related to the extensive necrosis that is frequently seen. Slow regression, transitory deterioration in one case, and localization only on the graft side in two cases, were observed. These morphological and evolutionary peculiarities must be known in order to optimize the diagnosis, and thus the prognosis, of these very original disorders. (orig.)

  20. Post-transplantation lymphoproliferative disorder: the spectrum of imaging appearances

    Energy Technology Data Exchange (ETDEWEB)

    Scarsbrook, A.F. [Department of Radiology, John Radcliffe Hospital, Oxford (United Kingdom); Warakaulle, D.R. [Department of Radiology, John Radcliffe Hospital, Oxford (United Kingdom); Dattani, M. [Department of Radiology, John Radcliffe Hospital, Oxford (United Kingdom); Traill, Z. [Department of Radiology, Churchill Hospital, Oxford (United Kingdom)]. E-mail: zoe.traill@orh.nhs.uk

    2005-01-01

    Post-transplantation lymphoproliferative disorder (PTLD) is a serious complication of chronic immunosuppression following solid organ transplantation. Clinical presentation is non-specific and almost any organ can be affected. Early diagnosis is associated with a better prognosis but requires tissue sampling to ascertain the histopathological subtype of disease which cannot be predicted on imaging features alone. The radiologist has a key role in detecting the disorder, guiding biopsy and monitoring response to treatment which often only involves a reduction in immunosuppressive therapy. The aim of this paper is to illustrate the wide spectrum of imaging features in PTLD and emphasize the more specific findings which allow the diagnosis to be suggested at an early stage.

  1. Lymphoproliferative disorders after renal transplantation: role of medical imaging

    Energy Technology Data Exchange (ETDEWEB)

    Claudon, M.; Lefevre, F. [Service de Radiologie, Hopital de Brabois, Vandoeuvre les Nancy (France); Kessler, M.; Hestin, D.; Renoult, E. [Service de Nephrologie, Hopital de Brabois, Vandoeuvre les Nancy (France); Champigneulle, J. [Laboratoire d`Anatomopathologie, Hopital de Brabois, Vandoeuvre les Nancy (France)

    1998-12-01

    Post-transplantation lymphoproliferative disorders (PTLD) are a complication of immunosuppressed transplant recipients, and their incidence is reported to be 20-120 times greater than the rate in the general population. After kidney transplantation, PTLD more likely arise within the renal transplant fossa. Radiological patterns of these forms are presented and discussed, according to a review of the literature, and illustrated by cases from our institution. Ultrasound plays an essential role in the early diagnosis of PTLD by detecting a urinary obstruction associated with adenopathy or an ill-defined mass not previously seen. However, in the case of an inconclusive US examination, CT or MRI should be performed to confirm the presence of a mass. Both techniques are useful in evaluating the extension of the process within the transplantation fossa; MRI seems more accurate and can be used for the follow-up, especially after reduction in immunosuppressive therapy without transplant removal. (orig.) With 4 figs., 1 tab., 38 refs.

  2. Relative adrenal insufficiency in post-transplant lymphoproliferative disorder.

    Directory of Open Access Journals (Sweden)

    Cinclair R

    2003-01-01

    Full Text Available Post-transplant lymphoproliferative disorder is treated with rapid decrement of immunosuppressive therapy. This cannot be achieved with ease in patients on long-term glucocorticoid therapy, as chronically suppressed adrenal glands may not be capable of mounting adequate response to stress. A 52-year-old Caucasian male presented with fever, orthostatic hypotension, lymphadenopathy and hyponatraemia. Serum cortisol levels were within normal levels with a sub optimal response to stimulation by ACTH. Hyponatraemia and orthostasis responded poorly to fluid restriction, saline and salt repletion but corrected after increasing the steroid dose. The normal baseline cortisol levels represented a stimulated adrenal gland, however, the ACTH stimulation had inadequate response. This sub optimal stimulation and a good response to increased steroids suggest the presence of relative or occult adrenal insufficiency. Relative adrenal insufficiency must be considered in patients who have received prolonged glucocorticoid therapy and have symptoms such as hypotension and/or hyponatraemia.

  3. Autoimmune hepatitis: an uncommon presentation of thymoma.

    Science.gov (United States)

    Mendogni, Paolo; Rosso, Lorenzo; Tosi, Davide; Palleschi, Alessandro; Righi, Ilaria; Minonzio, Francesca; Fusco, Nicola; Nosotti, Mario

    2016-11-11

    In a substantial proportion of patients with thymoma, many different types of paraneoplastic syndromes are observed. The association between thymoma and autoimmune liver diseases, however, has been found in very few cases. We report the case of a 31-year-old man affected by autoimmune hepatitis associated with myasthenia gravis and thymoma, successfully treated with extended thymectomy. The patient is free from neoplastic and hepatic disease 4 years after surgery. Eighteen months after thymectomy, an exacerbation of hepatitis was successfully treated with steroids. To the authors' knowledge, only 7 cases of myasthenia gravis associated with thymoma and autoimmune hepatitis have been reported in the English-language literature. The exact role of thymoma in immune-mediated hepatitis is unclear. It seems likely that thymoma-associated T-cell abnormalities, due to the presence of thymoma, may have a role in the development of this rare clinical triad of autoimmune hepatitis, thymoma and myasthenia gravis.

  4. Turner Syndrome

    Science.gov (United States)

    ... have an increased risk of an underactive thyroid (hypothyroidism) due to the autoimmune disorder Hashimoto's thyroiditis. They also have an increased risk of diabetes. Some women with Turner syndrome have gluten intolerance (celiac disease) or inflammatory bowel disease. Skeletal ...

  5. Familial Lymphoproliferative Malignancies and Tandem Duplication of NF1 Gene

    Directory of Open Access Journals (Sweden)

    Gustavo Fernandes

    2014-01-01

    Full Text Available Background. Neurofibromatosis type 1 is a genetic disorder caused by loss-of-function mutations in a tumor suppressor gene (NF1 which codifies the protein neurofibromin. The frequent genetic alterations that modify neurofibromin function are deletions and insertions. Duplications are rare and phenotype in patients bearing duplication of NF1 gene is thought to be restricted to developmental abnormalities, with no reference to cancer susceptibility in these patients. We evaluated a patient who presented with few clinical signs of neurofibromatosis type 1 and a conspicuous personal and familiar history of different types of cancer, especially lymphoproliferative malignancies. The coding region of the NF-1 gene was analyzed by real-time polymerase chain reaction and direct sequencing. Multiplex ligation-dependent probe amplification was performed to detect the number of mutant copies. The NF1 gene analysis showed the following alterations: mosaic duplication of NF1, TRAF4, and MYO1D. Fluorescence in situ hybridization using probes (RP5-1002G3 and RP5-92689 flanking NF1 gene in 17q11.2 and CEP17 for 17q11.11.1 was performed. There were three signals (RP5-1002G3conRP5-92689 in the interphases analyzed and two signals (RP5-1002G3conRP5-92689 in 93% of cells. These findings show a tandem duplication of 17q11.2. Conclusion. The case suggests the possibility that NF1 gene duplication may be associated with a phenotype characterized by lymphoproliferative disorders.

  6. Autoimmunity and Gastric Cancer

    OpenAIRE

    Nicola Bizzaro; Antonio Antico; Danilo Villalta

    2018-01-01

    Alterations in the immune response of patients with autoimmune diseases may predispose to malignancies, and a link between chronic autoimmune gastritis and gastric cancer has been reported in many studies. Intestinal metaplasia with dysplasia of the gastric corpus-fundus mucosa and hyperplasia of chromaffin cells, which are typical features of late-stage autoimmune gastritis, are considered precursor lesions. Autoimmune gastritis has been associated with the development of two types of gastri...

  7. Rituximab for lymphoproliferative disease prior to haematopoietic stem cell transplantation for X-linked severe combined immunodeficiency.

    Science.gov (United States)

    Trahair, Toby N; Wainstein, Brynn; Manton, Nicholas; Bourne, Anthony J; Ziegler, John B; Rice, Michael; Russell, Susan J

    2008-02-01

    Lymphoproliferative disease (LPD) is a complication of congenital and acquired immunodeficiency states. There are a number of treatment options for LPD arising after haematopoietic stem cell or solid organ transplantation including reduction of immunosuppression, targeted therapies, such as the anti-CD20 monoclonal antibody, rituximab, and EBV specific cytotoxic lymphocytes. Treatment of LPD in children with congenital immunodeficiency syndromes remains unsatisfactory and is associated with a high mortality rate. We recently managed an infant found to have polymorphic LPD concurrent with X-linked severe combined immunodeficiency (SCID). Haematopoietic stem cell transplantation (HSCT) had to be deferred because of progressive LPD. Treatment with rituximab resulted in regression of the LPD following which the patient received a 5/6 HLA matched umbilical cord blood (UCB) transplant. The patient remains well 20 months following transplantation. Rituximab treatment may have a useful role in the control of LPD associated with congenital immunodeficiency prior to HSCT. (c) 2007 Wiley-Liss, Inc.

  8. Helicobacter pylori and autoimmune disease: Cause or bystander

    Science.gov (United States)

    Smyk, Daniel S; Koutsoumpas, Andreas L; Mytilinaiou, Maria G; Rigopoulou, Eirini I; Sakkas, Lazaros I; Bogdanos, Dimitrios P

    2014-01-01

    Helicobacter pylori (H. pylori) is the main cause of chronic gastritis and a major risk factor for gastric cancer. This pathogen has also been considered a potential trigger of gastric autoimmunity, and in particular of autoimmune gastritis. However, a considerable number of reports have attempted to link H. pylori infection with the development of extra-gastrointestinal autoimmune disorders, affecting organs not immediately relevant to the stomach. This review discusses the current evidence in support or against the role of H. pylori as a potential trigger of autoimmune rheumatic and skin diseases, as well as organ specific autoimmune diseases. We discuss epidemiological, serological, immunological and experimental evidence associating this pathogen with autoimmune diseases. Although over one hundred autoimmune diseases have been investigated in relation to H. pylori, we discuss a select number of papers with a larger literature base, and include Sjögrens syndrome, rheumatoid arthritis, systemic lupus erythematosus, vasculitides, autoimmune skin conditions, idiopathic thrombocytopenic purpura, autoimmune thyroid disease, multiple sclerosis, neuromyelitis optica and autoimmune liver diseases. Specific mention is given to those studies reporting an association of anti-H. pylori antibodies with the presence of autoimmune disease-specific clinical parameters, as well as those failing to find such associations. We also provide helpful hints for future research. PMID:24574735

  9. Autoimmune Hemolytic Anemia.

    Science.gov (United States)

    Liebman, Howard A; Weitz, Ilene C

    2017-03-01

    Autoimmune hemolytic anemia is an acquired autoimmune disorder resulting in the production of antibodies directed against red blood cell antigens causing shortened erythrocyte survival. The disorders can present as a primary disorder (idiopathic) or secondary to other autoimmune disorders, malignancies, or infections. Treatment involves immune modulation with corticosteroids and other agents. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Autoreactive IgE in Chronic Spontaneous/Idiopathic Urticaria and Basophil/Mastocyte Priming Phenomenon, as a Feature of Autoimmune Nature of the Syndrome.

    Science.gov (United States)

    Panaszek, Bernard; Pawłowicz, Robert; Grzegrzółka, Jędrzej; Obojski, Andrzej

    2017-04-01

    Recent years of research have shed a new light on the role of IgE in immune reactions. It seems to be more than just a contribution to immediate type of allergic response. It appears that monomeric IgE may enhance mast cell activity without cross-linking of FcεRI by IgE specific allergen or autoreactive IgG anti-IgE antibodies. Monomeric IgE molecules are heterogeneous concerning their ability to induce survival and activation of mast cells only by binding the IgE to FcεRI, but not affecting degranulation of cells. It also turned out that IgE may react to autoantigens occurring in the blood not only in chronic spontaneous urticaria (CSU) but also in other autoimmune diseases. The aforementioned phenomena may promote the activity of mast cells/basophils in CSU that easily degranulate when influenced by various inner (autoreactive IgG against IgE and FcεRI, autoreactive IgE for self-antigens) and outer factors (cold, heat, pressure) or allergens. These findings forced the new approach to the role of autoimmunity, self-antigens and IgE autoantibodies in the pathology of CSU. CSU put in the scheme of autoreactive IgG and autoreactive IgE seems to be either a kind of an autoimmune disease or a clinical manifestation of some other defined autoimmune diseases or both.

  11. Autoimmunity, Not a Developmental Defect, is the Cause for Subfertility of Autoimmune Regulator (Aire) Deficient Mice.

    Science.gov (United States)

    Kekäläinen, E; Pöntynen, N; Meri, S; Arstila, T P; Jarva, H

    2015-05-01

    Autoimmune regulator's (AIRE) best characterized role is in the generation immunological tolerance, but it is also involved in many other processes such as spermatogenesis. Loss-of-function mutations in AIRE cause a disease called autoimmune polyendocrinopathy, candidiasis and ectodermal dystrophy (APECED; also called autoimmune polyendocrinopathy syndrome type 1, APS-1) that is dominated by various autoimmune manifestations, mainly endocrinopathies. Both patients with APECED and Aire(-/-) mice suffer from varying levels of infertility, but it is not clear if it is a result of an autoimmune tissue damage or more of a developmental defect. In this study, we wanted to resolve whether or not the reduced fertility of Aire(-/-) mice is dependent on the adaptive immune system and therefore a manifestation of autoimmunity in these mice. We generated lymphopenic mice without Aire expression that were devoid of the autoimmune manifestations previously reported in immunocompetent Aire(-/-) mice. These Aire(-/-) Rag1(-/-) mice regained full fertility. This confirms that the development of infertility in Aire(-/-) mice requires a functional adaptive immune system. We also show that only the male Aire(-/-) mice are subfertile, whereas Aire(-/-) females produce litters normally. Moreover, the male subfertility can be adoptively transferred with lymphocytes from Aire(-/-) donor mice to previously fertile lymphopenic Aire(-/-) recipients. Our data show that subfertility in Aire(-/-) mice is dependent on a functional adaptive immune system thus confirming its autoimmune aetiology. © 2015 John Wiley & Sons Ltd.

  12. Early onset post-transplant lymphoproliferative disease is associated with allograft localization

    NARCIS (Netherlands)

    Bakker, NA; van Imhoff, GW; Verschuuren, EAM; van Son, WJ; van der Heide, JJH; Veeger, NJGM; Kluin, PM; Kluin-Nelemans, HC

    Post-transplant lymphoproliferative disease (PTLD) is a major complication after solid organ transplantation. We analyzed incidence, patient characteristics, clinical presentation, and prognostic factors for treatment outcome and survival of PTLD patients transplanted at our center. Records from

  13. Early onset post-transplant lymphoproliferative disease is associated with allograft localization

    NARCIS (Netherlands)

    Bakker, Nicolaas A.; van Imhoff, Gustaaf W.; Verschuuren, Erik A. M.; van Son, Willem J.; Homan van der Heide, Jaap J.; Veeger, Nic J. G. M.; Kluin, Philip M.; Kluin-Nelemans, Hanneke C.

    2005-01-01

    Post-transplant lymphoproliferative disease (PTLD) is a major complication after solid organ transplantation. We analyzed incidence, patient characteristics, clinical presentation, and prognostic factors for treatment outcome and survival of PTLD patients transplanted at our center. Records from

  14. Evaluation of classical and novel autoantibodies for the diagnosis of Primary Biliary Cholangitis-Autoimmune Hepatitis Overlap Syndrome (PBC-AIH OS).

    Science.gov (United States)

    Nguyen, Henry H; Shaheen, Abdel Aziz; Baeza, Natalia; Lytvyak, Ellina; Urbanski, Stefan J; Mason, Andrew L; Norman, Gary L; Fritzler, Marvin J; Swain, Mark G

    2018-01-01

    Up to 20% of Primary Biliary Cholangitis (PBC) patients are estimated to have features that overlap with Autoimmune Hepatitis (AIH). Patients with PBC-AIH overlap syndrome (PBC-AIH OS) have been reported to exhibit suboptimal responses to ursodeoxycholic acid therapy, and are more likely to progress to cirrhosis. Anti-double stranded DNA (anti-dsDNA) and anti-p53 have been previously suggested to be potential autoantibodies for identifying patients with PBC-AIH OS. In our well defined PBC patient cohorts, a comprehensive assessment of various classical and novel autoantibodies was evaluated for their utility in identifying PBC-AIH OS patients. PBC-AIH OS was classified according to the Paris criteria and PBC as per the European Association for the Study of the Liver guidelines. Biobanked serum samples from 197 patients at the University of Calgary Liver Unit and the University of Alberta were analyzed for classical and novel autoantibodies. Anti-dsDNA was measured by the Crithidia luciliae immunofluorescence (CLIFT) assay (1:20 dilution) and chemiluminescence (CIA: QUANTA Flash®, Inova Diagnostics, San Diego). Anti-p53, anti-Ro52/TRIM21, anti-YB 1, anti-GW182, anti-Ge-1, and anti-Ago 2 were measured by either an addressable laser bead immunoassay (ALBIA) or line immunoassay (LIA). Autoantibodies against MIT3, gp210, sp100, LKM1, SLA, and the novel autoantibodies Hexokinase-1 (HK-1), and Kelch like protein 12 (KLHL-12) were measured using QUANTA Lite® ELISA assays. We applied non-parametric methods to compare the biomarkers frequencies between study groups. We used multivariate adjusted models and AUROC to compare the diagnostic accuracy of the different autoantibodies alone or in combination with serum biochemistry. 16 out of 197 PBC patients (8.1%) were classified as PBC-AIH OS. Compared to PBC patients, PBC-AIH OS patients were similar in age (median: 59 vs. 63, P = 0.21) and female predominance (94% vs. 89%, P = 1.00). Anti-dsDNA-by CLIFT (37.5% in PBC-AIH OS

  15. Cerebral Post-Transplant Lymphoproliferative Disorder Occurring after Renal Transplantation: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Suh, Jang Ho; Byun, Woo Mok; Kim, Hong Chul; Hwang, Min Su [Dept. of Radiology, Yeungnam University College of Medicine, Daegu (Korea, Republic of)

    2012-04-15

    Post-transplant lymphoproliferative disorder (PTLD) is a complication of organ transplantation and immunosuppression. A 36-year-old woman with a history of renal transplantation visited the hospital complaining of headache and on pathology was diagnosed with cerebral PTLD manifesting as multiple rim enhanced masses in both hemispheres. We report here a case of post-transplant lymphoproliferative disorder involving the cerebrum occurring after renal transplantation, and describe the MRI findings for this patient

  16. Cerebral Post-Transplant Lymphoproliferative Disorder Occurring after Renal Transplantation: A Case Report

    International Nuclear Information System (INIS)

    Suh, Jang Ho; Byun, Woo Mok; Kim, Hong Chul; Hwang, Min Su

    2012-01-01

    Post-transplant lymphoproliferative disorder (PTLD) is a complication of organ transplantation and immunosuppression. A 36-year-old woman with a history of renal transplantation visited the hospital complaining of headache and on pathology was diagnosed with cerebral PTLD manifesting as multiple rim enhanced masses in both hemispheres. We report here a case of post-transplant lymphoproliferative disorder involving the cerebrum occurring after renal transplantation, and describe the MRI findings for this patient

  17. Skin Manifestations Associated with Autoimmune Liver Diseases: a Systematic Review.

    Science.gov (United States)

    Terziroli Beretta-Piccoli, Benedetta; Invernizzi, Pietro; Gershwin, M Eric; Mainetti, Carlo

    2017-12-01

    Autoimmune liver diseases, which include mainly autoimmune hepatitis, primary biliary cholangitis, primary sclerosing cholangitis, and the variant syndromes, are often associated with extrahepatic autoimmune diseases. However, the association with cutaneous diseases is less well described. In the present article, we provide a systematic literature review on skin manifestations linked to each of these four autoimmune liver diseases, excluding skin manifestations of systemic diseases. The association of autoimmune hepatitis with vitiligo is well known, with a particular striking association with type 2 autoimmune hepatitis, a condition occurring almost entirely in children and adolescents, much rarer and more aggressive than type 1 autoimmune hepatitis; probable associations are also identified with alopecia areata, psoriasis, and pyoderma gangrenosum. Primary biliary cholangitis is not linked to lichen planus as previously assumed, but to vitiligo, psoriasis and the very rare amicrobial pustulosis of the folds. The proposed diagnostic criteria for this latter condition include the presence of anti-mitochondrial autoantibodies, the serological hallmark of primary biliary cholangitis. The very strong association of primary sclerosing cholangitis with inflammatory bowel diseases hampers the search for an association with skin diseases, since inflammatory bowel diseases have a strong association with various dermatological condition, including neutrophilic dermatoses and erythema nodosum. Nevertheless, a probable association of primary sclerosing cholangitis with psoriasis is identified in this review. Variant syndromes, also called overlap syndromes, are likely associated with vitiligo as well, which is not surprising, since autoimmune hepatitis is a feature of these conditions and they may share regions of the MHC.

  18. Immune Disorder HSCT Protocol

    Science.gov (United States)

    2017-11-17

    Immune Deficiency Disorders; Severe Combined Immunodeficiency; Chronic Granulomatous Disease; X-linked Agammaglobulinemia; Wiskott-Aldrich Syndrome; Hyper-IgM; DiGeorge Syndrome; Chediak-Higashi Syndrome; Common Variable Immune Deficiency; Immune Dysregulatory Disorders; Hemophagocytic Lymphohistiocytosis; IPEX; Autoimmune Lymphoproliferative Syndrome; X-linked Lymphoproliferative Syndrome

  19. Autoimmune diseases and infections: controversial issues.

    Science.gov (United States)

    Baio, P; Brucato, A; Buskila, D; Gershwin, M E; Giacomazzi, D; Lopez, L R; Luzzati, R; Matsuura, E; Selmi, C; Sarzi-Puttini, P; Atzeni, F

    2008-01-01

    The etiology and pathogenesis of certain types of disease remain controversial and stand like a bridge that crosses infectious, autoimmune and autoinflammatory pathways. Infection, for example, may initiate a disease, although it is the genetic regulation in the host, the interplay between virus or bacteria persistence and autoimmunity that produces the later phases of disease, the antigenic determinants responsible for inducing autoimmune disease, and the pathogenetic effector mechanisms. Infections agents cause pericarditis, but in 85% of cases it is "idiopathic". It has also been shown that persistent Clamydia pneumoniae, Porphyromonas gingivalis, and Helicobacter pylori infections cause host immunity and promote atherogenesis. A number of infectious agents have been suggested as potential triggers for primary biliary cirrhosis. Infections and vaccinations have also been linked to the pathogenesis of fibromyalgia syndrome, a common, chronic syndrome of widespread pain. Many factors are also responsible for fever of unknown origin such as: infections, autoimmunity disease, etc. However, it is difficult to determine a direct correlation between the infections agents in such a large group of diseases. The aim of this review is to analyze some of the controversies about the role of infections in autoimmune diseases.

  20. Autoimmune cytopenias related to common variable immunodeficiency

    Directory of Open Access Journals (Sweden)

    Vlasta Petric

    2011-09-01

    Full Text Available Background: Common variable immunodeficiency disorders are characterised by defective antibody production leading to recurrent infections. Noninfective complications are a consequence of autoimmunity, granuloma and polyclonal lymphoid infiltration. We often detect autoimmune cytopenias before primary immunodefciency is confirmed. Patients and methods: We report a case of 39-year old man with recurrent respiratory infections, autoimmune thrombocytopenia and haemolytic anemia who had common varible immunodeficiency confirmed. He had a lack of serum IgG, IgA and IgM, bronchiectasis, lymphadenopathy, splenomegaly, hepatic granuloma, autoimmune gastritis with B12 deficiency and Evans syndrome. We treated autoimmune cytopenias with methylprednisolon and cyclosporine. After substitution therapy with intravenous immunoglobulin the frequency of espiratory infections decreased. Occurrence of diarrhea is suspected for enteropathy, however, hystologic identification is required. Because of patologically changed gastric mucosa and signs of polyclonal lymphoid infiltration, the patient is at high risk for malignancy and the outcome of the disease remains unpredictable. Conclusions: Generally, we discover common variable immunodeficiency at management of noninfective complications, in wich intravenous immunoglobulin are not effective. Autoimmune cytopenias and some other complications are successfully treated with glucocorticoids. Careful monitorig of these patients is important because of a high risk for malignancy.

  1. Clinical aspects of autoimmune rheumatic diseases.

    Science.gov (United States)

    Goldblatt, Fiona; O'Neill, Sean G

    2013-08-31

    Multisystem autoimmune rheumatic diseases are heterogeneous rare disorders associated with substantial morbidity and mortality. Efforts to create international consensus within the past decade have resulted in the publication of new classification or nomenclature criteria for several autoimmune rheumatic diseases, specifically for systemic lupus erythematosus, Sjögren's syndrome, and the systemic vasculitides. Substantial progress has been made in the formulation of new criteria in systemic sclerosis and idiopathic inflammatory myositis. Although the autoimmune rheumatic diseases share many common features and clinical presentations, differentiation between the diseases is crucial because of important distinctions in clinical course, appropriate drugs, and prognoses. We review some of the dilemmas in the diagnosis of these autoimmune rheumatic diseases, and focus on the importance of new classification criteria, clinical assessment, and interpretation of autoimmune serology. In this era of improvement of mortality rates for patients with autoimmune rheumatic diseases, we pay particular attention to the effect of leading complications, specifically cardiovascular manifestations and cancer, and we update epidemiology and prognosis. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. Galectin-3 in autoimmunity and autoimmune diseases.

    Science.gov (United States)

    de Oliveira, Felipe L; Gatto, Mariele; Bassi, Nicola; Luisetto, Roberto; Ghirardello, Anna; Punzi, Leonardo; Doria, Andrea

    2015-08-01

    Galectin-3 (gal-3) is a β-galactoside-binding lectin, which regulates cell-cell and extracellular interactions during self/non-self-antigen recognition and cellular activation, proliferation, differentiation, migration and apoptosis. It plays a significant role in cellular and tissue pathophysiology by organizing niches that drive inflammation and immune responses. Gal-3 has some therapeutic potential in several diseases, including chronic inflammatory disorders, cancer and autoimmune diseases. Gal-3 exerts a broad spectrum of functions which differs according to its intra- or extracellular localization. Recombinant gal-3 strategy has been used to identify potential mode of action of gal-3; however, exogenous gal-3 may not reproduce the functions of the endogenous gal-3. Notably, gal-3 induces monocyte-macrophage differentiation, interferes with dendritic cell fate decision, regulates apoptosis on T lymphocytes and inhibits B-lymphocyte differentiation into immunoglobulin secreting plasma cells. Considering the influence of these cell populations in the pathogenesis of several autoimmune diseases, gal-3 seems to play a role in development of autoimmunity. Gal-3 has been suggested as a potential therapeutic agent in patients affected with some autoimmune disorders. However, the precise role of gal-3 in driving the inflammatory process in autoimmune or immune-mediated disorders remains elusive. Here, we reviewed the involvement of gal-3 in cellular and tissue events during autoimmune and immune-mediated inflammatory diseases. © 2015 by the Society for Experimental Biology and Medicine.

  3. Indolent T-cell lymphoproliferative disease of the gastrointestinal tract

    Science.gov (United States)

    Perry, Anamarija M.; Warnke, Roger A.; Hu, Qinglong; Gaulard, Philippe; Copie-Bergman, Christiane; Alkan, Serhan; Wang, Huan-You; Cheng, Jason X.; Bacon, Chris M.; Delabie, Jan; Ranheim, Erik; Kucuk, Can; Hu, XiaoZhou; Weisenburger, Dennis D.

    2013-01-01

    Primary gastrointestinal (GI) T-cell lymphoma is an infrequent and aggressive disease. However, rare indolent clonal T-cell proliferations in the GI tract have been described. We report 10 cases of GI involvement by an indolent T-cell lymphoproliferative disease, including 6 men and 4 women with a median age of 48 years (range, 15-77 years). Presenting symptoms included abdominal pain, diarrhea, vomiting, food intolerance, and dyspepsia. The lesions involved oral cavity, esophagus, stomach, small intestine, and colon. The infiltrates were dense, but nondestructive, and composed of small, mature-appearing lymphoid cells. Eight cases were CD4−/CD8+, 1 was CD4+/CD8−, and another was CD4−/CD8−. T-cell receptor-γ chain gene rearrangement identified a clonal population in all 10 cases. There was no evidence of STAT3 SH2 domain mutation or activation. Six patients received chemotherapy because of an initial diagnosis of peripheral T-cell lymphoma, with little or no response, whereas the other 4 were followed without therapy. After a median follow-up of 38 months (range, 9-175 months), 9 patients were alive with persistent disease and 1 was free of disease. We propose the name “indolent T-LPD of the GI tract” for these lesions that can easily be mistaken for intestinal peripheral T-cell lymphoma, and lead to aggressive therapy. PMID:24009234

  4. Ultra-early onset post-transplantation Lymphoproliferative disease

    Directory of Open Access Journals (Sweden)

    Hossein Khedmat

    2013-01-01

    Full Text Available Post-transplant lymphoproliferative disease (PTLD can present as early as days to as late as several decades after transplantation. This study, however, tries to research PTLD characteristics including histopathological and clinical features, predictors and prognosis of the disease when occurring within the first month post-transplantation. We conducted a comprehensive search for the available data using the Pubmed and Google scholar search engines for reports indicating presentation time in PTLD patients. Data from 25 previously published studies were included in the analysis. Finally, we found 355 recipients of organs presenting with "ultra-early onset PTLD." Transplant recipients with ultra-early onset PTLD were significantly more likely to have kidney allografts (P = 0.032. Transplant recipients with ultra-early onset PTLD were comparable to their counterparts in the control group in their demographics, histopathological findings and survival. Patients with ultra-early onset PTLD were significantly more likely to receive induction therapy (100% vs. 49%, respectively; P = 0.013. Pancreas transplant recipients were at a significantly higher risk for development of ultra-early onset PTLD (20% vs. 1%, respectively; P <0.001. Our findings emphasize the importance of immunosuppression potency as well as the type of allograft transplanted on the incidence of PTLD in the early stages after transplantation. However, we found no histopathological or outcome disparities for patients with ultra-early PTLD compared with controls. Further prospective studies with more comparable approaches to the patients are needed to confirm our findings.

  5. Ultra-early onset post-transplantation lymphoproliferative disease.

    Science.gov (United States)

    Khedmat, Hossein; Taheri, Saeed

    2013-11-01

    Post-transplant lymphoproliferative disease (PTLD) can present as early as days to as late as several decades after transplantation. This study, however, tries to research PTLD characteristics including histopathological and clinical features, predictors and prognosis of the disease when occurring within the first month post-transplantation. We conducted a comprehensive search for the available data using the Pubmed and Google scholar search engines for reports indicating presentation time in PTLD patients. Data from 25 previously published studies were included in the analysis. Finally, we found 355 recipients of organs presenting with "ultra-early onset PTLD." Transplant recipients with ultra-early onset PTLD were significantly more likely to have kidney allografts (P = 0.032). Transplant recipients with ultra-early onset PTLD were comparable to their counterparts in the control group in their demographics, histopathological findings and survival. Patients with ultra-early onset PTLD were significantly more likely to receive induction therapy (100% vs. 49%, respectively; P = 0.013). Pancreas transplant recipients were at a significantly higher risk for development of ultra-early onset PTLD (20% vs. 1%, respectively; P <0.001). Our findings emphasize the importance of immunosuppression potency as well as the type of allograft transplanted on the incidence of PTLD in the early stages after transplantation. However, we found no histopathological or outcome disparities for patients with ultra-early PTLD compared with controls. Further prospective studies with more comparable approaches to the patients are needed to confirm our findings.

  6. A nuclear proliferation antigen in chronic lymphoproliferative disease

    International Nuclear Information System (INIS)

    Hassab, A.H.; Nafae, M.H.

    1998-01-01

    To determine whether the proliferation rates of tumour cells, in chronic lymphoproliferative disorders may reflect disease activity and relate to prognosis, we studied the expression of Ki-67% (a nuclear proliferation marker) by alkaline phosphatase anti-alkaline phosphatase technique (APAAP), in peripheral blood and bone marrow mononuclear cells (separated on ficoll-hypaque) and in lymph-node biopsies, from patients with chronic lymphatic leukemia (Cll), chronic lymphatic leukemia/prolymphocytic leukemia (CLL/PLL), prolymphocytic leukemia (PLL) and non-hodgkin's lymphoma with leukemic plase. The proliferation rate was determined for these patients at presentation and again two months after therapy (to detect any change with therapy). We found that the highest rate of proliferation in each group was parallel to the degree of malignancy i.e. PLL showed higher proliferation than CLL/PLL, and CLL/PLL showed higher proliferation than CLL. In the NHL group the highest proliferation rate was found in the high high-grade NHL, followed by intermediate grade NHL then the low grade NHL. Lymph node biopsies also showed the same relation between proliferation rates and degree of malignancy. Bone marrow cells did not show a particular pattern probably due to interference from the erythroid element and contamination by peripheral blood. Ki-67% was compared to other proliferation markers serum B2 microglobulin and lactate dehydrogenase. It was found to be an independent marker of proliferation it is unaffected by hepatic, renal and gastrointestinal elements and thus its specificity for the tumour proliferation

  7. Celiac disease and autoimmune thyroid disease.

    Science.gov (United States)

    Ch'ng, Chin Lye; Jones, M Keston; Kingham, Jeremy G C

    2007-10-01

    Celiac disease (CD) or gluten sensitive enteropathy is relatively common in western populations with prevalence around 1%. With the recent availability of sensitive and specific serological testing, many patients who are either asymptomatic or have subtle symptoms can be shown to have CD. Patients with CD have modest increases in risks of malignancy and mortality compared to controls. The mortality among CD patients who comply poorly with a gluten-free diet is greater than in compliant patients. The pattern of presentation of CD has altered over the past three decades. Many cases are now detected in adulthood during investigation of problems as diverse as anemia, osteoporosis, autoimmune disorders, unexplained neurological syndromes, infertility and chronic hypertransaminasemia of uncertain cause. Among autoimmune disorders, increased prevalence of CD has been found in patients with autoimmune thyroid disease, type 1 diabetes mellitus, autoimmune liver diseases and inflammatory bowel disease. Prevalence of CD was noted to be 1% to 19% in patients with type 1 diabetes mellitus, 2% to 5% in autoimmune thyroid disorders and 3% to 7% in primary biliary cirrhosis in prospective studies. Conversely, there is also an increased prevalence of immune based disorders among patients with CD. The pathogenesis of co-existent autoimmune thyroid disease and CD is not known, but these conditions share similar HLA haplotypes and are associated with the gene encoding cytotoxic T-lymphocyte-associated antigen-4. Screening high risk patients for CD, such as those with autoimmune diseases, is a reasonable strategy given the increased prevalence. Treatment of CD with a gluten-free diet should reduce the recognized complications of this disease and provide benefits in both general health and perhaps life expectancy. It also improves glycemic control in patients with type 1 diabetes mellitus and enhances the absorption of medications for associated hypothyroidism and osteoporosis. It

  8. Bistability in autoimmune diseases

    DEFF Research Database (Denmark)

    Rapin, Nicolas; Mosekilde, Erik; Lund, Ole

    2011-01-01

    Autoimmune diseases damage host tissue, which, in turn, may trigger a stronger immune response. Systems characterized by such positive feedback loops can display co-existing stable steady states. In a mathematical model of autoimmune disease, one steady state may correspond to the healthy state...... and another to an autoimmune steady state characterized by widespread tissue damage and immune activation. We show how a triggering event may move the system from the healthy to the autoimmune state and how transient immunosuppressive treatment can move the system back to the healthy state....

  9. Introducing Polyautoimmunity: Secondary Autoimmune Diseases No Longer Exist

    Science.gov (United States)

    Rojas-Villarraga, Adriana; Amaya-Amaya, Jenny; Rodriguez-Rodriguez, Alberto; Mantilla, Rubén D.; Anaya, Juan-Manuel

    2012-01-01

    Similar pathophysiological mechanisms within autoimmune diseases have stimulated searches for common genetic roots. Polyautoimmunity is defined as the presence of more than one autoimmune disease in a single patient. When three or more autoimmune diseases coexist, this condition is called multiple autoimmune syndrome (MAS). We analyzed the presence of polyautoimmunity in 1,083 patients belonging to four autoimmune disease cohorts. Polyautoimmunity was observed in 373 patients (34.4%). Autoimmune thyroid disease (AITD) and Sjögren's syndrome (SS) were the most frequent diseases encountered. Factors significantly associated with polyautoimmunity were female gender and familial autoimmunity. Through a systematic literature review, an updated search was done for all MAS cases (January 2006–September 2011). There were 142 articles retrieved corresponding to 226 cases. Next, we performed a clustering analysis in which AITD followed by systemic lupus erythematosus and SS were the most hierarchical diseases encountered. Our results indicate that coexistence of autoimmune diseases is not uncommon and follows a grouping pattern. Polyautoimmunity is the term proposed for this association of disorders, which encompasses the concept of a common origin for these diseases. PMID:22454759

  10. Paraneoplastic Pemphigus. A Life-Threatening Autoimmune Blistering Disease.

    Science.gov (United States)

    Tirado-Sánchez, A; Bonifaz, A

    2017-12-01

    Paraneoplastic pemphigus (PNP), a subset of pemphigus, is a unique autoimmune blistering condition that can affect multiple organs other than the skin. It is a life-threatening disease associated with an underlying malignancy, most commonly of lymphoproliferative origin. The clinical picture may resemble pemphigus, pemphigoid, erythema multiforme, graft-versus-host disease, or lichen planus. The earliest and most consistent finding is a painful, severe, chronic and often recalcitrant stomatitis. Treatment of PNP is difficult. Immunosuppressive agents are required to decrease blistering, and treating the underlying tumor may control autoantibody production. In this review, we included essential diagnostic aspects of PNP and the most useful treatment options in the dermatologist practice. Copyright © 2017 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

  11. HTLV-1, Immune Response and Autoimmunity

    Directory of Open Access Journals (Sweden)

    Juarez A S Quaresma

    2015-12-01

    Full Text Available Human T-lymphotropic virus type-1 (HTLV-1 infection is associated with adult T-cell leukemia/lymphoma (ATL. Tropical spastic paraparesis/HTLV-1-associated myelopathy (PET/HAM is involved in the development of autoimmune diseases including Rheumatoid Arthritis (RA, Systemic Lupus Erythematosus (SLE, and Sjögren’s Syndrome (SS. The development of HTLV-1-driven autoimmunity is hypothesized to rely on molecular mimicry, because virus-like particles can trigger an inflammatory response. However, HTLV-1 modifies the behavior of CD4+ T cells on infection and alters their cytokine production. A previous study showed that in patients infected with HTLV-1, the activity of regulatory CD4+ T cells and their consequent expression of inflammatory and anti-inflammatory cytokines are altered. In this review, we discuss the mechanisms underlying changes in cytokine release leading to the loss of tolerance and development of autoimmunity.

  12. Fibromyalgia and chronic widespread pain in autoimmune thyroid disease.

    Science.gov (United States)

    Ahmad, Jowairiyya; Tagoe, Clement E

    2014-07-01

    Fibromyalgia and chronic widespread pain syndromes are among the commonest diseases seen in rheumatology practice. Despite advances in the management of these conditions, they remain significant causes of morbidity and disability. Autoimmune thyroid disease is the most prevalent autoimmune disorder, affecting about 10 % of the population, and is a recognized cause of fibromyalgia and chronic widespread pain. Recent reports are shedding light on the mechanisms of pain generation in autoimmune thyroid disease-associated pain syndromes including the role of inflammatory mediators, small-fiber polyneuropathy, and central sensitization. The gradual elucidation of these pain pathways is allowing the rational use of pharmacotherapy in the management of chronic widespread pain in autoimmune thyroid disease. This review looks at the current understanding of the prevalence of pain syndromes in autoimmune thyroid disease, their likely causes, present appreciation of the pathogenesis of chronic widespread pain, and how our knowledge can be used to find lasting and effective treatments for the pain syndromes associated with autoimmune thyroid disease.

  13. American Autoimmune Related Diseases Association

    Science.gov (United States)

    ... List Common Thread Women & Autoimmunity Diagnosis Tips Coping Tools Support Groups Education Modules Caregivers Patient/Caregiver Relationship The Male Caregiver AD Knowledge Base Autoimmune Disease List Common ...

  14. THE AUTOIMMUNE ECOLOGY.

    Directory of Open Access Journals (Sweden)

    Juan-Manuel eAnaya

    2016-04-01

    Full Text Available Autoimmune diseases (ADs represent a heterogeneous group of disorders that affect specific target organs or multiple organ systems. These conditions share common immunopathogenic mechanisms (i.e., the autoimmune tautology, which explain the clinical similarities they have among them as well as their familial clustering (i.e., coaggregation. As part of the autoimmune tautology, the influence of environmental exposure on the risk of developing ADs is paramount (i.e., the autoimmune ecology. In fact, environment, more than genetics, shapes immune system. Autoimmune ecology is akin to exposome, that is all the exposures - internal and external - across the lifespan, interacting with hereditary factors (both genetics and epigenetics to favor or protect against autoimmunity and its outcomes. Herein we provide an overview of the autoimmune ecology, focusing on the immune response to environmental agents in general, and microbiota, cigarette smoking, alcohol and coffee consumption, socioeconomic status, gender and sex hormones, vitamin D, organic solvents and vaccines in particular. Inclusion of the autoimmune ecology in disease etiology and health will improve the way personalized medicine is currently conceived and applied.

  15. Risk Factors for Autoimmune Diseases Development After Thrombotic Thrombocytopenic Purpura

    Science.gov (United States)

    Roriz, Mélanie; Landais, Mickael; Desprez, Jonathan; Barbet, Christelle; Azoulay, Elie; Galicier, Lionel; Wynckel, Alain; Baudel, Jean-Luc; Provôt, François; Pène, Frédéric; Mira, Jean-Paul; Presne, Claire; Poullin, Pascale; Delmas, Yahsou; Kanouni, Tarik; Seguin, Amélie; Mousson, Christiane; Servais, Aude; Bordessoule, Dominique; Perez, Pierre; Chauveau, Dominique; Veyradier, Agnès; Halimi, Jean-Michel; Hamidou, Mohamed; Coppo, Paul

    2015-01-01

    Abstract Autoimmune thrombotic thrombocytopenic purpura (TTP) can be associated with other autoimmune disorders, but their prevalence following autoimmune TTP remains unknown. To assess the prevalence of autoimmune disorders associated with TTP and to determine risk factors for and the time course of the development of an autoimmune disorder after a TTP episode, we performed a cross sectional study. Two-hundred sixty-one cases of autoimmune TTP were included in the French Reference Center registry between October, 2000 and May, 2009. Clinical and laboratory data available at time of TTP diagnosis were recovered. Each center was contacted to collect the more recent data and diagnosis criteria for autoimmunity. Fifty-six patients presented an autoimmune disorder in association with TTP, 9 years before TTP (median; min: 2 yr, max: 32 yr) (26 cases), at the time of TTP diagnosis (17 cases) or during follow-up (17 cases), up to 12 years after TTP diagnosis (mean, 22 mo). The most frequent autoimmune disorder reported was systemic lupus erythematosus (SLE) (26 cases) and Sjögren syndrome (8 cases). The presence of additional autoimmune disorders had no impact on outcomes of an acute TTP or the occurrence of relapse. Two factors evaluated at TTP diagnosis were significantly associated with the development of an autoimmune disorder during follow-up: the presence of antidouble stranded (ds)DNA antibodies (hazard ratio (HR): 4.98; 95% confidence interval (CI) [1.64–15.14]) and anti-SSA antibodies (HR: 9.98; 95% CI [3.59–27.76]). A follow-up across many years is necessary after an acute TTP, especially when anti-SSA or anti-dsDNA antibodies are present on TTP diagnosis, to detect autoimmune disorders early before immunologic events spread to prevent disabling complications. PMID:26496263

  16. A Challenging Form of Non-autoimmune Insulin-Dependent Diabetes in a Wolfram Syndrome Patient with a Novel Sequence Variant.

    Science.gov (United States)

    Paris, Liliana P; Usui, Yoshihiko; Serino, Josefina; Sá, Joaquim; Friedlander, Martin

    2015-06-01

    Wolfram syndrome type 1 is a rare, autosomal recessive, neurodegenerative disorder that is diagnosed when insulin-dependent diabetes of non-auto-immune origin and optic atrophy are concomitantly present. Wolfram syndrome is also designated by DIDMOAD that stands for its most frequent manifestations: diabetes insipidus, diabetes mellitus, optic atrophy and deafness. With disease progression, patients also commonly develop severe neurological and genito-urinary tract abnormalities. When compared to the general type 1 diabetic population, patients with Wolfram Syndrome have been reported to have a form of diabetes that is more easily controlled and with less microvascular complications, such as diabetic retinopathy. We report a case of Wolfram syndrome in a 16-year-old male patient who presented with progressive optic atrophy and severe diabetes with very challenging glycemic control despite intensive therapy since diagnosis at the age of 6. Despite inadequate metabolic control he did not develop any diabetic microvascular complications during the 10-year follow-up period. To further investigate potential causes for this metabolic idiosyncrasy, we performed genetic analyses that revealed a novel combination of homozygous sequence variants that are likely the cause of the syndrome in this family. The identified genotype included a novel sequence variant in the Wolfram syndrome type 1 gene along with a previously described one, which had initially been associated with isolated low frequency sensorineural hearing loss (LFSNHL). Interestingly, our patient did not show any abnormal findings with audiometry testing.

  17. Pulmonary lymphoproliferative disorders with affinity to lymphoma: a clinicopathoradiologic study of 16 cases

    International Nuclear Information System (INIS)

    Fernandez Cruz, J.; Gonzalez Garcia, A.; Escobar Casas, P.; Gomez Benitez, S.; Gonzalez Guirao, M.A.; Borderas, F.

    1993-01-01

    Pulmonary lymphoproliferative disorders include plasma cell granuloma, Castleman's disease, pseudolymphoma, lymphocytic interstitial pneumonia, angioimmunoblastic lymphadenopathy and lymphomatoid granulomatosis. We carried out a retrospective study for the purpose of analysing the clinical and radiological findings of 16 cases of pulmonary lymphoproliferative disorders seen during the decade 1980-1990. The cases comprised 8 lymphocytic interstitial pneumonia, 5 lymphomatoid granulomatosis, 2 plasma cell granuloma and 1 angioimmunoblastic lymphadenopathy. Owing to the overlap and low specificity of the radiological patterns in these processes, histopathological examination is required. In view of the frequent evolution of pulmonary lymphoproliferative disorders to malignant lymphoma (4 cases, 1 of lymphocytic interstitial pneumonia and 3 of lymphomatoid granulomatosis, in our series) we provide a description of the radiological changes that occur during this process. (orig.)

  18. Upper gastrointestinal symptoms in autoimmune gastritis

    Science.gov (United States)

    Carabotti, Marilia; Lahner, Edith; Esposito, Gianluca; Sacchi, Maria Carlotta; Severi, Carola; Annibale, Bruno

    2017-01-01

    Abstract Autoimmune gastritis is often suspected for its hematologic findings, and rarely the diagnosis is made for the presence of gastrointestinal symptoms. Aims of this cross-sectional study were to assess in a large cohort of patients affected by autoimmune gastritis the occurrence and the pattern of gastrointestinal symptoms and to evaluate whether symptomatic patients are characterized by specific clinical features. Gastrointestinal symptoms of 379 consecutive autoimmune gastritis patients were systematically assessed and classified following Rome III Criteria. Association between symptoms and anemia pattern, positivity to gastric autoantibodies, Helicobacter pylori infection, and concomitant autoimmune disease were evaluated. In total, 70.2% of patients were female, median age 55 years (range 17–83). Pernicious anemia (53.6%), iron deficiency anemia (34.8%), gastric autoantibodies (68.8%), and autoimmune disorders (41.7%) were present. However, 56.7% of patients complained of gastrointestinal symptoms, 69.8% of them had exclusively upper symptoms, 15.8% only lower and 14.4% concomitant upper and lower symptoms. Dyspepsia, subtype postprandial distress syndrome was the most represented, being present in 60.2% of symptomatic patients. Univariate and multivariate analyses showed that age gastritis is associated in almost 60% of cases with gastrointestinal symptoms, in particular dyspepsia. Dyspepsia is strictly related to younger age, no smoking, and absence of anemia. PMID:28072728

  19. A clinical approach to diagnosis of autoimmune encephalitis

    Science.gov (United States)

    Graus, Francesc; Titulaer, Maarten J; Balu, Ramani; Benseler, Susanne; Bien, Christian G; Cellucci, Tania; Cortese, Irene; Dale, Russell C; Gelfand, Jeffrey M; Geschwind, Michael; Glaser, Carol A; Honnorat, Jerome; Höftberger, Romana; Iizuka, Takahiro; Irani, Sarosh R; Lancaster, Eric; Leypoldt, Frank; Prüss, Harald; Rae-Grant, Alexander; Reindl, Markus; Rosenfeld, Myrna R; Rostásy, Kevin; Saiz, Albert; Venkatesan, Arun; Vincent, Angela; Wandinger, Klaus-Peter; Waters, Patrick; Dalmau, Josep

    2016-01-01

    Encephalitis is a severe inflammatory disorder of the brain with many possible causes and a complex differential diagnosis. Advances in autoimmune encephalitis research in the past 10 years have led to the identification of new syndromes and biomarkers that have transformed the diagnostic approach to these disorders. However, existing criteria for autoimmune encephalitis are too reliant on antibody testing and response to immunotherapy, which might delay the diagnosis. We reviewed the literature and gathered the experience of a team of experts with the aims of developing a practical, syndrome-based diagnostic approach to autoimmune encephalitis and providing guidelines to navigate through the differential diagnosis. Because autoantibody test results and response to therapy are not available at disease onset, we based the initial diagnostic approach on neurological assessment and conventional tests that are accessible to most clinicians. Through logical differential diagnosis, levels of evidence for autoimmune encephalitis (possible, probable, or definite) are achieved, which can lead to prompt immunotherapy. PMID:26906964

  20. Recent insights into the role and molecular mechanisms of the autoimmune regulator (AIRE) gene in autoimmunity.

    Science.gov (United States)

    Fierabracci, Alessandra

    2011-01-01

    Since many years immunologists have being tried to answer the tantalizing enigma of immunological tolerance. Complex mechanisms in both thymus (central tolerance) and peripheral lymphoid organs (peripheral tolerance) underly lymphocyte tolerance and its maintenance. The genesis of autoimmunity involves environmental and genetic mechanisms, both contributing to the disruption and deregulation of central and peripheral tolerance, allowing autoreactive pathogenetic T and B-cell clones arising. Among genetic factors the autoimmune regulator (AIRE) gene is one of the best candidates to understand the complex scenario of autoimmunity. Autoimmune polyendocrinopathy syndrome type 1 is a rare autosomal recessive disease caused by mutations in the AIRE gene. Therefore, the disorder has certainly been a powerful model to address the question concerning how a tolerant state is achieved or maintained and to explore how it has gone lost in the context of autoimmunity. AIRE has been proposed to function as a 'non classical' transcription factor, strongly implicated in the regulation of organ-specific antigen expression in thymic epithelial cells and in the imposition of T cell tolerance, thus regulating the negative selection of autoreactive T cell clones. A plethora of proposal have been suggested for AIRE's potential mechanism of action, thus regulating the negative selection of autoreactive T cells. In this review recent discoveries are presented into the role and molecular mechanisms of the AIRE protein in APECED and other autoimmune diseases. Copyright © 2010 Elsevier B.V. All rights reserved.

  1. Clinical, laboratory, and morphological characteristics of kidney damage in lymphoproliferative disorders

    Directory of Open Access Journals (Sweden)

    B. T. Dzhumabaeva

    2017-01-01

    Full Text Available Kidney involvement in the onset of lymphoproliferative diseases (LPD detected rarely, observed mainly at tumor progression or relapse.Objective: to determine the clinical and morphological features of kidney damage in the initial manifestation of LPD.Materials and methods: 19 patients with LPD and kidney damage were included in the study. The diagnosis of non-Hodgkin’s lymphomas was established according to 2008 WHO classification. Histological and immunohistochemical, immunofluorescent and electron microscopic studies of nephrobiopsy have been performed.Results. Patients were aged 46-83 years (median 63 years, of which 13 were men and 6 women. Chronic lymphocytic leukemia / small cell lymphocytic lymphoma was established in 12 patients, marginal zone lymphoma – in 4 pts, follicular lymphoma – in 1 patient, Waldenstrom's macroglobulinemia – in 1 patient and diffuse large B-cell lymphoma (DLBCL in 1 patient. Proteinuria was observed in 18 patients, microhematuria – in 6 pts, arterial hypertension – in 8 pts, nephrotic syndrome – in 3 pts and renal failure in 18 patients. The mean creatinine level was 330.9 ± 52.3 µmol/L, the average glomerular filtration rate was 25.7 ± 12.9 ml/min. Monoclonal IgMκ secretion was detected in 6 patients, BJκ protein – in 9 pts, increased free light chain level – in 4 pts, cryoglobulin – in 4 pts (type II cryoglobulin in 3 of them, type I – in 1 patient.Morphological study of nephrobiopsy revealed tumor lymphoid infiltration of kidney interstitium in 10 (52.6 % cases. Diffuse small cell lymphoid proliferation was detected in 1 patient, local infiltration – in 9 pts, in 3 of them in combination with glomerulonephritis, and in 4 cases with kidney carcinoma. Local large cell lymphoid proliferation was found in 1 patient with DLBCL. Amyloidosis was detected in 2 pts and thrombotic microangiopathy – in 2 patients. Glomerulopathy was revealed in 10 patients (52.6 %: mesangioproliferative

  2. Psoriasis and autoimmunity.

    Science.gov (United States)

    Sticherling, Michael

    2016-12-01

    Psoriasis is one of the most common chronic inflammatory human skin diseases. Though clinically well characterized, the exact etiological and pathogenic mechanisms are still not known in detail. Current knowledge indicates distinct overlap to other inflammatory as well as autoimmune disorders. However, the one or more relevant autoantigens could not be characterized so-far. On the other side, several autoimmune diseases were shown to be associated with psoriasis. In addition, serological autoimmune phenomena, namely diverse circulating specific autoantibodies could be demonstrated in the past. A matter of current debate is if psoriasis is a primary autoimmune disease or secondarily evolving into autoimmunity as seen in other chronic inflammatory diseases. Related to this aspect is the concept of autoinflammation versus autoimmunity where psoriasis shares mechanisms of both entities. Though T-cells remain among the most important cellular players in the pathogenesis of psoriasis and current therapeutic strategies successfully target these cells or their products irrespective of these concepts, autoimmunity if relevant will add to the treatment armamentarium by using protective and prophylactic antigen-specific modalities. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Neuroelectrophysiological studies on neurological autoimmune diseases

    Directory of Open Access Journals (Sweden)

    Yin-hong LIU

    2014-09-01

    Full Text Available The neuroelectrophysiological manifestations of four clinical typical neurological autoimmune diseases including multiple sclerosis (MS, Guillain-Barré syndrome (GBS, myasthenia gravis (MG, and polymyositis and dermatomyositis were reviewed in this paper. The diagnostic value of evoked potentials for multiple sclerosis, nerve conduction studies (NCS for Guillain-Barré syndrome, repetitive nerve stimulation (RNS and single-fiber electromyography (SFEMG for myasthenia gravis, and needle electromyography for polymyositis and dermatomyositis were respectively discussed. This review will help to have comprehensive understanding on electrophysiological examinations and their clinical significance in the diagnosis of neurological autoimmune diseases. doi: 10.3969/j.issn.1672-6731.2014.09.004

  4. Thyroid autoantibodies in autoimmune diseases Anticuerpos antitiroideos en enfermedades autoinmunes

    OpenAIRE

    Regina M. Innocencio; João H. Romaldini; Laura S. Ward

    2004-01-01

    Abnormalities in the thyroid function and thyroid autoantibodies have been frequently described in patients with autoimmune diseases but seldom in antiphospholipid syndrome patients. In order to determine the prevalence of thyroid function and autoimmune abnormalities, we compared serum thyrotropin (TSH, serum free thyroxine (T4) levels, thyroid antithyroglobulin (TgAb) and antithyroperoxidase (TPOAb) levels of 25 patients with systemic sclerosis, 25 patients with rheumatoid arthritis and 13 ...

  5. Aquaporin-4-autoimmunity in patients with systemic lupus erythematosus

    DEFF Research Database (Denmark)

    Asgari, Nasrin; Jarius, Sven; Laustrup, Helle

    2018-01-01

    .7%) neuropsychiatric SLE (NPSLE) patients both of whom had myelitis and antiphospholipid syndrome; one patient also had myasthenia gravis. None had MOG-IgG. PD-1.3A allele was not associated with SLE nor with NPSLE. CONCLUSION: AQP4-IgG autoimmune syndrome may rarely co-exist with SLE, and such patients have other...... NMOSD-typical syndromes such as myelitis....

  6. Targeting the splicing of mRNA in autoimmune diseases: BAFF inhibition in Sjögren's syndrome as a proof of concept

    NARCIS (Netherlands)

    Roescher, N.; Vosters, J. L.; Alsaleh, G.; Dreyfus, P.; Jacques, S.; Chiocchia, G.; Sibilia, J.; Tak, P. P.; Chiorini, J. A.; Mariette, X.; Gottenberg, Jacques-Eric

    2014-01-01

    BAFF (B-cell-activating factor of the tumor necrosis factor family), a pivotal cytokine for B-cell activation, is overexpressed by salivary gland (SG) epithelial cells in primary Sjogren's syndrome (pSS). ΔBAFF, a physiological inhibitor of BAFF, is a minor alternative splice variant of BAFF. A U7

  7. Stress proteins, autoimmunity, and autoimmune disease.

    Science.gov (United States)

    Winfield, J B; Jarjour, W N

    1991-01-01

    At birth, the immune system is biased toward recognition of microbial antigens in order to protect the host from infection. Recent data suggest that an important initial line of defense in this regard involves autologous stress proteins, especially conserved peptides of hsp60, which are presented to T cells bearing gamma delta receptors by relatively nonpolymorphic class lb molecules. Natural antibodies may represent a parallel B cell mechanism. Through an evolving process of "physiological" autoreactivity and selection by immunodominant stress proteins common to all prokaryotes, B and T cell repertoires expand during life to meet the continuing challenge of infection. Because stress proteins of bacteria are homologous with stress proteins of the host, there exists in genetically susceptible individuals a constant risk of autoimmune disease due to failure of mechanisms for self-nonself discrimination. That stress proteins actually play a role in autoimmune processes is supported by a growing body of evidence which, collectively, suggests that autoreactivity in chronic inflammatory arthritis involves, at least initially, gamma delta cells which recognize epitopes of the stress protein hsp60. Alternate mechanisms for T cell stimulation by stress proteins undoubtedly also exist, e.g., molecular mimicry of the DR beta third hypervariable region susceptibility locus for rheumatoid arthritis by a DnaJ stress protein epitope in gram-negative bacteria. While there still is confusion with respect to the most relevant stress protein epitopes, a central role for stress proteins in the etiology of arthritis appears likely. Furthermore, insight derived from the work thus far in adjuvant-induced arthritis already is stimulating analyses of related phenomena in autoimmune diseases other than those involving joints. Only limited data are available in the area of humoral autoimmunity to stress proteins. Autoantibodies to a number of stress proteins have been identified in SLE and

  8. Neurobiologia da síndrome de Tourette: a hipótese auto-imune pós-estreptocócica Neurobiology of Tourette's syndrome: the autoimmune post-streptococcal hypothesis

    Directory of Open Access Journals (Sweden)

    Fernando Machado Vilhena Dias

    2008-01-01

    Full Text Available CONTEXTO: A síndrome de Tourette (ST caracteriza-se pela presença de tiques motores e pelo menos um tique fônico. Algumas semelhanças clínicas com a coréia reumática ou de Sydenham (CS incentivaram a formulação da hipótese da existência de um grupo de transtornos neuropsiquiátricos associados a processo auto-imune decorrente de infecção estreptocócica (PANDAS. OBJETIVO: Revisar a literatura quanto às evidências em relação à hipótese de que mecanismos auto-imunes pós-estreptocócicos estão envolvidos na etiopatogênese da ST. MÉTODOS: Revisão sistemática na base de dados MedLine com os termos "Tourette", "tic", "PANDAS", "antibodies", "streptococcal" e "rheumatic". RESULTADOS: Retornaram 238 artigos da busca. Selecionaram-se 53 trabalhos, os quais tiveram suas referências bibliográficas também revisadas. São apresentados os resultados de estudos que avaliaram aspectos imunes na ST, incluindo anticorpos antiestreptocócicos e antinúcleos da base, e sua terapêutica imunebaseada, discutindo a validade do conceito de PANDAS. CONCLUSÕES: As evidências ainda não são satisfatórias no que tange a uma base auto-imune pós-estreptocócica para a ST. Um aprimoramento dos métodos investigativos e na seleção das amostras pode trazer maiores contribuições à questão.BACKGROUND: Tourette's syndrome (TS is characterized by the presence of motor tics and at least one phonic tic. Some clinical similarities with Sydenham's chorea (SC lead to the hypothesis of a new group of disorders associated with an autoimmune process due to a streptococcal infection (PANDAS. Objective: To review the literature in search of evidence on the existence of post-streptococcal autoimmune mechanisms involved with the etiopathogenesis of TS. METHODS: A systematic review with the terms "Tourette", "tic", "PANDAS", "antibodies", "streptococcal" and "rheumatic" was carried on using the MedLine. RESULTS: The search found 238 articles. Fifty and

  9. Yersinia enterocolitica Infection Simulating Lymphoproliferative Disease, after Liver Transplant

    Directory of Open Access Journals (Sweden)

    E. Jakobovich

    2014-01-01

    Full Text Available We describe a 14-year-old girl, who was 13 y after liver transplantation for biliary atresia with an unremarkable postoperative course. She presented with fever of up to 40°C, extreme fatigue, malaise, anorexia, and occasional vomiting. On physical examination the only finding was splenomegaly. Lab results showed hyperglobulinemia and an elevated sedimentation rate. Liver function tests were normal except for mild elevation of γGTP. Abdominal U/S and CT demonstrated an enlarged spleen with retroperitoneal and mesenteric lymph nodes enlargement. An exhaustive evaluation for infectious causes, autoimmune conditions, and malignancy was negative. A full recovery after 5 months prompted testing for self-limited infectious etiologies. Yersinia enterocolitica infection was diagnosed.

  10. Prolactin and Autoimmunity

    Directory of Open Access Journals (Sweden)

    Vânia Vieira Borba

    2018-02-01

    Full Text Available The great asymmetry of autoimmune diseases between genders represents one of the most enigmatic observations among the mosaic of autoimmunity. Sex hormones are believed to play a crucial role on this dimorphism. The higher prevalence of autoimmunity among women at childbearing ages, disease onset/relapses during pregnancy, and post-partum are some of the arguments that support this hypothesis. Certainly, motherhood represents one of the most remarkable challenges for the immune system, which not only has to allow for the conceptus, but also has to deal with complex endocrine alterations. Hormonal homeostasis is known to exert a crucial influence in achieving a competent and healthy immune system. Prolactin (PRL has a bioactive function acting as a hormone and a cytokine. It interferes with immune system modulation, mainly inhibiting the negative selection of autoreactive B lymphocytes. Likewise, hyperprolactinemia has been described in relation to the pathogenesis and activity of several autoimmune disorders. Dopamine is an effective inhibitor of PRL secretion due to either a direct influence on the hypophysis or stimulation of postsynaptic dopamine receptors in the hypothalamus, arousing the release of the PRL inhibitory factor. Hence, dopamine agonists have proven to offer clinical benefits among autoimmune patients and represent a promising therapy to be explored. In this review, we attempt to provide a critical overview of the link between PRL, autoimmune diseases, and motherhood.

  11. Nodal Involvement by CD30+ Cutaneous Lymphoproliferative Disorders and Its Challenging Differentiation From Classical Hodgkin Lymphoma.

    Science.gov (United States)

    Lezama, Lhara Sumarriva; Gratzinger, Dita

    2018-01-01

    Primary cutaneous lymphomas are defined as non-Hodgkin lymphomas that present in the skin with no evidence of extracutaneous disease at the time of diagnosis. Mycosis fungoides is the most common type of primary cutaneous T-cell lymphoma, representing almost 50% of primary cutaneous T-cell lymphomas, and primary cutaneous CD30 + T-cell lymphoproliferative disorders are the second most common group (30%). Transformed mycosis fungoides is usually CD30 + and can involve multiple nodal sites; other primary cutaneous CD30 + T-cell lymphoproliferative disorders can also involve draining regional nodes. Nodal involvement by CD30 + T-cell lymphoproliferative disorders can mimic classical Hodgkin lymphoma, which can aberrantly express T-cell antigens. The aim of this article is to briefly review salient clinical, histologic, immunophenotypic, and molecular features that can be used to distinguish lymph node involvement by CD30 + cutaneous T-cell lymphomas and lymphoproliferative disorders from classical Hodgkin lymphoma, a clinically important differential diagnosis that represents a challenging task for the pathologist.

  12. Yttrium Y 90 Ibritumomab Tiuxetan and Rituximab in Treating Patients With Post-Transplant Lymphoproliferative Disorder

    Science.gov (United States)

    2013-01-24

    Post-transplant Lymphoproliferative Disorder; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Waldenström Macroglobulinemia

  13. Presentation and early detection of post-transplant lymphoproliferative disorder after solid organ transplantation

    NARCIS (Netherlands)

    Bakker, Nicolaas A.; van Imhoff, Gustaaf W.; Verschuuren, Erik A. M.; van Son, Willem J.

    Post-transplant lymphoproliferative disorder (PTLD) is a serious and still frequently observed complication of solid organ transplantation. Despite the recent introduction of anti B-cell monoclonal antibody therapy (rituximab) for treatment of PTLD, mortality rates remain high. Because PTLD often

  14. Association of human leukocyte antigen haplotypes with posttransplant lymphoproliferative disease after solid organ transplantation

    NARCIS (Netherlands)

    Subklewe, Marion; Marquis, Rene; Choquet, Sylvain; Leblond, Veronique; Garnier, Jeanne-Luce; Hetzer, Roland; Swinnen, Lode J.; Oertel, Stephan; Papp-Vary, Matthias; Gonzalez-Barca, Eva; Hepkema, Bouke G.; Schoenemann, Constanze; May, Juergen; Pezzutto, Antonio; Riess, Hanno

    2006-01-01

    Background. Posttransplant lymphoproliferative disease (PTLD) after solid organ transplantation (SOT) is commonly characterized by Epstein-Barr virus (EBV)-driven proliferation of recipient B cells due to impaired immune surveillance in the context of immunosuppression. Because EBV-specific T-cell

  15. Extradural thoracic spinal cord compression : Unusual initial presentation of post-transplant lymphoproliferative disorder

    NARCIS (Netherlands)

    Bakker, Nicholas. A.; van Dijk, J. Marc C.; Slart, Riemer. H. J. A.; Coppes, Maarten. H.; van Imhoff, Gustaaf. W.; Verschuuren, Eric. A. M.

    2008-01-01

    Post-transplant lymphoproliferative disorder (PTLD) is a serious complication after solid-organ transplantation. We report a lung transplant recipient presenting with lower limb weakness as a result of extradural cord compression from PTLD. Diagnosis was made by laminectomy of T-3 with partial

  16. Donor Monoclonal Gammopathy May Cause Lymphoproliferative Disorders in Solid Organ Transplant Recipients.

    Science.gov (United States)

    Felldin, M; Ekberg, J; Polanska-Tamborek, D; Hansson, U; Sender, M; Rizell, M; Svanvik, J; Mölne, J

    2016-09-01

    Prior research on donor monoclonal gammopathy of undetermined significance (MGUS) has been inadequate regarding the risk for lymphoproliferative disease in solid organ transplantation recipients. Seven organ recipients from two different donors developed lymphoproliferative disease. The origin of the malignancy was determined by use of microsatellite analysis, and the plasma of the two donors was analyzed with the use of electrophoresis. The clinical courses of the seven recipients were followed for 36-60 months. One donor transmitted lymphoplasmacytic lymphoma to two kidney recipients and MGUS to a liver recipient, all IgMκ. A second donor caused IgGλ myeloma in two kidney and one liver recipient, and IgGλ gammopathy in a heart recipient. Transplant nephrectomy was performed in three kidney recipients and remission was achieved. The fourth kidney recipient has kept the graft and the disease has progressed. The liver recipient died from myeloma. There were no clinical signs of lymphoproliferative disease in the donors, but retrospective serum analyses showed M-components, IgMκ (37 g/L) and IgGλ (8 g/L). Donors with MGUS may cause donor-transmitted malignancies via passenger lymphocytes/plasma cells in solid organ recipients. The results call for a large register study of the incidence of donor MGUS and lymphoproliferative disease in their recipients. © Copyright 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.

  17. Environmental chemicals and autoimmune disease: cause and effect

    International Nuclear Information System (INIS)

    Hess, Evelyn V.

    2002-01-01

    Many important clues have been provided by the relationship of certain medications to lupus and other autoimmune syndromes. These are temporary conditions that resolve when the medication is removed. There are now over 70 such medications which have been reported related to these autoimmune conditions. Interest continues to grow in the potential for environmental substances to cause these syndromes. Among those under suspicion are hydrazines, tartrazines, hair dyes, trichloroethylene, industrial emissions and hazardous wastes. Other possible associations include silica, mercury, cadmium, gold and L canavanine. Two recognised outbreaks include 'toxic oil syndrome' related to contaminated rape seed oil in Spain in 1981 and exposure to a contaminated environmental substance associated with an autoimmune attack on muscle tissue in 1989. Recently, there have been proposals made for the definition and identification of environmentally associated immune disorders. The World Health Organisation (WHO) has also provided recent publications for other environmentally related problems. All these aspects will be presented and reviewed in detail

  18. A case of recurrent autoimmune hemolytic anemia during remission associated with acute pure red cell aplasia and hemophagocytic syndrome due to human parvovirus B19 infection successfully treated by steroid pulse therapy with a review of the literature.

    Science.gov (United States)

    Sekiguchi, Yasunobu; Shimada, Asami; Imai, Hidenori; Wakabayashi, Mutsumi; Sugimoto, Keiji; Nakamura, Noriko; Sawada, Tomohiro; Komatsu, Norio; Noguchi, Masaaki

    2014-01-01

    The patient was a 47-year-old man diagnosed as having autoimmune hemolytic anemia (AIHA) in April 2011. He also had a congenital chromosomal abnormality, a balanced translocation. Treatment with prednisolone (PSL) 60 mg/day resulted in resolution of the AIHA, and the treatment was completed in November 2011. While the patient no longer had anemia, the direct and indirect Coombs tests remained positive. In May 2013, he developed recurrent AIHA associated with acute pure red cell aplasia (PRCA) and hemophagocytic syndrome (HPS) caused by human parvovirus B19 (HPV B19) infection. Tests for anti-erythropoietin and anti-erythropoietin receptor antibodies were positive. Steroid pulse therapy resulted in resolution of the AIHA, PRCA, as well as HPS. The serum test for anti-erythropoietin antibodies also became negative after the treatment. However, although the serum was positive for anti-HPV B19 IgG antibodies, the patient continued to have a low CD4 lymphocyte count (CD4, <300/μL) and persistent HPV B19 infection (HPV B19 DNA remained positive), suggesting the risk of recurrence and bone marrow failure.

  19. Postural Orthostatic Tachycardia With Chronic Fatigue After HPV Vaccination as Part of the “Autoimmune/Auto-inflammatory Syndrome Induced by Adjuvants”

    OpenAIRE

    Lucija Tomljenovic PhD; Serena Colafrancesco MD; Carlo Perricone MD; Yehuda Shoenfeld MD, FRCP (Hon), MaACR

    2014-01-01

    We report the case of a 14-year-old girl who developed postural orthostatic tachycardia syndrome (POTS) with chronic fatigue 2 months following Gardasil vaccination. The patient suffered from persistent headaches, dizziness, recurrent syncope, poor motor coordination, weakness, fatigue, myalgias, numbness, tachycardia, dyspnea, visual disturbances, phonophobia, cognitive impairment, insomnia, gastrointestinal disturbances, and a weight loss of 20 pounds. The psychiatric evaluation ruled out t...

  20. Prevalence and patterns of renal involvement in imaging of malignant lymphoproliferative diseases

    International Nuclear Information System (INIS)

    Bach, Andreas Gunter; Behrmann, Curd; Spielmann, Rolf Peter; Surov, Alexey; Holzhausen, Hans Jurgen; Katzer, Michaela; Arnold, Dirk

    2012-01-01

    Background: Renal involvement in patients with lymphoproliferative disease is an uncommon radiological finding. Purpose: To determine its prevalence and radiological appearances in a patient population. Material and Methods: All forms of lymphoproliferative disease (ICD: C81-C96) were considered. From January 2005 to January 2010, 668 consecutive patients with lymphoproliferative disease were identified with the help of the radiological database and patient records. Inclusion criteria were complete staging including appropriate CT scan and/or MRI. All stored images (initial staging and follow-up examinations) were reviewed. Results: Review of all stored images revealed renal infiltration in patients with non-Hodgkin lymphoma (11 of 364 = 3.0%; median age = 65 years, m:f = 6:5) but also multiple myeloma (2 of 162 = 1.2%; median age = 72 years; m:f = 1:1) and leukemia (5 of 101 4.9%; median age = 12 years; m:f = 2:3). There were no cases of renal infiltration in 41 patients with Hodgkin's disease. In total there were six patients with solitary lesions, five patients with diffuse renal enlargement, four patients with perirenal lesions, and two patients with direct invasion of the kidney. Conclusion: In leukemia the most common imaging pattern is diffuse enlargement. In the other subtypes of lymphoproliferative disease no specific correlation between typical CT patterns and subtype of lymphoproliferative disease can be found. The prevalence of renal involvement is in line with earlier studies. Contrary to earlier reports, multiple lesions were not found to be a common pattern

  1. Substantiation for Approaches to Treatment of Latent Autoimmune Diabetes in Adults

    Directory of Open Access Journals (Sweden)

    T.M. Tykhonova

    2014-10-01

    Conclusions. Analysis of carbohydrate metabolism on the manifestation stage and over time development of latent autoimmune diabetes in adults as well as reduction of β-cells insulin-producing function associated with autoimmune insulitis and progressing while the development of this form of disease, substantiate the rational for insulin administration as this form of diabetes has been diagnosed. If patients with latent autoimmune diabetes in adults have metabolic syndrome clusters it is quite reasonable to add metformin to insulin.

  2. Anti-cytokine autoantibodies in autoimmune diseases

    Science.gov (United States)

    Cappellano, Giuseppe; Orilieri, Elisabetta; Woldetsadik, Abiy D; Boggio, Elena; Soluri, Maria F; Comi, Cristoforo; Sblattero, Daniele; Chiocchetti, Annalisa; Dianzani, Umberto

    2012-01-01

    An overview of the current literature is showing that autoantibodies (AutoAbs) against cytokines are produced in several pathological conditions, including autoimmune diseases, but can also be detected in healthy individuals. In autoimmune diseases, these AutoAbs may also be prognostic markers, either negative (such as AutoAbs to IL-8 and IL-1α in rheumatoid arthritis) or positive (such as AutoAbs to IL-6 in systemic sclerosis and those to osteopontin in rheumatoid arthritis). They may have neutralizing activity and influence the course of the physiological and pathological immune responses. High levels of AutoAbs against cytokines may even lead to immunodeficiency, such as those to IL-17 in autoimmune polyendocrine syndrome type I or those to IFN-γ in mycobacterial infections. Their role in human therapy may be exploited not only through passive immunization but also through vaccination, which may improve the costs for long lasting treatments of autoimmune diseases. Detection and quantification of these AutoAbs can be profoundly influenced by the technique used and standardization of these methods is needed to increase the value of their analysis. PMID:23885320

  3. Celiac disease in autoimmune cholestatic liver disorders.

    Science.gov (United States)

    Volta, Umberto; Rodrigo, Luis; Granito, Alessandro; Petrolini, Nunzio; Muratori, Paolo; Muratori, Luigi; Linares, Antonio; Veronesi, Lorenza; Fuentes, Dolores; Zauli, Daniela; Bianchi, Francesco B

    2002-10-01

    In this study, serological screening for celiac disease (CD) was performed in patients with autoimmune cholestasis to define the prevalence of such an association and to evaluate the impact of gluten withdrawal on liver disease associated with gluten sensitive enteropathy. Immunoglobulin A endomysial, human and guinea pig tissue transglutaminase antibodies, and immunoglobulin A and G gliadin antibodies were sought in 255 patients with primary biliary cirrhosis, autoimmune cholangitis, and primary sclerosing cholangitis. Immunoglobulin A endomysial and human tissue transglutaminase antibodies were positive in nine patients (seven primary biliary cirrhosis, one autoimmune cholangitis, and one primary sclerosing cholangitis), whose duodenal biopsy results showed villous atrophy consistent with CD. Two of these patients had a malabsorption syndrome, and one had iron-deficiency anemia. Clinical and biochemical signs of cholestasis did not improve after gluten withdrawal in the three patients with severe liver disease. A longer follow-up of the six celiac patients with mild liver damage is needed to clarify whether gluten restriction can contribute to slow down the progression of liver disease. The high prevalence of CD (3.5%) in autoimmune cholestasis suggests that serological screening for CD should be routinely performed in such patients by immunoglobulin A endomysial or human tissue transglutaminase antibodies.

  4. Dominant Mutations in the Autoimmune Regulator AIRE Are Associated with Common Organ-Specific Autoimmune Diseases.

    Science.gov (United States)

    Oftedal, Bergithe E; Hellesen, Alexander; Erichsen, Martina M; Bratland, Eirik; Vardi, Ayelet; Perheentupa, Jaakko; Kemp, E Helen; Fiskerstrand, Torunn; Viken, Marte K; Weetman, Anthony P; Fleishman, Sarel J; Banka, Siddharth; Newman, William G; Sewell, W A C; Sozaeva, Leila S; Zayats, Tetyana; Haugarvoll, Kristoffer; Orlova, Elizaveta M; Haavik, Jan; Johansson, Stefan; Knappskog, Per M; Løvås, Kristian; Wolff, Anette S B; Abramson, Jakub; Husebye, Eystein S

    2015-06-16

    The autoimmune regulator (AIRE) gene is crucial for establishing central immunological tolerance and preventing autoimmunity. Mutations in AIRE cause a rare autosomal-recessive disease, autoimmune polyendocrine syndrome type 1 (APS-1), distinguished by multi-organ autoimmunity. We have identified multiple cases and families with mono-allelic mutations in the first plant homeodomain (PHD1) zinc finger of AIRE that followed dominant inheritance, typically characterized by later onset, milder phenotypes, and reduced penetrance compared to classical APS-1. These missense PHD1 mutations suppressed gene expression driven by wild-type AIRE in a dominant-negative manner, unlike CARD or truncated AIRE mutants that lacked such dominant capacity. Exome array analysis revealed that the PHD1 dominant mutants were found with relatively high frequency (>0.0008) in mixed populations. Our results provide insight into the molecular action of AIRE and demonstrate that disease-causing mutations in the AIRE locus are more common than previously appreciated and cause more variable autoimmune phenotypes. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Autoimmune gastritis: Pathologist's viewpoint.

    Science.gov (United States)

    Coati, Irene; Fassan, Matteo; Farinati, Fabio; Graham, David Y; Genta, Robert M; Rugge, Massimo

    2015-11-14

    Western countries are seeing a constant decline in the incidence of Helicobacter pylori-associated gastritis, coupled with a rising epidemiological and clinical impact of autoimmune gastritis. This latter gastropathy is due to autoimmune aggression targeting parietal cells through a complex interaction of auto-antibodies against the parietal cell proton pump and intrinsic factor, and sensitized T cells. Given the specific target of this aggression, autoimmune gastritis is typically restricted to the gastric corpus-fundus mucosa. In advanced cases, the oxyntic epithelia are replaced by atrophic (and metaplastic) mucosa, creating the phenotypic background in which both gastric neuroendocrine tumors and (intestinal-type) adenocarcinomas may develop. Despite improvements in our understanding of the phenotypic changes or cascades occurring in this autoimmune setting, no reliable biomarkers are available for identifying patients at higher risk of developing a gastric neoplasm. The standardization of autoimmune gastritis histology reports and classifications in diagnostic practice is a prerequisite for implementing definitive secondary prevention strategies based on multidisciplinary diagnostic approaches integrating endoscopy, serology, histology and molecular profiling.

  6. Nutrition, geoepidemiology, and autoimmunity.

    Science.gov (United States)

    Selmi, Carlo; Tsuneyama, Koichi

    2010-03-01

    As well represented by the impaired immune function of malnourished individuals encountered in developing countries and the incidence of specific diseases following local nutrient deficiencies, nutrition and immunity have been linked to each other for centuries while the specific connection between dietary factors and autoimmunity onset or modulation is a more recent acquisition. Autoimmune diseases manifest limited prevalence rates in developing countries while numerous immunity-related claims have been proposed in the field of functional foods. Nevertheless, over the past years multiple lines of evidence have supported a major role for specific dietary factors (including vitamin D, vitamin A, selenium, zinc, omega-3 fatty acids, probiotics, and flavanols) in determining the immune responses involved in infections, allergies, and autoimmune diseases. Interestingly, the link between nutrition and autoimmunity may well contribute to the geoepidemiology observed for numerous conditions. In general terms, most data that will be discussed herein were obtained in experimental or animal models while human data from real-life clinical settings or randomized clinical trials remain largely unsatisfactory. Our current knowledge on the beneficial impact of nutrition on autoimmunity prompts us to encourage the search for evidence-based nutrition to support the everyday diet choices of patients. 2009 Elsevier B.V. All rights reserved.

  7. A rare association of localized scleroderma type morphea, vitiligo, autoimmune hypothyroidism, pneumonitis, autoimmune thrombocytopenic purpura and central nervous system vasculitis. Case report.

    Science.gov (United States)

    Bonilla-Abadía, Fabio; Muñoz-Buitrón, Evelyn; Ochoa, Carlos D; Carrascal, Edwin; Cañas, Carlos A

    2012-12-20

    The localized scleroderma (LS) known as morphea, presents a variety of clinical manifestations that can include systemic involvement. Current classification schemes divide morphea into categories based solely on cutaneous morphology, without reference to systemic disease or autoimmune phenomena. This classification is likely incomplete. Autoimmune phenomena such as vitiligo and Hashimoto thyroiditis associated with LS have been reported in some cases suggesting an autoimmune basis. To our knowledge this is the first case of a morphea forming part of a multiple autoimmune syndrome (MAS) and presenting simultaneously with autoimmune thrombocytopenic purpura and central nervous system vasculitis. We report an uncommon case of a white 53 year old female patient with LS as part of a multiple autoimmune syndrome associated with pneumonitis, autoimmune thrombocytopenic purpura and central nervous system vasculitis presenting a favorable response with thrombopoietin receptor agonists, pulses of methylprednisolone and cyclophosphamide. Is likely that LS have an autoimmune origin and in this case becomes part of MAS, which consist on the presence of three or more well-defined autoimmune diseases in a single patient.

  8. A rare association of localized scleroderma type morphea, vitiligo, autoimmune hypothyroidism, pneumonitis, autoimmune thrombocytopenic purpura and central nervous system vasculitis. Case report

    Directory of Open Access Journals (Sweden)

    Bonilla-Abadía Fabio

    2012-12-01

    Full Text Available Abstract Background The localized scleroderma (LS known as morphea, presents a variety of clinical manifestations that can include systemic involvement. Current classification schemes divide morphea into categories based solely on cutaneous morphology, without reference to systemic disease or autoimmune phenomena. This classification is likely incomplete. Autoimmune phenomena such as vitiligo and Hashimoto thyroiditis associated with LS have been reported in some cases suggesting an autoimmune basis. To our knowledge this is the first case of a morphea forming part of a multiple autoimmune syndrome (MAS and presenting simultaneously with autoimmune thrombocytopenic purpura and central nervous system vasculitis. Case presentation We report an uncommon case of a white 53 year old female patient with LS as part of a multiple autoimmune syndrome associated with pneumonitis, autoimmune thrombocytopenic purpura and central nervous system vasculitis presenting a favorable response with thrombopoietin receptor agonists, pulses of methylprednisolone and cyclophosphamide. Conclusion Is likely that LS have an autoimmune origin and in this case becomes part of MAS, which consist on the presence of three or more well-defined autoimmune diseases in a single patient.

  9. Autoimmune hemolytic anemia: From lab to bedside

    Directory of Open Access Journals (Sweden)

    R K Chaudhary

    2014-01-01

    Full Text Available Autoimmune hemolytic anemia (AIHA is not an uncommon clinical disorder and requires advanced, efficient immunohematological and transfusion support. Many AIHA patients have underlying disorder and therefore, it is incumbent upon the clinician to investigate these patients in detail, as the underlying condition can be of a serious nature such as lymphoproliferative disorder or connective tissue disorder. Despite advances in transfusion medicine, simple immunohematological test such as direct antiglobulin test (DAT still remains the diagnostic hallmark of AIHA. The sensitive gel technology has enabled the immunohematologist not only to diagnose serologically such patients, but also to characterize red cell bound autoantibodies with regard to their class, subclass and titer in a rapid and simplified way. Detailed characterization of autoantibodies is important, as there is a relationship between in vivo hemolysis and strength of DAT; red cell bound multiple immunoglobulins, immunoglobulin G subclass and titer. Transfusing AIHA patient is a challenge to the immunohematologist as it is encountered with difficulties in ABO grouping and cross matching requiring specialized serological tests such as alloadsorption or autoadsorption. At times, it may be almost impossible to find a fully matched unit to transfuse these patients. However, transfusion should not be withheld in a critically ill patient even in the absence of compatible blood. The "best match" or "least incompatible units" can be transfused to such patients under close supervision without any serious side-effects. All blood banks should have the facilities to perform the necessary investigations required to issue "best match" packed red blood cells in AIHA. Specialized techniques such as elution and adsorption, which at times are helpful in enhancing blood safety in AIHA should be established in all transfusion services.

  10. Autoimmune hemolytic anemia: From lab to bedside

    Science.gov (United States)

    Chaudhary, R. K.; Das, Sudipta Sekhar

    2014-01-01

    Autoimmune hemolytic anemia (AIHA) is not an uncommon clinical disorder and requires advanced, efficient immunohematological and transfusion support. Many AIHA patients have underlying disorder and therefore, it is incumbent upon the clinician to investigate these patients in detail, as the underlying condition can be of a serious nature such as lymphoproliferative disorder or connective tissue disorder. Despite advances in transfusion medicine, simple immunohematological test such as direct antiglobulin test (DAT) still remains the diagnostic hallmark of AIHA. The sensitive gel technology has enabled the immunohematologist not only to diagnose serologically such patients, but also to characterize red cell bound autoantibodies with regard to their class, subclass and titer in a rapid and simplified way. Detailed characterization of autoantibodies is important, as there is a relationship between in vivo hemolysis and strength of DAT; red cell bound multiple immunoglobulins, immunoglobulin G subclass and titer. Transfusing AIHA patient is a challenge to the immunohematologist as it is encountered with difficulties in ABO grouping and cross matching requiring specialized serological tests such as alloadsorption or autoadsorption. At times, it may be almost impossible to find a fully matched unit to transfuse these patients. However, transfusion should not be withheld in a critically ill patient even in the absence of compatible blood. The “best match” or “least incompatible units” can be transfused to such patients under close supervision without any serious side-effects. All blood banks should have the facilities to perform the necessary investigations required to issue “best match” packed red blood cells in AIHA. Specialized techniques such as elution and adsorption, which at times are helpful in enhancing blood safety in AIHA should be established in all transfusion services. PMID:24678166

  11. Role of the frequency of blood CD4{sup +} CXCR5{sup +} CCR6{sup +} T cells in autoimmunity in patients with Sjoegren's syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Li, Xue-yi; Wu, Zhen-biao; Ding, Jin; Zheng, Zhao-hui [Department of Clinical Immunology, State key Discipline of Cell Biology, Xi-jing Hospital, Fourth Military Medical University, Shaanxi Province (China); Li, Xiao-yan [Department of Endocrine and Metabolic Diseases, Shaanxi Provincial People' s Hospital, Xi' an, Shaanxi Province (China); Chen, Li-na [Department of Clinical Immunology, State key Discipline of Cell Biology, Xi-jing Hospital, Fourth Military Medical University, Shaanxi Province (China); Zhu, Ping, E-mail: zhuping@fmmu.edu.cn [Department of Clinical Immunology, State key Discipline of Cell Biology, Xi-jing Hospital, Fourth Military Medical University, Shaanxi Province (China)

    2012-06-01

    Highlights: Black-Right-Pointing-Pointer The frequency of CD4{sup +} CXCR5{sup +} CCR6{sup +} T cells increased in pSS patients and positively correlated with autoantibodies in the blood. Black-Right-Pointing-Pointer CD4{sup +} CXCR5{sup +} CCR6{sup +} T cells in blood invariably coexpressed PD-1, ICOS, CD40L, Bcl-6 and secreted IL-21 after stimulated by PHA. Black-Right-Pointing-Pointer CD4{sup +} CXCR5{sup +} CCR6{sup +} Tfh cells in blood may be suitable biomarkers for the evaluation of the active immune stage of pSS patients. -- Abstract: The blood CD4{sup +} CXCR5{sup +} T cells, known as 'circulating' Tfh, have been shown to efficiently induce naieve B cells to produce immunoglobulin. They play an important role in certain autoimmune diseases. In the present study, we show for the first time that the frequency of CD4{sup +} CXCR5{sup +} T cells is increased in pSS patients and positively correlated with autoantibodies in the blood. The concentration of Th17-like subsets (CD4{sup +} CXCR5{sup +} CCR6{sup +}) in pSS patients was found to be significantly higher than in healthy controls. Functional assays showed that activated Th17-like subtypes in the blood display the key features of Tfh cells, including invariably coexpressed PD-1, ICOS, CD40L and IL-21. Th17 subsets were found to highly express Bcl-6 protein and Th1 and Th2 were not. Bcl-6 is believed to be a master transforming factor for Tfh cell differentiation and facilitate B cell proliferation and somatic hypermutation within the germinal center. These data indicate that Th17 subsets of CD4{sup +} CXCR5{sup +} T cells in the blood may participate in the antibody-related immune responses and that high frequency of CD4{sup +} CXCR5{sup +} CCR6{sup +} Tfh cells in blood may be suitable biomarkers for the evaluation of the active immune stage of pSS patients. It might provide insights into the pathogenesis and perhaps help researchers identify novel therapeutic targets for pSS.

  12. Epigenetics and Autoimmune Diseases

    Science.gov (United States)

    Quintero-Ronderos, Paula; Montoya-Ortiz, Gladis

    2012-01-01

    Epigenetics is defined as the study of all inheritable and potentially reversible changes in genome function that do not alter the nucleotide sequence within the DNA. Epigenetic mechanisms such as DNA methylation, histone modification, nucleosome positioning, and microRNAs (miRNAs) are essential to carry out key functions in the regulation of gene expression. Therefore, the epigenetic mechanisms are a window to understanding the possible mechanisms involved in the pathogenesis of complex diseases such as autoimmune diseases. It is noteworthy that autoimmune diseases do not have the same epidemiology, pathology, or symptoms but do have a common origin that can be explained by the sharing of immunogenetic mechanisms. Currently, epigenetic research is looking for disruption in one or more epigenetic mechanisms to provide new insights into autoimmune diseases. The identification of cell-specific targets of epigenetic deregulation will serve us as clinical markers for diagnosis, disease progression, and therapy approaches. PMID:22536485

  13. Headache in autoimmune diseases.

    Science.gov (United States)

    John, Seby; Hajj-Ali, Rula A

    2014-03-01

    Autoimmune diseases are a group of heterogeneous inflammatory disorders characterized by systemic or localized inflammation, leading to ischemia and tissue destruction. These include disorders like systemic lupus erythematosus and related diseases, systemic vasculitides, and central nervous system (CNS) vasculitis (primary or secondary). Headache is a very common manifestation of CNS involvement of these diseases. Although headache characteristics can be unspecific and often non-diagnostic, it is important to recognize because headache can be the first manifestation of CNS involvement. Prompt recognition and treatment is necessary not only to treat the headache, but also to help prevent serious neurological sequelae that frequently accompany autoimmune diseases. In this review, we discuss headache associated with autoimmune diseases along with important mimics. © 2014 American Headache Society.

  14. [POEMS syndrome: role and value of interleukin-6].

    Science.gov (United States)

    Andrès, E; Courouau, F; Kaltenbach, G; Maloisel, F; Imler, M

    1996-01-01

    POEMS syndrome is a systemic disorder with peripheral neuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes. The association of POEMS syndrome with lympho-proliferative disorder is very commun. The pathogenesis remains poorly understood but implication of cytokines (interleukins 1 and 6) is suspected. We report a case of a classic POEMS syndrome (with polyneuropathy, hepatomegaly, diabetes melitus, hyperpigmentation, monoclonal IgG lambda, anasarca and solitary plasmocytoma), associated with high serum levels of interleukin 6.

  15. [Glycosylation of autoantibodies in autoimmunes diseases].

    Science.gov (United States)

    Goulabchand, R; Batteux, F; Guilpain, P

    2013-12-01

    Protein glycosylation is one of the most common post-translational modifications, involved in the well described protein biosynthesis process. Protein glycosylation seems to play a major role in the pathogenesis of auto-immune diseases. Herein are described the main alterations of autoantibody glycosylation associated with autoimmunes diseases such as rheumatoid arthritis, IgA glomerulonephritis, Schoenlein-Henoch purpura, Sjögren's syndrome, systemic scleroderma, systemic lupus erythematosus, myasthenia gravis and granulomatosis with polyangiitis (Wegener). Molecular identification of altered immunoglobulin glycosylation could lead to a better understanding of the pathogenesis of those diseases, might allow an evaluation of their biological activity and could even be a new therapeutic target. Copyright © 2013 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  16. Rheumatic Disease Autoantibodies in Autoimmune Liver Diseases.

    Science.gov (United States)

    Utiyama, Shirley R R; Zenatti, Katiane B; Nóbrega, Heloisa A J; Soares, Juliana Z C; Skare, Thelma L; Matsubara, Caroline; Muzzilo, Dominique A; Nisihara, Renato M

    2016-08-01

    Autoimmune liver diseases (ALDs) are known to be associated with systemic autoimmune rheumatic diseases (SARDs) and their autoantibodies. We aimed to study the prevalence of SARDs and related autoantibodies, as well as their prognostic implications in a group of patients with ALDs. This was a cross-sectional study. Sixty patients with ALDs (38.3% with autoimmune hepatitis; 11.7% with primary biliary cirrhosis; 25% with primary sclerosing cholangitis and 25% with overlap syndrome) were studied for the presence of SARDs and their autoantibodies. There was autoimmune rheumatic disease in 20% of the studied sample. Systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) were the commonest (11.6% and 5%, respectively). Antinuclear antibodies (ANAs) were present in 35% of the patients, followed by anti-Ro (20.0%); anti-nucleosome (18.3%); rheumatoid factor (10%) anti-CCP (8.3%); anti-RNP (8.3%); anti-ds-DNA (6.6%); anti-La (3.3%); anti-Sm (3.3%), anti-ribosomal P (3.3%). Anti-Ro (p = 0.0004), anti-La (p = 0.03), anti-RNP (p = 0.04) and anti-Sm (p = 0.03) were commonly found in patients with SARD, but not anti-DNA, anti-nucleosome and anti-ribosomal P. No differences were found in liver function tests regarding to the presence of autoantibodies. There was a high prevalence of SARD and their autoantibodies in ALD patients. Anti-Ro, anti-La, anti-RNP and anti-Sm positivity points to an association with systemic autoimmune rheumatic diseases. The presence of autoantibodies was not related to liver function tests.

  17. Sjögren syndrome

    Science.gov (United States)

    Xerostomia - Sjögren syndrome; Keratoconjunctivitis sicca - Sjögren; Sicca syndrome ... The cause of Sjögren syndrome is unknown. It is an autoimmune disorder. This means the body attacks healthy tissue by mistake. The syndrome occurs most ...

  18. A Case of Peripheral Ulcerative Keratitis Associated with Autoimmune Hepatitis

    Directory of Open Access Journals (Sweden)

    Hamoon Eshraghi

    2017-01-01

    Full Text Available Purpose. To describe a case of peripheral ulcerative keratitis in the setting of autoimmune hepatitis and possible overlap syndrome with primary sclerosing cholangitis. Case Report. A 48-year-old African American female with autoimmune hepatitis with possible overlap syndrome with primary sclerosing cholangitis presented with tearing, irritation, and injection of the left eye that was determined to be peripheral ulcerative keratitis. The patient was treated with topical and systemic steroids, immunosuppressant drugs (azathioprine and mycophenolate mofetil, a biologic (rituximab, and surgery (conjunctival resection, and the peripheral ulcerative keratitis epithelialized but ultimately led to corneal perforation. Conclusion. In this unique case, a patient with peripheral ulcerative keratitis who underwent treatment ultimately had a corneal perforation. This case may suggest a possible relationship between autoimmune hepatitis and peripheral ulcerative keratitis.

  19. Risk of Hematopoietic and Lymphoproliferative Malignancies among U. S. Radiologic Technologists

    International Nuclear Information System (INIS)

    Linet, M. S.; Fredman, D. M.; Mohan, A.; Morin Doody, M.; Ron, E.; Mabuchi, K.; Alexander, B. B.; Sigurdson, A.; Matanoski, G.; Hauptmann, M.

    2004-01-01

    To evaluate risks of hematopoietic and lymphoproliferative malignancies among medical workers exposed to protracted low-to-moderate-dose radiation exposures, a follow-up investigation was conducted in a nation wide cohort of U. S. radiologic technologists. eligible for this study were 71.894 technologists (78% female) certified for at least 2 years during 1926-82, who had responded to a baseline mail questionnaire during 1983-89, were cancer-free except for non-melanoma skin cancer at completion of the questionnaire, and completed a second questionnaire during 1994-98 or died through August 1998. There were 241 technologists with hematopoietic or lymphoproliferative malignancies, including 41 with leukemia subtypes associated with radiation exposures (specifically acute myeloid, acute lymphoid and chronic myeloid leukemias, hereafter designated radiogenic leukemias), 23 with chronic lymphocytic leukemia, 28 with multiple myeloma, 118 with non-Hodgkin lymphoma, and 31 with Hodgkin lymphoma. Of the 241 hematopoietic or lymphoproliferative malignancies identified among radiologic technologists, 85 percent were confirmed by medical records or death certificates, including 98 percent of radiogenic leukemia. Risks of the hematopoietic or lymphoproliferative malignancies were evaluated in relation to questionnaire-derived information on employment as a radiologic technologist, including procedures, work practices, and protective measures. cox proportional hazards regression analysis was used to compute relative risks and 95% confidence intervals, using age at diagnosis as the response, stratifying at baseline for birth cohort in 5-year intervals, and adjusting for potential confounding. Risks were not increased for any of the hematopoietic or lymphoproliferative neoplasms according to year first worked or total duration of years worked as radiologic technologist. For the combined radiogenic leukemias, risks rose significantly with an increasing number of years worked

  20. Risk of Hematopoietic and Lymphoproliferative Malignancies among U. S. Radiologic Technologists

    Energy Technology Data Exchange (ETDEWEB)

    Linet, M. S.; Fredman, D. M.; Mohan, A.; Morin Doody, M.; Ron, E.; Mabuchi, K.; Alexander, B. B.; Sigurdson, A.; Matanoski, G.; Hauptmann, M.

    2004-07-01

    To evaluate risks of hematopoietic and lymphoproliferative malignancies among medical workers exposed to protracted low-to-moderate-dose radiation exposures, a follow-up investigation was conducted in a nation wide cohort of U. S. radiologic technologists. eligible for this study were 71.894 technologists (78% female) certified for at least 2 years during 1926-82, who had responded to a baseline mail questionnaire during 1983-89, were cancer-free except for non-melanoma skin cancer at completion of the questionnaire, and completed a second questionnaire during 1994-98 or died through August 1998. There were 241 technologists with hematopoietic or lymphoproliferative malignancies, including 41 with leukemia subtypes associated with radiation exposures (specifically acute myeloid, acute lymphoid and chronic myeloid leukemias, hereafter designated radiogenic leukemias), 23 with chronic lymphocytic leukemia, 28 with multiple myeloma, 118 with non-Hodgkin lymphoma, and 31 with Hodgkin lymphoma. Of the 241 hematopoietic or lymphoproliferative malignancies identified among radiologic technologists, 85 percent were confirmed by medical records or death certificates, including 98 percent of radiogenic leukemia. Risks of the hematopoietic or lymphoproliferative malignancies were evaluated in relation to questionnaire-derived information on employment as a radiologic technologist, including procedures, work practices, and protective measures. cox proportional hazards regression analysis was used to compute relative risks and 95% confidence intervals, using age at diagnosis as the response, stratifying at baseline for birth cohort in 5-year intervals, and adjusting for potential confounding. Risks were not increased for any of the hematopoietic or lymphoproliferative neoplasms according to year first worked or total duration of years worked as radiologic technologist. For the combined radiogenic leukemias, risks rose significantly with an increasing number of years worked

  1. Sjogren syndrome

    NARCIS (Netherlands)

    Brito-Zeron, Pilar; Baldini, Chiara; Bootsma, Hendrika; Bowman, Simon J.; Jonsson, Roland; Mariette, Xavier; Sivils, Kathy; Theander, Elke; Tzioufas, Athanasios; Ramos-Casals, Manuel

    2016-01-01

    Sjogren syndrome (SjS) is a systemic autoimmune disease that primarily affects the exocrine glands (mainly the salivary and lacrimal glands) and results in the severe dryness of mucosal surfaces, principally in the mouth and eyes. This disease predominantly affects middle-aged women, but can also be

  2. Correlation between flow cytometry and histologic findings: ten year experience in the investigation of lymphoproliferative diseases

    OpenAIRE

    Bezerra, Alanna Mara Pinheiro Sobreira; Pasqualin, Denise da Cunha; Guerra, João Carlos de Campos; Colombini, Marjorie Paris; Velloso, Elvira Deolinda Rodrigues Pereira; Silveira, Paulo Augusto Achucarro; Mangueira, Cristovão Luis Pitangueira; Kanayama, Ruth Hissae; Nozawa, Sonia Tsukasa; Correia, Rodolfo; Apelle, Ana Carolina; Pereira, Welbert de Oliveira; Garcia, Rodrigo Gobbo; Bacal, Nydia Strachman

    2011-01-01

    Objective: To demonstrate the advantages of correlating flow cytometry immunophenotyping with the pathology/ immunohistochemistry of lymph nodes or nodules in the diagnosis of lymphoproliferative diseases. Methods: A retrospective study was carried out of 157 biopsy or fine-needle aspiration lymph nodes/ nodule specimens taken from 142 patients, from 1999 and 2009. The specimens were simultaneously studied with fow cytometry and pathology at Hospital Israelita Albert Einstein. The specimens ...

  3. Patogenetic correction of anemia with erythropoiesis-stimulating agents in lymphoproliferative disorders (literature review

    Directory of Open Access Journals (Sweden)

    N. A. Romanenko

    2014-07-01

    Full Text Available Literature review of anemia pathogenesis in patients with lymphatic system malignancies is presented. Advantages and disadvanta ges of eritropoiesis-stimulating preparations (ESP used for anemia correction are shown. Efficacy of anemia treatment with ESP in various types of lymphoproliferative disorders (LPD is presented. Prognostic factors that predict positive response on ESP in LPD pati ents and reduce treatment cost are identified.

  4. Patogenetic correction of anemia with erythropoiesis-stimulating agents in lymphoproliferative disorders (literature review

    Directory of Open Access Journals (Sweden)

    N. A. Romanenko

    2011-01-01

    Full Text Available Literature review of anemia pathogenesis in patients with lymphatic system malignancies is presented. Advantages and disadvanta ges of eritropoiesis-stimulating preparations (ESP used for anemia correction are shown. Efficacy of anemia treatment with ESP in various types of lymphoproliferative disorders (LPD is presented. Prognostic factors that predict positive response on ESP in LPD pati ents and reduce treatment cost are identified.

  5. HLA associations and risk of posttransplant lymphoproliferative disorder in Danish population-based cohort

    DEFF Research Database (Denmark)

    Vase, Maja Ølholm; Maksten, Eva Futtrup; Strandhave, Charlotte

    2015-01-01

    Background: Posttransplant lymphoproliferative disorder (PTLD) is a feared complication to organ transplantation, associated with substantial morbidity and inferior survival. Risk factors for PTLD include T cell–depleting induction therapy and primary infection or reactivation of Epstein-Barr virus....... Possible associations between certain HLA types and the risk of developing PTLD have been reported by other investigators; however, results are conflicting. Methods: We conducted a retrospective, population-based study on 4295 Danish solid organ transplant patients from the Scandiatransplant database...

  6. Post-transplant Lymphoproliferative Disorder Arising from Renal Allograft Parenchyma: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Park, Byung Kwan; Kim, Chan Kyo; Kwon, Ghee Young [Samsung Medical Center, Sungkyunkwan University College of Medicine, Seoul (Korea, Republic of)

    2010-06-15

    Post-transplant lymphoproliferative disorder (PTLD) is a rare but serious complication that occurs in patients undergoing kidney transplantation. PTLD usually manifests as a renal hilar mass comprised of histologically B-lymphocytes. We report our experience of managing a patient with PTLD arising from renal parenchyma. Ultrasonographic and MR imaging features of this unusual PTLD suggested differentiated renal cell carcinoma arising from the renal allograft

  7. Occurrence and prognostic relevance of CD30 expression in post-transplant lymphoproliferative disorders

    DEFF Research Database (Denmark)

    Vase, Maja Ølholm; Maksten, Eva Futtrup; Bendix, Knud

    2015-01-01

    Post-transplant lymphoproliferative disorders (PTLDs) are potentiallyfatal, often Epstein-Barr virus (EBV)-driven neoplasias developing in immunocompromised hosts. Initial treatment usually consists of a reduction in immunosuppressive therapy and/or rituximab with or without chemotherapy. However...... favorable outcome. For diffuse large B-cell lymphoma (DLBCL)-type PTLD this was regardless of EBV status, and remained significant in multivariate analysis. Cell-of-origin had no independent prognostic value in our series of DLBCL PTLD....

  8. Patogenetic correction of anemia with erythropoiesis-stimulating agents in lymphoproliferative disorders (literature review)

    OpenAIRE

    N. A. Romanenko; K. M. Abdulkadyrov

    2014-01-01

    Literature review of anemia pathogenesis in patients with lymphatic system malignancies is presented. Advantages and disadvanta ges of eritropoiesis-stimulating preparations (ESP) used for anemia correction are shown. Efficacy of anemia treatment with ESP in various types of lymphoproliferative disorders (LPD) is presented. Prognostic factors that predict positive response on ESP in LPD pati ents and reduce treatment cost are identified.

  9. Autoimmune diseases, bipolar disorder, and non-affective psychosis.

    Science.gov (United States)

    Eaton, William W; Pedersen, Marianne G; Nielsen, Philip R; Mortensen, Preben Bo

    2010-09-01

    Clinic-based studies of immune function, as well as comorbidity of autoimmune diseases, bipolar disorder, and schizophrenia, suggest a possible autoimmune etiology. Studies of non-affective psychosis and schizophrenia suggest common etiologies. The objective was to determine the degree to which 30 different autoimmune diseases are antecedent risk factors for bipolar disorder, schizophrenia, and non-affective psychosis. A cohort of 3.57 million births in Denmark was linked to the Psychiatric Case Register and the National Hospital Register. There were 20,317 cases of schizophrenia, 39,076 cases of non-affective psychosis, and 9,920 cases of bipolar disorder. As in prior studies, there was a range of autoimmune diseases which predicted raised risk of schizophrenia in individuals who had a history of autoimmune diseases, and also raised risk in persons whose first-degree relatives had an onset of autoimmune disease prior to onset of schizophrenia in the case. These relationships also existed for the broader category of non-affective psychosis. Only pernicious anemia in the family was associated with raised risk for bipolar disorder (relative risk: 1.7), suggesting a small role for genetic linkage. A history of Guillain-Barré syndrome, Crohn's disease, and autoimmune hepatitis in the individual was associated with raised risk of bipolar disorder. The familial relationship of schizophrenia to a range of autoimmune diseases extends to non-affective psychosis, but not to bipolar disorder. The data suggest that autoimmune processes precede onset of schizophrenia, but also non-affective psychosis and bipolar disorder. © 2010 John Wiley and Sons A/S.

  10. Psychosis: an autoimmune disease?

    Science.gov (United States)

    Al-Diwani, Adam A J; Pollak, Thomas A; Irani, Sarosh R; Lennox, Belinda R

    2017-11-01

    Psychotic disorders are common and disabling. Overlaps in clinical course in addition to epidemiological and genetic associations raise the possibility that autoimmune mechanisms may underlie some psychoses, potentially offering novel therapeutic approaches. Several immune loci including the major histocompatibility complex and B-cell markers CD19 and CD20 achieve genome-wide significance in schizophrenia. Emerging evidence suggests a potential role via neurodevelopment in addition to classical immune pathways. Additionally, lymphocyte biology is increasingly investigated. Some reports note raised peripheral CD19 + and reduced CD3 + lymphocyte counts, with altered CD4 : CD8 ratios in acute psychosis. Also, post-mortem studies have found CD3 + and CD20 + lymphocyte infiltration in brain regions that are of functional relevance to psychosis. More specifically, the recent paradigm of neuronal surface antibody-mediated (NSAb) central nervous system disease provides an antigen-specific model linking adaptive autoimmunity to psychopathology. NSAbs bind extracellular epitopes of signalling molecules that are classically implicated in psychosis such as NMDA and GABA receptors. This interaction may cause circuit dysfunction leading to psychosis among other neurological features in patients with autoimmune encephalitis. The detection of these cases is crucial as autoimmune encephalitis is ameliorated by commonly available immunotherapies. Meanwhile, the prevalence and relevance of these antibodies in people with isolated psychotic disorders is an area of emerging scientific and clinical interest. Collaborative efforts to achieve larger sample sizes, comparison of assay platforms, and placebo-controlled randomized clinical trials are now needed to establish an autoimmune contribution to psychosis. © 2017 John Wiley & Sons Ltd.

  11. Annotation: PANDAS--A Model for Human Autoimmune Disease

    Science.gov (United States)

    Swedo, Susan E.; Grant, Paul J.

    2005-01-01

    Background: Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus infections (PANDAS) is a recently recognized syndrome in which pre-adolescent children have abrupt onsets of tics and/or obsessive-compulsive symptoms, a recurring and remitting course of illness temporally related to streptococcal infections, and associated…

  12. Celiac Disease Autoimmunity in Patients with Autoimmune Diabetes and Thyroid Disease among Chinese Population.

    Directory of Open Access Journals (Sweden)

    Zhiyuan Zhao

    Full Text Available The prevalence of celiac disease autoimmunity or tissue transglutaminase autoantibodies (TGA amongst patients with type 1 diabetes (T1D and autoimmune thyroid disease (AITD in the Chinese population remains unknown. This study examined the rate of celiac disease autoimmunity amongst patients with T1D and AITD in the Chinese population. The study included 178 patients with type 1 diabetes and 119 with AITD where 36 had both T1D and AITD, classified as autoimmune polyglandular syndrome type 3 variant (APS3v. The study also included 145 patients with type 2 diabetes (T2D, 97 patients with non-autoimmune thyroid disease (NAITD, and 102 healthy controls. Serum islet autoantibodies, thyroid autoantibodies and TGA were measured by radioimmunoassay. TGA positivity was found in 22% of patients with either type 1 diabetes or AITD, much higher than that in patients with T2D (3.4%; p< 0.0001 or NAITD (3.1%; P < 0.0001 or healthy controls (1%; p<0.0001. The patients with APS3v having both T1D and AITD were 36% positive for TGA, significantly higher than patients with T1D alone (p = 0.040 or with AITD alone (p = 0.017. T1D and AITD were found to have a 20% and 30% frequency of overlap respectively at diagnosis. In conclusion, TGA positivity was high in the Chinese population having existing T1D and/or AITD, and even higher when both diseases were present. Routine TGA screening in patients with T1D or AITD will be important to early identify celiac disease autoimmunity for better clinical care of patients.

  13. ROLE OF SERUM EOSINOPHILIC CATIONIC PROTEIN AND TRYPTASE IN MYELOPROLIFERATIVE AND LYMPHOPROLIFERATIVE DISORDERS

    Directory of Open Access Journals (Sweden)

    L. S. Komarova

    2008-01-01

    Full Text Available Abstract. A role of intracellular proteins of eosinophils and mast cells remains unclear in the patients with hematological neoplasia. There is a substantial evidence that eosinophils possess some common mechanisms of cooperation with mast cells. Therapeutic interventions into key events controlling eosinophil migration may be a leading factor in treatment of hypereosinophylic states in onco-hematological disorders. Due to unknown functions of eosinophils in majority of eosinophilia-associated diseases, it would be useful to establish an algorithm of accurate diagnostics in the patients with eosinophilia, in order to choose more effective treatment in future.We studied serum levels of secretable eosinophil and mast cells proteins in oncohematological patients with increased eosinophil counts. The aim of our study was to test a significance of quantitative assay for tryptase and ECP in the patients with myelo- and lymphoproliferative diseases. The study group included thirty-eight patients with oncohematological diseases, accompanied by a marked eosinophilia (> 0.4 x 109/L. Eighteen patients with bronchial asthma (BA, and eight cases of solid tumors comprised a reference group for polyclonal eosinophilia. The levels of ECP and tryptase were measured in blood serum using a commercial fluoroimmunoenzyme assay («Pharmacia», Uppsala, Sweden. Total ECP levels were markedly increased in general group with hematological malignancies (p < 0.03, , and in cases of chronic GvHD (p < 0.03, and in a sub-group with lymphoproliferative disorders (р = 0.007 as compared to the group of non-hematological diseases.Serum levels of tryptase were significantly increased in the patients with chronic GvHD after allo-HSCT and lymphoproliferative diseases, as compared to the group of patients with solid tumors (р = 0.03, as well in GvHD compared with lymphoproliferative disorders (р < 0.05.A direct correlation was found between serum ECP levels and absolute

  14. Arterial thrombosis in the antiphospholipid syndrome

    NARCIS (Netherlands)

    Urbanus, R.T

    2008-01-01

    The antiphospholipid syndrome (APS) is a non-inflammatory autoimmune disease that mainly affects young women. The syndrome is characterized by recurrent thrombosis or pregnancy morbidity in association with the persistent serological presence of antiphospholipid antibodies. Antiphospholipid

  15. Recent advances in understanding autoimmune thyroid disease

    DEFF Research Database (Denmark)

    Bliddal, Sofie; Nielsen, Claus Henrik; Feldt-Rasmussen, Ulla

    2017-01-01

    Autoimmune thyroid disease (AITD) is often observed together with other autoimmune diseases. The coexistence of two or more autoimmune diseases in the same patient is referred to as polyautoimmunity, and AITD is the autoimmune disease most frequently involved. The occurrence of polyautoimmunity has...... led to the hypothesis that the affected patients suffer from a generalized dysregulation of their immune system. The present review summarizes recent discoveries unravelling the immunological mechanisms involved in autoimmunity, ranging from natural autoimmunity to disease-specific autoimmunity...

  16. Primary Diffuse Large B-Cell Lymphoma of the Liver in a Patient with Sjogren Syndrome

    Directory of Open Access Journals (Sweden)

    Vadim Gorodetskiy

    2016-01-01

    Full Text Available Sjögren’s syndrome (SS has the highest incidence of malignant lymphoproliferative disorders transformation among autoimmune diseases. We present a case of extranodal high grade lymphoma of the liver in a 52-year-old patient with long history of SS. Lymphoma manifested with sharp significant pain in the right hypochondrium, weakness, and profuse night sweats. Contrast-enhanced computed tomography scan (CT-scan of the abdomen revealed multiple low density foci with homogeneous structure and clear contours in both lobes of the liver. Histologically, proliferation of medium sized lymphoma cells with round-oval and slightly irregular nuclei with fine chromatin was shown. Immunohistochemical and molecular features of the tumors allowed diagnosis of diffuse large B-cell lymphoma (DLBCL. To exclude secondary liver lesion by non-Hodgkin lymphoma, chest and small pelvis CT-scan, endoscopy of upper and lower gastrointestinal tract and study of bone marrow were performed. After 8 cycles of R-CHOP chemotherapy (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone, the complete remission was achieved, which persists after 45 months of follow-up. Primary hepatic lymphomas are extremely rare, and previously only low-grade hepatic lymphomas have been described in SS. To our knowledge, the patient described here represents the first reported case of DLBCL with primary liver involvement in SS.

  17. Sarcoidosis and Thyroid Autoimmunity

    Directory of Open Access Journals (Sweden)

    Piera Fazzi

    2017-08-01

    Full Text Available Most of the studies have shown a higher risk for subclinical and clinical hypothyroidism, antithyroid autoantibodies [overall antithyroid peroxidase antibodies (TPOAb], and in general, thyroid autoimmunity, overall in the female gender in patients with sarcoidosis (S. A significantly higher prevalence of clinical hypothyroidism and Graves’ disease was also described in female S patients with respect to controls. Gallium-67 (Ga-67 scyntigraphy in S patients, in the case of thyroid uptake, suggests the presence of aggressive autoimmune thyroiditis and hypothyroidism. For this reason, ultrasonography and thyroid function should be done in the case of Ga-67 thyroid uptake. In conclusion, thyroid function, TPOAb measurement, and ultrasonography should be done to assess the clinical profile in female S patients, and the ones at high risk (female individuals, with TPOAb positivity, and hypoechoic and small thyroid should have periodically thyroid function evaluations and suitable treatments.

  18. Thymoma and autoimmunity

    OpenAIRE

    Shelly, Shahar; Agmon-Levin, Nancy; Altman, Arie; Shoenfeld, Yehuda

    2011-01-01

    The thymus is a central lymphatic organ that is responsible for many immunological functions, including the production of mature, functional T cells and the induction of self-tolerance. Benign or malignant tumors may originate from the thymus gland, with thymoma being the most common and accounting for 50% of anterior mediastinal tumors. Malignancies linked to thymoma include the loss of self-tolerance and the presence of autoimmunity. In this review, we compiled the current scientific eviden...

  19. [Autoimmune blistering diseases].

    Science.gov (United States)

    Duvert-Lehembre, S; Joly, P

    2014-03-01

    Autoimmune blistering diseases are characterized by the production of pathogenic autoantibodies that are responsible for the formation of epidermal blisters. Major advances in the understanding of the pathogenesis of these disorders have allowed the development of new therapeutic agents. Recent epidemiologic data showed that bullous pemphigoid mainly affects elderly patients. Bullous pemphigoid is often associated with degenerative neurologic disorders. A major increase in the incidence of bullous pemphigoid has been observed in France. Treatment of bullous pemphigoid is mainly based on superpotent topical corticosteroids. The role of desmosomal proteins has been demonstrated in the initiation, propagation and persistence of the autoimmune response in pemphigus. Several studies have shown a correlation between anti-desmoglein antibody titers and disease activity. Pemphigus susceptibility genes have been identified. Oral corticosteroids remain the mainstay of pemphigus treatment. Dramatic and long-lasting improvement has been recently obtained with rituximab in recalcitrant types of pemphigus. Other autoimmune junctional blistering diseases are rare entities, whose prognosis can be severe. Their diagnosis has been improved by the use of new immunological assays and immunoelectronic microscopy. Immunosupressants are widely used in severe types in order to prevent mucosal sequelae. Copyright © 2013 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  20. Thymoma and autoimmunity

    Science.gov (United States)

    Shelly, Shahar; Agmon-Levin, Nancy; Altman, Arie; Shoenfeld, Yehuda

    2011-01-01

    The thymus is a central lymphatic organ that is responsible for many immunological functions, including the production of mature, functional T cells and the induction of self-tolerance. Benign or malignant tumors may originate from the thymus gland, with thymoma being the most common and accounting for 50% of anterior mediastinal tumors. Malignancies linked to thymoma include the loss of self-tolerance and the presence of autoimmunity. In this review, we compiled the current scientific evidence detailing the various interactions between thymoma and autoimmune diseases, including myasthenia gravis, systemic lupus erythematosus, inappropriate antidiuretic hormone secretion, pure red cell aplasia, pernicious anemia, pemphigus and autoimmune thyroid diseases. In recent years, several mechanisms have been proposed to explain these interactions. Most are based on the assumption that the ‘sick' thymus, like the ‘normal' thymus, can generate mature T cells; however, the T cells generated by the sick thymus are impaired and thus may exert cellular autoreactivity. Here, we present several theories that may shed light on the loss of self-tolerance associated with this epithelial tumor of the thymus. PMID:21317916

  1. Resilience in women with autoimmune rheumatic diseases.

    Science.gov (United States)

    Rojas, Manuel; Rodriguez, Yhojan; Pacheco, Yovana; Zapata, Elizabeth; Monsalve, Diana M; Mantilla, Rubén D; Rodríguez-Jimenez, Monica; Ramírez-Santana, Carolina; Molano-González, Nicolás; Anaya, Juan-Manuel

    2017-12-28

    To evaluate the relationship between resilience and clinical outcomes in patients with autoimmune rheumatic diseases. Focus groups, individual interviews, and chart reviews were done to collect data on 188 women with autoimmune rheumatic diseases, namely rheumatoid arthritis (n=51), systemic lupus erythematosus (n=70), systemic sclerosis (n=35), and Sjögren's syndrome (n=32). Demographic, clinical, and laboratory variables were assessed including disease activity by patient reported outcomes. Resilience was evaluated by using the Brief Resilience Scale. Bivariate, multiple linear regression, and classification and regression trees were used to analyse data. Resilience was influenced by age, duration of disease, and socioeconomic status. Lower resilience scores were observed in younger patients (50years) had higher resilience scores regardless of socioeconomic status. There was no influence of disease activity on resilience. A particular behaviour was observed in systemic sclerosis in which patients with high socioeconomic status and regular physical activity had higher resilience scores. Resilience in patients with autoimmune rheumatic diseases is a continuum process influenced by age and socioeconomic status. The ways in which these variables along with exercise influence resilience deserve further investigation. Copyright © 2017 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

  2. International consensus: What else can we do to improve diagnosis and therapeutic strategies in patients affected by autoimmune rheumatic diseases (rheumatoid arthritis, spondyloarthritides, systemic sclerosis, systemic lupus erythematosus, antiphospholipid syndrome and Sjogren's syndrome)?: The unmet needs and the clinical grey zone in autoimmune disease management.

    Science.gov (United States)

    Giacomelli, Roberto; Afeltra, Antonella; Alunno, Alessia; Baldini, Chiara; Bartoloni-Bocci, Elena; Berardicurti, Onorina; Carubbi, Francesco; Cauli, Alberto; Cervera, Ricard; Ciccia, Francesco; Cipriani, Paola; Conti, Fabrizio; De Vita, Salvatore; Di Benedetto, Paola; Doria, Andrea; Drosos, Alexandros A; Favalli, Ennio Giulio; Gandolfo, Saviana; Gatto, Mariele; Grembiale, Rosa Daniela; Liakouli, Vasiliki; Lories, Rik; Lubrano, Ennio; Lunardi, Claudio; Margiotta, Domenico Paolo Emanuele; Massaro, Laura; Meroni, Pierluigi; Minniti, Antonia; Navarini, Luca; Pendolino, Monica; Perosa, Federico; Pers, Jacques-Olivier; Prete, Marcella; Priori, Roberta; Puppo, Francesco; Quartuccio, Luca; Ruffatti, Amelia; Ruscitti, Piero; Russo, Barbara; Sarzi-Puttini, Piercarlo; Shoenfeld, Yehuda; Somarakis, George A; Spinelli, Francesca Romana; Tinazzi, Elisa; Triolo, Giovanni; Ursini, Francesco; Valentini, Gabriele; Valesini, Guido; Vettori, Serena; Vitali, Claudio; Tzioufas, Athanasios G

    2017-09-01

    Autoimmune diseases are a complex set of diseases characterized by immune system activation and, although many progresses have been done in the last 15years, several unmet needs in the management of these patients may be still identified. Recently, a panel of international Experts, divided in different working groups according to their clinical and scientific expertise, were asked to identify, debate and formulate a list of key unmet needs within the field of rheumatology, serving as a roadmap for research as well as support for clinicians. After a systematic review of the literature, the results and the discussions from each working group were summarised in different statements. Due to the differences among the diseases and their heterogeneity, a large number of statements was produced and voted by the Experts to reach a consensus in a plenary session. At all the steps of this process, including the initial discussions by the steering committee, the identification of the unmet needs, the expansion of the working group and finally the development of statements, a large agreement was attained. This work confirmed that several unmet needs may be identified and despite the development of new therapeutic strategies as well as a better understanding of the effects of existing therapies, many open questions still remain in this field, suggesting a research agenda for the future and specific clinical suggestions which may allow physicians to better manage those clinical conditions still lacking of scientific clarity. Copyright © 2017. Published by Elsevier B.V.

  3. Update on antiphospholipid antibody syndrome.

    Science.gov (United States)

    Lopes, Michelle Remião Ugolini; Danowski, Adriana; Funke, Andreas; Rêgo, Jozelia; Levy, Roger; Andrade, Danieli Castro Oliveira de

    2017-11-01

    Antiphospholipid syndrome (APS) is an autoimmune disease characterized by antiphospholipid antibodies (aPL) associated with thrombosis and/or pregnancy morbidity. Most APS events are directly related to thrombotic events, which may affect small, medium or large vessels. Other clinical features like thrombocytopenia, nephropathy, cardiac valve disease, cognitive dysfunction and skin ulcers (called non-criteria manifestations) add significant morbidity to this syndrome and represent clinical situations that are challenging. APS was initially described in patients with systemic lupus erythematosus (SLE) but it can occur in patients without any other autoimmune disease. Despite the autoimmune nature of this syndrome, APS treatment is still based on anticoagulation and antiplatelet therapy.

  4. Post-translational modified proteins are biomarkers of autoimmune-processes: NETosis and the inflammatory-autoimmunity connection.

    Science.gov (United States)

    Bruschi, Maurizio; Petretto, Andrea; Bertelli, Roberta; Galetti, Maricla; Bonanni, Alice; Pratesi, Federico; Migliorini, Paola; Candiano, Giovanni; Vaglio, Augusto; Ghiggeri, Gian Marco

    2017-01-01

    Basic research is showing new mechanisms involved in early immune responses and Neutrophil Extracellular Trap (NET) formation (or NETosis) is of key importance as first line defense against bacteria, virus and protozoa. Enzymatic modification of arginine in citrulline in histones is the prerequisite of NETosis being it necessary for decondensation and extrusion of DNA from cells; it is conceivable that other post translational modifications may occur during this event. There is consensus in considering that post translational modified proteins may elicit an autoimmune response that leads to the formation of autoantibodies. Several autoimmune diseases seem to share these pathogenic mechanisms, in particular Rheumatoid arthritis, Systemic Lupus Erythematosus, Small Vessel Vasculitis and Anti-Phospholipid Syndrome, which are all characterized by high levels of circulating autoantibodies. Autoimmunity has, however, different targets and elicits different clinical responses. It seems reasonable to hypothesize that although NETosis is common to all the conditions above, NET components are different and potentially responsible for different autoimmune responses. On the other hand also showing whether circulating NET remnants are present as free structures in blood/biological fluids and determine their levels is relevant to autoimmunity. This review is intended to discuss the rationale for utilizing new discoveries that could be of rapid clinical application and lead to the development of early biomarkers of autoimmunity to predict and treat otherwise serious conditions. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Autoimmune diseases and pregnancy: analysis of a series of cases.

    Science.gov (United States)

    Gomes, Vânia; Mesquita, Alexandra; Capela, Carlos

    2015-06-04

    An autoimmune disease is characterized by tissue damage, caused by self-reactivity of different effector mechanisms of the immune system, namely antibodies and T cells. All autoimmune diseases, to some extent, have implications for fertility and obstetrics. Currently, due to available treatments and specialised care for pregnant women with autoimmune disease, the prognosis for both mother and child has improved significantly. However these pregnancies are always high risk. The purpose of this study is to analyse the fertility/pregnancy process of women with systemic and organ-specific autoimmune diseases and assess pathological and treatment implications. The authors performed an analysis of the clinical records and relevant obstetric history of five patients representing five distinct autoimmune pathological scenarios, selected from Autoimmune Disease Consultation at the Hospital of Braga, and reviewed the literature. The five clinical cases are the following: Case 1-28 years old with systemic lupus erythematosus, and clinical remission of the disease, under medication with hydroxychloroquine, prednisolone and acetylsalicylic acid, with incomplete miscarriage at 7 weeks of gestation without signs of thrombosis. Case 2-44 years old with history of two late miscarriages, a single preterm delivery (33 weeks) and multiple thrombotic events over the years, was diagnosed with antiphospholipid syndrome after acute myocardial infarction. Case 3-31 years old with polymyositis, treated with azathioprine for 3 years with complete remission of the disease, took the informed decision to get pregnant after medical consultation and full weaning from azathioprine, and gave birth to a healthy term new-born. Case 4-38 years old pregnant woman developed Behcet's syndrome during the final 15 weeks of gestation and with disease exacerbation after delivery. Case 5-36 years old with autoimmune thyroiditis diagnosed during her first pregnancy, with difficult control over the thyroid

  6. Outbreak of autoimmune disease in silicosis linked to artificial stone.

    Science.gov (United States)

    Shtraichman, O; Blanc, P D; Ollech, J E; Fridel, L; Fuks, L; Fireman, E; Kramer, M R

    2015-08-01

    There is a well-established association between inhalational exposure to silica and autoimmune disease. We recently observed an outbreak of silica-related autoimmune disease among synthetic stone construction workers with silicosis referred for lung transplantation assessment. To characterize the rheumatologic complications in silicosis within these highly exposed, clinically well-characterized patients. We systematically reviewed data from all cases of silicosis due to synthetic stone dust referred to our pulmonary institute for lung transplant assessment, which represents the national centre for all such referrals. In addition to silicosis-specific data, we extracted data relevant to the clinical and serological manifestations of autoimmune diseases present in these patients. Of 40 patients in our advanced silicosis national data, we identified nine (23%) with findings consistent with various autoimmune diseases. Among these nine, three also had findings consistent with pulmonary alveolar proteinosis. Based on an expected autoimmune disease prevalence of 3% (based on the upper-end estimate for this group of diseases in European international data), the proportion of disease in our group represents a >7-fold excess (prevalence ratio 7.5; 99% confidence interval 2.6-16.7). These cases underscore the strong link between silicosis and multiple distinct syndromes of autoimmune diseases. Vigilance is warranted for the recognition of autoimmune complications in persons with known silicosis; so too is consideration of the occupational exposure history in persons presenting with manifestations of autoimmune disease. © The Author 2015. Published by Oxford University Press on behalf of the Society of Occupational Medicine. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  7. B Cells in Autoimmune Diseases

    OpenAIRE

    Hampe, Christiane S.

    2012-01-01

    The role of B cells in autoimmune diseases involves different cellular functions, including the well-established secretion of autoantibodies, autoantigen presentation and ensuing reciprocal interactions with T cells, secretion of inflammatory cytokines, and the generation of ectopic germinal centers. Through these mechanisms B cells are involved both in autoimmune diseases that are traditionally viewed as antibody mediated and also in autoimmune diseases that are commonly classified as T cell...

  8. Familial autoimmunity and polyautoimmunity in 60 Brazilian Midwest patients with systemic sclerosis

    Directory of Open Access Journals (Sweden)

    Alex Magno Coelho Horimoto

    Full Text Available ABSTRACT Introduction: Systemic sclerosis (SSc is a connective tissue disease of unknown etiology, characterized by a triad of vascular injury, autoimmunity and tissue fibrosis. It is known that a positive family history is the greatest risk factor already identified for the development of SSc in a given individual. Preliminary observation of a high prevalence of polyautoimmunity and of familial autoimmunity in SSc patients support the idea that different autoimmune phenotypes may share common susceptibility variants. Objectives: To describe the frequency of familial autoimmunity and polyautoimmunity in 60 SSc patients in the Midwest region of Brazil, as well as to report the main autoimmune diseases observed in this association of comorbidities. Methods: A cross-sectional study with recruitment of 60 consecutive patients selected at the Rheumatology Department, University Hospital, Medicine School, Federal University of Mato Grosso do Sul (FMUFMS, as well as interviews of their relatives during the period from February 2013 to March 2014. Results: A frequency of 43.3% of polyautoimmunity and of 51.7% of familial autoimmunity in SSc patients was found. Patients with the presence of polyautoimmunity and familial autoimmunity presented primarily the diffuse form of SSc, but this indicator did not reach statistical significance. The autoimmune diseases most frequently observed in polyautoimmunity patients were: Hashimoto's thyroiditis (53.8%, Sjögren's syndrome (38.5%, and inflammatory myopathy (11.5%. The main autoimmune diseases observed in SSc patients' relatives were: Hashimoto's thyroiditis (32.3%, rheumatoid arthritis (22.6%, and SLE (22.6%. The presence of more than one autoimmune disease in SSc patients did not correlate with disease severity or activity. Conclusions: From the high prevalence of coexisting autoimmune diseases found in SSc patients, we stress the importance of the concept of shared autoimmunity, in order to promote a

  9. [Autoimmune hemolytic anemia in children].

    Science.gov (United States)

    Becheur, M; Bouslama, B; Slama, H; Toumi, N E H

    2015-01-01

    Autoimmune hemolytic anemia is a rare condition in children which differs from the adult form. It is defined by immune-mediated destruction of red blood cells caused by autoantibodies. Characteristics of the autoantibodies are responsible for the various clinical entities. Classifications of autoimmune hemolytic anemia include warm autoimmune hemolytic anemia, cold autoimmune hemolytic anemia, and paroxysmal cold hemoglobinuria. For each classification, this review discusses the epidemiology, etiology, clinical presentation, laboratory evaluation, and treatment options. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  10. Study Provides Insights into Diagnosis, Treatment of Rare Immune Disease: Autoimmmune Lymphoproliferative Syndrome ...

    Science.gov (United States)

    ... Publications Help Archive Site Map Información en español Employee Information Connect with NIAID Facebook Twitter Linkedin Google+ Youtube Flickr Instagram Pinterest Email Website Policies & Notices ...

  11. Autoimmune pancreatitis in Japan. Overview and perspective

    International Nuclear Information System (INIS)

    Shimosegawa, Tooru; Kanno, Atsushi

    2009-01-01

    Since the rediscovery and definition of autoimmune pancreatitis (AIP) by Yoshida et al. in 1995, the disease has been attracting attention because of its unique clinical features and practical issues. This disease shows very impressive imaging findings, serological changes, and characteristic histopathology. It occurs most commonly in elderly males with painless jaundice or mild abdominal pain; resemblance in imaging findings between AIP and pancreatobiliary cancers poses an important practical issue of differentiation. With increasing recognition of AIP and accumulation of cases, another important feature of this disease has been revealed, id est (i.e.), association of extrapancreatic organ involvements. Initially misunderstood because it can be accompanied by other autoimmune disorders, such as Sjogren's syndrome or primary sclerosing cholangitis (PSC), AIP is now known to be associated with unique types of sialadenitis and cholangitis distinct from Sjogren's syndrome or PSC. Now the concept of 'IgG4-related sclerosing disease' has become widely accepted and the list of organs involved continues to increase. With worldwide recognition, an emerging issue is the clinical definition of other possible types of autoimmune-related pancreatitis called 'idiopathic duct-centric chronic pancreatitis (IDCP)' and AIP with granulocyte epithelial lesion (GEL)' and their relation to AIP with lymphoplasmacytic sclerosing pancreatitis (LPSP). The time has arrived to establish clinical diagnostic criteria of AIP based on international consensus and to discuss regional and racial differences in the clinicopathological features of AIP. Consensus guidelines are also required for the ideal use of steroids in the treatment of AIP to suppress recurrence efficiently with minimal side effects. There are many issues to be settled in AIP; international collaboration of experts in the pancreas field is necessary to clarify the entire picture of this unique and important disease. (author)

  12. Autoimmune pancreatitis in Japan: overview and perspective.

    Science.gov (United States)

    Shimosegawa, Tooru; Kanno, Atsushi

    2009-01-01

    Since the rediscovery and definition of autoimmune pancreatitis (AIP) by Yoshida et al. in 1995, the disease has been attracting attention because of its unique clinical features and practical issues. This disease shows very impressive imaging findings, serological changes, and characteristic histopathology. It occurs most commonly in elderly males with painless jaundice or mild abdominal pain; resemblance in imaging findings between AIP and pancreatobiliary cancers poses an important practical issue of differentiation. With increasing recognition of AIP and accumulation of cases, another important feature of this disease has been revealed, i.e., association of extrapancreatic organ involvements. Initially misunderstood because it can be accompanied by other autoimmune disorders, such as Sjögren's syndrome or primary sclerosing cholangitis (PSC), AIP is now known to be associated with unique types of sialadenitis and cholangitis distinct from Sjögren's syndrome or PSC. Now the concept of "IgG4-related sclerosing disease" has become widely accepted and the list of organs involved continues to increase. With worldwide recognition, an emerging issue is the clinical definition of other possible types of autoimmune-related pancreatitis called "idiopathic duct-centric chronic pancreatitis (IDCP)" and "AIP with granulocyte epithelial lesion (GEL)" and their relation to AIP with lymphoplasmacytic sclerosing pancreatitis (LPSP). The time has arrived to establish clinical diagnostic criteria of AIP based on international consensus and to discuss regional and racial differences in the clinicopathological features of AIP. Consensus guidelines are also required for the ideal use of steroids in the treatment of AIP to suppress recurrence efficiently with minimal side effects. There are many issues to be settled in AIP; international collaboration of experts in the pancreas field is necessary to clarify the entire picture of this unique and important disease.

  13. Prevention of Human Lymphoproliferative Tumor Formation in Ovarian Cancer Patient-Derived Xenografts

    Directory of Open Access Journals (Sweden)

    Kristina A. Butler

    2017-08-01

    Full Text Available Interest in preclinical drug development for ovarian cancer has stimulated development of patient-derived xenograft (PDX or tumorgraft models. However, the unintended formation of human lymphoma in severe combined immunodeficiency (SCID mice from Epstein-Barr virus (EBV–infected human lymphocytes can be problematic. In this study, we have characterized ovarian cancer PDXs which developed human lymphomas and explore methods to suppress lymphoproliferative growth. Fresh human ovarian tumors from 568 patients were transplanted intraperitoneally in SCID mice. A subset of PDX models demonstrated atypical patterns of dissemination with mediastinal masses, hepatosplenomegaly, and CD45-positive lymphoblastic atypia without ovarian tumor engraftment. Expression of human CD20 but not CD3 supported a B-cell lineage, and EBV genomes were detected in all lymphoproliferative tumors. Immunophenotyping confirmed monoclonal gene rearrangements consistent with B-cell lymphoma, and global gene expression patterns correlated well with other human lymphomas. The ability of rituximab, an anti-CD20 antibody, to suppress human lymphoproliferation from a patient's ovarian tumor in SCID mice and prevent growth of an established lymphoma led to a practice change with a goal to reduce the incidence of lymphomas. A single dose of rituximab during the primary tumor heterotransplantation process reduced the incidence of CD45-positive cells in subsequent PDX lines from 86.3% (n = 117 without rituximab to 5.6% (n = 160 with rituximab, and the lymphoma rate declined from 11.1% to 1.88%. Taken together, investigators utilizing PDX models for research should routinely monitor for lymphoproliferative tumors and consider implementing methods to suppress their growth.

  14. Long-term follow-up of kidney transplant patients with posttransplant lymphoproliferative disorder

    DEFF Research Database (Denmark)

    Birkeland, S A; Hamilton-Dutoit, Stephen Jacques; Bendtzen, K

    2003-01-01

    Posttransplant lymphoproliferative disorder (PTLD) can be resolved in many transplant patients by the reduction or cessation of immunosuppression, after which many grafts continue to function as the result of a form of operational tolerance. When graft function deteriorates, retransplantation may...... be an option. Cytokines such as interleukin (IL)-10 and IL-18 may play a role in PTLD tolerance induction and tumor regression. We report long-term follow-up on the duration of graft tolerance and the course of retransplantation in a series of patients who underwent kidney transplantation and demonstrated PTLD...

  15. Genetics Home Reference: autoimmune Addison disease

    Science.gov (United States)

    ... of each kidney. It is classified as an autoimmune disorder because it results from a malfunctioning immune system ... disease or their family members can have another autoimmune disorder, most commonly autoimmune thyroid disease or type 1 ...

  16. [Keratitis - Infectious or Autoimmune?].

    Science.gov (United States)

    Messmer, E M

    2016-07-01

    Histopathological evaluation of ocular tissues is important in differentiating between infectious and autoimmune disease. Inflammation, necrosis and keratolysis are common to most forms of keratitis. Histopathology can be of great help in identifying the causative organism, establishing a final diagnosis and/or managing the patient with herpes simplex virus keratitis, mycotic keratitis, acanthamoeba keratitis or microsporidia keratoconjunctivitis. Important pathogenetic knowledge with therapeutic relevance has been gained from histopathological studies in nummular keratitis after epidemic keratoconjunctivitis and atopic keratoconjunctivitis. Georg Thieme Verlag KG Stuttgart · New York.

  17. Warm autoimmune hemolytic anemia.

    Science.gov (United States)

    Naik, Rakhi

    2015-06-01

    Warm autoimmune hemolytic anemia (AIHA) is defined as the destruction of circulating red blood cells (RBCs) in the setting of anti-RBC autoantibodies that optimally react at 37°C. The pathophysiology of disease involves phagocytosis of autoantibody-coated RBCs in the spleen and complement-mediated hemolysis. Thus far, treatment is aimed at decreasing autoantibody production with immunosuppression or reducing phagocytosis of affected cells in the spleen. The role of complement inhibitors in warm AIHA has not been explored. This article addresses the diagnosis, etiology, and treatment of warm AIHA and highlights the role of complement in disease pathology. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Nuclear Factor-kappaB in Autoimmunity: Man and Mouse.

    Science.gov (United States)

    Miraghazadeh, Bahar; Cook, Matthew C

    2018-01-01

    NF-κB (nuclear factor-kappa B) is a transcription complex crucial for host defense mediated by innate and adaptive immunity, where canonical NF-κB signaling, mediated by nuclear translocation of RelA, c-Rel, and p50, is important for immune cell activation, differentiation, and survival. Non-canonical signaling mediated by nuclear translocation of p52 and RelB contributes to lymphocyte maturation and survival and is also crucial for lymphoid organogenesis. We outline NF-κB signaling and regulation, then summarize important molecular contributions of NF-κB to mechanisms of self-tolerance. We relate these mechanisms to autoimmune phenotypes described in what is now a substantial catalog of immune defects conferred by mutations in NF-κB pathways in mouse models. Finally, we describe Mendelian autoimmune syndromes arising from human NF-κB mutations, and speculate on implications for understanding sporadic autoimmune disease.

  19. Celiac disease and other autoimmune diseases in patients with collagenous colitis.

    Science.gov (United States)

    Vigren, Lina; Tysk, Curt; Ström, Magnus; Kilander, Anders F; Hjortswang, Henrik; Bohr, Johan; Benoni, Cecilia; Larson, Lasse; Sjöberg, Klas

    2013-08-01

    Collagenous colitis (CC) is associated with autoimmune disorders. The aim of the present study was to investigate the relationship between CC and autoimmune disorders in a Swedish multicenter study. Patients with CC answered questionnaires about demographic data and disease activity. The patient's files were scrutinized for information about autoimmune diseases. A total number of 116 CC patients were included; 92 women, 24 men, median age 62 years (IQR 55-73). In total, 30.2% had one or more autoimmune disorder. Most common were celiac disease (CeD; 12.9%) and autoimmune thyroid disease (ATD, 10.3%), but they also had Sjögren's syndrome (3.4%), diabetes mellitus (1.7%) and conditions in skin and joints (6.0%). Patients with associated autoimmune disease had more often nocturnal stools. The majority of the patients with associated CeD or ATD got these diagnoses before the colitis diagnosis. Autoimmune disorders occurred in one-third of these patients, especially CeD. In classic inflammatory bowel disease (IBD), liver disease is described in contrast to CC where no cases occurred. Instead, CeD was prevalent, a condition not reported in classic IBD. Patients with an associated autoimmune disease had more symptoms. Patients with CC and CeD had an earlier onset of their colitis. The majority of the patients with both CC and CeD were smokers. Associated autoimmune disease should be contemplated in the follow-up of these patients.

  20. APPEARANCE OF AUTOIMMUNE DISEASES IN PATIENTS WITH ENDOMETRIOSIS

    Directory of Open Access Journals (Sweden)

    Nina Slabe

    2018-02-01

    Full Text Available Background. Endometriosis is a comon, complex gynecological syndrom defined as the growth of endometrial glands and stroma in an extra-uterine location. It affects 5 – 20 % of women of reproductive age.1 Nowadays, prevailing opinion about endometriosis is based on presumption, that endometriosis is a result of changed immune system, according to autoimmune theory.2, 3 Characteristics of autoimmune disease that are also found in endometriosis are female preponderance, multiorgan involvement, family occurence, possible genetic basis, response to hormonal manipulation, tissue damage, polyclonal B lymphocite activation, immunological abnormalities in T lymphocite and B lymphocite function and associated autoimmune disease. Women with endometriosis are more frequently affected by asthma, rheumatoid arthritis, systemic lupus erythematosus, Sjögren syndrom and Hashimoto’s thyroiditis. Autoimmune disease is characterized by the production of autoantibodies against components of apoptotic cells. Anti-endometrial antibodies of IgG and IgM classes could be detected in 60 % of endometriosis patients. They show reactivity in glandular epithelium and stroma. Anti-endothelial antibodies specifically react with vascular endothelium and might be with anti-endometrial antibodies partially responsible for failure of implantation leading to infertility, wich is common in endometriosis patients. Anti-nuclear antibodies are frequent serological findings in patients with autoimmune disease, and could be detected in 29–47 % of women with endometriosis.4 Generation of anti-nuclear antibodies is a risk factor for development of other autoimmune disease in women of reproductive age. Studies have shown conflicting results on the presence of anti-ovarian antibodies in the serum of endometriosis patients and in the peritoneal fluid. Their presence is one of the possible causes of infertility. Conclusions. Ethiopathogenesis of endometriosis still remains uncelar but

  1. Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy.

    Science.gov (United States)

    Kisand, Kai; Peterson, Pärt

    2015-07-01

    Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) is an autosomal recessive disease caused by mutations in the autoimmune regulator (AIRE) gene. This review focuses on the clinical and immunological features of APECED, summarizes the current knowledge on the function of AIRE and discusses the importance of autoantibodies in disease diagnosis and prognosis. Additionally, we review the outcome of recent immunomodulatory treatments in APECED patients.

  2. Is Tolerance Broken in Autoimmunity?

    Directory of Open Access Journals (Sweden)

    Dama Laxminarayana

    2017-11-01

    Full Text Available Autoimmune diseases are classified into about 80 different types based on their specificity related to system, organ and/or tissue. About 5% of the western population is affected by this anomaly, but its worldwide incidence is unknown. Autoimmune diseases are heterogeneous in nature and clinical manifestations range from benign disorders to life-threatening conditions. Autoimmunity strikes at any stage of life, but age and/or gender also play role in onset of some of these anomalies. The autoimmune pathogenesis is initiated by the origination of autoantigens, which leads to the development of autoantibodies followed by auto-immunogenicity and the ultimate onset of autoimmunity. There is a lack of suitable therapies to treat autoimmune diseases, because mechanisms involved in the onset of these anomalies were poorly understood. Present therapies are limited to symptomatic treatment and come with severe side effects. Here, I described the molecular mechanisms and cellular events involved in the initiation of autoimmunity and proposed better strategies to modulate such molecular and cellular anomalies, which will help in preventing and/or controlling autoimmune pathogenesis and ultimately aid in enhancing the quality of life.

  3. Postural ortostatisk takykardi-syndrom

    DEFF Research Database (Denmark)

    Brinth, Louise; Pors, Kirsten; Mehlsen, Jesper

    2015-01-01

    Postural orthostatic tachycardia syndrome (POTS) is a heterogeneous condition of dysautonomia and suspected autoimmunity characterized by abnormal increments in heart rate upon assumption of the upright posture accompanied by symptoms of cerebral hypoperfusion and sympathoexcitation. An increase...

  4. Current topics in autoimmune hepatitis.

    Science.gov (United States)

    Muratori, Luigi; Muratori, Paolo; Granito, Alessandro; Pappas, Giorgios; Cassani, Fabio; Lenzi, Marco

    2010-11-01

    Autoimmune hepatitis is a chronic liver disease of unknown aetiology characterized by interface hepatitis, hypergammaglobulinaemia and circulating autoantibodies. In the last decade a number of advancements have been made in the field of clinical and basic research: the simplified diagnostic criteria, the complete response defined as normalization of transaminase levels, the molecular identification of the antigenic targets of anti-liver cytosol antibody type 1 and anti-soluble liver antigen, the detection of anti-actin antibodies, the description of de novo autoimmune hepatitis after liver transplantation for non-autoimmune liver diseases, the characterization of autoimmune hepatitis with overlapping features of primary biliary cirrhosis or primary sclerosing cholangitis, the preliminary experience with novel treatment strategies based on cyclosporine, mycophenolate mofetil and budesonide, the role played by "impaired" regulatory T cells and the development of novel animal models of autoimmune hepatitis. Copyright © 2010 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  5. Genetic study of a new X-linked recessive immunodeficiency syndrome.

    OpenAIRE

    de Saint-Basile, G; Le Deist, F; Caniglia, M; Lebranchu, Y; Griscelli, C; Fischer, A

    1992-01-01

    Seven forms of X-linked (XL) immunodeficiency have been described (XL agammaglobulinemia, XL severe combined immunodeficiency [SCID], Wiskott-Aldrich syndrome, XL chronic granulomatous disease, XL hyper-IgM syndrome with low IgG and IgA, and XL lymphoproliferative syndrome), and properdine deficiency. Although there are (some) phenotypic variants, diagnosis is relatively simple on the basis of clinical, immunological, and genetic characteristics. We studied a family in which several males wer...

  6. Autoimmune comorbidity in achalasia patients.

    Science.gov (United States)

    Romero-Hernández, Fernanda; Furuzawa-Carballeda, Janette; Hernández-Molina, Gabriela; Alejandro-Medrano, Edgar; Núñez-Álvarez, Carlos A; Hernández-Ramírez, Diego F; Azamar-Llamas, Daniel; Olivares-Martínez, Elizabeth; Breña, Blanca; Palacios, Axel; Valdovinos, Miguel A; Coss-Adame, Enrique; Ramos-Ávalos, Bárbara; Torres-Landa, Samuel; Hernández-Ávila, Axel A; Flores-Nájera, Athenea; Torres-Villalobos, Gonzalo

    2018-01-01

    Idiopathic achalasia is a rare esophageal motor disorder. The disease state manifests local and systemic inflammation, and it appears that an autoimmune component and specific autoantibodies participate in the pathogenesis. The study aims to determine the prevalence of autoimmune and chronic inflammatory diseases in patients with achalasia and compare the results with those from patients with gastroesophageal reflux disease (GERD). It was a cross-sectional and included 114 patients with idiopathic achalasia and 114 age-matched and sex-matched control patients with GERD. Data on the presence of autoimmune and inflammatory diseases, the time of presentation, and any family history of autoimmune disease were obtained from the hospital's medical records. Seventy three (64%) were female patients (mean age: 42.3 ± 15.5; median disease duration: 12 months). We identified the presence of autoimmune disease in 19 patients with achalasia (16.7%), hypothyroidism was the main diagnosis, and it was present in 52.6% of patients compared with 4.2% in controls. Thirteen of the 19 achalasia patients (68.4%) with autoimmune disease had history of familial autoimmunity. We identified 11 achalasia (9.6%) and 5 GERD patients (4.16%) with an inflammatory condition. Compared with the GERD, the achalasia group was 3.8 times more likely to have an autoimmune disease (95% CI: 1.47-9.83), 3.0 times more likely to have thyroidopathies (95% CI: 1.00-9.03), and 3.02 times more likely to suffer from any chronic inflammatory disease (95% CI: 1.65-6.20). The non-negligible number of patients with autoimmune diseases identified among the patients with idiopathic achalasia supports the hypothesis that achalasia has an autoimmune component. © 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

  7. Lymphoproliferative disorders in inflammatory bowel disease patients on immunosuppression: Lessons from other inflammatory disorders.

    Science.gov (United States)

    Lam, Grace Y; Halloran, Brendan P; Peters, Anthea C; Fedorak, Richard N

    2015-11-15

    Immunosuppressive agents, such as thiopurines, methotrexate, and biologics, have revolutionized the treatment of inflammatory bowel disease (IBD). However, a number of case reports, case control studies and retrospective studies over the last decade have identified a concerning link between immunosuppression and lymphoproliferative disorders (LPDs), the oncological phenomenon whereby lymphocytes divide uncontrollably. These LPDs have been associated with Epstein-Barr virus (EBV) infection in which the virus provides the impetus for malignant transformation while immunosuppression hampers the immune system's ability to detect and clear these malignant cells. As such, the use of immunosuppressive agents may come at the cost of increased risk of developing LPD. While little is known about the LPD risk in IBD, more is known about immunosuppression in the post-transplantation setting and the development of EBV associated post-transplantation lymphoproliferative disorders (PTLD). In review of the PTLD literature, evidence is available to demonstrate that certain immune suppressants such as cyclosporine and T-lymphocyte modulators in particular are associated with an increased risk of PTLD development. As well, high doses of immunosuppressive agents and multiple immunosuppressive agent use are also linked to increased PTLD development. Here, we discuss these findings in context of IBD and what future studies can be taken to understand and reduce the risk of EBV-associated LPD development from immunosuppression use in IBD.

  8. Epstein-Barr Virus-related post-transplant lymphoproliferative disorders: pathogenetic insights for targeted therapy.

    Science.gov (United States)

    Nourse, J P; Jones, K; Gandhi, M K

    2011-05-01

    Post-transplant lymphoproliferative disorder (PTLD) is a spectrum of major, life-threatening lymphoproliferative diseases occurring in the post-transplant setting. The majority of PTLD is of B-cell origin and is associated with several risk factors, the most significant being Epstein-Barr virus (EBV) infection. EBV's in vitro transforming abilities, distinctive latency, clonality within the malignant cells and response to targeted therapies implicate a critical role in the biology of PTLD. This minireview focuses on EBV-related PTLD pathogenesis, in particular the interplay between aspects of the EBV life cycle and latency with nonviral factors resulting in the wide spectrum of histology and clinical presentations encountered in PTLD. With the increased prevalence of transplantation a rise in the incidence of PTLD may be expected. Therefore the importance of laboratory and animal models in the understanding of PTLD and the development of novel therapeutic approaches is discussed. © 2011 The Authors Journal compilation © 2011 The American Society of Transplantation and the American Society of Transplant Surgeons.

  9. Thymoma associated with autoimmune diseases: 85 cases and literature review.

    Science.gov (United States)

    Bernard, C; Frih, H; Pasquet, F; Kerever, S; Jamilloux, Y; Tronc, F; Guibert, B; Isaac, S; Devouassoux, M; Chalabreysse, L; Broussolle, C; Petiot, P; Girard, N; Sève, P

    2016-01-01

    To describe the clinical features, treatment, and outcome of autoimmune diseases (AD) in a cohort of patients with thymoma. Pathological records from three university hospitals, between 2005 and 2011, were reviewed to identify patients with thymoma. Patients with thymoma and AD were compared with patients with thymoma without AD. 47/85 (55%) cases of thymoma had AD, including myasthenia gravis (MG) (n=33), Hashimoto's thyroiditis (n=4), Isaac's syndrome (n=3), Morvan syndrome (n=2), pure red cell aplasia (n=2), systemic lupus (n=2), lichen planus (n=2), and one case of each following conditions: aplastic anemia, autoimmune hemolytic anemia, Good's syndrome, pemphigus, autoimmune hepatitis, Graves' disease, limbic encephalitis, and inflammatory myopathy. Six patients (7%) presented at least 2 ADs. The median duration of follow-up after surgery was 60 months (40-78 months). In 32 patients, the diagnosis of AD preceded the diagnosis of thymoma, in 9 patients, thymoma was diagnosed at the same time as the AD and 7 patients had been operated on when they developed an AD. We found a significative difference on the Masaoka stage between the MG patients and the patients who present another AD (p=0.028). No risk factor for developing an AD after thymectomy was identified. We describe here the long-term follow-up of a large series of AD related to thymoma. Our results confirm previous data concerning AD occurrence in patients with thymoma and suggest that preexisting autoimmunity is not a risk factor for developing autoimmune manifestations after thymectomy. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. Oversecretion of soluble CTLA-4 in various autoimmune diseases overlapping celiac disease.

    Science.gov (United States)

    Pesce, Giampaola; Auricchio, Renata; Bagnasco, Marcello; Saverino, Daniele

    2014-01-01

    To evaluate the levels of soluble CTLA-4 (sCTLA-4) in sera of celiac disease (CD) patients with overlapping autoimmune diseases (OAD; diabetes mellitus, autoimmune thyroid diseases, inflammatory bowel diseases, and autoimmune polyendocrine syndromes). Sera from Italian patients with CD were obtained and enzyme-linked immunosorbent assay was used to measure sCTLA-4. Consistently high serum sCTLA-4 levels were observed in CD (13.20 ng/mL, pautoimmune disease (namely, CD and OAD) versus patients with CD alone. Previously, the potential genetic associations of several CTLA-4 polymorphisms to susceptibility to autoimmune diseases have been described, although the relationship between CTLA-4 polymorphisms and the ability to produce the soluble form is not fully clarified. CTLA-4 is a strong actor in the adaptive response: our data give supportive evidence of the common background of autoimmune diseases.

  11. Autoimmune/Inflammatory Arthritis Associated Lymphomas: Who Is at Risk?

    Directory of Open Access Journals (Sweden)

    Sujani Yadlapati

    2016-01-01

    Full Text Available Specific autoimmune and inflammatory rheumatic diseases have been associated with an increased risk of malignant lymphomas. Conditions such as rheumatoid arthritis (RA, primary Sjögren’s syndrome (pSS, systemic lupus erythematosus (SLE, dermatomyositis, and celiac disease have been consistently linked to malignant lymphomas. Isolated cases of lymphomas associated with spondyloarthropathies and autoinflammatory diseases have also been reported. Direct association between autoimmunity and lymphomagenesis has been reinforced by large epidemiological studies. It is still uncertain whether disease specific determinants or phenotypic or treatment related characteristics increase likelihood of lymphomagenesis in these patients. For example, recent literature has indicated a positive correlation between severity of inflammation and risk of lymphomas among RA and Sjögren’s syndrome patients. It is also debated whether specific lymphoma variants are more commonly seen in accordance with certain chronic autoimmune arthritis. Previous studies have revealed a higher incidence of diffuse large B-cell lymphomas in RA and SLE patients, whereas pSS has been linked with increased risk of mucosa-associated lymphoid tissue lymphoma. This review summarizes recent literature evaluating risk of lymphomas in arthritis patients and disease specific risk determinants. We also elaborate on the association of autoimmune arthritis with specific lymphoma variants along with genetic, environmental, and therapeutic risk factors.

  12. Autoimmune premature ovarian failure

    Directory of Open Access Journals (Sweden)

    Beata Komorowska

    2017-02-01

    Full Text Available Premature ovarian failure (POF, also termed as primary ovarian insufficiency (POI, is a highly heterogenous condition affecting 0.5-3.0% of women in childbearing age. These young women comprise quite a formidable group with unique physical and psychological needs that require special attention. Premature ovarian senescence (POS in all of its forms evolves insidiously as a basically asymptomatic process, leading to complete loss of ovarian function, and POI/POF diagnoses are currently made at relatively late stages. Well-known and well-documented risk factors exist, and the presence or suspicion of autoimmune disorder should be regarded as an important one. Premature ovarian failure is to some degree predictable in its occurrence and should be considered while encountering young women with loss of menstrual regularity, especially when there is a concomitant dysfunction in the immune system.

  13. Selfie: Autoimmunity, boon or bane.

    Science.gov (United States)

    Ahsan, Haseeb

    2017-01-01

    The immune system provides protection to tissues damaged by infectious microrganisms or physical damage. In autoimmune diseases, the immune system recognizes and attacks its own tissues, i.e., self-destruction. Various agents such as genetic factors and environmental triggers are thought to play a major role in the development of autoimmune diseases. A common feature of all autoimmune diseases is the presence of autoantibodies and inflammation, including mononuclear phagocytes, autoreactive T lymphocytes, and autoantibody producing B cells (plasma cells). It has long been known that B cells produce autoantibodies and, thereby, contribute to the pathogenesis of many autoimmune diseases. Autoimmune diseases can be classified as organ-specific or non-organ specific depending on whether the autoimmune response is directed against a particular tissue or against widespread antigens as in chronic inflammatory autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Both SLE and RA are characterized by the presence of autoantibodies which play a major role in their etiopathogenesis. SLE is characterized by circulating antibodies and immune complex deposition that can trigger an inflammatory damage in organs. RA is a progressive inflammatory disease in which T cells, B cells, and pro-inflammatory cytokines play a key role in its pathophysiology.

  14. Autoimmune diseases in a Nigerian woman--a case report.

    Science.gov (United States)

    Talabi, O A; Owolabi, M O; Osotimehin, B O

    2003-12-01

    Autoimmune diseases (AD) are conditions in which there is the development of antibodies against self cells/ organs. AD could either be organ-specific or non-organ specific (systemic) in clinical presentation. Commonly reported ADs includes: Myasthenia gravis, Hashimoto thyroiditis, Guillian-Barre syndrome, vitiligo, type 1 diabetes mellitus, Graves diseases, Goodpastures syndrome, pemphigus, rheumatoid arthritis, systemic lupus erythematosis, Addisons disease, multiple sclerosis, pernicious anaemia, autoimmune haemolytic anaemia, chronic active hepatitis, idiopathic thrombocytopenic purpura. There is paucity of locally documented information on the occurrence of AD in same patient in our environment. We therefore report the case of a 66 year old woman who presented at the University College Hospital (UCH), Ibadan, with a spectrum of the AD, Vitiligo, rheumatoid arthritis, myasthenia gravis, impaired glucose tolerance.

  15. Bone Marrow and Peripheral Blood Leptin Levels in Lymphoproliferative Diseases - Relation to the Bone Marrow Fat and Infiltration

    Czech Academy of Sciences Publication Activity Database

    Gaja, A.; Churý, Z.; Pecen, Ladislav; Fraňková, H.; Jandáková, H.; Hejlová, N.

    2000-01-01

    Roč. 47, č. 5 (2000), s. 307-312 ISSN 0028-2685 Institutional research plan: AV0Z1030915 Keywords : leptin * bone marrow fat * bone marrow infiltration * lymphoproliferative disease Subject RIV: BA - General Mathematics Impact factor: 0.579, year: 2000

  16. The role of molecular analysis of immunoglobulin and T cell receptor gene rearrangements in the diagnosis of lymphoproliferative disorders

    NARCIS (Netherlands)

    Langerak, AW; van Krieken, JHJM; Wolvers-Tettero, ILM; Kerkhof, E; Mulder, AH; Vrints, LWMA; Coebergh, JW; Schuuring, E; Kluin, PM; van Dongen, JJM

    Aims-To investigate whether the analysis of immunoglobulin (Ig)/T cell receptor (TCR) rearrangements is useful in the diagnosis of lymphoproliferative disorders. Methods-In a series of 107 consecutive cases with initial suspicion of non-Hodgkin's lymphoma (NHL), Southern blot (SB) analysis of Ig/TCR

  17. Epstein-Barr Virus-Positive Posttransplant Lymphoproliferative Disease After Solid Organ Transplantation: Pathogenesis, Clinical Manifestations, Diagnosis, and Management

    NARCIS (Netherlands)

    Nijland, Marieke L.; Kersten, Marie José; Pals, Steven T.; Bemelman, Frederike J.; ten Berge, Ineke J. M.

    2016-01-01

    Posttransplant lymphoproliferative disease (PTLD) is a potentially fatal complication after (solid organ) transplantation, which is highly associated with Epstein-Barr virus (EBV). The EBV-specific cytotoxic T cell response that is essential in controlling the virus in healthy individuals is

  18. Effect of anti-CD 20 antibody rituximab in patients with post-transplant lymphoproliferative disorder (PTLD)

    NARCIS (Netherlands)

    Oertel, SHK; Verschuuren, E; Reinke, P; Zeidler, K; Papp-Vary, M; Babel, N; Trappe, RU; Jonas, S; Hummel, M; Anagnostopoulos, [No Value; Dorken, B; Riess, HB

    2005-01-01

    Post-transplant lymphoproliferative disorders (PTLD) are a life-threatening complication following solid organ transplantation. Treatment with rituximab, a humanized anti-CD20 monoclonal antibody, has proved to be a promising approach and shown a low toxicity profile. Between February 1999 and April

  19. Psoriasis and Hashimoto's thyroiditis in a child with down syndrome

    Directory of Open Access Journals (Sweden)

    Hilal Gokalp

    2016-01-01

    Full Text Available Down syndrome (DS, or trisomy 21, is the most common chromosomal disorder. DS has been associated with autoimmune diseases including autoimmune thyroiditis, Type 1 diabetes mellitus, celiac disease, autoimmune chronic active hepatitis, alopecia, vitiligo, hypoparathyroidism, psoriasis, and psoriatic arthritis. To our knowledge, we herein report the first concurrence of psoriasis and Hashimoto's thyroiditis in an individual with DS, emphasizing the predisposition of DS individuals to autoimmune diseases.

  20. Development of an Epstein-Barr virus-associated lymphoproliferative disorder in a patient treated with azacitidine for chronic myelomonocytic leukaemia.

    Science.gov (United States)

    Menter, T; Schlageter, M; Bastian, L; Haberthür, R; Rätz Bravo, A E; Tzankov, A

    2014-03-01

    Some chemotherapeutic agents can cause iatrogenic lymphoproliferative disorders. In analogy to what has been observed with other nucleoside analogues such as cladribine and fludarabine, we document the first case of an Epstein-Barr virus-positive, iatrogenic immunodeficiency-associated, lymphoproliferative disease, formally resembling polymorphic post-transplant lymphoproliferative disease in a patient treated with azacitidine (Vidaza) for chronic myelomonocytic leukaemia (CMML). A 78-year-old female patient was diagnosed with CMML in January 2012, and treatment with azacitidine was initiated, which lasted for five cycles from February until June 2012. The patient was hospitalized in June 2012 under the suspicion of pneumonia. Transformation of the CMML was suspected at that time too. During hospitalization, a generalized enlargement of the lymph nodes and the spleen was noticed. The patient rapidly deteriorated and finally died of respiratory insufficiency. At autopsy, an Epstein-Barr virus-associated lymphoproliferative disorder, resembling polymorphic post-transplant lymphoproliferative disease with involvement of the lymph nodes, the spleen and the lung and causing necrotizing pneumonia, was diagnosed. Diagnostic criteria for diffuse large B-cell lymphoma or infectious mononucleosis-like lymphoproliferative disease were not met. This is the first documented case of an azacitidine-associated lymphoproliferative disease, raising awareness for possible not yet known side effects of this drug, which should be kept in mind by oncologists and pathologists. Copyright © 2013 John Wiley & Sons, Ltd.

  1. Recent developments in our understanding of the antiphospholipid syndrome

    NARCIS (Netherlands)

    de Groot, P. G.; Meijers, J. C. M.; Urbanus, R. T.

    2012-01-01

    The antiphospholipid syndrome is an autoimmune disease that manifests clinically as recurrent thrombotic complications or foetal losses and serologically with elevated levels of antiphospholipid antibodies in the plasmas of these patients. The term 'antiphospholipid syndrome' is confusing, because

  2. Epigenetic alterations underlying autoimmune diseases.

    Science.gov (United States)

    Aslani, Saeed; Mahmoudi, Mahdi; Karami, Jafar; Jamshidi, Ahmad Reza; Malekshahi, Zahra; Nicknam, Mohammad Hossein

    2016-01-01

    Recent breakthroughs in genetic explorations have extended our understanding through discovery of genetic patterns subjected to autoimmune diseases (AID). Genetics, on the contrary, has not answered all the conundrums to describe a comprehensive explanation of causal mechanisms of disease etiopathology with regard to the function of environment, sex, or aging. The other side of the coin, epigenetics which is defined by gene manifestation modification without DNA sequence alteration, reportedly has come in to provide new insights towards disease apprehension through bridging the genetics and environmental factors. New investigations in genetic and environmental contributing factors for autoimmunity provide new explanation whereby the interactions between genetic elements and epigenetic modifications signed by environmental agents may be responsible for autoimmune disease initiation and perpetuation. It is aimed through this article to review recent progress attempting to reveal how epigenetics associates with the pathogenesis of autoimmune diseases.

  3. [Stress and auto-immunity].

    Science.gov (United States)

    Delévaux, I; Chamoux, A; Aumaître, O

    2013-08-01

    The etiology of auto-immune disorders is multifactorial. Stress is probably a participating factor. Indeed, a high proportion of patients with auto-immune diseases report uncommon stress before disease onset or disease flare. The biological consequences of stress are increasingly well understood. Glucocorticoids and catecholamines released by hypothalamic-pituitary-adrenal axis during stress will alter the balance Th1/Th2 and the balance Th17/Treg. Stress impairs cellular immunity, decreases immune tolerance and stimulates humoral immunity exposing individuals to autoimmune disease among others. The treatment for autoimmune disease should include stress management. Copyright © 2012 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  4. Psoriasis as an autoimmune disease

    OpenAIRE

    Agnieszka Owczarczyk-Saczonek; Waldemar Placek

    2014-01-01

    Nowadays it is known that psoriasis belongs to the group of autoimmune diseases and may coexist with other diseases in this group. Most often patients have psoriatic arthritis, rheumatoid arthritis, inflammatory bowel disease, autoimmune thyroid diseases and multiple sclerosis. The coexistence of these disorders can be a diagnostic and therapeutic problem (there is controversy over the use of corticosteroids). The common pathogenesis is still not explained. We know that the loss of immunotole...

  5. Celiac disease and endocrine autoimmunity.

    Science.gov (United States)

    Kahaly, George J; Schuppan, Detlef

    2015-01-01

    Celiac disease (CD) is a small-intestinal inflammatory disease that is triggered by the ingestion of the storage proteins (gluten) of wheat, barley and rye. Endocrine autoimmunity is prevalent in patients with CD and their relatives. The genes that predispose to endocrine autoimmune diseases, e.g. type 1 diabetes, autoimmune thyroid diseases, and Addison's disease, i.e. DR3-DQ2 and DR4-DQ8, are also the major genetic determinants of CD, which is the best understood HLA-linked disease. Thus, up to 30% of first-degree relatives both of patients with CD and/or endocrine autoimmunity are affected by the other disease. In CD, certain gluten proteins bind with high affinity to HLA-DQ2 or -DQ8 in the small-intestinal mucosa, to activate gluten-specific T cells which are instrumental in the destruction of the resorptive villi. Here, the autoantigen tissue transglutaminase increases the T cell response by generating deamidated gluten peptides that bind more strongly to DQ2 or DQ8. Classical symptoms such as diarrhea and consequences of malabsorption like anemia and osteoporosis are often absent in patients with (screening-detected) CD, but this absence does not significantly affect these patients' incidence of endocrine autoimmunity. Moreover, once autoimmunity is established, a gluten-free diet is not able to induce remission. However, ongoing studies attempt to address how far a gluten-free diet may prevent or retard the development of CD and endocrine autoimmunity in children at risk. The close relationship between CD and endocrine autoimmunity warrants a broader immune genetic and endocrine screening of CD patients and their relatives. © 2015 S. Karger AG, Basel.

  6. Diagnostic and functional imaging of thymic and mediastinal involvement in lymphoproliferative disorders.

    Science.gov (United States)

    Priola, Adriano Massimiliano; Galetto, Giorgio; Priola, Sandro Massimo

    2014-01-01

    Lymphoproliferative disorders of the anterior mediastinum may involve the thymus or lymph nodes as part of disseminated disease or as an isolated site. Imaging is crucial in managing patients with mediastinal lymphoma and is employed in pretreatment assessment, midtreatment evaluation of response, posttreatment restaging, and surveillance during follow-up. For decades, computed tomography (CT) has been the standard imaging technique, although in the last years, positron emission tomography (PET)-CT and magnetic resonance imaging (MRI) have been introduced. We discuss the role of different imaging techniques in the assessment of patients with mediastinal lymphoma, focusing on novel aspects of PET-CT and diffusion-weighted/MRI. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Posttransplant Lymphoproliferative Disorder in a Patient with Worsening Ascites after Liver Transplantation

    Directory of Open Access Journals (Sweden)

    Harsh D. Patel

    2017-01-01

    Full Text Available Posttransplant lymphoproliferative disorder (PTLD is a spectrum of diseases that involves abnormal lymphoid and/or plasmacytic proliferation in patients with solid organ or hematopoietic cell transplantation. It is a condition with a low incidence of 3.5–4.3% in liver transplant (LT recipients. This case involves a 63-year-old male with history of LT for chronic HCV induced cirrhosis who presented with abdominal distension related to worsening ascites. Cytological ascitic fluid analysis revealed EBV (+ malignant cells without a malignant focal point on imaging. Diagnosis of monomorphic PTLD with primary effusion lymphoma-like morphology and immunophenotype was established. This case highlights the complexity in diagnosis, different diagnostic modalities, and rare clinical presentations of PTLD.

  8. Diagnosis of post-transplant lymphoproliferative disorder in solid organ transplant recipients - BCSH and BTS Guidelines.

    Science.gov (United States)

    Parker, Anne; Bowles, Kristin; Bradley, J Andrew; Emery, Vincent; Featherstone, Carrie; Gupte, Girish; Marcus, Robert; Parameshwar, Jayan; Ramsay, Alan; Newstead, Charles

    2010-06-01

    A joint working group established by the Haemato-oncology subgroup of the British Committee for Standards in Haematology (BCSH) and the British Transplantation Society (BTS) has reviewed the available literature and made recommendations for the diagnosis and management of post-transplant lymphoproliferative disorder (PTLD) in adult recipients of solid organ transplants. This review details the risk factors predisposing to development, initial features and diagnosis. It is important that the risk of developing PTLD is considered when using post transplant immunosuppression and that the appropriate investigations are carried out when there are suspicions of the diagnosis. These must include tissue for histology and computed tomography scan to assess the extent of disease. These recommendations have been made primarily for adult patients, there have been some comments made with regard to paediatric practice.

  9. Suppressed peripheral and placental blood lymphoproliferative responses in first pregnancies: relevance to malaria

    DEFF Research Database (Denmark)

    Rasheed, F N; Bulmer, J N; Dunn, D T

    1993-01-01

    .003, and 190N P = 0.10). Reduced proliferative capacity of placental mononuclear cells may contribute to heavy parasite colonization of this organ. Proliferation to malarial and PPD but not Candida antigens was selectively suppressed in peripheral and placental blood of primiparae relative to multiparae (F32 P...... protein derivative [PPD]) were examined in the peripheral and placental blood of 102 Gambian women at the time of delivery. The lymphoproliferative responses of placental cells were poor to all antigens compared with those of peripheral blood (Candida P ... comparable among women of different parities and between peripheral and placental blood. Primigravidae may be more susceptible to malaria because of unique physiologic factors, such as higher levels of circulating immunosuppressive corticosteroids (P

  10. [Smoking and chronic autoimmune thyroiditis].

    Science.gov (United States)

    Buzoianu, Ioana Cristina; Arghir, Oana Cristina; Circo, E

    2010-01-01

    The chronic autoimmune thyroiditis are heterogeneous entities by the functional, lesional and evolutive point of view. Ethiopathogenic factors involved in chronic autoimmune thyroiditis are genetical factors, combines with environmental factors, hormonal factors, infectious factors etc. The exact role of smoking on the autoimmune mechanism is unclear, but smoking is known to have an antithyroid effect. Our study tries to estimate the influence of smoking on serum levels of antithyroid peroxidase antibodies and antithyroglobulin antibodies, in a group of patients with various clinical forms of chronic autoimmune thyroiditis. We studied a group consists of 310 patients with chronic autoimmune thyroiditis, hospitalised in the Endocrinology Department of Constanta County Hospital, between January 2006 - December 2009. We detected serum values of antithyroidperoxidase antibodies and antithyroglobulin antibodies of our patients. We also followed the age, sex and presence of smoking in our study group. For statistical processing of the data we use Student's t-test. In our study group 24.28% of patients were smokers. Serum levels of antithyroid peroxidase antibodies were significantly increased (p < 0.001) in the smokers patients, compared with the nonsmokers patients. Serum levels of antithyroglobulin antibodies were significantly increased (p < 0.01) in smokers patients, compared with those who were nonsmokers. Smoking increased the serum levels of antithyroid antibodies in patients with chronic autoimmune thyroiditis.

  11. Autoimmune liver diseases: internist’s guide from bench to bedside

    Directory of Open Access Journals (Sweden)

    Mario Visconti

    2015-03-01

    Full Text Available Autoimmune liver diseases are disorders of unknown etiology and immune pathogenesis, characterized by liver parenchyma inflammation (autoimmune hepatitis or by lesions of the intralobular biliary ducts (primary biliary cirrhosis or of the entire biliary system (primary sclerosing cholangitis. They differ with regard to the epidemiological, clinical, morphological and serological features; the possible evolution; the different associations with other immune diseases of the digestive or extra-digestive organs; the treatment options. All progressively can result in hepatic cirrhosis. More recently, overlap syndromes have been identified, in which patients exhibit overlapping clinical, morphological and serological features of the above indicated diseases. The frequency of overlap syndromes is progressively increasing, causing additional clinical difficulties. Here, I review the diagnostic and clinical problems of the definite autoimmune liver diseases and of the overlap syndromes, with more regard to the evidences that drive current practice.

  12. Post-Transplant Lymphoproliferative Disorder (PTLD) Manifesting in the Oral Cavity of a 13-Year-Old Liver Transplant Recipient (LTx).

    Science.gov (United States)

    Krasuska-Sławińska, Ewa; Minko-Chojnowska, Izabela; Pawłowska, Joanna; Dembowska-Bagińska, Bożenna; Pronicki, Maciej; Olczak-Kowalczyk, Dorota

    2015-08-18

    BACKGROUND Post-transplant lymphoproliferative disorder (PTLD) is a potential complication of solid organ or bone marrow transplants. The main PTLD risk factors are: the Epstein-Barr virus (EBV), transplant type, and use of immunosuppressants. It mainly consists of an uncontrolled growth of lymphocytes in transplant recipients under chronic immunosuppressive therapy. About 85% of PTLDs are EBV-containing B-cell proliferations; 14% are T-cell proliferations, of which only 40% contain EBV; and the remaining 1% is NK-cell or plasmocyte proliferations. PTLD may present various clinical manifestations, from non-specific mononucleosis-like syndrome to graft or other organ damage resulting from pathologic lymphocyte infiltration. PTLD may manifest in the oral cavity. CASE REPORT The objective of this study was to present the case of a 13-year-old female living-donor liver transplant recipient, resulting from biliary cirrhosis caused by congenital biliary atresia, with exophytic fibrous lesions on buccal mucosa and tongue. Exophytic and hyperplastic lesion of oral mucosa were removed and histopathological examination revealed polymorphic PTLD. The patient underwent 6 cycles of CHOP chemotherapy and all the oral lesions regressed completely. CONCLUSIONS All oral pathological lesions in organ transplant recipients need to be surgically removed and histopathologically examined because they present an increased risk of neoplastic transformations such as PTLD.

  13. Use of flow cytometry in the diagnosis of lymphoproliferative disorders in fluid specimens.

    Science.gov (United States)

    Yu, Gordon H; Vergara, Norge; Moore, Erika M; King, Rebecca L

    2014-08-01

    The diagnostic evaluation of fluid specimens, including serous effusions and cerebrospinal fluids (CSFs), can be challenging for a number of reasons. The evaluation of lymphoid proliferations in these specimens can be particularly problematic, given the frequent presence of coexisting inflammatory conditions and the manner in which these specimens are processed. As a result, immunophenotypic analysis of hematopoietic cell populations by flow cytometry has emerged as a useful ancillary study in the diagnosis of these specimens, both in patients with and without a previous history of a lymphoproliferative disorder. In this study, we review our experience with flow cytometry in fluid specimens over a four-year period. Flow cytometry was performed in 184 of 6,925 total cases (2.7% of all fluids). Flow cytometry was performed in 4.8% of pleural fluids (positive findings in 38%, negative in 40%, and atypical in 18%), 1.1% of peritoneal fluids (positive in 40%, negative in 50%, and atypical in 10%), 1.9% of pericardial fluids (positive in 67%, negative in 33%), and 1.9% of CSFs (positive in 23%, negative in 55%, atypical in 3%). The specimen submitted was inadequate for analysis in 9.2% of cases, most commonly with CSF specimens, but was not related to the volume of fluid submitted. Atypical flow cytometry findings and atypical morphologic findings in the context of negative flow cytometry results led to the definitive diagnosis of a lymphoproliferative disorder in a significant number of cases when repeat procedures and ancillary studies were performed. Copyright © 2014 Wiley Periodicals, Inc.

  14. Allogeneic hematopoietic stem cell transplantation in patients with advanced indolent lymphoproliferative disorders

    Directory of Open Access Journals (Sweden)

    Ana Marcela Rojas Fonseca-Hial

    2016-06-01

    Full Text Available ABSTRACT BACKGROUND: The role of allogeneic hematopoietic stem cell transplantation for advanced indolent lymphoproliferative disorders remains to be established. OBJECTIVE: This paper aims to describe the results of allogeneic hematopoietic stem cell transplantation in patients with advanced indolent lymphoproliferative disorders. METHODS: This article reports on 29 adult patients submitted to allogeneic transplantations from 1997 to 2010. RESULTS: Most had follicular non-Hodgkin lymphoma (n = 14 or chronic lymphocytic leukemia (n = 12. The median age was 44 years (range: 24-53 years and 65% of patients were male. Only 21% had had access to rituximab and 45% to fludarabine. All had advanced disease (stage IV with partial response or stable disease. Most underwent myeloablative conditioning n = 17 - 59%. In this scenario, refractory disease was observed in seven (24% patients, the 100-day mortality rate was 17% (n = 5 and relapse occurred in four patients (18%. The main cause of death throughout the follow up was refractory disease in six of the 12 patients who died. Moderate and severe chronic graft-versus-host disease was frequent; about 41% of 24 patients analyzed. The overall survival rates and disease free survival at 42 months were 56.7% and 45.4%, respectively. According to Kaplan-Meyer analysis, the median time from diagnosis to transplant predicted the overall survival; however age, gender and conditioning regimen did not predict the prognosis. It was impossible to reach other conclusions because of the small sample size in this study. CONCLUSIONS: The role of allogeneic transplantations should be re-evaluated in the era of targeted therapy.

  15. Expression of proliferation markers and cell cycle regulators in T cell lymphoproliferative skin disorders.

    Science.gov (United States)

    Gambichler, Thilo; Bischoff, Stefan; Bechara, Falk G; Altmeyer, Peter; Kreuter, Alexander

    2008-02-01

    Abnormal cell proliferation, which results from deregulation of the cell cycle, is fundamental in tumorigenesis. To investigate the expression of proliferation markers and cell cycle regulators in a range of T cell lymphoproliferative skin diseases. We studied skin specimens of 51 patients with parapsoriasis (PP), mycosis fungiodes (MF), or lymphomatoid papulosis (LyP). Immunohistochemistry was performed for Ki-67, proliferating cell nuclear antigen (PCNA), minichromosome maintenance protein 7 (MCM7), and p21. MF with stage IIB-IV and LyP showed a significantly greater number of Ki-67-positive cells than PP (P=0.02 and 0.001) and MF I-IIA (P=0.019 and 0.003), respectively. MCM7 staining revealed significantly higher labeling indices for MF IIB-IV and LyP when compared to PP (P=0.002 and 0.04) and MF I-IIA (P=0.0005 and 0.01), respectively. Compared to PP and MF I-IIA, MF IIB-IV was associated with significantly higher labeling indices for PCNA (P=0.006 and 0.0004). p21 staining was significantly increased in MF IIB-IV and LyP when compared to PP (P=0.006 and 0.003) and MF I-IIA (P=0.003). However, p21 staining was all in all very weak. Ki-67 and PCNA seem to be useful immunohistological parameters for the correlation with the clinical stage of MF. In the differentiation and prognostication of T cell lymphoproliferative skin disorders, MCM7 may serve as a novel biomarker which is, in contrast to Ki-67 and PCNA, stable throughout the cell cycle.

  16. EBV-positive mucocutaneous ulcer in organ transplant recipients: a localized indolent posttransplant lymphoproliferative disorder.

    Science.gov (United States)

    Hart, Melissa; Thakral, Beenu; Yohe, Sophia; Balfour, Henry H; Singh, Charanjeet; Spears, Michael; McKenna, Robert W

    2014-11-01

    Epstein-Barr virus (EBV)-positive mucocutaneous ulcer (EBV MCU) is a B-cell lymphoproliferative disorder occurring in elderly or iatrogenic immunocompromised patients. It has not been reported in solid organ transplant recipients. We observed 7 patients with EBV MCU in a cohort of 70 transplant recipients with EBV posttransplant lymphoproliferative disorder (PTLD). Transplants included: 5 renal, 1 heart, and 1 lung. Median patient age was 61; 5 were male. EBV MCU was observed in oral mucosa in 4 and gastrointestinal tract in 3. Duration of immunosuppressive therapy before EBV MCU was 0.6 to 13 years. Ulcers were undermined by inflammatory cells and polymorphic or monomorphic large cell lymphoproliferation. Reed-Sternberg-like cells were present in 5/7. Large B cells were CD20, CD30, and EBV-encoded RNA positive in all cases. Diagnosis in 3 recent patients was EBV MCU; 4 patients diagnosed before familiarity with EBV MCU were classified as monomorphic large cell (n=3) and polymorphic (n=1) PTLD. None of the patients had EBV DNA in their blood (<1000 copies/mL) at diagnosis or follow-up versus 35/44 transplant patients with systemic PTLD (P<0.001). All lesions resolved with reduced immunosuppression (7/7), change in immunosuppression (2/7), and rituximab (3/7). Five patients are living: 4 healthy, 1 awaiting second renal transplant. Two patients died 3 and 5 years after resolution of EBV MCU. No patient recurred with EBV MCU or other PTLDs. EBV MCU mimics more aggressive categories of PTLD but lacks EBV DNA in blood, which may be a useful distinguishing feature. Lesions are likely to resolve with conservative management. Awareness of EBV MCU in the posttransplant setting is necessary for appropriate diagnosis and treatment.

  17. Analysis of incidence of thromboembolic complications in patients with chronic lymphoproliferative diseases

    Directory of Open Access Journals (Sweden)

    Nikolovski Srđan

    2015-01-01

    Full Text Available Introduction: An increased risk for thromboembolism in cancer patients has been observed in patients with solid tumours, whereas little data exist on malignant lymphoma. Aim: Determination of the incidence of TE in patients with non Hodgkin lymphoma (NHL, Hodgkin lymphoma (HL and chronic lymphocytic leukemia (CLL treated in our institution. Material and methods: We reviewed medical records of patients with NHL, HL and CLL diagnosed according to the WHO classification and treated at our institution between January 2006. and December 2014. Results: A total of 1054 patients, 48.4% had high-grade NHL, 20.0% low-grade NHL, 14.5% HL, 7.1% other forms of lymphoma and 10.0% CLL. In group of lymphoma patients, 72 (6.8 % had at least one TE. TE included deep vein thrombosis (38.9%, jugular vein thrombosis (12.5%, pulmonary embolism (11.1%, CNS thrombosis (6.9%, superficial vein thrombosis (2.8%, acute myocardial infarction (1.4% and other (26.4%. In 49 patients thrombosis occurred during treatment or up to three months after therapy completion, whereas in 23 patients thrombosis was diagnosed prior to therapy. Patients with aggressive NHL and CLL had significantly higher incidence of TE (8.63%, 8.57% compared to other types of lymphoma patients (p = 0.009. There is no statistical significance of impact of different types of lymphoproliferative diseases on increased risk for TE. Conclusion: This study confirmed findings of some earlier studies of increased risk of thromboembolic events (TE in patients with aggressive forms of chronic lymphoproliferative diseasses, but there is no significantly impact of gender or age on that risk.

  18. Post-transplant lymphoproliferative disorder in the pelvis successfully treated with consolidative radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Habibeh, Omar; Elsayad, Khaled; Kriz, Jan; Haverkamp, Uwe; Eich, Hans Theodor [University Hospital of Muenster, Department of Radiation Oncology, Muenster (Germany)

    2017-01-15

    Post-transplant lymphoproliferative disorders (PTLDs) are aggressive malignancies which represent one of the major post-transplant complications. However, treatment options vary significantly and localized disease may be curatively treated with radiotherapy (RT) or surgery. We report a case of recurrent rectal PTLD, which was successfully treated by chemoimmunotherapy followed by RT. We describe a patient who developed a rectal lymphoproliferative lesion 11 years after kidney transplant, which was successfully treated with consolidative RT using 25.4 Gy sequential to chemoimmunotherapy (R-CHOP). RT was well tolerated and the patient showed no signs of grade 3 or 4 toxicity. This patient is free of recurrence 52 months after RT, with an overall survival of 62 months since diagnosis. Conventionally fractionated moderate-dose RT appears to be a tolerable and effective treatment option for localized PTLD if a sufficient systemic treatment cannot be applied. (orig.) [German] Posttransplantationslymphoproliferative Erkrankungen (PTLDs) sind eine haeufige Komplikation nach einer Organtransplantation. Nichtdestotrotz unterscheiden sich die Behandlungsmoeglichkeiten signifikant und vor allem lokalisierte Stadien koennen kurativ entweder mit Strahlentherapie (RT) und/oder Operation behandelt werden. Wir berichten ueber einen Fall einer rezidivierten rektalen PTLD, die erfolgreich mit einer Chemoimmuntherapie mit anschliessender RT behandelt wurde. Wir beschreiben einen Patienten der 11 Jahre nach einer Nierentransplantation eine PTLD entwickelte. Diese wurde erfolgreich mit konsolidierender RT (25,4 Gy) im Anschluss an eine Chemoimmuntherapie (R-CHOP) behandelt. Die RT wurde komplikationslos vertragen und es zeigten sich keine Nebenwirkungen. Das rezidivfreie Ueberleben betrug zum Zeitpunkt der letzten Nachsorgeuntersuchung 52 Monate mit einer Gesamtueberlebenszeit von 62 Monaten seit der Diagnose. Die konventionelle fraktionierte moderat dosierte RT scheint eine gut

  19. Idiopathic hypertrophic cranial pachymeningitis associated with Sweet's Syndrome

    International Nuclear Information System (INIS)

    Cano, Antonio; Ribes, Ramon; Riva, Andres de la; Rubio, Fernando Lopez; Sanchez, Carmen; Sancho, Jose L.

    2002-01-01

    A case of hypertrophic cranial pachymeningitis associated with Sweet's Syndrome is presented. Both entities have been described in association with several other chronic systemic inflammatory diseases and autoimmune conditions. To our knowledge the coexistence between Sweet's Syndrome and hypertrophic cranial pachymeningitis has not been reported up to date. We suggest a possible autoimmune or dysimmune mechanism in the pathogenesis of these two entities

  20. Small intestinal involvement by lymphoproliferative disorders post-renal transplantation: A report from the post-transplant lymphoproliferative disorder international survey

    Directory of Open Access Journals (Sweden)

    Hossein Khedmat

    2013-01-01

    Full Text Available In this study, data on post-renal transplant lymphoproliferative disorders (PTLD collected from the existing literature were pooled and analyzed to compare the characteristics, predictors and prognosis of small intestinal PTLDs. We performed a comprehensive search for the available data by Pubmed and Google scholar search engines for reports on this subject. Data from 18 previously published studies, comprising 120 renal allograft recipients, were included in the analysis. Renal transplant recipients with intestinal PTLD were significantly less likely to have Hogkin′s and Hogkin′s-like lesions (P = 0.044 and to be younger at the time of transplan-tation (P = 0.07. Except for Hodgkin′s-like lesions, histopathological evaluations elsewhere were comparable between the group with PTLD in the small intestine and age- and sex-matched renal transplant recipients with PTLD in other sites. The overall mortality was relatively higher in the control group (P = 0.09. When death only due to PTLD was used as the outcome, a trend toward better outcome was seen for the intestinal PTLD group compared with the other localizations (P = 0.1. The 1- and 5-year survival rates for intestinal PTLD patients were 57% and 37%, respectively, compared with 54% and 21%, respectively, for the control group. According to our findings based on analysis of international data, renal transplant patients with small intestinal PTLD are more likely to be of younger age but less frequently represent Hodgkin′s and Hodgkin′s-like lesions. They also have better patient survival compared with transplant recipients with PTLD in other locations. Further multi-center prospective studies are needed to confirm our results.

  1. Autoimmune ear disease: clinical and diagnostic relevance in Cogan’s sydrome

    Directory of Open Access Journals (Sweden)

    Luigi Maiolino

    2017-03-01

    Full Text Available The autoimmune inner ear disease is a clinical syndrome with uncertain pathogenesis that is often associated to rapidly progressive hearing loss that, especially at the early stages of disease, may be at monoaural localization, although more often it is at binaural localization. It usually occurs as a sudden deafness, or a rapidly progressive sensorineural hearing loss. In this study a particular form of autoimmune inner ear disease is described, Cogan’s syndrome. Cogan’s syndrome is a chronic inflammatory disorder that most commonly affects young adults. Clinical hallmarks are interstitial keratitis, vestibular and auditory dysfunction. Associations between Cogan’s syndrome and systemic vasculitis, as well as aortitis, also exist. We report a case of a young woman who presented audiological and systemic characteristics attributable to Cogan’s syndrome. In the description of the case we illustrate how the appearance and evolution of the disease presented.

  2. Use of Rituximab in Autoimmune Hemolytic Anemia Associated with Non-Hodgkin Lymphomas

    Science.gov (United States)

    Fozza, Claudio; Longinotti, Maurizio

    2011-01-01

    The association between non-Hodgkin lymphomas and autoimmune disorders is a well-known event. Also autoimmune hemolytic anemia (AHA), although much more frequent in patients with chronic lymphocytic leukemia (CLL), has been described in this group of patients. In recent years, among the more traditional therapeutic options, rituximab, an anti-CD20 monoclonal antibody, has shown interesting results in the treatment of primary AHA. Although this drug has been frequently used for AHA in patients with CLL, much less data are available on its use in NHL patients. However, considering that the main pathogenetic mechanism of AHA in course of lymphoproliferative disorders seems to be an antibody production directly or indirectly mediated by the neoplastic clone, this monoclonal antibody represents an ideal therapeutic approach. In this paper we will briefly describe some biological and clinical features of NHL-patients with AHA. We will then analyze some studies focusing on rituximab in primary AHA, finally reviewing the available literature on the use of this drug in NHL related AHA. PMID:21547266

  3. AUTOIMMUNE EPIDERMAL BLISTERING DISEASES

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    Ana Maria Abreu Velez

    2013-11-01

    Full Text Available Autoimmune bullous skin diseases (ABDs are uncommon, potentially fatal diseases of skin and mucous membranes which are associated with deposits of autoantibodies and complement against distinct molecules of the epidermis and dermal/epidermal basement membrane zone (BMZ. These autoantibodies lead to a loss in skin molecular integrity, which manifests clinically as formation of blisters or erosions. In pemphigus vulgaris, loss of adhesion occurs within the epidermis. The pioneering work of Ernst H. Beutner, Ph.D. and Robert E. Jordon, M.D. confirmed the autoimmune nature of these diseases. Walter F. Lever, M.D. contributed significantly to our understanding of the histopathologic features of these diseases. Walter Lever, M.D. and Ken Hashimoto, M.D. contributed electron microscopic studies of these diseases, especially in pemphigus vulgaris and bullous pemphigoid. In bullous pemphigoid (BP, linear IgA bullous dermatosis, epidermolysis bullosa acquisita (EBA and dermatitis herpetiformis (DH, loss of adhesion takes place within or underneath the BMZ. Classic EBA demonstrates extensive skin fragility; DH is commonly associated with gluten-sensitive enteropathy, and manifests clinically with pruritic papulovesicles on the extensor surfaces of the extremities and the lumbosacral area. The clinical spectrum of bullous pemphigoid includes tense blisters, urticarial plaques, and prurigo-like eczematous lesions. Pemphigoid gestationis mostly occurs during the last trimester of pregnancy, and mucous membrane pemphigoid primarily involves the oral mucosa and conjunctivae and leads to scarring. Linear IgA bullous dermatosis manifests with tense blisters in a „cluster of jewels”-like pattern in childhood (chronic bullous disease of childhood and is more clinically heterogeneous in adulthood. Many of the autoantigens in these disorders are known and have been well characterized. ABDs may be influenced by both genetic and exogenous factors. The diagnoses of

  4. Autoimmune hepatitis in association with lymphocytic colitis.

    LENUS (Irish Health Repository)

    Cronin, Edmond M

    2012-02-03

    Autoimmune hepatitis is a rare, chronic inflammatory disorder which has been associated with a number of other auto-immune conditions. However, there are no reports in the medical literature of an association with microscopic (lymphocytic) colitis. We report the case of a 53-year-old woman with several autoimmune conditions, including lymphocytic colitis, who presented with an acute hepatitis. On the basis of the clinical features, serology, and histopathology, we diagnosed autoimmune hepatitis. To our knowledge, this is the first report of autoimmune hepatitis in association with lymphocytic colitis, and lends support to the theory of an autoimmune etiology for lymphocytic colitis.

  5. Autoimmune AQP4 channelopathies and neuromyelitis optica spectrum disorders.

    Science.gov (United States)

    Hinson, Shannon R; Lennon, Vanda A; Pittock, Sean J

    2016-01-01

    Neuromyelitis optica (NMO) spectrum disorders (SD) represent an evolving group of central nervous system (CNS)-inflammatory autoimmune demyelinating diseases unified by a pathogenic autoantibody specific for the aquaporin-4 (AQP4) water channel. It was historically misdiagnosed as multiple sclerosis (MS), which lacks a distinguishing biomarker. The discovery of AQP4-IgG moved the focus of CNS demyelinating disease research from emphasis on the oligodendrocyte and myelin to the astrocyte. NMO is recognized today as a relapsing disease, extending beyond the optic nerves and spinal cord to include brain (especially in children) and skeletal muscle. Brain magnetic resonance imaging abnormalities, identifiable in 60% of patients at the second attack, are consistent with MS in 10% of cases. NMOSD-typical lesions (another 10%) occur in AQP4-enriched regions: circumventricular organs (causing intractable nausea and vomiting) and the diencephalon (causing sleep disorders, endocrinopathies, and syndrome of inappropriate antidiuresis). Advances in understanding the immunobiology of AQP4 autoimmunity have necessitated continuing revision of NMOSD clinical diagnostic criteria. Assays that selectively detect pathogenic AQP4-IgG targeting extracellular epitopes of AQP4 are promising prognostically. When referring to AQP4 autoimmunity, we suggest substituting the term "autoimmune aquaporin-4 channelopathy" for the term "NMO spectrum disorders." Randomized clinical trials are currently assessing the efficacy and safety of newer immunotherapies. Increasing therapeutic options based on understanding the molecular pathogenesis is anticipated to improve the outcome for patients with AQP4 channelopathy. © 2016 Elsevier B.V. All rights reserved.

  6. Cytokines in Sjögren's syndrome

    NARCIS (Netherlands)

    Roescher, N.; Tak, P. P.; Illei, G. G.

    2009-01-01

    Cytokines play a central role in the regulation of immunity and are often found to be deregulated in autoimmune diseases. Sjögren's syndrome is a chronic autoimmune disease characterized by inflammation and loss of secretory function of the salivary and lachrymal glands. This review highlights the

  7. Coxiella burnetii as a possible cause of autoimmune liver disease: a case report

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    Kaech Chloe

    2009-08-01

    Full Text Available Abstract Introduction Q fever is a zoonotic infection that may cause severe hepatitis. Q-fever hepatitis has not yet been associated with autoimmune hepatitis and/or primary biliary cirrhosis. Case presentation We describe a 39-year-old man of Sri Lankan origin with chronic Q-fever hepatitis who developed autoantibodies compatible with autoimmune hepatitis/primary biliary cirrhosis overlap syndrome. Ursodeoxycholic acid in addition to antibiotic therapy markedly improved hepatic enzyme levels suggesting that autoimmunity, potentially triggered by the underlying infection, was involved in the pathogenesis of liver damage. Conclusion We suggest that Coxiella burnetii might trigger autoimmune liver disease. Patients with Q-fever hepatitis who respond poorly to antibiotics should be investigated for serological evidence of autoimmune hepatitis, primary biliary cirrhosis or overlap syndrome, as these patients could benefit from adjunctive therapy with ursodeoxycholic acid. Conversely, C. burnetii serology might be necessary in patients with autoimmune liver disease in order to exclude underlying Coxiella infection.

  8. A rare association of Castleman′s disease and nephrotic syndrome

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    I Tazi

    2011-01-01

    Full Text Available Castleman′s Disease (CD is an uncommon and poorly understood disorder of lymph node hyperplasia of unknown etiology. This entity belongs to the atypical lymphoproliferative disorders, a heterogeneous group of diseases characterized by a hyperplastic reactive process involving the immune system. The association of the nephrotic syndrome and CD is extremely rare and their interrelation remains enigmatic. We report a case of CD of the hyaline-vascular type with unicentric localization complicated by nephrotic syndrome.

  9. Autoimmune Hemolytic Anemia in Children: Mayo Clinic Experience.

    Science.gov (United States)

    Sankaran, Janani; Rodriguez, Vilmarie; Jacob, Eapen K; Kreuter, Justin D; Go, Ronald S

    2016-04-01

    We studied 35 pediatric patients with autoimmune hemolytic anemia seen at Mayo Clinic from 1994 to 2014. The median age was 10.0 years and 65.7% were males. Most had warm antibodies (80.0%) and some secondary to viral (14.3%) or autoimmune disorders (31.4%). Seven (20.0%) patients presented with Evans syndrome, 3 of whom also had common variable immunodeficiency. The median hemoglobin at diagnosis was 6.1 g/dL and 62.8% patients required red cell transfusions. The severity of anemia was worse among children below 10 years (median 5.5 vs. 7.0 g/dL, P=0.01). Steroid was the initial treatment for 88.5% patients, with overall response rate of 82.7% (68.5% complete, 14.2% partial) and median response duration of 10.7 months (range, 0.2 to 129.7+ mo). After median follow-up of 26.6 months, 8 (22.8%) patients relapsed. Salvage treatments included splenectomy, intravenous immunoglobulin, rituximab, and mycophenolate mofetil. Infectious complications occurred in 9 (25.7%) patients and 1 patient died of cytomegalovirus infection. Four patients had cold agglutinin disease and 3 (75.0%) responded to steroids. Autoimmune hemolytic anemia is a rare disorder in pediatric population and most respond well to steroids regardless of the type of antibody. Infectious complications are common and screening for immunodeficiency is recommended among those with Evans syndrome.

  10. Systemic Epstein-Barr Virus-positive T-Cell Lymphoproliferative Disease of Childhood With Good Response to Steroid Therapy.

    Science.gov (United States)

    Kim, Do-Hoon; Kim, Myungshin; Kim, Yonggoo; Han, Kyungja; Han, Eunhee; Lee, Jae Wook; Chung, Nack-Gyun; Cho, Bin

    2017-11-01

    Systemic Epstein-Barr virus (EBV)-positive T-cell lymphoproliferative disease of childhood is a rare disease and has a very fulminant clinical course with high mortality. A 21-month-old female patient was referred to our hospital with a 1 week history of fever and was subsequently diagnosed with systemic Epstein-Barr virus-positive T-cell lymphoproliferative disease of childhood. After starting treatment with dexamethasone, she showed early defervescence and improvement of laboratory parameters, and has remained disease-free after stopping steroid treatment, although longer follow-up is necessary. Our report underscores the possibility that this disease entity may be heterogenous in terms of prognosis.

  11. Type 1 autoimmune pancreatitis.

    Science.gov (United States)

    Zen, Yoh; Bogdanos, Dimitrios P; Kawa, Shigeyuki

    2011-12-07

    Before the concept of autoimmune pancreatitis (AIP) was established, this form of pancreatitis had been recognized as lymphoplasmacytic sclerosing pancreatitis or non-alcoholic duct destructive chronic pancreatitis based on unique histological features. With the discovery in 2001 that serum IgG4 concentrations are specifically elevated in AIP patients, this emerging entity has been more widely accepted. Classical cases of AIP are now called type 1 as another distinct subtype (type 2 AIP) has been identified. Type 1 AIP, which accounts for 2% of chronic pancreatitis cases, predominantly affects adult males. Patients usually present with obstructive jaundice due to enlargement of the pancreatic head or thickening of the lower bile duct wall. Pancreatic cancer is the leading differential diagnosis for which serological, imaging, and histological examinations need to be considered. Serologically, an elevated level of IgG4 is the most sensitive and specific finding. Imaging features include irregular narrowing of the pancreatic duct, diffuse or focal enlargement of the pancreas, a peri-pancreatic capsule-like rim, and enhancement at the late phase of contrast-enhanced images. Biopsy or surgical specimens show diffuse lymphoplasmacytic infiltration containing many IgG4+ plasma cells, storiform fibrosis, and obliterative phlebitis. A dramatic response to steroid therapy is another characteristic, and serological or radiological effects are normally identified within the first 2 or 3 weeks. Type 1 AIP is estimated as a pancreatic manifestation of systemic IgG4-related disease based on the fact that synchronous or metachronous lesions can develop in multiple organs (e.g. bile duct, salivary/lacrimal glands, retroperitoneum, artery, lung, and kidney) and those lesions are histologically identical irrespective of the organ of origin. Several potential autoantigens have been identified so far. A Th2-dominant immune reaction and the activation of regulatory T-cells are assumed

  12. Type 1 autoimmune pancreatitis

    Directory of Open Access Journals (Sweden)

    Zen Yoh

    2011-12-01

    Full Text Available Abstract Before the concept of autoimmune pancreatitis (AIP was established, this form of pancreatitis had been recognized as lymphoplasmacytic sclerosing pancreatitis or non-alcoholic duct destructive chronic pancreatitis based on unique histological features. With the discovery in 2001 that serum IgG4 concentrations are specifically elevated in AIP patients, this emerging entity has been more widely accepted. Classical cases of AIP are now called type 1 as another distinct subtype (type 2 AIP has been identified. Type 1 AIP, which accounts for 2% of chronic pancreatitis cases, predominantly affects adult males. Patients usually present with obstructive jaundice due to enlargement of the pancreatic head or thickening of the lower bile duct wall. Pancreatic cancer is the leading differential diagnosis for which serological, imaging, and histological examinations need to be considered. Serologically, an elevated level of IgG4 is the most sensitive and specific finding. Imaging features include irregular narrowing of the pancreatic duct, diffuse or focal enlargement of the pancreas, a peri-pancreatic capsule-like rim, and enhancement at the late phase of contrast-enhanced images. Biopsy or surgical specimens show diffuse lymphoplasmacytic infiltration containing many IgG4+ plasma cells, storiform fibrosis, and obliterative phlebitis. A dramatic response to steroid therapy is another characteristic, and serological or radiological effects are normally identified within the first 2 or 3 weeks. Type 1 AIP is estimated as a pancreatic manifestation of systemic IgG4-related disease based on the fact that synchronous or metachronous lesions can develop in multiple organs (e.g. bile duct, salivary/lacrimal glands, retroperitoneum, artery, lung, and kidney and those lesions are histologically identical irrespective of the organ of origin. Several potential autoantigens have been identified so far. A Th2-dominant immune reaction and the activation of

  13. Autoimmune pancreatitis. An update

    International Nuclear Information System (INIS)

    Helmberger, T.

    2016-01-01

    Autoimmune pancreatitis (AIP) is a rare disease, the pathophysiological understanding of which has been greatly improved over the last years. The most common form, type 1 AIP belongs to the IgG4-related diseases and must be distinguished from type 2 AIP, which is a much rarer entity associated with chronic inflammatory bowel disease. Clinically, there is an overlap with pancreatic cancer. Imaging and further criteria, such as serological and histological parameters are utilized for a differentiation between both entities in order to select the appropriate therapy and to avoid the small but ultimately unnecessary number of pancreatectomies. The diagnostics of AIP are complex, whereby the consensus criteria of the International Association of Pancreatology have become accepted as the parameters for discrimination. These encompass five cardinal criteria and one therapeutic criterion. By applying these criteria AIP can be diagnosed with a sensitivity of 84.9 %, a specificity of 100 % and an accuracy of 93.8 %. The diagnosis of AIP is accomplished by applying several parameters of which two relate to imaging. As for the routine diagnostics of the pancreas these are ultrasound, computed tomography (CT) and magnetic resonance imaging (MRI). Important for the differential diagnosis is the exclusion of signs of local and remote tumor spread for which CT and MRI are established. The essential diagnostic parameter of histology necessitates sufficient sample material, which cannot usually be acquired by a fine needle biopsy. CT or MRI are the reference standard methods for identification of the optimal puncture site and imaging-assisted (TruCut) biopsy. In patients presenting with unspecific upper abdominal pain, painless jaundice combined with the suspicion of a pancreatic malignancy in imaging but a mismatch of secondary signs of malignancy, AIP should also be considered as a differential diagnosis. As the diagnosis of AIP only partially relies on imaging radiologists also

  14. Shaking Out Clues to Autoimmune Disease

    Science.gov (United States)

    ... into how an immune cell involved in several autoimmune disorders is regulated. Among their findings was a potential ... but they’ve also been linked with several autoimmune disorders. Th17 cells, along with other types of helper ...

  15. [One case of type 1 auto-immune polyendocrinopathy or APECED].

    Science.gov (United States)

    Puzenat, E; Pepin, L; Bertrand, A-M; Pelletier, F; Monnier, D; Levang, J; Mermet, I; Humbert, P; Aubin, F

    2010-12-01

    autoimmune polyendocrinopathy with candidiasis and ectodermal dystrophy (APECED) is a rare autosomal recessive disorder caused by mutations in the autoimmune regulator gene (AIRE). We report the case of a young girl with APECED. an 18 year-old girl born to consanguineous parents consulted for diffuse alopecia. Dermatological examination showed nail and dental enamel dystrophy and angular cheilitis. She had a history of mineralocorticoid deficiency (Addison's disease), hypoparathyroidism, hypogonadism and Biermer's disease, and she had also had chronic mucocutaneous candidiasis since childhood. She was presenting APECED with autoimmune endocrine failure, chronic mucocutaneous candidiasis and abnormalities of ectoderm-derived tissue. Analysis of mutation in the AIRE gene showed the c.769C>T homozygous mutation in exon 6. APECED, a rare autosomal recessive disorder, is a potentially life-threatening autoimmune disease. Chronic mucocutaneous candidiasis is a common and early feature in children. Dermatologists are likely to be the first physicians to diagnose this syndrome. 2010. Published by Elsevier Masson SAS.

  16. Autoimmunity and autoinflammation as the yin and yang of idiopathic recurrent acute pericarditis.

    Science.gov (United States)

    Cantarini, Luca; Lopalco, Giuseppe; Selmi, Carlo; Napodano, Salvatore; De Rosa, Gabriella; Caso, Francesco; Costa, Luisa; Iannone, Florenzo; Rigante, Donato

    2015-02-01

    Autoimmunity and autoinflammation are generally considered as mutually exclusive mechanisms of diseases but may concur to specific syndromes. Idiopathic recurrent acute pericarditis (IRAP) is defined as the recurrence of pericardial symptoms at any point following the prior cessation of acute pericarditis, and the latency is generally 6 weeks. Manifestations of pericarditis such as pericardial friction rub, electrocardiographic changes, and pericardial effusion are less frequent in the subsequent episodes compared to the index attack, and in some cases the only clinical sign is represented by a suggestive chest pain. Several autoimmune diseases may manifest with pericarditis which is often related to viral infections, while postviral pericarditis may in turn display a nonspecific autoimmune background. Similarly, autoinflammatory syndromes such as familial Mediterranean fever and tumor necrosis factor receptor-associated periodic syndrome are characterized by self-limiting pericardial symptoms. Corticosteroids are generally effective, thus supporting the autoimmune nature of IRAP, but dramatic results are obtained with interleukin-1 blocking agents in corticosteroid-dependent cases, pointing to a pathogenic role for the inflammasome. Based on these observations, we submit that IRAP represents a paradigmatic example of the putative coexistence of autoimmunity and autoinflammation: the main aim of this review is to critically discuss the hypothesis as well as the current understanding of this enigmatic clinical condition. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Very late onset lymphoproliferative disorders occurring over 10 years post-renal transplantation: PTLD.Int. Survey.

    Science.gov (United States)

    Khedmat, Hossein; Taheri, Saeed

    2011-01-01

    Knowledge of the significance of post-transplant lymphoproliferative disorders (PTLD) that occur "very late" or more 10 years after renal transplantation is limited. thus, we analysed and compared characteristics and prognosis of the disease in renal transplant patients with very late onset PTLD vs. early- and late-onset PTLD. Retrospective study of data obtained from comprehensive search of medical literature We searched for available data using the Pubmed and Google scholar search engines for reports of lymphoproliferative disorders occurring in renal transplant patients by disease presentation time. We analyzed data from 27 studies that included 303 patients with lymphoproliferative disorders after renal transplantation. Renal graft recipients with very late onset PTLD were significantly less likely to be under mycophenolate mofetil (MMF)- and/or tacrolimus (FK-506) (vs. azathioprine) -based immunosuppression (P=.035) and less likely to have a history of antibody induction immunosuppression (P.1 for all). Older renal transplant patients are at increased risk for development of very late onset PTLD, and should be strictly followed. further multi-institutional prospective studies are needed to confirm our results.

  18. Treatment of post-transplantation lymphoproliferative disorders after kidney transplant with rituximab and conversion to m-TOR inhibitor.

    Science.gov (United States)

    Nieto-Rios, John Fredy; Gómez de Los Ríos, Sandra Milena; Serna-Higuita, Lina María; Ocampo-Kohn, Catalina; Aristizabal-Alzate, Arbey; Gálvez-Cárdenas, Kenny Mauricio; Zuluaga-Valencia, Gustavo Adolfo

    2016-12-30

    Post-transplantation lymphoproliferative disorders are serious complications of organ transplantation which treatment is not yet standardized. To describe the clinical response, overall and graft survival of patients in our center with this complication after kidney transplantation, which received rituximab as part of their treatment as well as conversion to m-TOR. Retrospective study, which included patients, diagnosed with post-transplant lymphoproliferative disorders after kidney transplantation from January 2011 to July 2014. Eight cases were found with a wide spectrum of clinical presentations. Most had monomorphic histology, 85% were associated with Epstein-Barr virus, 25% of patients had tumor involvement of the renal graft, and 12.5% ​​had primary central nervous system lymphoma. All patients were managed with reduction of immunosuppression, conversion to m-TOR (except one who lost the graft at diagnosis) and rituximab-based therapy. The overall response rate was 87.5% (62.5% complete response, 25% partial response). Survival was 87.5% with a median follow-up of 34 months. An additional patient lost the graft, with chronic nephropathy already known. All the remaining patients had stable renal function. There are no standardized treatment regimens for lymphoproliferative disorders after kidney transplantation, but these patients can be managed successfully with reduction of immunosuppression, conversion to m-TOR and rituximab-based schemes.

  19. An autosomal locus causing autoimmune disease: Autoimmune polyglandular disease type I assigned to chromosome 21

    NARCIS (Netherlands)

    J. Aaltonen (Johanna); P. Björses (Petra); L.A. Sandkuijl (Lodewijk); J. Perheentupa (Jaakko); L. Peltonen (Leena Johanna)

    1994-01-01

    textabstractAutoimmune polyglandular disease type I (APECED) is an autosomal recessive autoimmune disease characterized by a variable combination of the failure of the endocrine glands. The pathogenesis of this unique autoimmune disease is unknown; unlike many other autoimmune diseases, APECED does

  20. Correlation between flow cytometry and histologic findings: ten year experience in the investigation of lymphoproliferative diseases

    Directory of Open Access Journals (Sweden)

    Alanna Mara Pinheiro Sobreira Bezerra

    2011-06-01

    Full Text Available Objective: To demonstrate the advantages of correlatingflow cytometry immunophenotyping with the pathology/immunohistochemistry of lymph nodes or nodules in the diagnosisof lymphoproliferative diseases. Methods: A retrospective studywas carried out of 157 biopsy or fine-needle aspiration lymph nodes/nodule specimens taken from 142 patients, from 1999 and 2009.The specimens were simultaneously studied with flow cytometryand pathology at Hospital Israelita Albert Einstein. The specimenswere prepared in hematoxylin/eosin, Giemsa, or monoclonal antibodystained slides for detecting specific antibodies for the purposesof pathology/immunohistochemical analysis. The samples werehemolyzed and marked with different monoclonal antibody panels fordifferent antigens in flow cytometry immunophenotyping. Results:The diagnostic results of pathology/immunohistochemical studiesand flow cytometry immunophenotyping agreed in 115 patients(81%, corresponding to 127 specimens, as follows according tothe pathologic diagnosis: 63 patients with non-Hodgkin’s B-celllymphoma; 26 patients with reactive lymphoid hyperplasia; 5 patientswith non-Hodgkin’s T-cell lymphoma; 4 patients with atypical lymphoidproliferation; 5 patients with a chronic granulomatous inflammatoryprocess; 5 patients with a non-hematologic diagnosis; 2 patientswith granulocytic sarcoma; 2 patients with thymoma; 1 patientwith byphenotypic leukemia; 1 patient with kappa plasmocytoma;1 patient with Hodgkin’s lymphoma. Subtypes of lymphomas couldbe classified by associating the two techniques: 19 patients withfollicular lymphoma; 15 patients with diffuse large B-cell lymphoma; 7patients with small lymphocytic B-cell lymphoma/chronic lymphocyticleukemia; 3 patients with mantle cell lymphoma; 1 patient withBurkitt’s lymphoma; 1 patient with MALT type lymphoma; 1 patientwith post-transplant lymphoproliferative disease; 2 patients with highgrade non-Hodgkin’s B-cell lymphoma; 1 patient with low grade

  1. A minimum number of autoimmune T cells to induce autoimmunity?

    Czech Academy of Sciences Publication Activity Database

    Bosch, A.J.T.; Bolinger, B.; Keck, S.; Štěpánek, Ondřej; Ozga, A.J.; Galati-Fournier, V.; Stein, J.V.; Palmer, E.

    2017-01-01

    Roč. 316, jaro (2017), s. 21-31 ISSN 0008-8749 R&D Projects: GA ČR GJ16-09208Y Institutional support: RVO:68378050 Keywords : T cell * Tolerance * Autoimmunity Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Immunology Impact factor: 3.172, year: 2016

  2. [Immunomodulatory properties of stem mesenchymal cells in autoimmune diseases].

    Science.gov (United States)

    Sánchez-Berná, Isabel; Santiago-Díaz, Carlos; Jiménez-Alonso, Juan

    2015-01-20

    Autoimmune diseases are a cluster of disorders characterized by a failure of the immune tolerance and a hyperactivation of the immune system that leads to a chronic inflammation state and the damage of several organs. The medications currently used to treat these diseases usually consist of immunosuppressive drugs that have significant systemic toxic effects and are associated with an increased risk of opportunistic infections. Recently, several studies have demonstrated that mesenchymal stem cells have immunomodulatory properties, a feature that make them candidates to be used in the treatment of autoimmune diseases. In the present study, we reviewed the role of this therapy in the treatment of systemic lupus erythematosus, Sjögren's syndrome, systemic sclerosis, Crohn's disease and multiple sclerosis, as well as the potential risks associated with its use. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

  3. Multiplex autoantibody detection for autoimmune liver diseases and autoimmune gastritis.

    Science.gov (United States)

    Vanderlocht, Joris; van der Cruys, Mart; Stals, Frans; Bakker-Jonges, Liesbeth; Damoiseaux, Jan

    2017-09-01

    Autoantibody detection for autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC) and autoimmune gastritis (AIG) is traditionally performed by IIF on a combination of tissues. Multiplex line/dot blots (LIA/DIA) offer multiple advantages, i.e. automation, objective reading, no interfering reactivities, no coincidental findings. In the current study we evaluated automated DIA (D-Tek) for detecting autoantibodies related to autoimmune diseases of the gastrointestinal tract. We tested samples of the Dutch EQC program and compared the results with the consensus of the participating labs. For the autoimmune liver diseases and AIG, respectively, 64 and 36 samples were tested. For anti-mitochondrial and anti-smooth muscle antibodies a concordance rate of 97% and 88% was observed, respectively. The concordance rate for anti-parietal cell antibodies was 92% when samples without EQC consensus (n=15) were excluded. For antibodies against intrinsic factor a concordance of 96% was observed. For all these antibodies discrepancies were identified that relate to the different test characteristics and the preponderance of IIF utilizing labs in the EQC program. In conclusion, we observed good agreement of the tested DIA blots with the consensus results of the Dutch EQC program. Taken together with the logistic advantages these blots are a good alternative for autoantibody detection in the respective diseases. A large prospective multicenter study is warranted to position these novel tests further in the whole spectrum of assays for the detection of these antibodies in a routine autoimmune laboratory. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Elucidating the Role of Hyposalivation and Autoimmunity in Oral Candidiasis

    Science.gov (United States)

    Billings, Monisha; Dye, Bruce A.; Iafolla, Timothy; Grisius, Margaret; Alevizos, Ilias

    2016-01-01

    Introduction Oral candidiasis (OC) is a potential oral complication in Sjögren’s Syndrome (SS). Some studies indicate that the low stimulated salivary flow and not low unstimulated salivary flow is associated with OC in SS, while others report that the underlying autoimmune disorders contributes to OC, based solely on correlation coefficients. Given the conflicting and limited existing evidence, we purposed to ascertain the role of both salivary gland dysfunction (hyposalivation based on unstimulated and stimulated flow rates) and autoimmunity (SS, other autoimmune disorders) in OC among those with SS, other salivary gland dysfunction and non-salivary gland dysfunction controls (NSGD). Methods A nested case-control study was designed within a larger NIH/NIDCR cohort. Descriptive analyses, non-parametric tests, comparative analyses, and multivariate logistic regression analyses were undertaken. Results Data on 1,526 subjects (701 SS, 247 ISS, 355 Sicca, and 223 NSGD) were obtained from the source cohort of 2,046 and analyzed for this current study. The median whole unstimulated salivary flow rate (WUS, ml/15min) was lower in SS (0.8, interquartile range (IQR) 1.8) compared to ISS (5.5, IQR 5.2, pcandidiasis. Conclusion Salivary gland dysfunction (hyposalivation with WUS being a stronger predictor than TSS) and autoimmunity (SS, other autoimmune disorders, medications i.e., DMARDS) are both independent predictors of OC. Diabetes mellitus is an independent predictor of OC among those with salivary gland dysfunction. Our findings suggest that these independent predictors should be considered in the prevention and management of OC in this population. PMID:27998016

  5. Elucidating the role of hyposalivation and autoimmunity in oral candidiasis.

    Science.gov (United States)

    Billings, M; Dye, B A; Iafolla, T; Grisius, M; Alevizos, I

    2017-04-01

    Oral candidiasis (OC) is a potential oral complication in Sjögren's syndrome (SS). Some studies indicate that the low stimulated salivary flow and not low unstimulated salivary flow is associated with OC in SS, while others report that the underlying autoimmune disorders contribute to OC, based solely on correlation coefficients. Given the conflicting and limited existing evidence, we purposed to ascertain the role of both salivary gland dysfunction (hyposalivation based on unstimulated and stimulated flow rates) and autoimmunity (SS, other autoimmune disorders) in OC among those with SS, other salivary gland dysfunction, and non-salivary gland dysfunction controls (NSGD). A nested case-control study was designed within a larger NIH/NIDCR cohort. Descriptive analyses, nonparametric tests, comparative analyses, and multivariate logistic regression analyses were undertaken. Data on 1526 subjects (701 SS, 247 ISS, 355 Sicca, and 223 NSGD) were obtained from the source cohort of 2046 and analyzed for this study. The median whole unstimulated salivary flow rate (WUS, ml 15 min -1 ) was lower in SS (0.8, interquartile range (IQR) 1.8) compared to ISS (5.5, IQR: 5.2, P oral candidiasis. Salivary gland dysfunction (hyposalivation with WUS being a stronger predictor than TSS) and autoimmunity (SS, other autoimmune disorders, medications, i.e., DMARDS) are both independent predictors of OC. Diabetes mellitus is an independent predictor of OC among those with salivary gland dysfunction. Our findings suggest that these independent predictors should be considered in the prevention and management of OC in this population. © Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

  6. Loss of P2X7 receptor plasma membrane expression and function in pathogenic B220+ double-negative T lymphocytes of autoimmune MRL/lpr mice.

    Directory of Open Access Journals (Sweden)

    Sylvain M Le Gall

    Full Text Available Lupus is a chronic inflammatory autoimmune disease influenced by multiple genetic loci including Fas Ligand (FasL and P2X7 receptor (P2X7R. The Fas/Fas Ligand apoptotic pathway is critical for immune homeostasis and peripheral tolerance. Normal effector T lymphocytes up-regulate the transmembrane tyrosine phosphatase B220 before undergoing apoptosis. Fas-deficient MRL/lpr mice (lpr mutation exhibit lupus and lymphoproliferative syndromes due to the massive accumulation of B220(+ CD4(-CD8(- (DN T lymphocytes. The precise ontogeny of B220(+ DN T cells is unknown. B220(+ DN T lymphocytes could be derived from effector CD4(+ and CD8(+ T lymphocytes, which have not undergone activation-induced cell death due to inactivation of Fas, or from a special cell lineage. P2X7R is an extracellular ATP-gated cell membrane receptor involved in the release of proinflammatory cytokines and TNFR1/Fas-independent cell death. P2X7R also regulate early signaling events involved in T-cell activation. We show herein that MRL/lpr mice carry a P2X7R allele, which confers a high sensitivity to ATP. However, during aging, the MRL/lpr T-cell population exhibits a drastically reduced sensitivity to ATP- or NAD-mediated stimulation of P2X7R, which parallels the increase in B220(+ DN T-cell numbers in lymphoid organs. Importantly, we found that this B220(+ DN T-cell subpopulation has a defect in P2X7R-mediated responses. The few B220(+ T cells observed in normal MRL(+/+ and C57BL/6 mice are also resistant to ATP or NAD treatment. Unexpectedly, while P2X7R mRNA and proteins are present inside of B220(+ T cells, P2X7R are undetectable on the plasma membrane of these T cells. Our results prompt the conclusion that cell surface expression of B220 strongly correlates with the negative regulation of the P2X7R pathway in T cells.

  7. Cochlear Impairment and Autoimmune Ear Disorder in a Patient with Breast Cancer.

    Science.gov (United States)

    Fioretti, Alessandra; Di Rubbo, Vittoria; Peri, Giorgia; Vitti, Elisa; Cisternino, Sara; Varakliotis, Theodoros; Eibenstein, Alberto

    2017-02-01

    The purpose of this study was to consider the possible role of autoimmune diseases and paraneoplastic syndrome in the genesis of tinnitus. The incidence of autoimmune inner ear disease (AIED) is rare, accounting for autoimmunity tests were positive and a diagnosis of mixed connective tissue disease with notes of fibromyalgia was made . Pure tone audiometry testing revealed bilateral fluctuating mild hearing loss on high frequencies. The tinnitus was successfully treated with bilateral wideband sound generators (listening 8-9 h for day) regulated at the mixing point. At 12 months follow up THI has shrunk considerably (THI: 4) and the patient has continued treatment only with the sound pillow. In conclusion significant progress is needed to better understand the role of autoantibodies in the pathogenesis and diagnosis of paraneoplastic cochleovestibulopathy. To our knowledge, our study is the first in which hearing loss and tinnitus is considered as a manifestation of a paraneoplastic syndrome.

  8. Rebooting autoimmunity with autologous HSCT.

    Science.gov (United States)

    Snowden, John A

    2016-01-07

    Autologous hematopoietic stem cell transplantation (HSCT) is increasingly used for severe autoimmune and inflammatory diseases, but the mechanisms involved have yet to be elucidated. In this issue of Blood, Delemarre et al report their findings in both animal and human models which provide insights into restoration of functionality and diversity within the regulatory T-cell (Treg) compartment following HSCT.

  9. Vitiligo and Autoimmune Thyroid Disorders

    Directory of Open Access Journals (Sweden)

    Enke Baldini

    2017-10-01

    Full Text Available Vitiligo represents the most common cause of acquired skin, hair, and oral depigmentation, affecting 0.5–1% of the population worldwide. It is clinically characterized by the appearance of disfiguring circumscribed skin macules following melanocyte destruction by autoreactive cytotoxic T lymphocytes. Patients affected by vitiligo usually show a poorer quality of life and are more likely to suffer from depressive symptoms, particularly evident in dark-skinned individuals. Although vitiligo is a non-fatal disease, exposure of affected skin to UV light increases the chance of skin irritation and predisposes to skin cancer. In addition, vitiligo has been associated with other rare systemic disorders due to the presence of melanocytes in other body districts, such as in eyes, auditory, nervous, and cardiac tissues, where melanocytes are thought to have roles different from that played in the skin. Several pathogenetic models have been proposed to explain vitiligo onset and progression, but clinical and experimental findings point mainly to the autoimmune hypothesis as the most qualified one. In this context, it is of relevance the strong association of vitiligo with other autoimmune diseases, in particular with autoimmune thyroid disorders, such as Hashimoto thyroiditis and Graves’ disease. In this review, after a brief overview of vitiligo and its pathogenesis, we will describe the clinical association between vitiligo and autoimmune thyroid disorders and discuss the possible underlying molecular mechanism(s.

  10. Leaky gut and autoimmune diseases.

    Science.gov (United States)

    Fasano, Alessio

    2012-02-01

    Autoimmune diseases are characterized by tissue damage and loss of function due to an immune response that is directed against specific organs. This review is focused on the role of impaired intestinal barrier function on autoimmune pathogenesis. Together with the gut-associated lymphoid tissue and the neuroendocrine network, the intestinal epithelial barrier, with its intercellular tight junctions, controls the equilibrium between tolerance and immunity to non-self antigens. Zonulin is the only physiologic modulator of intercellular tight junctions described so far that is involved in trafficking of macromolecules and, therefore, in tolerance/immune response balance. When the zonulin pathway is deregulated in genetically susceptible individuals, autoimmune disorders can occur. This new paradigm subverts traditional theories underlying the development of these diseases and suggests that these processes can be arrested if the interplay between genes and environmental triggers is prevented by re-establishing the zonulin-dependent intestinal barrier function. Both animal models and recent clinical evidence support this new paradigm and provide the rationale for innovative approaches to prevent and treat autoimmune diseases.

  11. Characterization of skin blister fluids from children with Epstein-Barr virus-associated lymphoproliferative disease.

    Science.gov (United States)

    Wada, Taizo; Toma, Tomoko; Miyazawa, Hanae; Koizumi, Eiko; Shirahashi, Tetsujiro; Matsuda, Yusuke; Yachie, Akihiro

    2018-01-20

    Epstein-Barr virus (EBV)-associated T- or natural killer (NK)-cell lymphoproliferative disease (LPD) is a heterogeneous group of disorders characterized by chronic proliferation of EBV-infected lymphocytes. Patients may present with severe skin manifestations, including hypersensitivity to mosquito bites (HMB) and hydroa vacciniforme (HV)-like eruption, which are characterized by blister formation and necrotic ulceration. Skin biopsy specimens show inflammatory reactions comprising EBV-infected lymphocytes. However, blister fluids have not been fully assessed in patients with this disease. Blister fluids were collected from three patients with EBV-associated LPD: two with HMB and one with HV. Immunophenotyping of blister lymphocytes and measurement of tumor necrosis factor (TNF)-α in blister fluids were performed. The patients with HMB and HV exhibited markedly increased percentages of NK and γδ T cells, respectively, in both peripheral blood and blister fluids. These NK and γδ T cells strongly expressed the activation marker human leukocyte antigen-DR and were considered to be cellular targets of EBV infections. TNF-α was highly elevated in all blister fluids. Severe local skin reactions of EBV-associated LPD may be associated with infiltrating EBV-infected lymphocytes and a high TNF-α concentration in blister fluids. © 2018 Japanese Dermatological Association.

  12. Recurrent posttransplant lymphoproliferative disorder involving the larynx and trachea: case report and review of the literature.

    Science.gov (United States)

    Banks, Caroline A; Meier, Jeremy D; Stallworth, Christina R; White, David R

    2012-05-01

    Posttransplant lymphoproliferative disorder (PTLD) is a well-recognized complication of solid organ transplantation and commonly affects upper airway lymphoid tissue. Tracheal and laryngeal involvement in patients with PTLD, however, is rare. We present one such case. We report the case of a patient with recurrent PTLD involving the larynx and trachea and describe the presentation, evaluation, management, and outcome. An 11-year-old boy who underwent bilateral nephrectomy and renal transplantation as an infant was admitted to the hospital with chronic cough, fever, stridor, and dyspnea. His post-transplantation course was complicated by PTLD in cervical lymph nodes at 9 years of age that was successfully treated with chemotherapy. A computed tomographic scan during his present admission revealed supraglottic swelling, a distal tracheal mass, and paratracheal lymph node enlargement. The patient underwent laryngoscopy and bronchoscopy with biopsy specimens taken from the right laryngeal ventricle and distal trachea. Pathologic examination yielded a diagnosis of Epstein-Barr virus-positive PTLD. The patient was treated with chemotherapy, which resulted in resolution of the airway lesions, as seen on repeat bronchoscopy. This is the first report, to our knowledge, of recurrent PTLD involving simultaneous lesions in the larynx and the trachea. PTLD in the head and neck can present as lymphoid hypertrophy, airway obstruction, stridor, or cough. A high degree of clinical suspicion is essential for prompt diagnosis of this life-threatening complication.

  13. Molecular Surveillance for Lymphoproliferative Disease Virus in Wild Turkeys (Meleagris gallopavo from the Eastern United States.

    Directory of Open Access Journals (Sweden)

    Jesse M Thomas

    Full Text Available Lymphoproliferative disease virus (LPDV is a poorly understood, oncogenic avian retrovirus of domestic turkeys that has historically been restricted to Europe and Israel. However, a recent study reported LPDV in multiple wild turkey diagnostic cases from throughout the eastern United States of America (USA. To better understand the distribution of LPDV in the eastern USA, we surveyed 1,164 reportedly asymptomatic hunter-harvested wild turkeys from 17 states for the presence of LPDV proviral DNA by PCR. In total, 564/1,164 (47% turkeys were positive for LPDV. Wild turkeys from each state had a relatively high prevalence of LPDV, although statewide prevalence varied from 26 to 83%. Phylogenetic analysis revealed two major clades of LPDV in the USA, although one was at a low frequency suggesting restricted transmission, as well as significant clustering by state of isolation. To determine the best tissue to target for diagnostic purposes, liver, spleen, and bone marrow were tested from a subset of 15 hunter-harvested wild turkeys and 20 wild turkey diagnostic cases. Overall, bone marrow provided the highest level of detection for both hunter-harvested turkeys and diagnostic cases. The sensitivity of LPDV detection between tissues was not significantly different for diagnostic cases, but was for hunter-harvested birds. These results indicate that LPDV infection is common and widespread in wild turkey populations throughout the eastern USA, even without overt signs of disease.

  14. LYMPHO-PROLIFERATIVE RESPONSES TO VARIOUS FASCIOLA HEPATICA WORM'S ANTIGENS: AN IN VITRO STUDY.

    Science.gov (United States)

    Sharaf, Osama F; Amir, Elamir M; Hawash, Yousry A

    2016-04-01

    Fascioliasis is an important zoonotic disease with approximately 2-4 million people infected worldwide and a further 180 million at risk of infection. F. hepatica can survive within the bile ducts for many years through its ability to suppress the host immunity with Fasciola cathepsin L1 cysteine protease and Glutathione S transferase playing an important role. The aim of the present study is to investigate the in vitro lympho-proliferative responses of hepatic hilar lymphocytes (HLN) of infected sheep in response to different F. hepatica antigens. The suppressive effects of Fasciola excretory/secretory (ES) and tegument (TEG) and their fractions were also investigated. Our results showed that both ES and TEG had significant suppressive effects on lympho-proliferation, up to 74% and 92%, respectively. When these antigens were fractionated, fraction 3 (MW of >10000-30000) of both ES (64%) and TEG (59%) in addition to fraction 4 (MW of ≤ 10000) of TEG (38%) inherited the suppressive effects. Identification of the potential molecule(s) with such suppressive effects on lymphocytes in TEG fraction 4 could reveal vaccine candidates.

  15. Posttransplant Lymphoproliferative Disorder After Clinical Islet Transplantation: Report of the First Two Cases.

    Science.gov (United States)

    Peters, A; Olateju, T; Deschenes, J; Shankarnarayan, S H; Chua, N; Shapiro, A M J; Senior, P

    2017-09-01

    We report the first two cases of posttransplant lymphoproliferative disorder (PTLD) in recipients of islet transplants worldwide. First, a 44-year-old recipient of three islet infusions developed PTLD 80 months after his initial transplantation, presenting with abdominal pain and diffuse terminal ileum thickening on imaging. He was treated with surgical excision, reduction of immunosuppression, and rituximab. Seven months later, he developed central nervous system PTLD, presenting with vertigo and diplopia; immunosuppression was discontinued, resulting in graft loss, and he was given high-dose methotrexate and underwent consolidative autologous stem cell transplantation. He remains in remission 37 months after the initial diagnosis. Second, a 58-year-old female recipient of two islet infusions developed PTLD 24 months after initial islet infusion, presenting with pancytopenia secondary to extensive bone marrow involvement. Immunosuppression was discontinued, resulting in graft loss, and she received rituximab and chemotherapy, achieving complete remission. Both patients were monomorphic B cell PTLD subtype by histology and negative for Epstein-Barr virus in tissue or blood. These cases document the first occurrences of this rare complication in islet transplantation, likely secondary to prolonged, intensive immunosuppression, and highlight the varying clinical manifestations of PTLD. Further studies are needed to determine incidence rate and risk factors in islet transplantation. © 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.

  16. Clonality assessment of lymphoproliferative lesions using the polymerase chain reaction: An analysis of two methods

    Directory of Open Access Journals (Sweden)

    Nikhil Moorchung

    2011-01-01

    Full Text Available Background: Lymphoid malignancies are a heterogeneous group of disorders which may be difficult to differentiate from reactive proliferations even after immunohistochemistry. Polymerase chain reaction (PCR is believed to be a good adjunct tool for diagnosis. Materials and Methods: We examined 24 cases of neoplastic and non-neoplastic lymphoproliferative lesions in this study and evaluated the PCR as an additional tool in the confirmation of the diagnosis. Two different PCR methodologies were evaluated. Results: In the evaluation of the T-cell PCR, it was seen that the correlation using both the commercial kits and the custom-synthesized primers was highly significant at a P value of 0.05. Conclusions: Both the methods showed an excellent concordance for T-cell γ gene rearrangements, However, the same was not seen in the B-cell receptor rearrangements. This may be because of the small sample size or the inability of consensus V primers to recognize complementary DNA sequences in all of the V segments.

  17. Low incidence of lymphoproliferative disease post kidney transplantation with prevalent use of alemtuzumab

    Directory of Open Access Journals (Sweden)

    John Fredy Nieto-Ríos

    2014-01-01

    Full Text Available Introduction: It is well known that the incidence of malignancy is significantly higher in transplanted patients than in general population. The incidence of lymphoproliferative disease post-transplantation (PTLD is approximately of 1% to 2% in kidney transplantation recipients. Objective: The main objective of this study was to evaluate the PTLD incidence when monitoring kidney transplanted patients between the years 2005 and 2010. Methods: Kidney transplanted patients’ data was retrospectively taken between the years 2005 to 2010 in order to determine the number of PTLD cases according to the inductor scheme used. Results: 425 patients were transplanted between 2005 and 2010. They received alemtuzumab 76.2%, daclizumab 10.7%, basiliximab 3.6% and thymoglobulin 2.4%. The 7% did not receive antibody induction. During this period 2 cases of PTLD ocurred: One with multiple myeloma and the other with lymphoma. One of them had been treated with alemtuzumab and the other with thymoglobulin. Conclusions: The PTLD incidence in our group, where alemtuzumab was used predominantly as inductor, was very low; this might suggest that alemtuzumab is a medication that does not increase the risk of this kind of neoplasia.

  18. Leflunomide/teriflunomide inhibit Epstein-Barr virus (EBV)- induced lymphoproliferative disease and lytic viral replication.

    Science.gov (United States)

    Bilger, Andrea; Plowshay, Julie; Ma, Shidong; Nawandar, Dhananjay; Barlow, Elizabeth A; Romero-Masters, James C; Bristol, Jillian A; Li, Zhe; Tsai, Ming-Han; Delecluse, Henri-Jacques; Kenney, Shannon C

    2017-07-04

    EBV infection causes mononucleosis and is associated with specific subsets of B cell lymphomas. Immunosuppressed patients such as organ transplant recipients are particularly susceptible to EBV-induced lymphoproliferative disease (LPD), which can be fatal. Leflunomide (a drug used to treat rheumatoid arthritis) and its active metabolite teriflunomide (used to treat multiple sclerosis) inhibit de novo pyrimidine synthesis by targeting the cellular dihydroorotate dehydrogenase, thereby decreasing T cell proliferation. Leflunomide also inhibits the replication of cytomegalovirus and BK virus via both "on target" and "off target" mechanisms and is increasingly used to treat these viruses in organ transplant recipients. However, whether leflunomide/teriflunomide block EBV replication or inhibit EBV-mediated B cell transformation is currently unknown. We show that teriflunomide inhibits cellular proliferation, and promotes apoptosis, in EBV-transformed B cells in vitro at a clinically relevant dose. In addition, teriflunomide prevents the development of EBV-induced lymphomas in both a humanized mouse model and a xenograft model. Furthermore, teriflunomide inhibits lytic EBV infection in vitro both by preventing the initial steps of lytic viral reactivation, and by blocking lytic viral DNA replication. Leflunomide/teriflunomide might therefore be clinically useful for preventing EBV-induced LPD in patients who have high EBV loads yet require continued immunosuppression.

  19. Oncogenic Notch signaling in T-cell and B-cell lymphoproliferative disorders.

    Science.gov (United States)

    Chiang, Mark Y; Radojcic, Vedran; Maillard, Ivan

    2016-07-01

    This article highlights recent discoveries about Notch activation and its oncogenic functions in lymphoid malignancies, and discusses the therapeutic potential of Notch inhibition. NOTCH mutations arise in a broad spectrum of lymphoid malignancies and are increasingly scrutinized as putative therapeutic targets. In T-cell acute lymphoblastic leukemia (T-ALL), NOTCH1 mutations affect the extracellular negative regulatory region and lead to constitutive Notch activation, although mutated receptors remain sensitive to Notch ligands. Other NOTCH1 mutations in T-ALL and NOTCH1/2 mutations in multiple B-cell malignancies truncate the C-terminal proline (P), glutamic acid (E), serine (S), threonine (T)-rich (PEST) domain, leading to decreased Notch degradation after ligand-mediated activation. Thus, targeting Notch ligand-receptor interactions could provide therapeutic benefits. In addition, we discuss recent reports on clinical testing of Notch inhibitors in T-ALL that influenced contemporary thinking on the challenges of targeting Notch in cancer. We review advances in the laboratory to address these challenges in regards to drug targets, the Notch-driven metabolome, and the sophisticated protein-protein interactions at Notch-dependent superenhancers that underlie oncogenic Notch functions. Notch signaling is a recurrent oncogenic pathway in multiple T- and B-cell lymphoproliferative disorders. Understanding the complexity and consequences of Notch activation is critical to define optimal therapeutic strategies targeting the Notch pathway.

  20. Autoimmune reaction after anti-tetanus vaccination-description of four cases and review of the literature.

    Science.gov (United States)

    Ruhrman-Shahar, N; Torres-Ruiz, J; Rotman-Pikielny, P; Levy, Y

    2017-02-01

    Autoimmune reaction after vaccination is sporadically reported in the medical literature. Vaccinations are generally safe and have an important role in eradicating endemic diseases worldwide. Nevertheless, the question arises as to whether there is a possibility of post-vaccination autoimmune phenomena. The anti-tetanus vaccine is being used since 1924, and it is part of the recommended immunization schedules for children. There are few reports of autoimmune diseases, such as rheumatoid arthritis and anti-phospholipid syndrome after anti-tetanus vaccination. Herein, we describe four cases, of which we believe, show a clear temporal relation between anti-tetanus vaccination and the appearance of dermatomyositis, systemic lupus erythematosus, type 1 diabetes mellitus and anti-phospholipid syndrome. We also suggest some of the pathogenic mechanisms that promote a pathogenic autoimmune response.

  1. Hereditary periodic fever syndromes

    NARCIS (Netherlands)

    McDermott, MF; Frenkel, J

    Hereditary periodic fever syndromes are defined by recurrent attacks of generalised inflammation for which no infectious or auto-immune cause can be identified. For most of these disorders, the molecular basis has recently been elucidated. This has opened the prospect of novel therapeutic

  2. Utility of the American-European Consensus Group and American College of Rheumatology Classification Criteria for Sjögren's syndrome in patients with systemic autoimmune diseases in the clinical setting.

    Science.gov (United States)

    Hernández-Molina, Gabriela; Avila-Casado, Carmen; Nuñez-Alvarez, Carlos; Cárdenas-Velázquez, Francisco; Hernández-Hernández, Carlos; Luisa Calderillo, María; Marroquín, Verónica; Recillas-Gispert, Claudia; Romero-Díaz, Juanita; Sánchez-Guerrero, Jorge

    2015-03-01

    The aim of this study was to evaluate the feasibility and performance of the American-European Consensus Group (AECG) and ACR Classification Criteria for SS in patients with systemic autoimmune diseases. Three hundred and fifty patients with primary SS, SLE, RA or scleroderma were randomly selected from our patient registry. Each patient was clinically diagnosed as probable/definitive SS or non-SS following a standardized evaluation including clinical symptoms and manifestations, confirmatory tests, fluorescein staining test, autoantibodies, lip biopsy and medical chart review. Using the clinical diagnosis as the gold standard, the degree of agreement with each criteria set and between the criteria sets was estimated. One hundred fifty-four (44%) patients were diagnosed with SS. The AECG criteria were incomplete in 36 patients (10.3%) and the ACR criteria in 96 (27.4%; P vs 62.3 and a specificity of 94.3 vs 91.3, respectively. Either set of criteria was met by 123 patients (80%); 95 (61.7%) met the AECG criteria and 96 (62.3%) met the ACR criteria, but only 68 (44.2%) patients met both sets. The concordance rate between clinical diagnosis and AECG or ACR criteria was moderate (k statistic 0.58 and 0.55, respectively). Among 99 patients with definitive SS sensitivity was 83.3 vs 77.7 and specificity was 90.8 vs 85.6, respectively. A discrepancy between clinical diagnosis and criteria was seen in 59 patients (17%). The feasibility of the SS AECG criteria is superior to that of the ACR criteria, however, their performance was similar among patients with systemic autoimmune diseases. A subset of SS patients is still missed by both criteria sets. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  3. Autoimmunity in dengue pathogenesis

    Directory of Open Access Journals (Sweden)

    Shu-Wen Wan

    2013-01-01

    Full Text Available Dengue is one of the most important vector-borne viral diseases. With climate change and the convenience of travel, dengue is spreading beyond its usual tropical and subtropical boundaries. Infection with dengue virus (DENV causes diseases ranging widely in severity, from self-limited dengue fever to life-threatening dengue hemorrhagic fever and dengue shock syndrome. Vascular leakage, thrombocytopenia, and hemorrhage are the major clinical manifestations associated with severe DENV infection, yet the mechanisms remain unclear. Besides the direct effects of the virus, immunopathogenesis is also involved in the development of dengue disease. Antibody-dependent enhancement increases the efficiency of virus infection and may suppress type I interferon-mediated antiviral responses. Aberrant activation of T cells and overproduction of soluble factors cause an increase in vascular permeability. DENV-induced autoantibodies against endothelial cells, platelets, and coagulatory molecules lead to their abnormal activation or dysfunction. Molecular mimicry between DENV proteins and host proteins may explain the cross-reactivity of DENV-induced autoantibodies. Although no licensed dengue vaccine is yet available, several vaccine candidates are under development. For the development of a safe and effective dengue vaccine, the immunopathogenic complications of dengue disease need to be considered.

  4. Thyroid dysfunction in Down's syndrome.

    OpenAIRE

    Loudon, M M; Day, R E; Duke, E M

    1985-01-01

    One hundred and sixteen children with Down's syndrome, living in the community, were examined for clinical or laboratory evidence of thyroid dysfunction. Three were hypothyroid and one was hyperthyroid. Twenty eight (29%) had thyroid autoantibodies. Autoimmune conditions were present in first or second degree relatives of 35 (30%) of the children, and in 17 (15%) this was a thyroid disorder. The families of normal control children also showed a 30% incidence of overt autoimmune conditions, an...

  5. On chronic fatigue syndrome and nosological categories.

    Science.gov (United States)

    Sharif, Kassem; Watad, Abdulla; Bragazzi, Nicola Luigi; Lichtbroun, Michael; Martini, Mariano; Perricone, Carlo; Amital, Howard; Shoenfeld, Yehuda

    2018-02-07

    Chronic fatigue syndrome (CFS) is a heterogeneous disease which presents with pronounced disabling fatigue, sleep disturbances, and cognitive impairment that negatively affects patients' functional capability. CFS remains a poorly defined entity and its etiology is still in question. CFS is neither a novel diagnosis nor a new medical condition. From as early as the eighteenth century, a constellation of perplexing symptoms was observed that resembled symptoms of CFS. Commencing with "febricula" and ending with CFS, many names for the disease were proposed including neurocirculatory asthenia, atypical poliomyelitis, Royal Free disease, effort syndrome, Akureyri disease, Tapanui disease, chronic Epstein-Barr virus syndrome, and myalgic encephalitis. To date, it remains unclear whether CFS has an autoimmune component or is a condition that precedes a full-blown autoimmune disease. Research suggests that CFS may overlap with other diseases including postural orthostatic tachycardia syndrome (POTS), autoimmune syndrome induced by adjuvants (ASIA), and Sjögren's syndrome. Additionally, it has been postulated that the earliest manifestations of some autoimmune diseases can present with vague non-specific symptoms similar to CFS. Sometimes only when exposed to a secondary stimulus (e.g., antigen) which could accelerate the natural course of the disease would an individual develop the classic autoimmune disease. Due to the similarity of symptoms, it has been postulated that CFS could simply be an early manifestation of an autoimmune disease. This paper will provide a historical background review of this disease and a discussion of CFS as an entity overlapping with multiple other conditions.

  6. Properdin-dependent activation and control of immune-homeostasis and autoimmunity

    NARCIS (Netherlands)

    O'Flynn, Joseph

    2014-01-01

    The complement system has been shown to have a role in various systemic autoimmune (AI) diseases which have a renal component. This includes systemic lupus erythematosus (SLE), goodpastures syndrome and anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitides. In particular the classical

  7. Expression of the Autoimmune Regulator Gene and Its Relevance to the Mechanisms of Central and Peripheral Tolerance

    OpenAIRE

    Perniola, Roberto

    2012-01-01

    The autoimmune polyendocrine syndrome type 1 (APS-1) is a monogenic disease due to pathogenic variants occurring in the autoimmune regulator (AIRE) gene. Its related protein, AIRE, activates the transcription of genes encoding for tissue-specific antigens (TsAgs) in a subset of medullary thymic epithelial cells: the presentation of TsAgs to the maturating thymocytes induces the apoptosis of the autoreactive clones and constitutes the main form of central tolerance. Dysregulation of thymic AIR...

  8. Elevated Adiponectin Serum Levels in Women with Systemic Autoimmune Diseases

    Directory of Open Access Journals (Sweden)

    Éric Toussirot

    2010-01-01

    Full Text Available Adipose tissue produces a wide range of proteins that may influence the immune system. In this study, we assessed the serum levels of leptin, adiponectin, and ghrelin, in association with the measurements of body composition, in 15 female patients with various autoimmune diseases (systemic lupus erythematosus, primary Sjögren's syndrome, sarcoidosis, mixed connective tissue disease, vasculitis, CREST syndrome, and polymyositis and in 15 healthy female controls. There were no statistically significant differences between the patients and controls with regard to serum leptin, serum ghrelin, global fat mass, adiposity, and fat mass in the android or gynoid regions, whereas serum adiponectin levels were higher in patients than controls (16.3±1.6 μg/mL versus 9.7±0.6 μg/mL; =.01. As adiponectin is known to exhibit potent anti-inflammatory properties, a high adiponectinemia in patients with systemic autoimmune disease may mitigate the inflammatory response. However, the precise consequences of these elevated serum adiponectin levels on the metabolic syndrome development and atherosclerotic cardiovascular risk in this patient population still needs to be determined.

  9. Histopathological changes in exocrine glands of murine transplantation chimeras. I: The development of Sjögren's syndrome-like changes secondary to GVH induced lupus syndrome

    DEFF Research Database (Denmark)

    Sørensen, Inger; Ussing, Anne Phaff; Prause, J.U.

    1992-01-01

    Autoimmune disease, systemic lupus erythematosus, chronic graft-versus-host reaction, renal insufficiency, Sjögren's syndrome, inbred mouse strains......Autoimmune disease, systemic lupus erythematosus, chronic graft-versus-host reaction, renal insufficiency, Sjögren's syndrome, inbred mouse strains...

  10. The role of the autoimmunity laboratory in autoimmune diseases

    Directory of Open Access Journals (Sweden)

    SS Hasson

    2012-04-01

    Full Text Available Laboratory testing is of great value when evaluating a patient with a suspected autoimmune disease. The results can confirm a diagnosis, estimate disease severity, aid in assessing prognosis and are useful to follow disease activity. Components of the laboratory exam include complete blood count with differential, comprehensive metabolic panel, inflammatory markers, autoantibodies, and flow cytometry. Currently, autoimmunity laboratories are very vibrant owing to the constant and increasing availability of new tests, mainly due to the detection of new autoantibodies. The main characteristic that differentiates the autoimmunity laboratory from other laboratories is the use of immunoassays such as enzyme-linked immunosorbent assay (ELISA, as basic techniques which determines antibodies (autoantibodies and not antigens. For this reason, immunoassay techniques must employ antigens as reagents. However, over the last few years, a significant trend at autoimmunity laboratories has been the gradual replacement of immunofluorescence microscopy by immunoassay. Nowadays the revolution of new technology has taken place significantly, for examples; recombinant DNA technology has allowed the production of large quantities of antigens for autoantibody analysis. Flow cytometry for the analysis of microsphere-based immunoassays allows the simultaneous measurement of several autoantibodies. In the same way, autoantigen microarrays provide a practical means to analyse biological fluids in the search for a high number of autoantibodies. We are now at the beginning of an era of multiplexed analysis, with a high capacity of autoantibody specificities. The future tendency in this field will include immunoassays with greater analytical sensitivity, specificity, simultaneous multiplexed capability, the use of protein microarrays, and the use of other technologies such as microfluidics.

  11. AIRE genetic variants and predisposition to polygenic autoimmune disease: The case of Graves' disease and a systematic literature review.

    Science.gov (United States)

    Colobran, Roger; Giménez-Barcons, Mireia; Marín-Sánchez, Ana; Porta-Pardo, Eduard; Pujol-Borrell, Ricardo

    2016-08-01

    Autoimmune Regulator (AIRE) is a transcriptional regulator that is crucial for establishing central tolerance as illustrated by the Mendelian Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy (APECED) syndrome associated with AIRE-inactivating recessive or dominant mutations. Polymorphisms in AIRE have been proposed to be implicated in genetic susceptibility to non-Mendelian organ specific autoimmune diseases. Because there is evidence that in predisposition to Graves' disease (GD) central tolerance is crucial, we investigated whether AIRE polymorphisms could modulate risk of GD. A case-control association study using 29 variants and conducted in 150 GD patients and 200 controls did not detect any significant association. This result is not exceptional: a systematic review of the literature, including GWAS, on the association of AIRE variants with organ specific autoimmune diseases did not show clear associations; similarly heterozygous recessive mutations are not associated to non-Mendelian autoimmunity. Dominant negative mutations of AIRE are associated to autoimmunity but as mild forms of APECED rather than to non-Mendelian organ specific autoimmunity. The lack of association of common AIRE polymorphisms with polygenic autoimmune diseases is counterintuitive as many other genes less relevant for immunological tolerance have been found to be associated. These findings give rise to the intriguing possibility that evolution has excluded functionally modifying polymorphisms in AIRE. Copyright © 2016 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

  12. Looking into a paradox - Lupus anticoagulant and its relation to thrombosis in the antiphospholipid syndrome

    NARCIS (Netherlands)

    Molhoek, J.E.

    2017-01-01

    The antiphospholipid syndrome is an autoimmune disease characterized by thrombosis and pregnancy morbidity. One of the diagnostic hallmarks of the antiphospholipid syndrome is a prolonged clotting time. A prolonged clotting time is normally suggestive for bleeding tendency. The combination

  13. Fine-needle aspiration biopsy of lymphoproliferative disorders--interpretations based on morphologic criteria alone: results from the College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytopathology.

    Science.gov (United States)

    Young, Nancy A; Moriarty, Ann T; Haja, Jennifer C; Wilbur, David C

    2006-12-01

    Diagnosis of lymphoproliferative disorders is one of the most challenging tasks faced by the cytologist. The initial cytomorphologic evaluation of lymphoproliferative lesions directs the choice of ancillary studies that ultimately lead to a diagnosis based on the World Health Organization classification system using a composite of clinical, morphologic, immunophenotypic, and molecular features. To evaluate the ability of participating laboratories in the College of American Pathologists Interlaboratory Comparison Program in Non-Gynecologic Cytopathology to appropriately categorize lymphoproliferative lesions based solely on cytomorphologic criteria. Laboratory responses for lymph node aspirates were examined. All responses were based on review of glass slides without ancillary immunologic or molecular data available. The benchmarking data provided for each specific diagnosis were analyzed, with a focus on the performance for evaluation of lymphoproliferative lesions. Based on morphology alone, responses for lymph node aspirates in the Non-Gynecologic Cytopathology program were correct to the exact reference diagnosis for 87.1% of Hodgkin lymphoma. Non-Hodgkin lymphoma was identified in 69.5% of the large cell non-Hodgkin lymphoma cases, of which 66.8% were correctly classified as large cell type. Non-Hodgkin lymphoma was identified in 68.1% of non-Hodgkin lymphoma, other than large cell cases, and of these, 94.7% were identified as other than large cell type. The spectrum of specific responses was consistent for lymphoproliferative lesions, with a reasonable differential diagnosis based on cytomorphology alone, which, in practice, facilitates the appropriate choice of immunophenotypic markers and other ancillary studies.

  14. Update on antiphospholipid antibody syndrome

    Directory of Open Access Journals (Sweden)

    Michelle Remião Ugolini Lopes

    Full Text Available Summary Antiphospholipid syndrome (APS is an autoimmune disease characterized by antiphospholipid antibodies (aPL associated with thrombosis and/or pregnancy morbidity. Most APS events are directly related to thrombotic events, which may affect small, medium or large vessels. Other clinical features like thrombocytopenia, nephropathy, cardiac valve disease, cognitive dysfunction and skin ulcers (called non-criteria manifestations add significant morbidity to this syndrome and represent clinical situations that are challenging. APS was initially described in patients with systemic lupus erythematosus (SLE but it can occur in patients without any other autoimmune disease. Despite the autoimmune nature of this syndrome, APS treatment is still based on anticoagulation and antiplatelet therapy.

  15. Lupus-like panniculitis in a patient with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED).

    Science.gov (United States)

    Füchtenbusch, M; Vogel, A; Achenbach, P; Gummer, M; Ziegler, A G; Albert, E; Standl, E; Manns, M P

    2003-08-01

    Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare autosomal recessive disorder, characterised by a loss of self-tolerance to endocrine tissues, chronic candidiasis and ectodermal disorders. APECED is associated with mutations of a single gene, designated autoimmune regulator (AIRE). We describe a 31-year-old APECED patient with non-traumatic, cutaneous ulcers on both forearms with features of a lupus-like panniculitis. On admission to the ICU in September 2001, the patient suffered from a ketoacidotic, hyperglycemic coma and adrenal crisis due to an Enterobacter-cloacae sepsis, originating from multiple, necrotising deep cutaneous ulcers. These ulcers spontaneously developed on both forearms, some of which were just emerging, full blown or healing with scars. Histological examination showed signs of a scarring panniculitis and vasculitis. Immunohistochemistry and direct immunofluorescence with characterisation of immunoglobulin and complement-factor binding pattern revealed features of a lupus-like panniculitis. Sequence analysis of all 14 exons of the AIRE gene revealed a R257 X mutation in exon 6 resulting in a nonsense mutation at codon 257 confirming the diagnosis of APECED. Oral treatment with 60 mg/day corticosteroids for two weeks led to complete resolution of all ulcers. In conclusion, mutations in the AIRE gene may provide the genetic background against which additional factors can initiate an autoimmune process. Here, autoimmune panniculitis appears to be an associated feature of the APECED syndrome. Our findings support the use of immunosuppressive therapy for autoimmune disease components of the APECED syndrome.

  16. Management strategies for autoimmune pancreatitis.

    Science.gov (United States)

    Kamisawa, Terumi; Takuma, Kensuke; Hara, Seiichi; Tabata, Taku; Kuruma, Sawako; Inaba, Yoshihiko; Gopalakrishna, Rajesh; Egawa, Naoto; Itokawa, Fumihide; Itoi, Takao

    2011-10-01

    Autoimmune pancreatitis (AIP) is a newly developed concept for a peculiar type of pancreatitis, and at present is recognized as a pancreatic lesion reflecting IgG4-related systemic disease. It is of utmost importance to differentiate AIP from pancreatic cancer to avoid unnecessary surgery. The current management strategies for AIP, including its clinical features, diagnostic criteria, clinical subtypes, steroid therapy and prognosis are discussed, based on our 66 AIP cases and papers searched in PubMed from 1992 to March 2011, using the term 'autoimmune pancreatitis'. A new clinicopathological entity, an 'IgG4-related sclerosing disease' is also mentioned. AIP should be considered in the differential diagnosis in elderly male patients presented with obstructive jaundice and pancreatic mass. Steroids are a standard therapy for AIP, but their regimen including maintenance therapy should be evaluated in prospective trials.

  17. [Latent autoimmune diabetes in adults].

    Science.gov (United States)

    Pollak, Felipe; Vásquez, Tatiana

    2012-11-01

    Latent Autoimmune Diabetes in Adults (LADA) is the term used to describe adults who have a slowly progressive form of diabetes mellitus (DM) of autoimmune etiology, but that may be treated initially without insulin. Although it shares some immunological and genetic aspects with type 1 DM, it affects an age group that is typically affected by type 2 DM. Therefore, it could be considered an intermediate type. Diagnosis is based on clinical and laboratory criteria: age of onset, initial response to oral hypoglycemic agents and the presence of specific antibodies for diabetes. Although the definitive treatment is insulin, glitazones may be useful in early stages of the disease. Currently, its management represents a challenge for the physician, including specialists, and it is a form of DM to keep in mind.

  18. Long-term follow-up of kidney transplant patients with posttransplant lymphoproliferative disorder: duration of posttransplant lymphoproliferative disorder-induced operational graft tolerance, interleukin-18 course, and results of retransplantation

    DEFF Research Database (Denmark)

    Birkeland, Søren; Dutoit, Stephen Jacques Hamilton; Bendtzen, K

    2003-01-01

    Posttransplant lymphoproliferative disorder (PTLD) can be resolved in many transplant patients by the reduction or cessation of immunosuppression, after which many grafts continue to function as the result of a form of operational tolerance. When graft function deteriorates, retransplantation may...... be an option. Cytokines such as interleukin (IL)-10 and IL-18 may play a role in PTLD tolerance induction and tumor regression. We report long-term follow-up on the duration of graft tolerance and the course of retransplantation in a series of patients who underwent kidney transplantation and demonstrated PTLD...

  19. Epstein-Barr virus load in transplant patients: Early detection of post-transplant lymphoproliferative disorders.

    Science.gov (United States)

    Fellner, María Dolores; Durand, Karina A; Solernou, Veronica; Bosaleh, Andrea; Balbarrey, Ziomara; García de Dávila, María T; Rodríguez, Marcelo; Irazu, Lucía; Alonio, Lidia V; Picconi, María A

    2016-01-01

    High levels of circulating EBV load are used as a marker of post-transplant lymphoproliferative disorders (PTLD). There is no consensus regarding the threshold level indicative of an increase in peripheral EBV DNA. The aim of the study was to clinically validate a developed EBV quantification assay for early PTLD detection. Transversal study: paired peripheral blood mononuclear cells (PBMC), plasma and oropharyngeal lymphoid tissue (OLT) from children undergoing a solid organ transplant with (n=58) and without (n=47) PTLD. Retrospective follow-up: 71 paired PBMC and plasma from recipients with (n=6) and without (n=6) PTLD history. EBV load was determined by real-time PCR. The diagnostic ability to detect all PTLD (categories 1-4), advanced PTLD (categories 2-4) or neoplastic PTLD (categories 3 and 4) was estimated by analyzing the test performance at different cut-off values or with a load variation greater than 0.5log units. The higher diagnostic performance for identifying all, advanced or neoplastic PTLD, was achieved with cut-off values of 1.08; 1.60 and 2.47log EBVgEq/10(5) PBMC or 2.30; 2.60; 4.47loggEq/10(5) OLT cells, respectively. EBV DNA detection in plasma showed high specificity but low (all categories) or high (advanced/neoplastic categories) sensitivity for PTLD identification. Diagnostic performance was greater when: (1) a load variation in PBMC or plasma was identified; (2) combining the measure of EBV load in PBMC and plasma. The best diagnostic ability to identify early PTLD stages was achieved by monitoring EBV load in PBMC and plasma simultaneously; an algorithm was proposed. Copyright © 2016 Asociación Argentina de Microbiología. Publicado por Elsevier España, S.L.U. All rights reserved.

  20. Viral induction and targeted inhibition of galectin-1 in EBV+ posttransplant lymphoproliferative disorders.

    Science.gov (United States)

    Ouyang, Jing; Juszczynski, Przemyslaw; Rodig, Scott J; Green, Michael R; O'Donnell, Evan; Currie, Treeve; Armant, Myriam; Takeyama, Kunihiko; Monti, Stefano; Rabinovich, Gabriel A; Ritz, Jerome; Kutok, Jeffery L; Shipp, Margaret A

    2011-04-21

    Posttransplant lymphoproliferative disorders (PTLDs) are potentially fatal, EBV-driven B-cell malignancies that develop in immunocompromised solid organ or hematopoietic stem cell recipients. In PTLD, the expression of EBV proteins, including latent membrane protein 1 (LMP1) and LMP2A, viral immune evasion strategies, and impaired host immune surveillance foster the proliferation of EBV-transformed B cells. Current PTLD treatment strategies include reduction of immunosuppression, which increases the risk of graft rejection, anti-CD20 treatment, combination chemotherapy, and administration of EBV-specific cytotoxic T cells. In the present study, we report that EBV-transformed lymphoblastoid B-cell lines (LCLs) and primary PTLDs overexpress galectin-1 (Gal1), a carbohydrate-binding lectin that induces tolerogenic dendritic cells and triggers the selective apoptosis of CD4(+) Th1 and Th17 cells and cytotoxic T cells. In transcriptional reporter assays, LMP2A and LMP1 each increased Gal1-driven luciferase expression, and the combination of LMP2A and LMP1 was additive. In addition, small interfering RNA (siRNA)-mediated depletion of LMP2A decreased Gal1 protein abundance in EBV-transformed LCLs. Gal1 expression in LCLs was dependent on both activating protein 1 (AP-1) and PI3K. A newly developed neutralizing Gal1 mAb selectively inhibited Gal1-mediated apoptosis of EBV-specific CD8(+) T cells. Given the tolerogenic and immunosuppressive function of Gal1, antibody-mediated Gal1 neutralization may represent a novel immunotherapeutic strategy for PTLD and other Gal1-expressing tumors.

  1. Vitamin D in autoimmune liver disease.

    Science.gov (United States)

    Smyk, Daniel S; Orfanidou, Timoklia; Invernizzi, Pietro; Bogdanos, Dimitrios P; Lenzi, Marco

    2013-11-01

    The development of autoimmune disease is based on the interaction of genetic susceptibility and environmental causes. Environmental factors include infectious and non-infectious agents, with some of these factors being implicated in several autoimmune diseases. Vitamin D is now believed to play a role in the development (or prevention) of several autoimmune diseases, based on its immunomodulatory properties. As well, the increasing incidence of autoimmune disease as one moves away from the equator, may be due to the lack of sunlight, which is crucial for the maintenance of normal vitamin D levels. A deficiency in vitamin D levels or vitamin D receptors is commonly indicated in autoimmune diseases, with multiple sclerosis (MS) being one of the best-studied and well-known examples. However, the role of vitamin D in other autoimmune diseases is not well defined, including autoimmune liver diseases such as primary biliary cirrhosis, autoimmune hepatitis, and primary sclerosing cholangitis. This review will examine the role of vitamin D as an immunomodulator, followed by a comparison of vitamin D in MS versus autoimmune liver disease. From this comparison, it will become clear that vitamin D likely plays a role in the development of autoimmune liver disease, but this area requires further investigation. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  2. M. paratuberculosis Heat Shock Protein 65 and Human Diseases: Bridging Infection and Autoimmunity

    Directory of Open Access Journals (Sweden)

    Coad Thomas Dow

    2012-01-01

    Full Text Available Mycobacterium avium subspecies paratuberculosis (MAP is the known infectious cause of Johne’s disease, an enteric inflammatory disease mostly studied in ruminant animals. MAP has also been implicated in the very similar Crohn’s disease of humans as well as sarcoidosis. Recently, MAP has been associated with juvenile sarcoidosis (Blau syndrome, autoimmune diabetes, autoimmune thyroiditis, and multiple sclerosis. While it is intuitive to implicate MAP in granulomatous diseases where the microbe participates in the granuloma, it is more difficult to assign a role for MAP in diseases where autoantibodies are a primary feature. MAP may trigger autoimmune antibodies via its heat shock proteins. Mycobacterial heat shock protein 65 (HSP65 is an immunodominant protein that shares sequential and conformational elements with several human host proteins. This molecular mimicry is the proposed etiopathology by which MAP stimulates autoantibodies associated with autoimmune (type 1 diabetes, autoimmune (Hashimoto’s thyroiditis, and multiple sclerosis. This paper proposes that MAP is a source of mycobacterial HSP65 and acts as a trigger of autoimmune disease.

  3. Does vitamin D play a role in autoimmune endocrine disorders? A proof of concept.

    Science.gov (United States)

    Altieri, Barbara; Muscogiuri, Giovanna; Barrea, Luigi; Mathieu, Chantal; Vallone, Carla V; Mascitelli, Luca; Bizzaro, Giorgia; Altieri, Vincenzo M; Tirabassi, Giacomo; Balercia, Giancarlo; Savastano, Silvia; Bizzaro, Nicola; Ronchi, Cristina L; Colao, Annamaria; Pontecorvi, Alfredo; Della Casa, Silvia

    2017-09-01

    In the last few years, more attention has been given to the "non-calcemic" effect of vitamin D. Several observational studies and meta-analyses demonstrated an association between circulating levels of vitamin D and outcome of many common diseases, including endocrine diseases, chronic diseases, cancer progression, and autoimmune diseases. In particular, cells of the immune system (B cells, T cells, and antigen presenting cells), due to the expression of 1α-hydroxylase (CYP27B1), are able to synthesize the active metabolite of vitamin D, which shows immunomodulatory properties. Moreover, the expression of the vitamin D receptor (VDR) in these cells suggests a local action of vitamin D in the immune response. These findings are supported by the correlation between the polymorphisms of the VDR or the CYP27B1 gene and the pathogenesis of several autoimmune diseases. Currently, the optimal plasma 25-hydroxyvitamin D concentration that is necessary to prevent or treat autoimmune diseases is still under debate. However, experimental studies in humans have suggested beneficial effects of vitamin D supplementation in reducing the severity of disease activity. In this review, we summarize the evidence regarding the role of vitamin D in the pathogenesis of autoimmune endocrine diseases, including type 1 diabetes mellitus, Addison's disease, Hashimoto's thyroiditis, Graves' disease and autoimmune polyendocrine syndromes. Furthermore, we discuss the supplementation with vitamin D to prevent or treat autoimmune diseases.

  4. Psoriasis as an autoimmune disease

    Directory of Open Access Journals (Sweden)

    Agnieszka Owczarczyk-Saczonek

    2014-09-01

    Full Text Available Nowadays it is known that psoriasis belongs to the group of autoimmune diseases and may coexist with other diseases in this group. Most often patients have psoriatic arthritis, rheumatoid arthritis, inflammatory bowel disease, autoimmune thyroid diseases and multiple sclerosis. The coexistence of these disorders can be a diagnostic and therapeutic problem (there is controversy over the use of corticosteroids. The common pathogenesis is still not explained. We know that the loss of immunotolerance leads to formation of autoreactive Th1 and Th17 lymphocytes which recognize self-antigens and lead to their destruction in the target organ. Some features of immune mechanisms, observed in psoriasis, suggest its autoimmune background. In psoriasis the main role is played by the activation of the axis IL-12/Th1/IFN- and Th17/Il-23. Il-12 probably acts on naive T cells and the Th1 response is initiated. Il-23 maintains the Th1-mediated inflammatory reaction, stimulates maturation and effects of Th17, and maintains a certain amount of memory cells. We also observe dysfunction of Treg cells, which are responsible for the destruction of autoreactive lymphocytes. In addition, psoriatic keratinocytes have increased resistance to apoptosis, which eliminate damaged cells so that they cannot be recognized as a foreign antigen. However, researchers have suggested that initially the polyclonal activation of T lymphocytes is induced by superantigens (e.g. streptococcal M protein, peptidoglycan or skin trauma (Koebner phenomenon, whereas in the later phase self-antigens in the epidermis are recognized by autoreactive T cells (keratin K 17, HPV 5 proteins L1, Pso p27, leading to autoimmunity.

  5. Helminth Immunomodulation in Autoimmune Disease

    OpenAIRE

    John J. Miles; John J. Miles; John J. Miles; John J. Miles; Taylor B. Smallwood; Paul R. Giacomin; Alex Loukas; Jason P. Mulvenna; Jason P. Mulvenna; Jason P. Mulvenna; Richard J. Clark

    2017-01-01

    Helminths have evolved to become experts at subverting immune surveillance. Through potent and persistent immune tempering, helminths can remain undetected in human tissues for decades. Redirecting the immunomodulating “talents” of helminths to treat inflammatory human diseases is receiving intensive interest. Here, we review therapies using live parasitic worms, worm secretions, and worm-derived synthetic molecules to treat autoimmune disease. We review helminth therapy in both mouse models ...

  6. Autoimmune diseases and reproductive aging

    OpenAIRE

    Bove, Riley

    2013-01-01

    As the population ages, more individuals with autoimmune diseases are experiencing reproductive senescence. Understanding the impact of menopause and age-related androgen decline on disease onset and course, as well as the potential for hormonal interventions, is critically important. In men, lupus erythematosis (SLE), rheumatoid arthritis (RA), and multiple sclerosis (MS) are associated with lower androgen levels. However, the impact of age-related declines in testosterone, as well as of tes...

  7. Autoimmune Thyroiditis and Myasthenia Gravis

    Directory of Open Access Journals (Sweden)

    Angela Lopomo

    2017-07-01

    Full Text Available Autoimmune diseases (AIDs are the result of specific immune responses directed against structures of the self. In normal conditions, the molecules recognized as “self” are tolerated by immune system, but when the self-tolerance is lost, the immune system could react against molecules from the body, causing the loss of self-tolerance, and subsequently the onset of AID that differs for organ target and etiology. Autoimmune thyroid disease (ATD is caused by the development of autoimmunity against thyroid antigens and comprises Hashimoto’s thyroiditis and Graves disease. They are frequently associated with other organ or non-organ specific AIDs, such as myasthenia gravis (MG. In fact, ATD seems to be the most associated pathology to MG. The etiology of both diseases is multifactorial and it is due to genetic and environmental factors, and each of them has specific characteristics. The two pathologies show many commonalities, such as the organ-specificity with a clear pathogenic effect of antibodies, the pathological mechanisms, such as deregulation of the immune system and the implication of the genetic predisposition. They also show some differences, such as the mode of action of the antibodies and therapies. In this review that focuses on ATD and MG, the common features and the differences between the two diseases are discussed.

  8. Vitamin D and autoimmune diseases

    Directory of Open Access Journals (Sweden)

    E. A. Potrokhova

    2017-01-01

    Full Text Available The review discusses the effect of vitamin D on the tolerogenic modulation of an immune response, its relationship to cells of the monocyte-macrophage series, including dendritic cells, monocytes, and macrophages, in the context of the impact of the expression of anti-inflammatory proinflammatory cytokines in some autoimmune diseases (rheumatoid arthritis, systemic scleroderma, multiple sclerosis, type 1 diabetes mellitus, systemic lupus erythematosus, and Crohn`s disease. It discusses the role of vitamin D in the development of innate and adaptive immunity. Despite some conflicting evidence, the immune regulatory function of vitamin D is generally directed toward inhibition of the components of innate and acquired immunity, which are responsible for the induction of autoimmune reactions; in this connection there are a growing number of publications devoted to the issues of vitamin D supplementation in patients with autoimmune diseases, the preventive effect of vitamin D intake on the risk of an abnormality and that of therapeutic doses of the vitamin on its course. The maintenance of the threshold value for serum 25(OHD3 at least 30 ng/ml, which is achieved by the intake of about 2000 IU of vitamin D, is shown to be required for its immune regulatory function. The data given raise the question as to whether it is necessity to revise the Russian recommended daily dietary allowances for vitamin D through its infant food fortification.

  9. Stochastic Effects in Autoimmune Dynamics

    Directory of Open Access Journals (Sweden)

    Farzad Fatehi

    2018-02-01

    Full Text Available Among various possible causes of autoimmune disease, an important role is played by infections that can result in a breakdown of immune tolerance, primarily through the mechanism of “molecular mimicry”. In this paper we propose and analyse a stochastic model of immune response to a viral infection and subsequent autoimmunity, with account for the populations of T cells with different activation thresholds, regulatory T cells, and cytokines. We show analytically and numerically how stochasticity can result in sustained oscillations around deterministically stable steady states, and we also investigate stochastic dynamics in the regime of bi-stability. These results provide a possible explanation for experimentally observed variations in the progression of autoimmune disease. Computations of the variance of stochastic fluctuations provide practically important insights into how the size of these fluctuations depends on various biological parameters, and this also gives a headway for comparison with experimental data on variation in the observed numbers of T cells and organ cells affected by infection.

  10. Autoimmune Thyroiditis and Myasthenia Gravis

    Science.gov (United States)

    Lopomo, Angela; Berrih-Aknin, Sonia

    2017-01-01

    Autoimmune diseases (AIDs) are the result of specific immune responses directed against structures of the self. In normal conditions, the molecules recognized as “self” are tolerated by immune system, but when the self-tolerance is lost, the immune system could react against molecules from the body, causing the loss of self-tolerance, and subsequently the onset of AID that differs for organ target and etiology. Autoimmune thyroid disease (ATD) is caused by the development of autoimmunity against thyroid antigens and comprises Hashimoto’s thyroiditis and Graves disease. They are frequently associated with other organ or non-organ specific AIDs, such as myasthenia gravis (MG). In fact, ATD seems to be the most associated pathology to MG. The etiology of both diseases is multifactorial and it is due to genetic and environmental factors, and each of them has specific characteristics. The two pathologies show many commonalities, such as the organ-specificity with a clear pathogenic effect of antibodies, the pathological mechanisms, such as deregulation of the immune system and the implication of the genetic predisposition. They also show some differences, such as the mode of action of the antibodies and therapies. In this review that focuses on ATD and MG, the common features and the differences between the two diseases are discussed. PMID:28751878

  11. Human Cytomegalovirus and Autoimmune Disease

    Science.gov (United States)

    2014-01-01

    Human cytomegalovirus (HCMV) represents a prototypic pathogenic member of the β-subgroup of the herpesvirus family. A range of HCMV features like its lytic replication in multiple tissues, the lifelong persistence through periods of latency and intermitting reactivation, the extraordinary large proteome, and extensive manipulation of adaptive and innate immunity make HCMV a high profile candidate for involvement in autoimmune disorders. We surveyed the available literature for reports on HCMV association with onset or exacerbation of autoimmune disease. A causative linkage between HCMV and systemic lupus erythematosus (SLE), systemic sclerosis (SSc), diabetes mellitus type 1, and rheumatoid arthritis (RA) is suggested by the literature. However, a clear association of HCMV seroprevalence and disease could not be established, leaving the question open whether HCMV could play a coresponsible role for onset of disease. For convincing conclusions population-based prospective studies must be performed in the future. Specific immunopathogenic mechanisms by which HCMV could contribute to the course of autoimmune disease have been suggested, for example, molecular mimicry by UL94 in SSc and UL83/pp65 in SLE patients, as well as aggravation of joint inflammation by induction and expansion of CD4+/CD28− T-cells in RA patients. Further studies are needed to validate these findings and to lay the grounds for targeted therapeutic intervention. PMID:24967373

  12. Altered B cell homeostasis and Toll-like receptor 9-driven response in patients affected by autoimmune polyglandular syndrome Type 1: Altered B cell phenotype and dysregulation of the B cell function in APECED patients.

    Science.gov (United States)

    Perri, Valentina; Gianchecchi, Elena; Scarpa, Riccardo; Valenzise, Mariella; Rosado, Maria Manuela; Giorda, Ezio; Crinò, Antonino; Cappa, Marco; Barollo, Susi; Garelli, Silvia; Betterle, Corrado; Fierabracci, Alessandra

    2017-02-01

    APECED is a T-cell mediated disease with increased frequencies of CD8+ effector and reduction of FoxP3+ T regulatory cells. Antibodies against affected organs and neutralizing to cytokines are found in the peripheral blood. The contribution of B cells to multiorgan autoimmunity in Aire-/- mice was reported opening perspectives on the utility of anti-B cell therapy. We aimed to analyse the B cell phenotype of APECED patients compared to age-matched controls. FACS analysis was conducted on PBMC in basal conditions and following CpG stimulation. Total B and switched memory (SM) B cells were reduced while IgM memory were increased in patients. In those having more than 15 years from the first clinical manifestation the defect included also mature and transitional B cells; total memory B cells were increased, while SM were unaffected. In patients with shorter disease duration, total B cells were unaltered while SM and IgM memory behaved as in the total group. A defective B cell proliferation was detected after 4day-stimulation. In conclusion APECED patients show, in addition to a significant alteration of the B cell phenotype, a dysregulation of the B cell function involving peripheral innate immune mechanisms particularly those with longer disease duration. Copyright © 2016 Elsevier GmbH. All rights reserved.

  13. Autoimmune Gastrointestinal Paralysis: Failure of Conventional Treatment without Immunomodulation

    Directory of Open Access Journals (Sweden)

    Craig Weinkauf

    2014-01-01

    Full Text Available The treatment of the rare enteric nervous system (ENS manifestations of paraneoplastic syndromes, which are most frequently associated with small cell lung cancer (SCLC, is poorly understood and described. Patients with neuroendocrine-derived tumors can develop B-cell reactivity towards the tumor with cross-reactivity for neurons located in the submucosal and myenteric ganglia of the ENS. The ensuing autoimmune neuritis causes aperistalsis and severe gastrointestinal (GI dysfunction. Immune-directed therapy is not the standard of care but may be paramount for patient recovery. Our patient, a 63-year-old man with recent symptoms of esophageal dysmotility and newly diagnosed SCLC was hospitalized with nausea, emesis, and constipation. After an extensive work-up that included laparoscopy and celiotomy with bowel resection, we diagnosed what we refer to as Autoimmune Paraneoplastic Chronic Intestinal Pseudoobstruction (AP-CIPO. Unlike the few clinically similar reports, SCLC and AP-CIPO were diagnosed in our patient within weeks of each other, which presented the dilemma of treating the two processes simultaneously. In this report, we review the relevant literature and describe our patient’s course. We believe standard chemotherapy is not effective treatment for AP-CIPO. Based on evidence discussed herein, we suggest initiating autoimmune-directed therapy before or simultaneous with cancer-directed therapy.

  14. The immunobiology of Campylobacter jejuni: Innate immunity and autoimmune diseases.

    Science.gov (United States)

    Phongsisay, Vongsavanh

    2016-04-01

    The Gram-negative bacterium Campylobacter jejuni causes gastroenteritis and Guillain-Barré syndrome in humans. Recent advances in the immunobiology of C. jejuni have been made. This review summarizes C. jejuni-binding innate receptors and highlights the role of innate immunity in autoimmune diseases. This human pathogen produces a variety of glycoconjugates, including human ganglioside-like determinants and multiple activators of Toll-like receptors (TLRs). Furthermore, C. jejuni targets MyD88, NLRP3 inflammasome, TIR-domain-containing adapter-inducing interferon-β (TRIF), sialic acid-binding immunoglobulin-like lectins (Siglecs), macrophage galactose-type lectin (MGL), and immunoglobulin-like receptors (TREM2, LMIR5/CD300b). The roles of these innate receptors and signaling molecules have been extensively studied. MyD88-mediated TLR activation or inflammasome-dependent IL-1β secretion is essential for autoimmune induction. TRIF mediates the production of type I interferons that promote humoral immune responses and immunoglobulin class-switching. Siglec-1 and Siglec-7 interact directly with gangliosides. Siglec-1 activation enhances phagocytosis and inflammatory responses. MGL internalizes GalNAc-containing glycoconjugates. TREM2 is well-known for its role in phagocytosis. LMIR5 recognizes C. jejuni components and endogenous sulfoglycolipids. Several lines of evidence from animal models of autoimmune diseases suggest that simultaneous activation of innate immunity in the presence of autoreactive lymphocytes or antigen mimicry may link C. jejuni to immunopathology. Copyright © 2015 Elsevier GmbH. All rights reserved.

  15. Subcutaneous immunoglobulin in lymphoproliferative disorders and rituximab-related secondary hypogammaglobulinemia: a single-center experience in 61 patients.

    Science.gov (United States)

    Compagno, Nicolò; Cinetto, Francesco; Semenzato, Gianpietro; Agostini, Carlo

    2014-06-01

    Intravenous immunoglobulin replacement therapy represents the standard treatment for hypogammaglobulinemia secondary to B-cell lymphoproliferative disorders. Subcutaneous immunoglobulin infusion is an effective, safe and well-tolerated treatment approach in primary immunodeficiencies but no extensive data are available on their use in secondary hypogammaglobulinemia, a frequent phenomenon occurring after treatment with anti-CD20 monoclonal antibodies in lymphoproliferative disorders. In this retrospective study we evaluated efficacy (serum IgG trough levels, incidence of infections per year, need for antibiotics) and safety (number of adverse events) of intravenous (300 mg/kg/4 weeks) versus subcutaneous (75 mg/kg/week) immunoglobulin replacement therapy in 61 patients. In addition, the impact of the infusion methods on quality of life was compared. All patients were treated with subcutaneous immunoglobulin, and 33 out of them had been previously treated with intravenous immunoglobulin. Both treatments appeared to be effective in replacing Ig production deficiency and in reducing the incidence of infectious events and the need for antibiotics. Subcutaneous immunoglobulin obtained a superior benefit when compared to intravenous immunoglobulin achieving higher IgG trough levels, lower incidence of overall infection and need for antibiotics. The incidence of serious bacterial infections was similar with both infusion ways. As expected, a lower number of adverse events was registered with subcutaneous immunoglobulin, compared to intravenous immunoglobulin, with no serious adverse events. Finally, we observed an improvement in health-related quality of life parameters after the switch to subcutaneous immunoglobulin. Our results suggest that subcutaneous immunoglobulin is safe and effective in patients with hypogammaglobulinemia associated to lymphoproliferative disorders. Copyright© Ferrata Storti Foundation.

  16. Isolated Post-Transplantation Lymphoproliferative Disease Involving the Breast and Axilla as Peripheral T-cell Lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Hwang, Ji-Young [Department of Radiology, Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul 150-950 (Korea, Republic of); Cha, Eun Suk; Lee, Jee Eun [Department of Radiology, Ewha Womans University School of Medicine, Seoul 158-710 (Korea, Republic of); Sung, Sun Hee [Department of Pathology, Ewha Womans University School of Medicine, Seoul 158-710 (Korea, Republic of)

    2013-07-01

    Post-transplantation lymphoproliferative disorders (PTLDs) are a heterogeneous group of diseases that represent serious complications following immunosuppressive therapy for solid organ or hematopoietic-cell recipients. In contrast to B-cell PTLD, T-cell PTLD is less frequent and is not usually associated with Epstein Barr Virus infection. Moreover, to our knowledge, isolated T-cell PTLD involving the breast is extremely rare and this condition has never been reported previously in the literature. Herein, we report a rare case of isolated T-cell PTLD of the breast that occurred after a patient had been treated for allogeneic peripheral blood stem cell transplantation due to acute myeloblastic leukemia.

  17. [A case of lymphoproliferative disorder in the entire small intestine after renal transplantation detected by wireless capsule endoscopy].

    Science.gov (United States)

    Sonoda, Akira; Katsuta, Makoto; Yada, Mika; Mizukami, Kazuhiro; Okamoto, Kazuhisa; Ogawa, Ryo; Okimoto, Tadayoshi; Kodama, Masaaki; Murakami, Kazunari

    2015-04-01

    A 42-year-old woman underwent renal transplantation in 200X. After the transplant, she received tacrolimus as immunosuppressant therapy. Eleven years after the transplant, diffuse large B-cell lymphomas were detected in the duodenum and terminal ileum. Wireless capsule endoscopy (WCE) revealed multiple lymphoma lesions in the entire small intestine. The patient achieved complete response through the administration of R-CHOP therapy and discontinuation of immunosuppressant therapy. Post-transplant lymphoproliferative disorder (PTLD) is a rare complication and WCE may be useful for diagnosing PTLD of the small intestine.

  18. Management of post-transplant lymphoproliferative disorder in adult solid organ transplant recipients - BCSH and BTS Guidelines.

    Science.gov (United States)

    Parker, Anne; Bowles, Kristin; Bradley, J Andrew; Emery, Vincent; Featherstone, Carrie; Gupte, Girish; Marcus, Robert; Parameshwar, Jayan; Ramsay, Alan; Newstead, Charles

    2010-06-01

    A joint working group established by the Haemato-oncology subgroup of the British Committee for Standards in Haematology (BCSH) and the British Transplantation Society (BTS) has reviewed the available literature and made recommendations for the diagnosis and management of post-transplant lymphoproliferative disorder in adult recipients of solid organ transplants. This review details the therapeutic options recommended including reduction in immunosuppression (RIS), transplant organ resection, radiotherapy and chemotherapy. Effective therapy should be instituted before progressive disease results in declining performance status and multi-organ dysfunction. The goal of treatment should be a durable complete remission with retention of transplanted organ function with minimal toxicity.

  19. Associations between specific autoimmune diseases and subsequent dementia: retrospective record-linkage cohort study, UK.

    Science.gov (United States)

    Wotton, Clare J; Goldacre, Michael J

    2017-06-01

    To determine whether hospital admission for autoimmune disease is associated with an elevated risk of future admission for dementia. Retrospective, record-linkage cohort study using national hospital care and mortality administrative data, 1999-2012. Cohorts of people admitted to hospital with a range of autoimmune diseases were constructed, along with a control cohort, and followed forward in time to see if they developed dementia. 1 833 827 people were admitted to hospital with an autoimmune disease; the number of people in cohorts for each autoimmune disease ranged from 1019 people in the Goodpasture's syndrome cohort, to 316 043 people in the rheumatoid arthritis cohort. The rate ratio for dementia after admission for an autoimmune disease, compared with the control cohort, was 1.20 (95% CI 1.19 to 1.21). Where dementia type was specified, the rate ratio was 1.06 (1.04 to 1.08) for Alzheimer's disease and 1.28 (1.26 to 1.31) for vascular dementia. Of 25 autoimmune diseases studied, 18 showed significant positive associations with dementia at pdisease (1.48, 1.34 to 1.64), multiple sclerosis (1.97, 1.88 to 2.07), psoriasis (1.29, 1.25 to 1.34) and systemic lupus erythematosus (1.46, 1.32 to 1.61). The associations with vascular dementia may be one component of a broader association between autoimmune diseases and vascular damage. Though findings were significant, effect sizes were small. Clinicians should be aware of the possible coexistence of autoimmune disease and dementia in individuals. Further studies are needed to confirm or refute our findings and to explore possible mechanisms mediating any elevation of risk. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  20. Autoimmune diseases in adults with atopic dermatitis

    DEFF Research Database (Denmark)

    Andersen, Yuki M F; Egeberg, Alexander; Gislason, Gunnar H.

    2017-01-01

    Background: An increased susceptibility to autoimmune disease has been shown in patients with atopic dermatitis (AD), but data remain scarce and inconsistent. Objective: We examined the co-occurrence of selected autoimmune diseases in adult patients with AD. Methods: Nationwide health registers...... were used. Adult patients with a hospital diagnosis of AD in Denmark between 1997 and 2012 were included as cases (n = 8112) and matched with controls (n = 40,560). The occurrence of autoimmune diseases was compared in the 2 groups. Logistic regression was used to estimate odds ratios. Results: AD...... was significantly associated with 11 of 22 examined autoimmune diseases. In addition, AD was associated with having multiple autoimmune comorbidities. Patients with a history of smoking had a significantly higher occurrence of autoimmune comorbidities compared to nonsmokers. Limitations: This study was limited...

  1. [Pulmonary arterial hypertension: a flavor of autoimmunity].

    Science.gov (United States)

    Perros, Frédéric; Humbert, Marc; Cohen-Kaminsky, Sylvia

    2013-01-01

    It is admitted that autoimmunity results from a combination of risks such as genetic background, environmental triggers, and stochastic events. Pulmonary arterial hypertension (PAH) shares with the so-called prototypic autoimmune diseases, genetic risk factors, female predominance and sex hormone influence, association with other chronic inflammatory and autoimmune diseases, defects in regulatory T cells function, and presence of autoantibodies. Case reports have been published indicating the beneficial effect of some immunosuppressive and anti-inflammatory therapies in PAH, supporting the potential role of immune mechanisms in the pathophysiology of the disease. In this review, we discuss the current knowledge on autoimmune mechanisms operating in PAH, especially mounting a local autoimmune response inside the pulmonary tissue, namely pulmonary lymphoid neogenesis. A better understanding of the role of autoimmunity in pulmonary vascular remodelling may help develop targeted immunomodulatory strategies in PAH. © 2013 médecine/sciences – Inserm.

  2. [Membranous nephropathy associated to autoimmune thyroiditis, chronic pancreatitis and suprarrenal insufficiency].

    Science.gov (United States)

    Merino, J L; Fernández Lucas, M; Teruel, J L; Valer, P; Moreira, V; Arambarri, M; Ortuño, J

    2004-01-01

    A 33 year old female was admitted to the hospital to study aedema and bocio, A nephrotic syndrome was diagnosed and the renal biopsy demonstrated membranous glomerulonephritis, stage II. She was also diagnosed of Hashimoto's autoinmmune thyroiditis: TSH (41.5 uUl/ml), T4 (0.07 ng/dl), antithyroglobuline (1/2560) and antimicrosome (1/6400). Four year latter she was diagnosed of autoinmmune pancreatitis, without evidence of diabetes mellitus or exocrine pancreatic insufficiency. Eight years latter she was diagnosed of primary autoimmune suprarrenal insufficiency: basal cortisol: 2.7 mcg/dl, post ACTH estimulated cortisol: 5.6 mcg/dl, antinuclear antibody (1/160) and antiparietal (1/320). We present a pluriglandular autoimmune syndrome with membranous glomerulonephritis, thyroiditis, pancreatitis and suprarrenal insufficiency. To the best of our knowledge this complex syndrome has not been previously described.

  3. Mucocutaneous candidiasis and autoimmunity against cytokines in APECED and thymoma patients: clinical and pathogenetic implications.

    Science.gov (United States)

    Kisand, Kai; Lilic, Desa; Casanova, Jean-Laurent; Peterson, Pärt; Meager, Anthony; Willcox, Nick

    2011-06-01

    Much has been learnt about the mechanisms of thymic self-tolerance induction from work on both the rare autosomal recessive disease autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) and the autoimmune regulator (AIRE) protein mutated in this disease. Normally, AIRE drives low-level expression of huge numbers of peripheral tissue-specific antigens (TSAgs) in medullary thymic epithelial cells (mTECs), leading to the deletion of TSAg-reactive thymocytes maturing nearby. The very recently discovered neutralizing autoantibodies (autoAbs) against Th17-related cells and cytokines in two autoimmunity-related syndromes associated with AIRE-mutant thymi or AIRE-deficient thymomas help to explain the chronic mucocutaneous candidiasis (CMC) seen in both syndromes. The surprising parallels between these syndromes also demand new hypotheses and research into the consequences of AIRE deficiency and the ensuing autoimmunizing pathways, and suggest more appropriate treatment regimens as discussed in this review. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Effect of chemotherapy on autoimmune hepatitis in thymoma: a case report and literature review

    OpenAIRE

    Mejri, Nesrine; Chabchoub, Imen; Gargouri, Ines; Belaid, Imtinen; Ezairi, Faten; Hmissa, Sihem; Ben Ahmed, Slim

    2013-01-01

    Autoimmune hepatitis (AIH) has rarely been described as an autoimmune paraneoplastic syndrome of thymoma. This case is the seventh case of AIH revealed by cholestasis few years after the diagnosis of thymoma and the first case treated with chemotherapy alone. We report in this paper a new approach to this rare severe condition. A 29 year-old man presented with chest pain and dyspnea with a history of thymoma surgically removed 4 years ago. CT scan showed the recurrence of an anterior mediasti...

  5. Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy from the pediatric perspective.

    Science.gov (United States)

    Capalbo, D; Improda, N; Esposito, A; De Martino, L; Barbieri, F; Betterle, C; Pignata, C; Salerno, M

    2013-11-01

    Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare autosomal recessive disease caused by mutations of the AutoImmune REgulator gene. The clinical spectrum of the disease encompasses several autoimmune endocrine and non-endocrine manifestations, which may lead to acute metabolic alterations and eventually life-threatening events. The clinical diagnosis is defined by the presence of at least two components of the classic triad including chronic mucocoutaneous candidiasis (CMC), chronic hypoparathyroidism (CH), Addison's disease (AD). Other common features of the disease are hypergonadotropic hypogonadism, alopecia, vitiligo, autoimmune hepatitis, Type 1 diabetes, gastrointestinal dysfunction. APECED usually begins in childhood. CMC is the first manifestation to appear, usually before the age of 5 yr, followed by CH and then by AD. The clinical phenotype may evolve over several years and many components of the disease may not appear until the 4th or 5th decade of life. The phenotypical expression of the syndrome shows a wide variability even between siblings with the same genotype. In view of this heterogeneity, an early diagnosis of APECED can be very challenging often leading to a considerable diagnostic delay. Therefore, clinicians should be aware that the presence of even a minor component of APECED in children should prompt a careful investigation for other signs and symptoms of the disease, thus allowing an early diagnosis and prevention of severe and life-threatening events. Aim of this review is to focus on clinical presentation, diagnosis and management of the major components of APECED in children particularly focusing on endocrine features of the disease.

  6. Microbiota and Autoimmunity: exploring new avenues

    OpenAIRE

    Yurkovetskiy, Leonid; Pickard, Joseph M.; Chervonsky, Alexander V.

    2015-01-01

    Given the recognized role of the commensal microbiota in regulating host immunity to pathogens, it is not surprising that microbiota are also capable of regulating autoimmune responses. The underlying mechanisms of autoimmune regulation by the microbiota are just beginning to emerge. Here, we discuss possible pressure points towards the development of autoimmune diseases that can be influenced by the microbiota. Besides acting on the adaptive and innate arms of the immune response, the microb...

  7. Diagnosing autoimmune pancreatitis with the Unifying-Autoimmune-Pancreatitis-Criteria.

    Science.gov (United States)

    Schneider, Alexander; Michaely, Henrik; Rückert, Felix; Weiss, Christel; Ströbel, Philipp; Belle, Sebastian; Hirth, Michael; Wilhelm, Torsten J; Haas, Stephan L; Jesenofsky, Ralf; Schönberg, Stefan; Marx, Alexander; Singer, Manfred V; Ebert, Matthias P; Pfützer, Roland H; Löhr, J Matthias

    We had developed the Unifying-Autoimmune-Pancreatitis-Criteria (U-AIP) to diagnose autoimmune pancreatitis (AiP) within the M-ANNHEIM classification of chronic pancreatitis. In 2011, International-Consensus-Diagnostic-Criteria (ICDC) to diagnose AiP have been published. We had applied the U-AIP long before the ICDC were available. The aims of the study were, first, to describe patients with AiP diagnosed by the U-AIP; second, to compare diagnostic accuracies of the U-AIP and other diagnostic systems; third, to evaluate the clinical applicability of the U-AIP. From 1998 until 2008, we identified patients with AiP using U-AIP, Japanese-, Korean-, Asian-, Mayo-HISORt-, Revised-Mayo-HISORt- and Italian-criteria. We retrospectively verified the diagnosis by ICDC and Revised-Japanese-2011-criteria, compared diagnostic accuracies of all systems and evaluated all criteria in consecutive patients with pancreatitis (2009 until 2010, Pancreas-Outpatient-Clinic-Cohort, n = 84). We retrospectively validated our diagnostic approach in consecutive patients with a pancreatic lesion requiring surgery (Surgical-Cohort, n = 98). Overall, we identified 21 patients with AiP. Unifying-Autoimmune-Pancreatitis-Criteria and ICDC presented the highest diagnostic accuracies (each 98.8%), highest Youden indices (each 0.95238), and highest proportions of diagnosed patients (each n = 20/21, U-AIP/ICDC vs. other diagnostic systems, p Pancreatitis-Criteria revealed a satisfactory clinical applicability and offered an additional approach to diagnose AiP. Copyright © 2017 IAP and EPC. Published by Elsevier B.V. All rights reserved.

  8. Exophthalmos in Cushing's syndrome.

    Science.gov (United States)

    Kelly, W

    1996-08-01

    Exophthalmos was noted in 4 of the 12 patients reported by Harvey Cushing in 1932. Although exophthalmos has often been included in clinical descriptions, no previous study has reported actual measurements in patients with active and treated Cushing's syndrome, and in control patients. The aim of this study was to obtain these measurements. Thirty-one patients with active Cushing's syndrome (19 iatrogenic), 15 with treated Cushing's syndrome, 18 with Graves' ophthalmopathy, 59 control patients, and 3 patients with active Cushing's syndrome plus a family or personal history of thyroid disease. A consecutive series of patients with active and treated Cushing's syndrome were assessed. They were compared with patients with Graves' ophthalmopathy, and with control patients. Exophthalmos was assessed by the author using a Hertel meter. Urinary free cortisol was measured on patients with Cushing's syndrome, and serum thyroxine was estimated for them, and for the patients with Graves' ophthalmopathy. Exophthalmos exceeding 16 mm (> 2 SD above normal mean) was found in 45% of active Cushing's syndrome, 21% of iatrogenic Cushing's syndrome, 20% of treated Cushing's syndrome, 2% of normal controls, and 77% of patients with Graves' ophthalmopathy. No patient with Cushing's syndrome had significant symptoms due to exophthalmos. Patients with active Cushing's syndrome have statistically significant exophthalmos. This rarely causes symptoms, and diminishes when cortisol concentrations become normal. Cushing's syndrome and autoimmune thyroid disease may coexist in patients with exophthalmos.

  9. IL17 Mediates Pelvic Pain in Experimental Autoimmune Prostatitis (EAP.

    Directory of Open Access Journals (Sweden)

    Stephen F Murphy

    Full Text Available Chronic pelvic pain syndrome (CPPS is the most common form of prostatitis, accounting for 90-95% of all diagnoses. It is a complex multi-symptom syndrome with unknown etiology and limited effective treatments. Previous investigations highlight roles for inflammatory mediators in disease progression by correlating levels of cytokines and chemokines with patient reported symptom scores. It is hypothesized that alteration of adaptive immune mechanisms results in autoimmunity and subsequent development of pain. Mouse models of CPPS have been developed to delineate these immune mechanisms driving pain in humans. Using the experimental autoimmune prostatitis (EAP in C57BL/6 mice model of CPPS we examined the role of CD4+T-cell subsets in the development and maintenance of prostate pain, by tactile allodynia behavioral testing and flow cytometry. In tandem with increased CD4+IL17A+ T-cells upon EAP induction, prophylactic treatment with an anti-IL17 antibody one-day prior to EAP induction prevented the onset of pelvic pain. Therapeutic blockade of IL17 did not reverse pain symptoms indicating that IL17 is essential for development but not maintenance of chronic pain in EAP. Furthermore we identified a cytokine, IL7, to be associated with increased symptom severity in CPPS patients and is increased in patient prostatic secretions and the prostates of EAP mice. IL7 is fundamental to development of IL17 producing cells and plays a role in maturation of auto-reactive T-cells, it is also associated with autoimmune disorders including multiple sclerosis and type-1 diabetes. More recently a growing body of research has pointed to IL17's role in development of neuropathic and chronic pain. This report presents novel data on the role of CD4+IL17+ T-cells in development and maintenance of pain in EAP and CPPS.

  10. Clinicopathologic Assessment of Ocular Adnexal Lymphoproliferative Lesions at a Tertiary Eye Hospital in Iran.

    Science.gov (United States)

    Asadi-Amoli, Fahimeh; Nozarian, Zohreh; Bonaki, Hirbod Nasiri; Mehrtash, Vahid; Entezari, Samaneh

    2016-01-01

    The most common type of ocular lymphoma is non-Hodgkin lymphoma (NHL), categorized into two groups: indolent (slow growing) and aggressive (rapid growing). Differentiating benign reactive lymphoid hyperplasia (RLH) from malignant ocular adnexal lymphoma (OAL) is challenging. Histopathology, immunohistochemistry (IHC) and ow cytometry have been used as diagnostic tools in such cases. In this retrospective case series, from 2002 to 2013 at Farabi Eye Center, 110 patients with ocular lymphoproliferative disease were enrolled. Prevalence, anatomical locations, mean age at diagnosis and the nal diagnosis of the disease with IHC were assessed. Comparison between previous pathologic diagnoses and results of IHC was made. Immunoglobulin light chains and B-cell and T-cell markers and other immuno-phenotyping markers including CD20, CD3, CD5, CD23, CD10, CYCLIND1 and BCL2 were evaluated to determine the most accurate diagnosis. The lymphomas were categorized based on revised European-American lymphoma (REAL) classi cation. Mean age±SD (years) of the patients was 55.6 ±19.3 and 61% were male. Patients with follicular lymphoma, large B-cell lymphoma or chronic lymphocytic leukemia/small cell lymphoma (CLL/SLL) tended to be older. Nine patients with previous diagnoses of low grade B-cell lymphoma were re-evaluated by IHC and the new diagnoses were as follows: extranodal marginal zone lymphoma(EMZL) (n=1), SLL(n=1), mantle cell lymphoma (MCL) (n=3), reactive lymphoid hyperplasia RLH (n=2). Two cases were excluded due to poor blocks. Flow cytometry reports in these seven patients revealed SLL with positive CD5 and CD23, MCL with positive CD5 and CyclinD1 and negative CD23, EMZL with negative CD5,CD23 and CD10. One RLH patient was negative for Kappa/Lambda and positive for CD3 and CD20 and the other was positive for all of the light chains, CD3 and CD20. Orbit (49.1%), conjunctiva (16.1%) and lacrimal glands (16.1%) were the most common sites of involvement. Accurate

  11. Incidence of post-transplantation lymphoproliferative disease in Andalusia (1990-2009).

    Science.gov (United States)

    Govantes, M A Gentil; Esteve, A Franco; Ramos, M Toro; Gracia De Guindo, M C; Sánchez, L Fuentes; Blanca, M A Mazuecos; Rodríguez-Benot, A; Blandino, M Vidal; De la Nuez, P Castro; Rodríguez, D Burgos

    2013-01-01

    Post-transplantation lymphoproliferative disease (PTLD) is a severe complication of renal transplantation (RT) but information about its incidence and predisposing factors is diverse, varying according to geographic area and study period. We analyzed the incidence of PTLD after all RT performed at adult transplantation centers in Andalusia from January 1, 1990 to December 31, 2009, recorded in the Andalusian Transplant Co-ordination Information System (SICATA) regional computerized database (n = 5577). We calculated the risk of PTLD using the Kaplan-Meier curve, censoring for organ failure and incidence rate per patient-year of exposure. Log-rank comparisons were made by center (n = 5), decade (1990-1999 vs 2000-2009), age group, recipient gender, hepatitis C virus (HCV) serology, transplantation number, and duration of pre-RT replacement therapy (per quartiles). We identified 60 cases of PTLD. The pre-RT treatment time was 48.2 ± 60 months; 11.7% were retransplantations, and 10.4% had a positive HCV serology. The median post-RT time before diagnosis of PTLD was 5.98 years. At the time of the database analysis, only 11 patients (18%) were alive with a functioning transplant; 10% had returned to dialysis and 72% had died. The actuarial incidence of PTLD at 1, 5, 10, and 20 years post-RT was 0.2%, 0.5%, 1.6%, and 2.9%, respectively; the exposure rate was 14.71 PTLD/10,000 patient-years (95% confidence interval [CI], 12.3-17.1). Although the incidence tended to be higher in 1990-1999 than 2000-2009 (16.8 vs 12.1 cases/10,000 patient-years), in the actuarial study the difference was far from significant (at 7.5 years, 1.2 vs 0.8%; P = .4). Nor were there significant differences in the curves of incidence per RT center (1%-1.2% of patients) or recipient characteristics. The cumulative incidence of PTLD in Andalusia in patients with a functioning kidney transplant during 1990-2009 was 2.9% at 20 years. There was no significant variation between the RT centers or over

  12. Autoimmune atrophic gastritis: current perspectives

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    Minalyan A

    2017-02-01

    Full Text Available Artem Minalyan,1 Jihane N Benhammou,1 Aida Artashesyan,1 Michael S Lewis,2 Joseph R Pisegna1 1Division of Gastroenterology, Hepatology and Parenteral Nutrition, 2Department of Pathology and Laboratory Medicine, VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA Abstract: At present there is no universally accepted classification for gastritis. The first successful classification (The Sydney System that is still commonly used by medical professionals was first introduced by Misiewicz et al in Sydney in 1990. In fact, it was the first detailed classification after the discovery of Helicobacter pylori by Warren and Marshall in 1982. In 1994, the Updated Sydney System was proposed during the International Workshop on the Histopathology of Gastritis followed by the publication in The American Journal of Surgical Pathology by Dixon et al. Using the new classification, distinction between atrophic and nonatrophic gastritis was revised, and the visual scale grading was incorporated. According to the Updated Sydney System Classification, atrophic gastritis is categorized into multifocal (H. pylori, environmental factors, specific diet and corpus-predominant (autoimmune. Since metaplasia is a key histological characteristic in patients with atrophic gastritis, it has been recommended to use the word “metaplastic” in both variants of atrophic gastritis: autoimmune metaplastic atrophic gastritis (AMAG and environmental metaplastic atrophic gastritis. Although there are many overlaps in the course of the disease and distinction between those two entities may be challenging, the aim of this review article was to describe the etiology, epidemiology, pathogenesis, diagnosis, clinical manifestations and treatment in patients with AMAG. However, it is important to mention that H. pylori is the most common etiologic factor for the development of gastritis in the world. Keywords: autoimmune gastritis, pernicious anemia, gastric carcinoid

  13. Immunoglobulin E-Mediated Autoimmunity

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    Marcus Maurer

    2018-04-01

    Full Text Available The study of autoimmunity mediated by immunoglobulin E (IgE autoantibodies, which may be termed autoallergy, is in its infancy. It is now recognized that systemic lupus erythematosus, bullous pemphigoid (BP, and chronic urticaria, both spontaneous and inducible, are most likely to be mediated, at least in part, by IgE autoantibodies. The situation in other conditions, such as autoimmune uveitis, rheumatoid arthritis, hyperthyroid Graves’ disease, autoimmune pancreatitis, and even asthma, is far less clear but evidence for autoallergy is accumulating. To be certain of an autoallergic mechanism, it is necessary to identify both IgE autoantibodies and their targets as has been done with the transmembrane protein BP180 and the intracellular protein BP230 in BP and IL-24 in chronic spontaneous urticaria. Also, IgE-targeted therapies, such as anti-IgE, must have been shown to be of benefit to patients as has been done with both of these conditions. This comprehensive review of the literature on IgE-mediated autoallergy focuses on three related questions. What do we know about the prevalence of IgE autoantibodies and their targets in different diseases? What do we know about the relevance of IgE autoantibodies in different diseases? What do we know about the cellular and molecular effects of IgE autoantibodies? In addition to providing answers to these questions, based on a broad review of the literature, we outline the current gaps of knowledge in our understanding of IgE autoantibodies and describe approaches to address them.

  14. Recent advances in the risk factors, diagnosis and management of Epstein-Barr virus post-transplant lymphoproliferative disease

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    Paibel Aguayo-Hiraldo

    2016-01-01

    Full Text Available Fifty years after the first reports of Epstein-Barr virus (EBV-associated endemic Burkitt's lymphoma, EBV has emerged as the third most prevalent oncogenic virus worldwide. EBV infection is associated with various malignancies including Hodgkin and non-Hodgkin lymphoma, NK/T-cell lymphoma and nasopharyngeal carcinoma. Despite the highly specific immunologic control in the immunocompetent host, EBV can cause severe complications in the immunocompromised host (namely, post-transplant lymphoproliferative disease. This is particularly a problem in patients with delayed immune reconstitution post-hematopoietic stem cell transplant or solid organ transplant. Despite advances in diagnostic techniques and treatment algorithms allowing earlier identification and treatment of patients at highest risk, mortality rates remain as high as 90% if not treated early. The cornerstones of treatment include reduction in immunosuppression and in vivo B cell depletion with an anti-CD20 monoclonal antibody. However, these treatment modalities are not always feasible due to graft rejection, emergence of graft vs. host disease, and toxicity. Newer treatment modalities include the use of adoptive T cell therapy, which has shown promising results in various EBV-related malignancies. In this article we will review recent advances in risk factors, diagnosis and management of EBV-associated malignancies, particularly post-transplant lymphoproliferative disease. We will also discuss new and innovative treatment options including adoptive T cell therapy as well as management of special situations such as chronic active EBV and EBV-associated hemophagocytic lymphohistiocytosis.

  15. Risk factors, diagnosis, and management of posttransplant lymphoproliferative disorder: improving patient outcomes with a multidisciplinary treatment approach

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    Ligeti K

    2017-01-01

    Full Text Available Kinga Ligeti, Lutz P Müller, Carsten Müller-Tidow, Thomas Weber Department of Hematology and Oncology, University Hospital Halle (Saale and Martin-Luther-University Halle-Wittenberg, Halle (Saale, Germany Abstract: Posttransplant lymphoproliferative disease (PTLD is a major complication after solid organ transplantation and allogeneic hematopoietic stem cell transplantation. The spectrum of PTLD ranges from benign hyperplasia to malignant lymphoma, representing one of the most relevant malignancies in these patients. Most PTLDs are driven by latent Epstein–Barr virus infections. The backbone of treatment is reduction of immunosuppression. Further treatment depends on the type of PTLD and the type of transplantation. A multidisciplinary approach involving transplant team, hematologists, and other disciplines is crucial for the diagnosis and treatment of PTLD and for concurrent preservation of the transplant function. In this study, known pathomechanisms, risk factors, preemptive management, and especially emerging treatment algorithms in PTLD were reviewed. Keywords: lymphoproliferative disease, Epstein-Barr virus, management, rituximab, ­preemptive therapy

  16. Epstein-Barr Virus-Negative Post-Transplant Lymphoproliferative Diseases: Three Distinct Cases from a Single Center

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    Şule Mine Bakanay

    2014-03-01

    Full Text Available Three cases of Epstein-Barr virus (EBV-negative post-transplant lymphoproliferative disease that occurred 6 to 8 years after renal transplantation are reported. The patients respectively had gastric mucosa-associated lymphoid tissue lymphoma, gastric diffuse large B-cell lymphoma, and atypical Burkitt lymphoma. Absence of EBV in the tissue samples was demonstrated by both in situ hybridization for EBV early RNA and polymerase chain reaction for EBV DNA. Patients were treated with reduction in immunosuppression and combined chemotherapy plus an anti-CD20 monoclonal antibody, rituximab. Despite the reduction in immunosuppression, patients had stable renal functions without loss of graft functions. The patient with atypical Burkitt lymphoma had an abnormal karyotype, did not respond to treatment completely, and died due to disease progression. The other patients are still alive and in remission 5 and 3 years after diagnosis, respectively. EBV-negative post-transplant lymphoproliferative diseases are usually late-onset and are reported to have poor prognosis. Thus, reduction in immunosuppression is usually not sufficient for treatment and more aggressive approaches like rituximab with combined chemotherapy are required.

  17. Prevention of EBV lymphoma development by oncolytic myxoma virus in a murine xenograft model of post-transplant lymphoproliferative disease

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    Kim, Manbok, E-mail: manbok66@dankook.ac.kr [Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, FL 32610 (United States); Rahman, Masmudur M. [Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, FL 32610 (United States); Cogle, Christopher R. [Department of Hematology/Oncology, University of Florida, Gainesville, FL 32610 (United States); McFadden, Grant [Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, FL 32610 (United States)

    2015-07-10

    Epstein–Barr virus (EBV) has been associated with a variety of epithelial and hematologic malignancies, including B-, T- and NK cell-lymphomas, Hodgkin's disease (HD), post-transplant lymphoproliferative diseases (LPDs), nasopharyngeal and gastric carcinomas, smooth muscle tumors, and HIV-associated lymphomas. Currently, treatment options for EBV-associated malignancies are limited. We have previously shown that myxoma virus specifically targets various human solid tumors and leukemia cells in a variety of animal models, while sparing normal human or murine tissues. Since transplant recipients of bone marrow or solid organs often develop EBV-associated post-transplant LPDs and lymphoma, myxoma virus may be of utility to prevent EBV-associated malignancies in immunocompromised transplant patients where treatment options are frequently limited. In this report, we demonstrate the safety and efficacy of myxoma virus purging as a prophylactic strategy for preventing post-transplant EBV-transformed human lymphomas, using a highly immunosuppressed mouse xenotransplantation model. This provides support for developing myxoma virus as a potential oncolytic therapy for preventing EBV-associated LPDs following transplantation of bone marrow or solid organ allografts. - Highlights: • Myxoma virus effectively infects and purges EBV lymphoma cells in vivo. • Oncolytic myxoma virus effectively eradicates oncogenic EBV tumorigenesis. • Ex vivo pre-treatment of myxoma virus can be effective as a preventive treatment modality for post-transplant lymphoproliferative diseases.

  18. [Cramp-fasciculation syndrome].

    Science.gov (United States)

    Lagueny, A

    2005-12-01

    The cramp-fasciculation syndrome is a rare clinical entity in comparison with the frequency of cramps and isolated fasciculations in the general population. It is recognized as a benign syndrome without weakness and atrophy, however a few reports suggest that it may precede the occurrence of a motor neuron disease. Most often, the cramp-fasciculation syndrome is idiopathic and may be a component of a hyperexcitable peripheral nerve syndrome including other activities such as myokymia and neuromyotonia where antibodies to voltage-gated potassium channels (VGKCs) appear to be one of the effector mechanisms. The most complete form of this hyperexcitable peripheral nerve syndrome is Isaacs' syndrome. The central nervous system is also concerned with anti-VGKC antibodies found in Morvan's disease and limbic encephalitis which is often a paraneoplastic condition. These findings extend the spectrum of the anti-VGKC syndrome that may be associated with other auto-immune diseases, chiefly myasthenia gravis with thymoma. Carbamazepine and phenytoin cause reduction of the clinical and electrophysiological signs of the nerve hyperexcitability, and plasmapheresis and (or) immunosuppressors are useful when an auto-immune origin is considered.

  19. Regulation of an Autoimmune Model for Multiple Sclerosis in Th2-Biased GATA3 Transgenic Mice

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    Viromi Fernando

    2014-01-01

    Full Text Available T helper (Th2 cells have been proposed to play a neuroprotective role in multiple sclerosis (MS. This is mainly based on “loss-of-function” studies in an animal model for MS, experimental autoimmune encephalomyelitis (EAE, using blocking antibodies against Th2 related cytokines, and knockout mice lacking Th2-related molecules. We tested whether an increase of Th2 responses (“gain-of-function” approach could alter EAE, the approach of novel GATA binding protein 3 (GATA3-transgenic (tg mice that overexpress GATA3, a transcription factor required for Th2 differentiation. In EAE induced with myelin oligodendrocyte glycoprotein (MOG35−55 peptide, GATA3-tg mice had a significantly delayed onset of disease and a less severe maximum clinical score, compared with wild-type C57BL/6 mice. Histologically, GATA3-tg mice had decreased levels of meningitis and demyelination in the spinal cord, and anti-inflammatory cytokine profiles immunologically, however both groups developed similar levels of MOG-specific lymphoproliferative responses. During the early stage, we detected higher levels of interleukin (IL-4 and IL-10, with MOG and mitogen stimulation of regional lymph node cells in GATA3-tg mice. During the late stage, only mitogen stimulation induced higher IL-4 and lower interferon-γ and IL-17 production in GATA3-tg mice. These results suggest that a preexisting bias toward a Th2 immune response may reduce the severity of inflammatory demyelinating diseases, including MS.

  20. Helminth Immunomodulation in Autoimmune Disease.

    Science.gov (United States)

    Smallwood, Taylor B; Giacomin, Paul R; Loukas, Alex; Mulvenna, Jason P; Clark, Richard J; Miles, John J

    2017-01-01

    Helminths have evolved to become experts at subverting immune surveillance. Through potent and persistent immune tempering, helminths can remain undetected in human tissues for decades. Redirecting the immunomodulating "talents" of helminths to treat inflammatory human diseases is receiving intensive interest. Here, we review therapies using live parasitic worms, worm secretions, and worm-derived synthetic molecules to treat autoimmune disease. We review helminth therapy in both mouse models and clinical trials and discuss what is known on mechanisms of action. We also highlight current progress in characterizing promising new immunomodulatory molecules found in excretory/secretory products of helminths and their potential use as immunotherapies for acute and chronic inflammatory diseases.