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Sample records for autoimmune disease classification

  1. Autoimmune disease classification by inverse association with SNP alleles.

    Directory of Open Access Journals (Sweden)

    Marina Sirota

    2009-12-01

    Full Text Available With multiple genome-wide association studies (GWAS performed across autoimmune diseases, there is a great opportunity to study the homogeneity of genetic architectures across autoimmune disease. Previous approaches have been limited in the scope of their analysis and have failed to properly incorporate the direction of allele-specific disease associations for SNPs. In this work, we refine the notion of a genetic variation profile for a given disease to capture strength of association with multiple SNPs in an allele-specific fashion. We apply this method to compare genetic variation profiles of six autoimmune diseases: multiple sclerosis (MS, ankylosing spondylitis (AS, autoimmune thyroid disease (ATD, rheumatoid arthritis (RA, Crohn's disease (CD, and type 1 diabetes (T1D, as well as five non-autoimmune diseases. We quantify pair-wise relationships between these diseases and find two broad clusters of autoimmune disease where SNPs that make an individual susceptible to one class of autoimmune disease also protect from diseases in the other autoimmune class. We find that RA and AS form one such class, and MS and ATD another. We identify specific SNPs and genes with opposite risk profiles for these two classes. We furthermore explore individual SNPs that play an important role in defining similarities and differences between disease pairs. We present a novel, systematic, cross-platform approach to identify allele-specific relationships between disease pairs based on genetic variation as well as the individual SNPs which drive the relationships. While recognizing similarities between diseases might lead to identifying novel treatment options, detecting differences between diseases previously thought to be similar may point to key novel disease-specific genes and pathways.

  2. Autoimmune Diseases

    Science.gov (United States)

    ... Some examples of CAM are herbal products, chiropractic , acupuncture , and hypnosis . If you have an autoimmune disease, ... Toll-Free: 877-226-4267 National Institute of Diabetes and Digestive and Kidney Diseases, NIH, HHS Phone: ...

  3. Autoimmune disease

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    2005164 Optimal cut-point of glutamic acid decar-boxylase antibody (GAD-Ab) for differentiating two subtypes of latent autoimmune diabetes in adults (LADA). LI Xia(李霞), et al. Dept Endocrinol, 2nd Xiangya Hosp, Central South Univ, Changsha, 410011. Chin J Diabetes, 2005;13(1) :34-38. Objective: To investigate the optimal cut-point of glutamate decarboxylase antibody (GAD-Ab) for differentiating two subtypes of latent autoimmune diabetes in adults (I. ADA). Methods: The frequency

  4. Autoantibodies in autoimmune liver diseases.

    Science.gov (United States)

    Sener, Asli Gamze

    2015-11-01

    Autoimmune hepatitis is a chronic hepatitis of unknown etiology characterized by clinical, histological, and immunological features, generally including circulating autoantibodies and a high total serum and/or gamma globulin. Liver-related autoantibodies are very significant for the correct diagnosis and classification of autoimmune liver diseases (AILD), namely autoimmune hepatitis types 1 and 2 (AIH-1 and 2), primary biliary cirrhosis (PBC), and the sclerosing cholangitis types in adults and children. This article intends to review recent studies that investigate autoantibodies in autoimmune liver diseases from a microbiological perspective.

  5. 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...

  6. Questions and Answers on Autoimmunity and Autoimmune Diseases

    Science.gov (United States)

    ... dermatomyositis . What are some of the treatments for autoimmune diseases? Of first importance in treating any autoimmune disease ... being researched. What is the family connection in autoimmune diseases? The ability to develop an autoimmune disease is ...

  7. American Autoimmune Related Diseases Association

    Science.gov (United States)

    ... Its 25th Anniversary With #25FOR25 Campaign During National Autoimmune Disease Awareness Month AARDA officially kicks of National Autoimmune ... will benefit AARDA. Click here to read more. Autoimmune Disease Awareness Month AARDA and the NCAPG held two ...

  8. Autoimmune liver diseases

    Institute of Scientific and Technical Information of China (English)

    Pietro Invernizzi; Ian R Mackay

    2008-01-01

    The liver was one of the earliest recognized sites among autoimmune diseases yet autoimmune hepatitis,primary biliary cirrhosis,primary sclerosing cholangitis,and their overlap forms,are still problematic in diagnosis and causation.The contributions herein comprise 'pairs of articles' on clinical characteristics,and concepts of etiopathogenesis,for each of the above diseases,together with childhood autoimmune liver disease,overlaps,interpretations of diagnostic serology,and liver transplantation.This issue is timely,since we are witnessing an ever increasing applicability of immunology to a wide variety of chronic diseases,hepatic and non-hepatic,in both developed and developing countries.The 11 invited expert review articles capture the changing features over recent years of the autoimmune liver diseases,the underlying immunomolecular mechanisms of development,the potent albeit still unexplained genetic influences,the expanding repertoire of immunoserological diagnostic markers,and the increasingly effective therapeutic possibilities.

  9. Sirolimus for Autoimmune Disease of Blood Cells

    Science.gov (United States)

    2016-04-22

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

  10. Autoimmune thyroid disease and other non-endocrine autoimmune diseases

    Directory of Open Access Journals (Sweden)

    Todorović-Đilas Ljiljana

    2011-01-01

    Full Text Available Introduction, 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. Autoimmune 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. Conclusions. 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.

  11. Epigenomics of autoimmune diseases.

    Science.gov (United States)

    Gupta, Bhawna; Hawkins, R David

    2015-03-01

    Autoimmune diseases are complex disorders of largely unknown etiology. Genetic studies have identified a limited number of causal genes from a marginal number of individuals, and demonstrated a high degree of discordance in monozygotic twins. Studies have begun to reveal epigenetic contributions to these diseases, primarily through the study of DNA methylation, but chromatin and non-coding RNA changes are also emerging. Moving forward an integrative analysis of genomic, transcriptomic and epigenomic data, with the latter two coming from specific cell types, will provide an understanding that has been missed from genetics alone. We provide an overview of the current state of the field and vision for deriving the epigenomics of autoimmunity.

  12. [Diagnostics of autoimmune diseases].

    Science.gov (United States)

    Beleznay, Zsuzsanna; Regenass, Stephan

    2008-09-01

    Autoantibodies play a key role in diagnostic laboratories as markers of autoimmune diseases. In addition to their role as markers they mediate diverse effects in vivo. Autoantibodies with protective effect have been described. Natural protective IgM autoantibodies against tumour-antigens of malignant cells or their precursors may contribute to increased survival rates of carcinoma patients. In a mouse model of systemic lupus erythematosus it has been shown that anti-dsDNA IgM autoantibodies protect from glomerular damage. In contrast, a direct pathogenic role of autoantibodies has been well established e.g. in myasthenia gravis or in Goodpasture syndrome. Similarly autoantibodies against SSA Ro52 are detrimental in neonatal lupus erythematosus with congenital heart block. Moreover, putatively protective autoantibodies may become pathogenic during the course of the disease such as the onconeuronal autoantibodies whose pathogenicity depends on their compartmentalisation. In patients with paraneoplastic syndromes tumour cells express proteins that are also naturally present in the brain. Anti-tumour autoantibodies which temporarily suppress tumour growth can provoke an autoimmune attack on neurons once having crossed the blood-brain barrier and cause specific neurological symptoms. Only a restricted number of autoantibodies are useful follow-up markers for the effectiveness of treatment in autoimmune diseases. Certain autoantibodies hold prognostic value and appear years or even decades before the diagnosis of disease such as the antimitochondrial antibodies in primary biliary cirrhosis or anti-citrullinated protein (CCP)-antibodies in rheumatoid arthritis. It is crucial to know whether the autoantibodies in question recognise linear or conformational epitopes in order to choose the appropriate detection methods. Indirect immunofluorescence microscopy remains a very useful tool for confirmation of results of commercially available immunoassays and for detection of

  13. Autoimmune thyroid disease and other non-endocrine autoimmune diseases

    OpenAIRE

    Todorović-Đilas Ljiljana; Ičin Tijana; Novaković-Paro Jovanka; Bajkin Ivana

    2011-01-01

    Introduction, 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...

  14. Infections and autoimmune diseases.

    Science.gov (United States)

    Bach, Jean-François

    2005-01-01

    The high percentage of disease-discordant pairs of monozygotic twins demonstrates the central role of environmental factors in the etiology of autoimmune diseases. Efforts were first focussed on the search for triggering factors. The study of animal models has clearly shown that infections may trigger autoimmune diseases, as in the case of Coxsackie B4 virus in type I diabetes and the encephalomyocarditis virus in autoimmune myositis, two models in which viruses are thought to act by increasing immunogenicity of autoantigens secondary to local inflammation. The induction of a Guillain-Barré syndrome in rabbits after immunization with a peptide derived from Campylobacter jejuni is explained by mimicry between C. jejuni antigens and peripheral nerve axonal antigens. Other models involve chemical modification of autoantigens, as in the case of iodine-induced autoimmune thyroiditis. These mechanisms have so far only limited clinical counterparts (rheumatic fever, Guillain-Barré syndrome and drug-induced lupus or myasthenia gravis) but one may assume that unknown viruses may be at the origin of a number of chronic autoimmune diseases, such as type I diabetes and multiple sclerosis) as illustrated by the convergent data incriminating IFN-alpha in the pathophysiology of type I diabetes and systemic lupus erythematosus. Perhaps the difficulties met in identifying the etiologic viruses are due to the long lag time between the initial causal infection and onset of clinical disease. More surprisingly, infections may also protect from autoimmune diseases. Western countries are being confronted with a disturbing increase in the incidence of most immune disorders, including autoimmune and allergic diseases, inflammatory bowel diseases, and some lymphocyte malignancies. Converging epidemiological evidence indicates that this increase is linked to improvement of the socio-economic level of these countries, posing the question of the causal relationship and more precisely the

  15. Autoimmune Thyroid Diseases in Children

    OpenAIRE

    Francesca Crea; Carla Bizzarri; Marco Cappa

    2011-01-01

    The two major autoimmune thyroid diseases (ATDs) include Graves' disease (GD) and autoimmune thyroiditis (AT); both of which are characterized by infiltration of the thyroid by T and B cells reactive to thyroid antigens, by the production of thyroid autoantibodies and by abnormal thyroid function (hyperthyroidism in GD and hypothyroidism in AT). While the exact etiology of thyroid autoimmunity is not known, it is believed to develop when a combination of genetic susceptibility and environment...

  16. Mast Cell and Autoimmune Diseases

    OpenAIRE

    Yunzhi Xu; Guangjie Chen

    2015-01-01

    Mast cells are important in innate immune system. They have been appreciated as potent contributors to allergic reaction. However, increasing evidence implicates the important role of mast cells in autoimmune disease like rheumatoid arthritis and multiple sclerosis. Here we review the current stage of knowledge about mast cells in autoimmune diseases.

  17. AUTOIMMUNE EPIDERMAL BLISTERING DISEASES

    Directory of Open Access Journals (Sweden)

    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

  18. Autoimmune Inner Ear Disease (AIED)

    Science.gov (United States)

    ... to order. Mention “VEDA” to receive a 15% discount. Paid Advertisement Disclaimer Information on this website is ... treatment of autoimmune inner ear disease. Although drug companies are not directly studying treatments for inner ear ...

  19. Estrogens and autoimmune diseases.

    Science.gov (United States)

    Cutolo, Maurizio; Capellino, Silvia; Sulli, Alberto; Serioli, Bruno; Secchi, Maria Elena; Villaggio, Barbara; Straub, Rainer H

    2006-11-01

    Sex hormones are implicated in the immune response, with estrogens as enhancers at least of the humoral immunity and androgens and progesterone (and glucocorticoids) as natural immune-suppressors . Several physiological, pathological, and therapeutic conditions may change the serum estrogen milieu and/or peripheral conversion rate, including the menstrual cycle, pregnancy, postpartum period, menopause, being elderly, chronic stress, altered circadian rhythms, inflammatory cytokines, and use of corticosteroids, oral contraceptives, and steroid hormonal replacements, inducing altered androgen/estrogen ratios and related effects. In particular, cortisol and melatonin circadian rhythms are altered, at least in rheumatoid arthritis (RA), and partially involve sex hormone circadian synthesis and levels as well. Abnormal regulation of aromatase activity (i.e., increased activity) by inflammatory cytokine production (i.e., TNF-alpha, IL-1, and IL-6) may partially explain the abnormalities of peripheral estrogen synthesis in RA (i.e., increased availability of 17-beta estradiol and possible metabolites in synovial fluids) and in systemic lupus erythematosus, as well as the altered serum sex-hormone levels and ratio (i.e., decreased androgens and DHEAS). In the synovial fluids of RA patients, the increased estrogen concentration is observed in both sexes and is more specifically characterized by the hydroxylated forms, in particular 16alpha-hydroxyestrone, which is a mitogenic and cell proliferative endogenous hormone. Local effects of sex hormones in autoimmune rheumatic diseases seems to consist mainly in modulation of cell proliferation and cytokine production (i.e., TNF-alpha, Il-1, IL-12). In this respect, it is interesting that male patients with RA seem to profit more from anti-TNFalpha strategies than do female patients. PMID:17261796

  20. Therapeutic apheresis in autoimmune diseases

    Directory of Open Access Journals (Sweden)

    Bambauer R

    2013-11-01

    Full Text Available Rolf Bambauer,1 Reinhard Latza,2 Carolin Bambauer,3 Daniel Burgard,4 Ralf Schiel5 1Institute for Blood Purification, Homburg, 2Laboratorium of Medicine, St Ingbert, 3Main Hospital Darmstadt, Darmstadt, 4Herz Zentrum, Cardiology, Völklingen, 5Inselklinik Heringsdorf GmbH, Seeheilbad Heringsdorf, Germany Abstract: Systemic autoimmune diseases based on an immune pathogenesis produce autoantibodies and circulating immune complexes, which cause inflammation in the tissues of various organs. In most cases, these diseases have a bad prognosis without treatment. Therapeutic apheresis in combination with immunosuppressive therapies has led to a steady increase in survival rates over the last 35 years. Here we provide an overview of the most important pathogenic aspects indicating that therapeutic apheresis can be a supportive therapy in some systemic autoimmune diseases, such as systemic lupus erythematosus, antiphospholipid syndrome, rheumatoid arthritis, and inflammatory eye disease. With the introduction of novel and effective biologic agents, therapeutic apheresis is indicated only in severe cases, such as in rapid progression despite immunosuppressive therapy and/or biologic agents, and in patients with renal involvement, acute generalized vasculitis, thrombocytopenia, leucopenia, pulmonary, cardiac, or cerebral involvement. In mild forms of autoimmune disease, treatment with immunosuppressive therapies and/or biologic agents seems to be sufficient. The prognosis of autoimmune diseases with varying organ manifestations has improved considerably in recent years, due in part to very aggressive therapy schemes. Keywords: therapeutic apheresis, autoimmune diseases, systemic lupus erythematosus, antiphospholipid syndrome, rheumatoid arthritis, inflammatory eye disease

  1. Common mechanisms of autoimmune diseases (the autoimmune tautology).

    Science.gov (United States)

    Anaya, Juan-Manuel

    2012-09-01

    The fact that autoimmune diseases share subphenotypes, physiopathological mechanisms and genetic factors has been called autoimmune tautology, and indicates that they have a common origin. The autoimmune phenotypes vary depending on the target cell and the affected organ, gender, ancestry, trigger factors and age at onset. Ten shared characteristics supporting this logical theory are herein reviewed.

  2. Psoriasis and autoimmune skin diseases

    Directory of Open Access Journals (Sweden)

    Poljački Mirjana N.

    2002-01-01

    Full Text Available Introduction Presuming that psoriasis is an autoimmune skin disease, the aim of this study was to establish its association with other autoimmune skin diseases. The material was obtained at the Dermatovenereological Clinic Clinical Center Novi Sad. Material and methods This 10-year retrospective study (1990-1999 included 1743 psoriasis patients. The control group consisted of 7492 nonpsoriatic dermatological patients. Results Association of psoriasis with other dermatological diseases of autoimmune nature has been established in 13 (0.74 % patients. The most frequent association was with lichen ruber planus in five patients, with alopecia areata and vitiligo in three patients, and in one with bullous pemphigoid and herpetiform dermatitis. Using Fisher's test no significant association was established. Discussion and conclusion According to literature data association of psoriasis with other autoimmune diseases is well known, but rare, which is in accordance with our results. The question arises whether this association is the matter of poor coexistence or the matter of genetic mutations. However, once established, these associations can further highlight the autoimmune nature of psoriasis. The research of autoimmunity would lead us to epithelial cells in thymus, and their badly learnt cognitive function about what is own, and what is not.

  3. Epilepsy as an Autoimmune Disease

    OpenAIRE

    J Gordon Millichap; John J Millichap

    2014-01-01

    Investigators at University of New South Wales, Sydney, Australia, and Boston Children's Hospital, Harvard Medical School, conducted a retrospective population-level study of the relationship between epilepsy and 12 common autoimmune diseases: type 1 diabetes mellitus, psoriasis, rheumatoid arthritis, Graves disease, Hashimoto thyroiditis, Crohn disease, ulcerative colitis, systemic lupus erythematosus, antiphospholipid syndrome, Sjogren syndrome, myasthenia gravis, and celiac ...

  4. Autoimmune paediatric liver disease

    Institute of Scientific and Technical Information of China (English)

    Giorgina Mieli-Vergani; Diego Vergani

    2008-01-01

    Liver disorders with a likely autoimmune pathogenesis in childhood include autoimmune hepatitis (AIH), autoimmune sclerosing cholangitis (ASC),and de novo AIH after liver transplantation.AIH is divided into two subtypes according to seropositivity for smooth muscle and/or antinuclear antibody (SMA/ANA,type 1) or liver kidney microsomal antibody (LKM1,type 2).There is a female predominance in both.LKM1 positive patients tend to present more acutely,at a younger age,and commonly have partial IgA deficiency,while duration of symptoms before diagnosis,clinical signs,family history of autoimmunity, presence of associated autoimmune disorders,response to treatment,and long-term prognosis are similar in both groups. The most common type of paediatric sclerosing cholangitis is ASC.The clinical,biochemical, immunological,and histological presentation of ASC is often indistinguishable from that of AIH type 1.In both,there are high IgG,non-organ specific autoantibodies,and interface hepatitis.Diagnosis is made by cholangiography.Children with ASC respond to immunosuppression satisfactorily and similarly to AIH in respect to remission and relapse rates,times to normalization of biochemical parameters, and decreased inflammatory activity on follow up liver biopsies. However,the cholangiopathy can progress.There may be evolution from AIH to ASC over the years,despite treatment.De novo AIH after liver transplantation affects patients not transplanted for autoimmune disorders and is strikingly reminiscent of classical AIH,including elevated titres of serum antibodies, hypergammaglobulinaemia,and histological findings of interface hepatitis,bridging fibrosis,and collapse.Like classical AIH,it responds to treatment with prednisolone and azathioprine.De novo AIH post liver transplantation may derive from interference by calcineurin inhibitors with the intrathymic physiological mechanisms of T-cell maturation and selection.Whether this condition is a distinct entity or a form of

  5. [Infectious agents and autoimmune diseases].

    Science.gov (United States)

    Riebeling-Navarro, C; Madrid-Marina, V; Camarena-Medellín, B E; Peralta-Zaragoza, O; Barrera, R

    1992-01-01

    In this paper the molecular aspects of the relationships between infectious agents and autoimmune diseases, the mechanisms of immune response to infectious agents, and the more recent hypotheses regarding the cause of autoimmune diseases are discussed. The antigens are processed and selected by their immunogenicity, and presented by HLA molecules to the T cell receptor. These events initiate the immune response with the activation and proliferation of T-lymphocytes. Although there are several hypotheses regarding the cause of autoimmune diseases and too many findings against and in favor of them, there is still no conclusive data. All these hypothesis and findings are discussed in the context of the more recent advances. PMID:1615352

  6. Therapeutic apheresis in autoimmune diseases

    Science.gov (United States)

    Bambauer, Rolf; Latza, Reinhard; Bambauer, Carolin; Burgard, Daniel; Schiel, Ralf

    2013-01-01

    Systemic autoimmune diseases based on an immune pathogenesis produce autoantibodies and circulating immune complexes, which cause inflammation in the tissues of various organs. In most cases, these diseases have a bad prognosis without treatment. Therapeutic apheresis in combination with immunosuppressive therapies has led to a steady increase in survival rates over the last 35 years. Here we provide an overview of the most important pathogenic aspects indicating that therapeutic apheresis can be a supportive therapy in some systemic autoimmune diseases, such as systemic lupus erythematosus, antiphospholipid syndrome, rheumatoid arthritis, and inflammatory eye disease. With the introduction of novel and effective biologic agents, therapeutic apheresis is indicated only in severe cases, such as in rapid progression despite immunosuppressive therapy and/or biologic agents, and in patients with renal involvement, acute generalized vasculitis, thrombocytopenia, leucopenia, pulmonary, cardiac, or cerebral involvement. In mild forms of autoimmune disease, treatment with immunosuppressive therapies and/or biologic agents seems to be sufficient. The prognosis of autoimmune diseases with varying organ manifestations has improved considerably in recent years, due in part to very aggressive therapy schemes.

  7. American Autoimmune Related Diseases Association

    Science.gov (United States)

    ... to navigate the health-care system in the age of the Affordable Care Act. News in the world of AARDA’s Grassroots ... was the “Status of Autoimmune Disease in the Age of the Affordable Care Act. Watch the briefing video View the power ...

  8. Coeliac disease with autoimmune haemolytic anaemia.

    OpenAIRE

    Miller, D. G.

    1984-01-01

    Two patients are described who have developed autoimmune haemolytic anaemia in association with their coeliac disease. Autoimmune haemolytic anaemia may represent an extension of immunological disorders linked with coeliac disease, centred on the histocompatibility antigen B8.

  9. 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

  10. Autoimmune Skin Diseases in the Dog

    OpenAIRE

    Parker, W M

    1981-01-01

    Diagnoses of autoimmune skin diseases require very careful observation of the skin lesions, and selection of an intact vesicle for histopathological examination. If available, immunofluorescent studies can be very useful in confirming the diagnosis of autoimmune skin disease. Seven autoimmune skin diseases are briefly reviewed. Therapy must be aggressive and owner warned of the guarded prognosis.

  11. An autosomal locus causing autoimmune disease: Autoimmune polyglandular disease type I assigned to chromosome 21

    OpenAIRE

    Aaltonen, Johanna; Björses, Petra; Sandkuijl, Lodewijk; Perheentupa, Jaakko; 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 not show association to specific HLA haplotypes. Unravelling the APECED locus will identify a novel gene outside the HLA loci influencing the outcome of autoimmune diseases. We have assigned the di...

  12. Diagnosis and classification of autoimmune optic neuropathy.

    Science.gov (United States)

    Petzold, Axel; Plant, Gordon T

    2014-01-01

    The spectrum of autoimmune optic neuropathies (ON) is extending. The phenotypic spectrum includes single isolated optic neuritis (SION), relapsing isolated optic neuritis (RION), chronic relapsing inflammatory optic neuropathy (CRION), the neuromyelitis optica (NMO) spectrum disorder, multiple sclerosis associated optic neuritis (MSON) and unclassified optic neuritis (UCON) forms. Epidemiological data suggests a slight female predominance. The ethnic heritage is relevant as Caucasian patients are more likely to suffer from MSON, whilst SION, RION, CRION and NMO are more frequent in non-Caucasian patients. Importantly, prognosis for recovery of visual function is good in MSON, but poorer in NMO and CRION which also have a high chance for recurrent episodes. Testing for serum anti-AQP4 autoantibodies is advised in all patients with severe, atypical or recurrent ON because of the high diagnostic specificity. The diagnostic specificity may be aided by testing for glial biomarkers in the CSF and prognostic accuracy by testing for biomarkers for neuroaxonal degeneration. Optical coherence tomography is a highly accurate tool to document the final outcome. The current clinical classification criteria rely on the phenotype, response to treatment and presence of anti-AQP4 autoantibodies.

  13. Refractory disease in autoimmune diseases

    NARCIS (Netherlands)

    Vasconcelos, Carlos; Kallenberg, Cees; Shoenfeld, Yehuda

    2011-01-01

    Refractory disease (RD) definition has different meanings but it is dynamic, according to knowledge and the availability of new drugs. It should be differentiated from severe disease and damage definitions and it must take into account duration of adequate therapy and compliance of the patient. It c

  14. Propylthiouracil-induced autoimmune disease

    Directory of Open Access Journals (Sweden)

    Santosh Paiaulla

    2015-01-01

    Full Text Available Hyperthyroidism is a condition characterized by excessive production of thyroid hormones. Propylthiouracil (PTU is commonly used as first line drug in the management of hyperthyroidism. This is a case report of 24-year-old female, a known case of hyperthyroidism since 4 years, who came with a history of fever and myalgia since 3 days and dyspnea with coughing out of blood since 1 day. Patient was taking PTU (100 mg per day since 4 years for hyperthyroidism. Patient was immediately intubated for type-II respiratory failure. Diagnosed to be having PTU-induced autoimmune disease. PTU was stopped and treated with methylprednisolone and cyclophosphamide. Clinical features improved over a period of 8 days and discharged home successfully. Having a high suspicion for the onset of autoimmune disease in hyperthyroidism patients who are on PTU therapy and timely treatment with immunosuppressants and supportive care along with the withdrawal of the drug can make a difference in morbidity and mortality.

  15. Undifferentiated CTD: a wide spectrum of autoimmune diseases.

    Science.gov (United States)

    Mosca, Marta; Tani, Chiara; Carli, Linda; Bombardieri, Stefano

    2012-02-01

    The existence of systemic autoimmune diseases not fulfilling classification criteria for defined connective tissue diseases (CTDs) is a common clinical experience. These conditions have been variably defined as incomplete lupus erythematosus, early undifferentiated connective tissue diseases and undifferentiated connective tissue diseases (UCTDs). However, the definition of UCTD includes a wide spectrum of diseases ranging from 'organ-dominant' conditions (e.g., idhiopatic non-specific interstitial pneumonia) to simplified conditions (stable UCTD), to early CTDs or mild forms of CTDs. In the present article, the literature data on undifferentiated diseases and their clinical spectrum as well as the importance of the definition of new classificative criteria are discussed. PMID:22424194

  16. Rett syndrome: An autoimmune disease?

    Science.gov (United States)

    De Felice, Claudio; Leoncini, Silvia; Signorini, Cinzia; Cortelazzo, Alessio; Rovero, Paolo; Durand, Thierry; Ciccoli, Lucia; Papini, Anna Maria; Hayek, Joussef

    2016-04-01

    Rett syndrome (RTT) is a devastating neurodevelopmental disease, previously included into the autistic spectrum disorders, affecting almost exclusively females (frequency 1:10,000). RTT leads to intellective deficit, purposeful hands use loss and late major motor impairment besides featuring breathing disorders, epilepsy and increased risk of sudden death. The condition is caused in up to 95% of the cases by mutations in the X-linked methyl-CpG binding protein 2 (MECP2) gene. Our group has shown a number of previously unrecognized features, such as systemic redox imbalance, chronic inflammatory status, respiratory bronchiolitis-associated interstitial lung disease-like lung disease, and erythrocyte morphology changes. While evidence on an intimate involvement of MeCP2 in the immune response is cumulating, we have recently shown a cytokine dysregulation in RTT. Increasing evidence on the relationship between MeCP2 and an immune dysfunction is reported, with, apparently, a link between MECP2 gene polymorphisms and autoimmune diseases, including primary Sjögren's syndrome, systemic lupus erythematosus, rheumatoid arthritis, and systemic sclerosis. Antineuronal (i.e., brain proteins) antibodies have been shown in RTT. Recently, high levels of anti-N-glucosylation (N-Glc) IgM serum autoantibodies [i.e., anti-CSF114(N-Glc) IgMs] have been detected by our group in a statistically significant number of RTT patients. In the current review, the Authors explore the current evidence, either in favor or against, the presence of an autoimmune component in RTT. PMID:26807990

  17. Pathogenesis of Autoimmune Diseases: A Short Review

    Directory of Open Access Journals (Sweden)

    Jithin Jose

    2014-01-01

    Full Text Available Autoimmunity is characterized by the reaction of cells (auto reactive T-lymphocytes or products (autoantibodies of the immune system against the organism’s own antigens (autoantigen. It may be part of the physiological immune response (natural autoimmunity or pathologically induced, which may eventually lead to development of clinical abnormalities (autoimmune disease. Different mechanisms are involved in the induction and progression of autoimmunity. These include genetic or acquired defects in immune tolerance or immune regulatory pathways, molecular mimicry to viral or bacterial protein, an impaired clearance of apoptotic cell material. A A number of diseases have been identified in which there is autoimmunity, due to copious production of autoantibodies and autoreactive cells. The aim of the present article is to review on the pathogenesis of autoimmune diseases.

  18. Parkinson's disease: Autoimmunity and neuroinflammation.

    Science.gov (United States)

    De Virgilio, Armando; Greco, Antonio; Fabbrini, Giovanni; Inghilleri, Maurizio; Rizzo, Maria Ida; Gallo, Andrea; Conte, Michela; Rosato, Chiara; Ciniglio Appiani, Mario; de Vincentiis, Marco

    2016-10-01

    Parkinson's disease is a neurodegenerative disease that causes the death of dopaminergic neurons in the substantia nigra. The resulting dopamine deficiency in the basal ganglia leads to a movement disorder that is characterized by classical parkinsonian motor symptoms. Parkinson's disease is recognized as the most common neurodegenerative disorder after Alzheimer's disease. PD ethiopathogenesis remains to be elucidated and has been connected to genetic, environmental and immunologic conditions. The past decade has provided evidence for a significant role of the immune system in PD pathogenesis, either through inflammation or an autoimmune response. Several autoantibodies directed at antigens associated with PD pathogenesis have been identified in PD patients. This immune activation may be the cause of, rather than a response to, the observed neuronal loss. Parkinsonian motor symptoms include bradykinesia, muscular rigidity and resting tremor. The non-motor features include olfactory dysfunction, cognitive impairment, psychiatric symptoms and autonomic dysfunction. Microscopically, the specific degeneration of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies, which are brain deposits containing a substantial amount of α-synuclein, have been recognized. The progression of Parkinson's disease is characterized by a worsening of motor features; however, as the disease progresses, there is an emergence of complications related to long-term symptomatic treatment. The available therapies for Parkinson's disease only treat the symptoms of the disease. A major goal of Parkinson's disease research is the development of disease-modifying drugs that slow or stop the neurodegenerative process. Drugs that enhance the intracerebral dopamine concentrations or stimulate dopamine receptors remain the mainstay treatment for motor symptoms. Immunomodulatory therapeutic strategies aiming to attenuate PD neurodegeneration have become an attractive option and

  19. Pulmonary hypertension in autoimmune rheumatic diseases

    OpenAIRE

    L. Massironi; R. Cossutta; Massarotti, M.; Marasini, B; A. Mantero

    2011-01-01

    Objective. Pulmonary hypertension is a severe and rapidly progressive disease, particularly frequent in patients with rheumatic diseases. The aims of this study were the following: to determine the prevalence of pulmonary hypertension in Italian patients with autoimmune rheumatic diseases, and to evaluate if the presence of a rheumatic disease in general, or of a specific autoimmune rheumatic disease, is a risk factor for the development of pulmonary hypertension. Patients and Methods. One hu...

  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 Turner's syndrome is characterized by diseases with a female or male predominance. METHODS: Using the Danish Cytogenetic Central Register, the Danish National Patient Register, and the Danish Civil Registration System, we estimated relative risk of 46 different autoimmune diseases in a cohort of 798...... Danish women with Turner's syndrome followed up for 12,461 person-years between 1980 and 2004. Standardized incidence ratios (SIRs) of first hospitalization for autoimmune disease and 95% confidence intervals (95% CIs) were used as measures of relative risk. RESULTS: The overall risk of autoimmune...

  1. Autoimmune diseases associated with neurofibromatosis type 1.

    Science.gov (United States)

    Nanda, Arti

    2008-01-01

    Associations of autoimmune diseases with neurofibromatosis type 1 have been rarely described. In the present report, we describe two patients of neurofibromatosis type 1 having an association with vitiligo in one, and alopecia areata and autoimmune thyroiditis in another. The associations of neurofibromatosis type 1 with vitiligo, alopecia areata, and autoimmune thyroiditis have not been reported earlier. Whether these associations reflect a causal relationship with neurofibromatosis type 1 or are coincidental needs to be settled.

  2. Recurrence of autoimmune liver diseases after livertransplantation

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Liver transplantation (LT) is the most effective treatmentmodality for end stage liver disease caused by manyetiologies including autoimmune processes. That said,the need for transplantation for autoimmune hepatitis(AIH) and primary biliary cirrhosis (PBC), but not forprimary sclerosing cholangitis (PSC), has decreasedover the years due to the availability of effective medicaltreatment. Autoimmune liver diseases have superiortransplant outcomes than those of other etiologies. WhileAIH and PBC can recur after LT, recurrence is of limitedclinical significance in most, but not all cases. RecurrentPSC, however, often progresses over years to a stagerequiring re-transplantation. The exact incidence andthe predisposing factors of disease recurrence remaindebated. Better understanding of the pathogenesis andthe risk factors of recurrent autoimmune liver diseasesis required to develop preventive measures. In thisreview, we discuss the current knowledge of incidence,diagnosis, risk factors, clinical course, and treatmentof recurrent autoimmune liver disease (AIH, PBC, PSC)following LT.

  3. Transplantation in autoimmune liver diseases

    Institute of Scientific and Technical Information of China (English)

    Marcus Mottershead; James Neuberger

    2008-01-01

    Liver transplantation remains an effective treatment for those with end-stage disease and with intractable liver-related symptoms.The shortage of organs for transplantation has resulted in the need for rationing.A variety of approaches to selection and allocation have been developed and vary from country to country.The shortage of donors has meant that new approaches have to be adopted to make maximal use of the available organs;these include splitting grafts,use of extended criteria livers,livers from nonheart-beating donors and from living donors.Post transplantation, most patients will need life-long immunosuppression,although a small proportion can have immunosuppression successfully withdrawn.Newer immunosuppressive drugs and different strategies may allow a more targeted approach with a reduction in sideeffects and so improve the patient and graft survival.For autoimmune diseases, transplantation is associated with significant improvement in the quality and length of life.Disease may recur after transplantation and may affect patient and graft survival.

  4. Large leg ulcers due to autoimmune diseases

    OpenAIRE

    Rozin, Alexander P; Egozi, Dana; Ramon, Yehuda; Toledano, Kohava; Braun-Moscovici, Yolanda; Markovits, Doron; Schapira, Daniel; Bergman, Reuven; Melamed, Yehuda; Ullman, Yehuda; Balbir-Gurman, Alexandra

    2011-01-01

    Summary Background Large leg ulcers (LLU) may complicate autoimmune diseases. They pose a therapeutic challenge and are often resistant to treatment. To report three cases of autoimmune diseases complicated with LLU. Case Report Case 1. A 55-year old woman presented with long-standing painful LLU due to mixed connective tissue disease (MCTD). Biopsy from the ulcer edge showed small vessel vasculitis. IV methylprednisolone (MethP) 1 G/day, prednisolone (PR) 1mg/kg, monthly IV cyclophosphamide ...

  5. Coeliac disease and autoimmune disease-genetic overlap and screening

    NARCIS (Netherlands)

    Lundin, Knut E. A.; Wijmenga, Cisca

    2015-01-01

    Coeliac disease is a treatable, gluten-induced disease that often occurs concurrently with other autoimmune diseases. In genetic studies since 2007, a partial genetic overlap between these diseases has been revealed and further insights into the pathophysiology of coeliac disease and autoimmunity ha

  6. Environmental factors affecting autoimmune thyroid disease

    Energy Technology Data Exchange (ETDEWEB)

    Safran, M.; Paul, T.L.; Roti, E.; Braverman, L.E.

    1987-06-01

    A number of environmental factors affect the incidence and progression of autoimmune thyroid disease. Exposure to excess iodine, certain drugs, infectious agents and pollutants, and stress have all been implicated.

  7. Epidemiology of autoimmune diseases in Denmark

    DEFF Research Database (Denmark)

    Eaton, William W.; Rose, N.R.; Kalaydijan, A.;

    2007-01-01

    An epidemiologic study of the autoimmune diseases taken together has not been done heretofore. The National Patient Register of Denmark is used to estimate the population prevalence of 31 possible or probable autoimmune diseases. Record linkage is used to estimate 465 pairwise co-morbidities in...... diseases and weak across diseases. These data confirm the importance of the autoimmune diseases as a group and suggest that common etiopathologies exist among them...... individuals among the 31 diseases, and familial aggregation among sibs, parents and offspring. The prevalence of any of the 31 diseases in the population is more than 5%. Within individuals, there is extensive comorbidity across the 31 diseases. Within families, aggregation is strongest for individual...

  8. [Autoimmune connective tissue diseases and vaccination].

    Science.gov (United States)

    Więsik-Szewczyk, Ewa; Jahnz-Różyk, Karina

    2015-12-31

    The idea that infectious agents can induce autoimmune diseases in genetically susceptible subjects has been a matter of discussion for years. Moreover, increased incidence of autoimmune diseases and introduction of prophylactic vaccinations from early childhood suggest that these two trends are linked. In the medical literature and even non-professional media, case reports or events temporally related to vaccination are reported. It raises the issue of vaccination safety. In everyday practice medical professionals, physicians, rheumatologists and other specialists will be asked their opinion of vaccination safety. The decision should be made according to evidence-based medicine and the current state of knowledge. The purpose of this paper is to discuss a potential mechanism which links infections, vaccinations and autoimmunity. We present an overview of published case reports, especially of systemic connective tissue diseases temporally related to vaccination and results from case-nested studies. As yet, no conclusive evidence supports a causal relationship between vaccination and autoimmune diseases. It has to be determined whether the performed studies are sufficiently sensitive to detect the link. The debate is ongoing, and new data may be required to explain the pathogenesis of autoimmunity. We would like to underscore the need for prophylactic vaccination in patients with autoimmune rheumatic diseases and to break down the myth that the vaccines are contraindicated in this target group.

  9. The Emerging Link Between Autoimmune Disorders and Neuropsychiatric Disease

    OpenAIRE

    Kayser, Matthew S; Dalmau, Josep

    2011-01-01

    Abnormal autoimmune activity has been implicated in a number of neuropsychiatric disorders. In this review, the authors discuss a newly recognized class of synaptic autoimmune encephalitides as well as behavioral and cognitive manifestations of systemic autoimmune diseases.

  10. Acute recurrent pancreatitis: An autoimmune disease?

    Institute of Scientific and Technical Information of China (English)

    Raffaele Pezzilli

    2008-01-01

    In this review article,we will briefly describe the main characteristics of autoimmune pancreatitis and then we will concentrate on our aim,namely,evaluating the clinical characteristics of patients having recurrence of pain from the disease.In fact,the open question is to evaluate the possible presence of autoimmune pancreatitis in patients with an undefined etiology of acute pancreatitis and for this reason we carried out a search in the literature in order to explore this issue.In cases of recurrent attacks of pain in patients with "idiopathic"pancreatitis,we need to keep in mind the possibility that our patients may have autoimmune pancreatitis.Even though the frequency of this disease seems to be quite low,we believe that in the future,by increasing our knowledge on the subject,we will be able to diagnose an ever-increasing number of patients having acute recurrence of pain from autoimmune pancreatitis.

  11. Autism and Autoimmune Disease: A Family Study

    Science.gov (United States)

    Money, John; And Others

    1971-01-01

    Described in a family in which the youngest boy has early infantile autism, Addison's disease, and moniliasis and two older boys have autoimmune disease with hypoparathyroidism, Addison's disease, moniliasis, and either alopecia totalis or diabetes mellitus, while the oldest boy and parents are symptom free. (KW)

  12. Autoimmune Inner Ear Disease- A Clinical Viewpoint

    Directory of Open Access Journals (Sweden)

    Amirala Khalessi

    2010-10-01

    Full Text Available Recent developments in medicine have given us a better insight into a group of disorders known as autoimmune diseases. In particular, advances have occurred in our understanding of the Autoimmune Inner Ear Disease (AIED. In this article, the authors review the different postulated theories in the pathogenesis of this disease. The clinical presentation, the available para-clinical diagnostic tools, and the important differential diagnoses will be summarized. The management methods, including steroid therapy, immunosuppressive medications, other biological agents and intra-tympanic injections, will be addressed. Cochlear implantation as a final solution to the advanced stages of the disease, causing total deafness, will also be discussed.

  13. Worldwide Incidence of Autoimmune Liver Disease

    DEFF Research Database (Denmark)

    Jepsen, Peter; Grønbæk, Lisbet; Vilstrup, Hendrik

    2015-01-01

    BACKGROUND: The variation that occurs in the incidence patterns of autoimmune liver diseases may provide insight into the risk factors causing the diseases. We systematically reviewed studies on the incidence of autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), primary sclerosing...... England. Most studies of PSC found incidence rates around 1 per 100,000 population per year, but there were no incident cases among 100,000 Alaska natives during the period 1984-2000. The incidence of IAC remains unknown. CONCLUSIONS: The incidence of the autoimmune liver diseases is around 1-2 per 100......,000 population per year for each disease. The variation in incidence over time and place suggests that there are differences in the prevalence of risk factors for the diseases, but the studies used different methods and so it is difficult to draw firm conclusions. We recommend that groups of investigators...

  14. Alcoholic Cirrhosis Increases Risk for Autoimmune Diseases

    DEFF Research Database (Denmark)

    Grønbæk, Lisbet; Vilstrup, Hendrik; Deleuran, Bent;

    2015-01-01

    BACKGROUND & AIMS: Alcoholic cirrhosis is associated with hyperactivation and dysregulation of the immune system. In addition to its ability to increase risk for infections, it also may increase the risk for autoimmune diseases. We studied the incidence of autoimmune diseases among patients...... with alcohol-associated cirrhosis vs controls in Denmark. METHODS: We collected data from nationwide health care registries to identify and follow up all citizens of Denmark diagnosed with alcoholic cirrhosis from 1977 through 2010. Each patient was matched with 5 random individuals from the population...... diagnosed with alcoholic cirrhosis, 532 developed an autoimmune disease, yielding an overall increased adjusted incidence rate ratio (aIRR) of 1.36 (95% confidence interval [CI], 1.24-1.50). The strongest associations were with Addison's disease (aIRR, 2.47; 95% CI, 1.04-5.85), inflammatory bowel disease (a...

  15. NK cell autoreactivity and autoimmune diseases

    Directory of Open Access Journals (Sweden)

    Alessandro ePoggi

    2014-02-01

    Full Text Available Increasing evidences have pointed out the relevance of Natural Killer (NK cells in organ specific and systemic autoimmune diseases. NK cells bear a plethora of activating and inhibiting receptors that can play a role in regulating reactivity with autologous cells. The activating receptors recognize natural ligands upregulated on virus-infected or stressed or neoplastic cells. Of note, several autoimmune diseases are thought to be linked to viral infections as one of the first event in inducing autoimmunity. Also, it is conceivable that autoimmunity can be triggered when a dysregulation of innate immunity occurs, activating T and B lymphocytes to react with self-components. This would imply that NK cells can play a regulatory role during adaptive immunity; indeed, innate lymphoid cells (ILC, comprising the classical CD56+ NK cells, have a role in maintaining or alterating tissue homeostasis secreting protective and/or proinflammatory cytokines. In addition, NK cells display activating receptors involved in natural cytotoxicity and the activating isoforms of receptors for HLA class I that can interact with healthy host cells and induce damage without any evidence of viral infection or neoplastic-induced alteration. In this context, the interrelationship among ILC, extracellular matrix components and mesenchymal stromal cells can be considered a key point for the control of homeostasis. Herein, we summarize evidences for a role of NK cells in autoimmune diseases and will give a point of view of the interplay between NK cells and self-cells in triggering autoimmunity.

  16. Cardiovascular disease in autoimmune rheumatic diseases.

    Science.gov (United States)

    Hollan, Ivana; Meroni, Pier Luigi; Ahearn, Joseph M; Cohen Tervaert, J W; Curran, Sam; Goodyear, Carl S; Hestad, Knut A; Kahaleh, Bashar; Riggio, Marcello; Shields, Kelly; Wasko, Mary C

    2013-08-01

    Various autoimmune rheumatic diseases (ARDs), including rheumatoid arthritis, spondyloarthritis, vasculitis and systemic lupus erythematosus, are associated with premature atherosclerosis. However, premature atherosclerosis has not been uniformly observed in systemic sclerosis. Furthermore, although experimental models of atherosclerosis support the role of antiphospholipid antibodies in atherosclerosis, there is no clear evidence of premature atherosclerosis in antiphospholipid syndrome (APA). Ischemic events in APA are more likely to be caused by pro-thrombotic state than by enhanced atherosclerosis. Cardiovascular disease (CVD) in ARDs is caused by traditional and non-traditional risk factors. Besides other factors, inflammation and immunologic abnormalities, the quantity and quality of lipoproteins, hypertension, insulin resistance/hyperglycemia, obesity and underweight, presence of platelets bearing complement protein C4d, reduced number and function of endothelial progenitor cells, apoptosis of endothelial cells, epigenetic mechanisms, renal disease, periodontal disease, depression, hyperuricemia, hypothyroidism, sleep apnea and vitamin D deficiency may contribute to the premature CVD. Although most research has focused on systemic inflammation, vascular inflammation may play a crucial role in the premature CVD in ARDs. It may be involved in the development and destabilization of both atherosclerotic lesions and of aortic aneurysms (a known complication of ARDs). Inflammation in subintimal vascular and perivascular layers appears to frequently occur in CVD, with a higher frequency in ARD than in non-ARD patients. It is possible that this inflammation is caused by infections and/or autoimmunity, which might have consequences for treatment. Importantly, drugs targeting immunologic factors participating in the subintimal inflammation (e.g., T- and B-cells) might have a protective effect on CVD. Interestingly, vasa vasorum and cardiovascular adipose tissue may

  17. Bullous Skin Diseases: Classical Types of Autoimmune Diseases

    Directory of Open Access Journals (Sweden)

    Jan Damoiseaux

    2013-01-01

    Full Text Available The prototypic bullous skin diseases, pemphigus vulgaris, pemphigus foliaceus, and bullous pemphigoid, are characterized by the blister formation in the skin and/or oral mucosa in combination with circulating and deposited autoantibodies reactive with (hemidesmosomes. Koch’s postulates, adapted for autoimmune diseases, were applied on these skin diseases. It appears that all adapted Koch’s postulates are fulfilled, and, therefore, these bullous skin diseases are to be considered classical autoimmune diseases within the wide and expanding spectrum of autoimmune diseases.

  18. Shared genetic origins of allergy and autoimmune diseases

    DEFF Research Database (Denmark)

    Waage, J. E.; Kreiner-Møller, E.; Standl, M.;

    2015-01-01

    Parallel increases in allergy and autoimmune disease prevalence in recent time suggest shared, but yet unknown, etiologies. Here, we investigated shared genetic loci and molecular pathways to identify possible shared disease mechanisms between allergy and autoimmune diseases....

  19. Autoimmune thyroid disease and chronic urticaria.

    Science.gov (United States)

    Monge, Cecilia; Demarco, Paul; Burman, Kenneth D; Wartofsky, Leonard

    2007-09-01

    We report six cases of autoimmune thyroid disease associated with chronic urticaria and briefly review the literature, including the histopathological nature of such lesions, and their aetiology and pathogenesis. In view of the prevalence of thyroid disease in patients with chronic urticaria, screening measurements of thyrotropin and anti-thyroperoxidase antibodies are recommended, although negative antibodies do not exclude a relationship between urticaria and thyroid autoimmunity. After failure of conventional therapy for urticaria, patients who are apparently clinically euthyroid may be considered for a trial with levothyroxine. Improvement of urticaria was seen with levothyroxine treatment in three of four patients with only marginal abnormalities in thyroid function.

  20. Macrophage activation syndrome in autoimmune disease.

    Science.gov (United States)

    Deane, Sean; Selmi, Carlo; Teuber, Suzanne S; Gershwin, M Eric

    2010-01-01

    Macrophage activation syndrome (MAS) is a phenomenon characterized by cytopenia, organ dysfunction, and coagulopathy associated with an inappropriate activation of macrophages. Current diagnostic criteria are imprecise, but the syndrome is now recognized as a form of hemophagocytic lymphohistiocytosis that is characteristically associated with autoimmune diatheses. The diagnosis of incipient MAS in patients with autoimmune disease requires a high index of suspicion, as several characteristics of the disorder may be present in the underlying condition or infectious complications associated with the treatment thereof. Proposed treatment regimens include aggressive approaches that require validation in future controlled studies. This review discusses the major aspects of the pathophysiology, diagnosis, and management of MAS with a focus on the association with autoimmune disease. PMID:20407267

  1. Genomics and proteomics: Applications in autoimmune diseases

    Directory of Open Access Journals (Sweden)

    Wolfgang Hueber

    2009-08-01

    Full Text Available Wolfgang Hueber1,2,3, William H Robinson1,21VA Palo Alto Health Care System, Palo Alto, CA, USA; 2Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, CA, USA; 3Novartis Institutes of Biomedical Research, Novartis, Basle, SwitzerlandAbstract: Tremendous progress has been made over the past decade in the development and refinement of genomic and proteomic technologies for the identification of novel drug targets and molecular signatures associated with clinically important disease states, disease subsets, or differential responses to therapies. The rapid progress in high-throughput technologies has been preceded and paralleled by the elucidation of cytokine networks, followed by the stepwise clinical development of pathway-specific biological therapies that revolutionized the treatment of autoimmune diseases. Together, these advances provide opportunities for a long-anticipated personalized medicine approach to the treatment of autoimmune disease. The ever-increasing numbers of novel, innovative therapies will need to be harnessed wisely to achieve optimal long-term outcomes in as many patients as possible while complying with the demands of health authorities and health care providers for evidence-based, economically sound prescription of these expensive drugs. Genomic and proteomic profiling of patients with autoimmune diseases holds great promise in two major clinical areas: (1 rapid identification of new targets for the development of innovative therapies and (2 identification of patients who will experience optimal benefit and minimal risk from a specific (targeted therapy. In this review, we attempt to capture important recent developments in the application of genomic and proteomic technologies to translational research by discussing informative examples covering a diversity of autoimmune diseases.Keywords: proteomics, genomics, autoimmune diseases, antigen microarrays, 2-Dih, rheumatoid arthritis

  2. Capillaroscopy in diagnostic of systemic autoimmune diseases

    International Nuclear Information System (INIS)

    The diagnosis of systemic autoimmune diseases is carried out by combining clinical, paraclinical, imaging and anatomopathological data. However, in many cases is necessary to access other guiding parameters. The capillaroscopy is a technique that consists in the observation of capillary microcirculation in the proximal nail fold hands. The methods used are the videocapillaroscopy (microscopy, stereoscopic)

  3. The complement system in systemic autoimmune disease

    NARCIS (Netherlands)

    Chen, Min; Daha, Mohamed R.; Kallenberg, Cees G. M.

    2010-01-01

    Complement is part of the innate immune system. Its major function is recognition and elimination of pathogens via direct killing and/or stimulation of phagocytosis. Activation of the complement system is, however, also involved in the pathogenesis of the systemic autoimmune diseases. Activation via

  4. Tips for Getting a Proper Diagnosis of an Autoimmune Disease

    Science.gov (United States)

    Tips for Getting a Proper Diagnosis of an Autoimmune Disease Do your own family medical history. Take an ... research points to a genetic component in most autoimmune diseases, you should know the health histories of your ...

  5. MicroRNAs in autoimmune rheumatic diseases

    Directory of Open Access Journals (Sweden)

    G.D. Sebastiani

    2012-03-01

    Full Text Available The etiology of autoimmune diseases remains largely unknown. In recent years, besides genetic factors, several studies proposed that the epigenome may hold the key to a better understanding of autoimmunity initiation and perpetuation. More specifically epigenetic regulatory mechanisms comprise DNA methylation, a variety of histone modifications, and microRNA (miRNA activity, all of which act upon gene and protein expression levels. In particular it is well known that epigenetic mechanisms are important for controlling the pattern of gene expression during development, the cell cycle, and the response to biological or environmental changes. In the present review a description of the most frequent epigenetic deregulations, in particular the role of miRNA, in rheumatic autoimmune disorders will be analyzed.

  6. Gene expression profiling in autoimmune diseases

    DEFF Research Database (Denmark)

    Bovin, Lone Frier; Brynskov, Jørn; Hegedüs, Laszlo;

    2007-01-01

    A central issue in autoimmune disease is whether the underlying inflammation is a repeated stereotypical process or whether disease specific gene expression is involved. To shed light on this, we analysed whether genes previously found to be differentially regulated in rheumatoid arthritis (RA...... differences in peripheral blood mononuclear cell (MNC) gene expression patterns between 15 newly diagnosed HT patients and 15 matched healthy controls. However, the MNC expression levels of five genes were significantly upregulated in 25 IBD patients, compared to 18 matched healthy controls (CD14, FACL2, FCN1...... immunoinflammatory diseases, but only if accompanied by pronounced systemic manifestations. This suggests that at least some of the genes activated in RA are predominantly or solely related to general and disease-nonspecific autoimmune processes...

  7. Rituximab for autoimmune blistering diseases: recent studies, new insights

    OpenAIRE

    Lunardon, Luisa; Payne, Aimee S.

    2012-01-01

    Rituximab, an anti-CD20 monoclonal antibody, has been successfully used off-label for treatment of autoimmune blistering diseases. We discuss rituximab mechanisms of action, host factors that may affect response to rituximab, and the efficacy and safety of rituximab in autoimmune blistering diseases, incorporating recent data on the use of rituximab in other autoimmune disease patients.

  8. Imaging combined autoimmune and infectious disease microarrays

    Science.gov (United States)

    Ewart, Tom; Raha, Sandeep; Kus, Dorothy; Tarnopolsky, Mark

    2006-09-01

    Bacterial and viral pathogens are implicated in many severe autoimmune diseases, acting through such mechanisms as molecular mimicry, and superantigen activation of T-cells. For example, Helicobacter pylori, well known cause of stomach ulcers and cancers, is also identified in ischaemic heart disease (mimicry of heat shock protein 65), autoimmune pancreatitis, systemic sclerosis, autoimmune thyroiditis (HLA DRB1*0301 allele susceptibility), and Crohn's disease. Successful antibiotic eradication of H.pylori often accompanies their remission. Yet current diagnostic devices, and test-limiting cost containment, impede recognition of the linkage, delaying both diagnosis and therapeutic intervention until the chronic debilitating stage. We designed a 15 minute low cost 39 antigen microarray assay, combining autoimmune, viral and bacterial antigens1. This enables point-of-care serodiagnosis and cost-effective narrowly targeted concurrent antibiotic and monoclonal anti-T-cell and anti-cytokine immunotherapy. Arrays of 26 pathogen and 13 autoimmune antigens with IgG and IgM dilution series were printed in triplicate on epoxysilane covalent binding slides with Teflon well masks. Sera diluted 1:20 were incubated 10 minutes, washed off, anti-IgG-Cy3 (green) and anti-IgM-Dy647 (red) were incubated for 5 minutes, washed off and the slide was read in an ArrayWoRx(e) scanning CCD imager (Applied Precision, Issaquah, WA). As a preliminary model for the combined infectious disease-autoimmune diagnostic microarray we surveyed 98 unidentified, outdated sera that were discarded after Hepatitis B antibody testing. In these, significant IgG or IgM autoantibody levels were found: dsDNA 5, ssDNA 11, Ro 2, RNP 7, SSB 4, gliadin 2, thyroglobulin 13 cases. Since control sera showed no autoantibodies, the high frequency of anti-DNA and anti-thyroglobulin antibodies found in infected sera lend increased support for linkage of infection to subsequent autoimmune disease. Expansion of the antigen

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

    Science.gov (United States)

    Zhao, Zhiyuan; Zou, Jing; Zhao, Lingling; Cheng, Yan; Cai, Hanqing; Li, Mo; Liu, Edwin; Yu, Liping; Liu, Yu

    2016-01-01

    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%; pdiseases 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. PMID:27427767

  10. Oral Tolerance: Therapeutic Implications for Autoimmune Diseases

    Directory of Open Access Journals (Sweden)

    Ana M. C. Faria

    2006-01-01

    Full Text Available Oral tolerance is classically defined as the suppression of immune responses to antigens (Ag that have been administered previously by the oral route. Multiple mechanisms of tolerance are induced by oral Ag. Low doses favor active suppression, whereas higher doses favor clonal anergy/deletion. Oral Ag induces Th2 (IL-4/IL-10 and Th3 (TGF-β regulatory T cells (Tregs plus CD4+CD25+ regulatory cells and LAP+T cells. Induction of oral tolerance is enhanced by IL-4, IL-10, anti-IL-12, TGF-β, cholera toxin B subunit (CTB, Flt-3 ligand, anti-CD40 ligand and continuous feeding of Ag. In addition to oral tolerance, nasal tolerance has also been shown to be effective in suppressing inflammatory conditions with the advantage of a lower dose requirement. Oral and nasal tolerance suppress several animal models of autoimmune diseases including experimental allergic encephalomyelitis (EAE, uveitis, thyroiditis, myasthenia, arthritis and diabetes in the nonobese diabetic (NOD mouse, plus non-autoimmune diseases such as asthma, atherosclerosis, colitis and stroke. Oral tolerance has been tested in human autoimmune diseases including MS, arthritis, uveitis and diabetes and in allergy, contact sensitivity to DNCB, nickel allergy. Positive results have been observed in phase II trials and new trials for arthritis, MS and diabetes are underway. Mucosal tolerance is an attractive approach for treatment of autoimmune and inflammatory diseases because of lack of toxicity, ease of administration over time and Ag-specific mechanism of action. The successful application of oral tolerance for the treatment of human diseases will depend on dose, developing immune markers to assess immunologic effects, route (nasal versus oral, formulation, mucosal adjuvants, combination therapy and early therapy.

  11. [Vaccinations in patients with autoimmune diseases].

    Science.gov (United States)

    Bühler, Silja; Hatz, Christoph

    2016-01-01

    The number of individuals with autoimmune diseases treated with immunosuppressive drugs is increasing steadily. The variety of immunosuppressive drugs and in particular biological therapies is also rising. The autoimmune disease itself as well as the immunosuppressive therapy increases the risk of infection in this population. Particularly the risk of vaccine-preventable infections is elevated. Thus, preventing infections by the means of vaccination is of utmost importance. The Division of Infectious Diseases of the Epidemiology, Biostatistics and Prevention Institute, University of Zurich, performed a literature search on the topic of vaccinations in patients with autoimmune diseases upon request by the Swiss Federal Commission for Vaccination Issues. Overall, data are scarce. The following main points were retrieved from the literature: Inactivated vaccines are safe, but their immunogenicity may be reduced under immunosuppressive therapy. In addition to the generally recommended basic vaccinations, specific vaccinations, such as influenza and pneumococcal vaccination are indicated in these patient groups. Live vaccines are generally contraindicated under immunosuppressive therapy due to safety concerns. However, specific exceptions apply. Furthermore, certain time intervals for the administration of live vaccines after pausing or ceasing an immunosuppressive therapy should be respected. PMID:27268452

  12. Experimental models of autoimmune inflammatory ocular diseases

    Directory of Open Access Journals (Sweden)

    Fabio Gasparin

    2012-04-01

    Full Text Available Ocular inflammation is one of the leading causes of blindness and loss of vision. Human uveitis is a complex and heterogeneous group of diseases characterized by inflammation of intraocular tissues. The eye may be the only organ involved, or uveitis may be part of a systemic disease. A significant number of cases are of unknown etiology and are labeled idiopathic. Animal models have been developed to the study of the physiopathogenesis of autoimmune uveitis due to the difficulty in obtaining human eye inflamed tissues for experiments. Most of those models are induced by injection of specific photoreceptors proteins (e.g., S-antigen, interphotoreceptor retinoid-binding protein, rhodopsin, recoverin, phosducin. Non-retinal antigens, including melanin-associated proteins and myelin basic protein, are also good inducers of uveitis in animals. Understanding the basic mechanisms and pathogenesis of autoimmune ocular diseases are essential for the development of new treatment approaches and therapeutic agents. The present review describes the main experimental models of autoimmune ocular inflammatory diseases.

  13. Cirrhosis and autoimmune liver disease: Current understanding

    Science.gov (United States)

    Liberal, Rodrigo; Grant, Charlotte R

    2016-01-01

    Primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH) constitute the classic autoimmune liver diseases (AILDs). While AIH target the hepatocytes, in PBC and PSC the targets of the autoimmune attack are the biliary epithelial cells. Persistent liver injury, associated with chronic AILD, leads to un-resolving inflammation, cell proliferation and the deposition of extracellular matrix proteins by hepatic stellate cells and portal myofibroblasts. Liver cirrhosis, and the resultant loss of normal liver function, inevitably ensues. Patients with cirrhosis have higher risks or morbidity and mortality, and that in the decompensated phase, complications of portal hypertension and/or liver dysfunction lead to rapid deterioration. Accurate diagnosis and monitoring of cirrhosis is, therefore of upmost importance. Liver biopsy is currently the gold standard technique, but highly promising non-invasive methodology is under development. Liver transplantation (LT) is an effective therapeutic option for the management of end-stage liver disease secondary to AIH, PBC and PSC. LT is indicated for AILD patients who have progressed to end-stage chronic liver disease or developed intractable symptoms or hepatic malignancy; in addition, LT may also be indicated for patients presenting with acute liver disease due to AIH who do not respond to steroids. PMID:27729952

  14. Autoimmune disease and epigenome regulation.

    Science.gov (United States)

    Fujio, Keishi

    2016-01-01

      Epigenetic modifications play a central role in the cellular programming of gene expression. Two of the most characterized epigenetic modifications are DNA methylation and histone modification. Recent observation that a number of GWAS SNP for immunological diseases localize to immune enhancers suggests the importance of epigenetic modifications that control enhancer activity. Epigenome-wide analysis of DNA-methylation in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) revealed differential DNA methylation in a number of disease-related gene pathways. With regard to histone mark, the requirement of millions of cells for established protocol prevents application to clinical samples. However, recent technical advances enable us to capture open chromatin in small amount of patient samples. As epigenetic modifications function as an integrator of environmental stimulation and the underlying genetic variant, detailed epigenetic analysis combined with genetic and environmental factors may facilitate the understanding of the progression of human immunological diseases. PMID:27181231

  15. 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

  16. Clinical implications of shared genetics and pathogenesis in autoimmune diseases

    NARCIS (Netherlands)

    Zhernakova, Alexandra; Withoff, Sebo; Wijmenga, Cisca

    2013-01-01

    Many endocrine diseases, including type 1 diabetes mellitus, Graves disease, Addison disease and Hashimoto disease, originate as an autoimmune reaction that affects disease-specific target organs. These autoimmune diseases are characterized by the development of specific autoantibodies and by the pr

  17. Antigenic Challenge in the Etiology of Autoimmune Disease in Women

    OpenAIRE

    Mary A M Rogers; Levine, Deborah A.; Blumberg, Neil; Fisher, Gwenith G.; Kabeto, Mohammed; Kenneth M. Langa

    2011-01-01

    Infection has long been implicated as a trigger for autoimmune disease. Other antigenic challenges include receipt of allogeneic tissue or blood resulting in immunomodulation. We investigated antigenic challenges as possible risk factors for autoimmune disease in women using the Health and Retirement Study, a nationally representative longitudinal study, linked to Medicare files, years 1991–2007. The prevalence of autoimmune disease (rheumatoid arthritis, Hashimoto’s disease, Graves’ disease,...

  18. Autoimmune diseases and fungal infections: immunological mechanisms and therapeutic approaches

    Institute of Scientific and Technical Information of China (English)

    ZHANG Jian-zhong

    2009-01-01

    @@ Autoimmune disease represents a breakdown of natural tolerance to autoreactive antigens.Pemphigus and lupus erythematosus are common autoimmune diseases either skin-specific or with predominant skin involvement. During the past decades,much progress has been made in understanding the mechanism of autoimmune diseases and the immunological mechanism in some infectious diseases such as fungal infections. Various novel approaches have been developed in the treatment of these diseases.

  19. Narcolepsy as an autoimmune disease

    DEFF Research Database (Denmark)

    Partinen, Markku; Kornum, Birgitte Rahbek; Plazzi, Giuseppe;

    2014-01-01

    of as an immune-mediated disease. Other risk genes, such as T-cell-receptor α chain and purinergic receptor subtype 2Y11, are also implicated. Interest in narcolepsy has increased since the epidemiological observations that H1N1 infection and vaccination are potential triggering factors, and an increase...... in the incidence of narcolepsy after the pandemic AS03 adjuvanted H1N1 vaccination in 2010 from Sweden and Finland supports the immune-mediated pathogenesis. Epidemiological observations from studies in China also suggest a role for H1N1 virus infections as a trigger for narcolepsy. Although the pathological...... mechanisms are unknown, an H1N1 virus-derived antigen might be the trigger....

  20. Overlap syndromes among autoimmune liver diseases

    Institute of Scientific and Technical Information of China (English)

    Christian Rust; Ulrich Beuers

    2008-01-01

    The three major immune disorders of the liver are autoimmune hepatitis (AIH),primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC).Variant forms of these diseases are generally called overlap syndromes,although there has been no standardised definition.Patients with overlap syndromes present with both hepatitic and cholestatic serum liver tests and have histological features of AIH and PBC or PSC.The AIH-PBC overlap syndrome is the most common form,affecting almost 10% of adults with AIH or PBC.Single cases of AIH and autoimmune cholangitis (AMA-negative PBC) overlap syndrome have also been reported.The AIH-PSC overlap syndrome is predominantly found in children,adolescents and young adults with AIH or PSC.Interestingly,transitions from one autoimmune to another have also been reported in a minority of patients,especially transitions from PBC to AIH-PBC overlap syndrome.Overlap syndromes show a progressive course towards liver cirrhosis and liver failure without treatment.Therapy for overlap syndromes is empiric,since controlled trials are not available in these rare disorders.Anticholestatic therapy with ursodeoxycholic acid is usually combined with immunosuppressive therapy with corticosteroids and/or azathioprine in both AIH-PBC and AIH-PSC overlap syndromes.In end-stage disease,liver transplantation is the treatment of choice.

  1. Stem cell therapy for severe autoimmune diseases

    Directory of Open Access Journals (Sweden)

    Marmont Alberto M.

    2002-01-01

    Full Text Available Intense immunosuppresion followed by alogenic or autogenic hematopoietic stem cell transplantation is a relatively recent procedure which was used for the first time in severe, refractory cases of systemic lupus erythematosus. Currently three agressive procedures are used in the treatment of autoimmune diseases: high dose chemotherapy without stem cell rescue, intense immunosuppression with subsequent infusion of the alogenic hematopoietic stem cell transplantation combined with or without the selection of CD34+ cells, and the autogenic hematopoietic stem cell transplantation. Proof of the graft-versus-leukemia effect observed define SCT as a form of immunotherapy, with additional evidence of an similar Graft-vs-Autoimmunity effect which is suggestive of a cure for autoimmune diseases in this type of therapy. The use of alogenic SCT improved due to its safety compared to autogenic transplantations. In this report, data of multiply sclerosis and systemic lupus erythematosus are reported, with the conclusion that Immunoablation followed by SCT is clearly indicated in such cases.

  2. Genetics of autoimmune diseases: a multistep process.

    OpenAIRE

    Johannesson, Martina; Hultqvist, Malin; Holmdahl, Rikard

    2006-01-01

    It has so far been difficult to identify genes behind polygenic autoimmune diseases such as rheumatoid arthritis (RA), multiple sclerosis (MS), and type I diabetes (T1D). With proper animal models, some of the complexity behind these diseases can be reduced. The use of linkage analysis and positional cloning of genes in animal models for RA resulted in the identification of one of the genes regulating severity of arthritis in rats and mice, the Ncf1 gene. The Ncf1 gene encodes for the Ncf1 pr...

  3. Coeliac disease in endocrine diseases of autoimmune origin.

    Science.gov (United States)

    Miśkiewicz, Piotr; Kępczyńska-Nyk, Anna; Bednarczuk, Tomasz

    2012-01-01

    Abstract Coeliac disease (CD, sometimes called gluten-sensitive enteropathy or nontropical sprue) is an inflammatory disorder of the small intestine of autoimmune origin. It occurs in genetically predisposed people and is induced by a gluten protein, which is a component of wheat. The prevalence of histologically confirmed CD is estimated in screening studies of adults in the United States and Europe to be between 0.2% and 1.0%. The results of previous studies have indicated that the prevalence of CD is increased in patients with other autoimmune disorders such as: autoimmune thyroid diseases, type 1 diabetes mellitus, and Addison's disease. A coincidence of the above diseases constitutes autoimmune polyglandular syndrome (APS). The high prevalence of CD in APS is probably due to the common genetic predisposition to the coexistent autoimmune diseases. The majority of adult patients have the atypical or silent type of the disease. This is the main reason why CD so often goes undiagnosed or the diagnosis is delayed. CD, if undiagnosed and untreated, is associated with many medical disorders including haematological (anaemia), metabolical (osteopenia/osteoporosis), obstetric-gynaecological (infertility, spontaneous abortions, late puberty, early menopause), neurological (migraine, ataxia, epilepsy) as well as with an increased risk of malignancy, especially: enteropathy-associated T-cell lymphoma, small intestine adenocarcinoma, and oesophageal and oropharyngeal carcinomas. Early introduction of a gluten-free diet and lifelong adherence to this treatment decreases the risk of these complications. PMID:22744631

  4. 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.

  5. The complement system in systemic autoimmune disease.

    Science.gov (United States)

    Chen, Min; Daha, Mohamed R; Kallenberg, Cees G M

    2010-05-01

    Complement is part of the innate immune system. Its major function is recognition and elimination of pathogens via direct killing and/or stimulation of phagocytosis. Activation of the complement system is, however, also involved in the pathogenesis of the systemic autoimmune diseases. Activation via the classical pathway has long been recognized in immune complex-mediated diseases such as cryoglobulinemic vasculitis and systemic lupus erythematosus (SLE). In SLE, the role of complement is somewhat paradoxical. It is involved in autoantibody-initiated tissue damage on the one hand, but, on the other hand, it appears to have protective features as hereditary deficiencies of classical pathway components are associated with an increased risk for SLE. There is increasing evidence that the alternative pathway of complement, even more than the classical pathway, is involved in many systemic autoimmune diseases. This is true for IgA-dominant Henoch Schönlein Purpura, in which additional activation of the lectin pathway contributes to more severe disease. In anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis the complement system was considered not to be involved since immunoglobulin deposition is generally absent in the lesions. However, recent studies, both in human and animal models, demonstrated complement activation via the alternative pathway as a major pathogenic mechanism. Insight into the role of the various pathways of complement in the systemic autoimmune diseases including the vasculitides opens up new ways of treatment by blocking effector pathways of complement. This has been demonstrated for monoclonal antibodies to C5 or C5a in experimental anti-phospholipid antibody syndrome and ANCA-associated vasculitis.

  6. Sex bias in CNS autoimmune disease mediated by androgen control of autoimmune regulator.

    Science.gov (United States)

    Zhu, Meng-Lei; Bakhru, Pearl; Conley, Bridget; Nelson, Jennifer S; Free, Meghan; Martin, Aaron; Starmer, Joshua; Wilson, Elizabeth M; Su, Maureen A

    2016-01-01

    Male gender is protective against multiple sclerosis and other T-cell-mediated autoimmune diseases. This protection may be due, in part, to higher androgen levels in males. Androgen binds to the androgen receptor (AR) to regulate gene expression, but how androgen protects against autoimmunity is not well understood. Autoimmune regulator (Aire) prevents autoimmunity by promoting self-antigen expression in medullary thymic epithelial cells, such that developing T cells that recognize these self-antigens within the thymus undergo clonal deletion. Here we show that androgen upregulates Aire-mediated thymic tolerance to protect against autoimmunity. Androgen recruits AR to Aire promoter regions, with consequent enhancement of Aire transcription. In mice and humans, thymic Aire expression is higher in males compared with females. Androgen administration and male gender protect against autoimmunity in a multiple sclerosis mouse model in an Aire-dependent manner. Thus, androgen control of an intrathymic Aire-mediated tolerance mechanism contributes to gender differences in autoimmunity. PMID:27072778

  7. Ovarian autoimmune disease: clinical concepts and animal models

    OpenAIRE

    Warren, Bryce D; Kinsey, William K; McGinnis, Lynda K; Christenson, Lane K.; Jasti, Susmita; Stevens, Anne M.; Petroff, Brian K.; Petroff, Margaret G.

    2014-01-01

    The ovary is not an immunologically privileged organ, but a breakdown in tolerogenic mechanisms for ovary-specific antigens has disastrous consequences on fertility in women, and this is replicated in murine models of autoimmune disease. Isolated ovarian autoimmune disease is rare in women, likely due to the severity of the disease and the inability to transmit genetic information conferring the ovarian disease across generations. Nonetheless, autoimmune oophoritis is often observed in associ...

  8. Future perspective for diagnosis in autoimmune diseases

    Directory of Open Access Journals (Sweden)

    Luis E. C. Andrade

    2009-09-01

    Full Text Available Human beings have taken successive approaches for the understanding and management of diseases. Initially brewed in supernatural concepts and mystical procedures, a vigorous scientific approach has emerged on the grounds of fundamental disciplines such as anatomy, microbiology, biochemistry, physiology, immunology, pathology, and pharmacology. The resulting integrated knowledge contributed to the current classification of diseases and the way Medicine is carried out today. Despite considerable progress, this approach is rather insufficient when it comes to systemic inflammatory conditions, such as systemic lupus erythematosus, that covers clinical conditions ranging from mild pauci-symptomatic diseases to rapidly fatal conditions. The treatment for such conditions is often insufficient and novel approaches are needed for further progress in these areas of Medicine. A recent breakthrough has been achieved with respect to chronic auto-inflammatory syndromes, in which molecular dissection of underlying gene defects has provided directions for target-oriented therapy. Such approach may be amenable to application in systemic auto-immune diseases with the comprehension that such conditions may be the consequence of interaction of specific environmental stimuli and an array of several and interconnected gene polymorphisms. On the bulk of this transformation, the application of principles of pharmacogenetics may lead the way towards a progressively stronger personalized Medicine.O homem tem buscado sucessivas abordagens para o entendimento e manejo das doenças. Partindo de conceitos sobrenaturais e procedimentos místicos, uma abordagem científica vigorosa vicejou com base em disciplinas fundamentais como a anatomia, microbiologia, bioquímica, fisiologia, imunologia, patologia e farmacologia. O conhecimento integrado resultante contribuiu para a atual classificação das doenças e a formacom que a Medicina atual é praticada. Apesar deste consider

  9.  An autoimmune polyglandular syndrome complicated with celiac disease and autoimmune hepatitis.

    Science.gov (United States)

    Dieli-Crimi, Romina; Núñez, Concepción; Estrada, Lourdes; López-Palacios, Natalia

    2016-01-01

     Autoimmune polyglandular syndrome (APS) is a combination of different autoimmune diseases. The close relationship between immune-mediated disorders makes it mandatory to perform serological screening periodically in order to avoid delayed diagnosis of additional autoimmune diseases. We studied a patient with type 1 diabetes (T1D) who later developed an autoimmune thyroid disease (ATD) and was referred to our hospital with a serious condition of his clinical status. The patient was suffering from an advance stage of celiac disease (CD), the delay in its diagnosis and in the establishment of a gluten-free dietled the patient to a severe proteincalorie malnutrition. Later, the patient developed an autoimmune hepatitis (AIH). We consider that clinical deterioration in patients with APS should alert physicians about the possible presence of other immune-mediated diseases. Periodic screening for autoantibodies would help to prevent delayed diagnosis and would improve patient's quality of life. PMID:27236159

  10. Autoimmune vitiligo in rheumatic disease in the mestizo Mexican population

    Science.gov (United States)

    Avalos-Díaz, Esperanza; Pérez-Pérez, Elena; Rodríguez-Rodríguez, Mayra; Pacheco-Tovar, María-Guadalupe; Herrera-Esparza, Rafael

    2016-01-01

    Vitiligo is a chronic disease characterized by the dysfunction or destruction of melanocytes with secondary depigmentation. The aim of the present study was to determine the prevalence of vitiligo associated with autoimmune rheumatic diseases. The clinical records from a 10-year database of patients with rheumatic diseases and associated vitiligo was analysed, with one group of patients having autoimmune rheumatic disease and another non-autoimmune rheumatic disease. Available serum samples were used to assess the anti-melanocyte antibodies. A total of 5,251 individual clinical files were archived in the last 10 years, and these patients underwent multiple rheumatology consultations, with 0.3% of the group presenting with vitiligo. The prevalence of vitiligo in the autoimmune rheumatic disease group was 0.672%, which was mainly associated with lupus and arthritis. However, patients with more than one autoimmune disease had an increased relative risk to develop vitiligo, and anti-melanocyte antibodies were positive in 92% of these patients. By contrast, the prevalence was 0.082% in the group that lacked autoimmune rheumatic disease and had negative autoantibodies. In conclusion, the association between vitiligo and autoimmune rheumatic diseases was relatively low. However, the relative risk increased when there were other autoimmune comorbidities, such as thyroiditis or celiac disease. Therefore, the presence of multiple autoimmune syndromes should be suspected. PMID:27446537

  11. Sex Differences in Autoimmune Disease from a Pathological Perspective

    OpenAIRE

    Fairweather, DeLisa; Frisancho-Kiss, Sylvia; Rose, Noel R.

    2008-01-01

    Autoimmune diseases affect ∼8% of the population, 78% of whom are women. The reason for the high prevalence in women is unclear. Women are known to respond to infection, vaccination, and trauma with increased antibody production and a more T helper (Th)2-predominant immune response, whereas a Th1 response and inflammation are usually more severe in men. This review discusses the distribution of autoimmune diseases based on sex and age, showing that autoimmune diseases progress from an acute p...

  12. Imaging B lymphocytes in autoimmune inflammatory diseases

    International Nuclear Information System (INIS)

    B cells arise from stem cells precursor and develop through a tightly regulated and selective process that lead to the generation of different B cell populations such as transitional, mature, memory and plasma cells. These B cell subsets can be identified using flow cytometry by the expression of specific surface antigens. The growing knowledge of the pivotal role played by B cells in the development and progression of autoimmune diseases combined with the advances in monoclonal antibody technology, led in the last years to the generation of different biological agents targeting B cells. In this context, nuclear medicine can offer the possibility to use a panel of biologic radiopharmaceuticals for molecular imaging of inflammatory diseases. Radiopharmaceuticals bind to their targets with high affinity and specificity and have an excellent imaging diagnostic potential for the evaluation of disease activity, selection and monitoring of immune therapies. Several molecules have been radiolabelled for the imaging of T lymphocytes whereas, by now, the anti CD20 rituximab is the only biological therapy targeting B cells that demonstrated to be efficiently radiolabelled and used to detect inflammation in autoimmune patients

  13. Autoimmune diseases in the TH17 era.

    Science.gov (United States)

    Mesquita Jr, D; Cruvinel, W M; Câmara, N O S; Kállas, E G; Andrade, L E C

    2009-06-01

    A new subtype of CD4+ T lymphocytes characterized by the production of interleukin 17, i.e., TH17 cells, has been recently described. This novel T cell subset is distinct from type 1 and type 2 T helper cells. The major feature of this subpopulation is to generate significant amounts of pro-inflammatory cytokines, therefore appearing to be critically involved in protection against infection caused by extracellular microorganisms, and in the pathogenesis of autoimmune diseases and allergy. The dynamic balance among subsets of T cells is important for the modulation of several steps of the immune response. Disturbances in this balance may cause a shift from normal immunologic physiology to the development of immune-mediated disorders. In autoimmune diseases, the fine balance between the proportion and degree of activation of the various T lymphocyte subsets can contribute to persistent undesirable inflammatory responses and tissue replacement by fibrosis. This review highlights the importance of TH17 cells in this process by providing an update on the biology of these cells and focusing on their biology and differentiation processes in the context of immune-mediated chronic inflammatory diseases. PMID:19448894

  14. Autoimmune diseases in the TH17 era

    Directory of Open Access Journals (Sweden)

    D. Mesquita Jr.

    2009-06-01

    Full Text Available A new subtype of CD4+ T lymphocytes characterized by the production of interleukin 17, i.e., TH17 cells, has been recently described. This novel T cell subset is distinct from type 1 and type 2 T helper cells. The major feature of this subpopulation is to generate significant amounts of pro-inflammatory cytokines, therefore appearing to be critically involved in protection against infection caused by extracellular microorganisms, and in the pathogenesis of autoimmune diseases and allergy. The dynamic balance among subsets of T cells is important for the modulation of several steps of the immune response. Disturbances in this balance may cause a shift from normal immunologic physiology to the development of immune-mediated disorders. In autoimmune diseases, the fine balance between the proportion and degree of activation of the various T lymphocyte subsets can contribute to persistent undesirable inflammatory responses and tissue replacement by fibrosis. This review highlights the importance of TH17 cells in this process by providing an update on the biology of these cells and focusing on their biology and differentiation processes in the context of immune-mediated chronic inflammatory diseases.

  15. Pulmonary hypertension in autoimmune rheumatic diseases

    Directory of Open Access Journals (Sweden)

    L. Massironi

    2011-09-01

    Full Text Available Objective. Pulmonary hypertension is a severe and rapidly progressive disease, particularly frequent in patients with rheumatic diseases. The aims of this study were the following: to determine the prevalence of pulmonary hypertension in Italian patients with autoimmune rheumatic diseases, and to evaluate if the presence of a rheumatic disease in general, or of a specific autoimmune rheumatic disease, is a risk factor for the development of pulmonary hypertension. Patients and Methods. One hundred and thirteen Italian patients with connective tissue diseases (105 females, 8 males, aged 19 to 83 yrs, entered the study. Fifty-one had systemic sclerosis (SSc: 49 were females, 2 males, aged 34 to 83 yrs; 41 had limited cutaneous SSc, 8 diffuse cutaneous SSc, and 2 SSc sine scleroderma. Thirty-three patients had systemic lupus erythematosus (SLE: all but one were females, their age ranged from 19 to 82 yrs. Twenty-five had rheumatoid arthritis (RA: 21 females, 4 males, aged 26 to 45 yrs. Three females and one male, 51-77 yrs, had mixed connective tissue disease (MCTD. Systolic pulmonary arterial pressure (SPAP was assessed by Doppler echocardiography. Results. Twenty three patients had pulmonary hypertension, which was more frequent in MCTD than in SLE (75% vs 6.1%, p=0.0002 or in AR (20%, p=0.0313. Pulmonary hypertension was more frequent in SSc than in SLE (25.5% vs 6.1%, p=0.0028 and in limited than in diffuse SSc(21.6% vs 3.9%. SPAP was significanly related to age (R=0.35, P=0.0275, with patients with pulmonary hypertension older than patients with normal SPAP (66±13 vs 52±16 yrs, p=0.0003. Conclusions. These data show a significant association between pulmonary hypertension and autoimmune rheumatic diseases. Therefore pulmonary hypertension assessment seems mandatory, at least in MCTD and SSc. However, more studies are needed to clarify the relationship between age and pulmonary hypertension and to verify whether the low prevalence of

  16. Psoriasis is not an autoimmune disease?

    Science.gov (United States)

    Fry, Lionel; Baker, Barbara S; Powles, Anne V; Engstrand, Lars

    2015-04-01

    The concept that psoriasis is an autoimmune disease needs to be questioned. The autoimmune label has been based on molecular mimicry between streptococcal and keratin proteins and the existence of homologous peptides between these proteins. However, it is only peripheral blood CD8, and not CD4, T lymphocytes that respond to the homologous peptides. This ignores the fact that it is CD4 T cells which are necessary to initiate psoriasis. Recent studies on skin bacterial microbiota have found a variety of bacteria in both normal skin and psoriatic lesions. In biopsy specimens, the most common phylum was Firmicutes and the most common genus streptococcus in both psoriasis and normal skin. The innate immune system is activated in psoriasis, and recent genetic findings have shown the majority of susceptibility loci are associated with innate immunity. There is a known clinical relationship between both Crohn's disease (CD) and periodontitis, and psoriasis, and patients with psoriasis share mutations in some innate immunity genes with individuals with CD. It is now accepted that CD is due to a breakdown of immune tolerance (dysbiosis) to bacteria in the intestine. These findings suggest that psoriasis is initiated by an abnormal response to bacteria in the skin due to genetic factors.

  17. Autoimmune Diseases Co-Existing with Hepatitis C Virus Infection

    Directory of Open Access Journals (Sweden)

    Zohreh Jadali

    2010-12-01

    Full Text Available Autoimmunity and viral infections are closely associated fields, and viruses have been proposed as a likely aetiological, contributory or triggering factors of systemic autoimmune diseases. Hepatitis C virus seems to be the virus usually associated with the appearance of autoimmune diseases, and the relationship between chronic hepatitis C virus infection and some autoimmune disease has been studied. For some of these disorders their association with hepatitis C virus infection is well recognized while for others it remains probable or weak. Examples of autoimmune phenomena observed in chronic hepatitis C virus infection include rheumatoid arthritis, thyroid disease, cryoglobulinaemia, immune thrombocytopenic purpura, systemic lupus erythematosus and sjogren syndrome. To date, the etiological role and the pathogenetic involvement of the hepatitis C infection remains unknown.The aim of this study is to assess the presence of different autoimmune manifestations of hepatitis C virus infection reported in literature.

  18. Applications of Next-generation Sequencing in Systemic Autoimmune Diseases

    Institute of Scientific and Technical Information of China (English)

    Yiyangzi Ma; Na Shi; Mengtao Li; Fei Chen; Haitao Niu

    2015-01-01

    Systemic autoimmune diseases are a group of heterogeneous disorders caused by both genetic and environmental factors. Although numerous causal genes have been identified by genome-wide association studies (GWAS), these susceptibility genes are correlated to a relatively low disease risk, indicating that environmental factors also play an important role in the pathogen-esis of disease. The intestinal microbiome, as the main symbiotic ecosystem between the host and host-associated microorganisms, has been demonstrated to regulate the development of the body’s immune system and is likely related to genetic mutations in systemic autoimmune diseases. Next-generation sequencing (NGS) technology, with high-throughput capacity and accuracy, provides a powerful tool to discover genomic mutations, abnormal transcription and intestinal microbiome identification for autoimmune diseases. In this review, we briefly outlined the applications of NGS in systemic autoimmune diseases. This review may provide a reference for future studies in the pathogenesis of systemic autoimmune diseases.

  19. Infections as a cause of autoimmune rheumatic diseases.

    Science.gov (United States)

    Sakkas, Lazaros I; Bogdanos, Dimitrios P

    2016-12-01

    Exogenous and endogenous environmental exposures and particularly infections may participate in the breakage of tolerance and the induction of autoimmunity in rheumatic diseases. Response to infections apparently occurs years before clinical manifestations and features of autoimmunity, such as autoantibodies, are detected years before clinical manifestations in autoimmune rheumatic diseases. In this review, we summarize the current evidence for a potential causal link between infectious agents and rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, Sjogren's syndrome and ANCA-associated vasculitis. PMID:27629582

  20. Pharmacometabolomics-aided Pharmacogenomics in Autoimmune Disease

    Directory of Open Access Journals (Sweden)

    Theodora Katsila

    2016-03-01

    Full Text Available Inter-individual variability has been a major hurdle to optimize disease management. Precision medicine holds promise for improving health and healthcare via tailor-made therapeutic strategies. Herein, we outline the paradigm of “pharmacometabolomics-aided pharmacogenomics” in autoimmune diseases. We envisage merging pharmacometabolomic and pharmacogenomic data (to address the interplay of genomic and environmental influences with information technologies to facilitate data analysis as well as sense- and decision-making on the basis of synergy between artificial and human intelligence. Humans can detect patterns, which computer algorithms may fail to do so, whereas data-intensive and cognitively complex settings and processes limit human ability. We propose that better-informed, rapid and cost-effective omics studies need the implementation of holistic and multidisciplinary approaches.

  1. Pharmacometabolomics-aided Pharmacogenomics in Autoimmune Disease.

    Science.gov (United States)

    Katsila, Theodora; Konstantinou, Evangelia; Lavda, Ioanna; Malakis, Harilaos; Papantoni, Ioanna; Skondra, Lamprini; Patrinos, George P

    2016-03-01

    Inter-individual variability has been a major hurdle to optimize disease management. Precision medicine holds promise for improving health and healthcare via tailor-made therapeutic strategies. Herein, we outline the paradigm of "pharmacometabolomics-aided pharmacogenomics" in autoimmune diseases. We envisage merging pharmacometabolomic and pharmacogenomic data (to address the interplay of genomic and environmental influences) with information technologies to facilitate data analysis as well as sense- and decision-making on the basis of synergy between artificial and human intelligence. Humans can detect patterns, which computer algorithms may fail to do so, whereas data-intensive and cognitively complex settings and processes limit human ability. We propose that better-informed, rapid and cost-effective omics studies need the implementation of holistic and multidisciplinary approaches.

  2. Introducing Polyautoimmunity: Secondary Autoimmune Diseases No Longer Exist

    Directory of Open Access Journals (Sweden)

    Adriana Rojas-Villarraga

    2012-01-01

    Full Text Available 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.

  3. Neuromuscular disease classification system.

    Science.gov (United States)

    Sáez, Aurora; Acha, Begoña; Montero-Sánchez, Adoración; Rivas, Eloy; Escudero, Luis M; Serrano, Carmen

    2013-06-01

    Diagnosis of neuromuscular diseases is based on subjective visual assessment of biopsies from patients by the pathologist specialist. A system for objective analysis and classification of muscular dystrophies and neurogenic atrophies through muscle biopsy images of fluorescence microscopy is presented. The procedure starts with an accurate segmentation of the muscle fibers using mathematical morphology and a watershed transform. A feature extraction step is carried out in two parts: 24 features that pathologists take into account to diagnose the diseases and 58 structural features that the human eye cannot see, based on the assumption that the biopsy is considered as a graph, where the nodes are represented by each fiber, and two nodes are connected if two fibers are adjacent. A feature selection using sequential forward selection and sequential backward selection methods, a classification using a Fuzzy ARTMAP neural network, and a study of grading the severity are performed on these two sets of features. A database consisting of 91 images was used: 71 images for the training step and 20 as the test. A classification error of 0% was obtained. It is concluded that the addition of features undetectable by the human visual inspection improves the categorization of atrophic patterns. PMID:23804164

  4. Celiac Disease and Autoimmune-Associated Conditions

    Directory of Open Access Journals (Sweden)

    Eugenia Lauret

    2013-01-01

    Full Text Available Celiac disease (CD is frequently accompanied by a variety of extradigestive manifestations, thus making it a systemic disease rather than a disease limited to the gastrointestinal tract. This is primarily explained by the fact that CD belongs to the group of autoimmune diseases. The only one with a known etiology is related to a permanent intolerance to gluten. Remarkable breakthroughs have been achieved in the last decades, due to a greater interest in the diagnosis of atypical and asymptomatic patients, which are more frequent in adults. The known presence of several associated diseases provides guidance in the search of oligosymptomatic cases as well as studies performed in relatives of patients with CD. The causes for the onset and manifestation of associated diseases are diverse; some share a similar genetic base, like type 1 diabetes mellitus (T1D; others share pathogenic mechanisms, and yet, others are of unknown nature. General practitioners and other specialists must remember that CD may debut with extraintestinal manifestations, and associated illnesses may appear both at the time of diagnosis and throughout the evolution of the disease. The implementation of a gluten-free diet (GFD improves the overall clinical course and influences the evolution of the associated diseases. In some cases, such as iron deficiency anemia, the GFD contributes to its disappearance. In other disorders, like T1D, this allows a better control of the disease. In several other complications and/or associated diseases, an adequate adherence to a GFD may slow down their evolution, especially if implemented during an early stage.

  5. Biological and clinical aspects of autoimmune inner ear disease.

    OpenAIRE

    Griffith, A J

    1992-01-01

    The clinical presentation, diagnosis, and management of autoimmune inner ear disease are reviewed. Recent studies indicating an autoimmune etiology and pathogenesis are discussed, along with a comparative analysis of several promising new animal models. Further studies to define the natural history, pathogenesis, and diagnosis of the disease are suggested.

  6. Selected Aspects in the Pathogenesis of Autoimmune Diseases

    Directory of Open Access Journals (Sweden)

    György Nagy

    2015-01-01

    Full Text Available Autoimmune processes can be found in physiological circumstances. However, they are quenched with properly functioning regulatory mechanisms and do not evolve into full-blown autoimmune diseases. Once developed, autoimmune diseases are characterized by signature clinical features, accompanied by sustained cellular and/or humoral immunological abnormalities. Genetic, environmental, and hormonal defects, as well as a quantitative and qualitative impairment of immunoregulatory functions, have been shown in parallel to the relative dominance of proinflammatory Th17 cells in many of these diseases. In this review we focus on the derailed balance between regulatory and Th17 cells in the pathogenesis of autoimmune diseases. Additionally, we depict a cytokine imbalance, which gives rise to a biased T-cell homeostasis. The assessment of Th17/Treg-cell ratio and the simultaneous quantitation of cytokines, may give a useful diagnostic tool in autoimmune diseases. We also depict the multifaceted role of dendritic cells, serving as antigen presenting cells, contributing to the development of the pathognomonic cytokine signature and promote cellular and humoral autoimmune responses. Finally we describe the function and role of extracellular vesicles in particular autoimmune diseases. Targeting these key players of disease progression in patients with autoimmune diseases by immunomodulating therapy may be beneficial in future therapeutic strategies.

  7. Celiac Disease and Autoimmune Thyroid Disease

    OpenAIRE

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

    2007-01-01

    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 patien...

  8. Pervasive Sharing of Genetic Effects in Autoimmune Disease

    NARCIS (Netherlands)

    Cotsapas, Chris; Voight, Benjamin F.; Rossin, Elizabeth; Lage, Kasper; Neale, Benjamin M.; Wallace, Chris; Abecasis, Goncalo R.; Barrett, Jeffrey C.; Behrens, Timothy; Cho, Judy; De Jager, Philip L.; Elder, James T.; Graham, Robert R.; Gregersen, Peter; Klareskog, Lars; Siminovitch, Katherine A.; van Heel, David A.; Wijmenga, Cisca; Worthington, Jane; Todd, John A.; Hafler, David A.; Rich, Stephen S.; Daly, Mark J.

    2011-01-01

    Genome-wide association (GWA) studies have identified numerous, replicable, genetic associations between common single nucleotide polymorphisms (SNPs) and risk of common autoimmune and inflammatory (immune-mediated) diseases, some of which are shared between two diseases. Along with epidemiological

  9. Anti-neutrophil cytoplasm autoantibodies (ANCA) in autoimmune liver diseases

    NARCIS (Netherlands)

    Roozendaal, C.; Kallenberg, Cees

    1999-01-01

    Anti-neutrophil cytoplasm antibodies (ANCA) are autoantibodies directed against cytoplasmic constituents of neutrophil granulocytes and monocytes. ANCA have been detected in serum from patients with inflammatory bowel diseases (mainly ulcerative colitis) and autoimmune mediated liver diseases (mainl

  10. The Epidemiologic Evidence Linking Autoimmune Diseases and Psychosis

    DEFF Research Database (Denmark)

    Benros, Michael E; Eaton, William W; Mortensen, Preben B

    2014-01-01

    with genetic markers of the immune system and with excess autoreactivity and other immune alterations. A range of psychiatric disorders, including psychosis, have been observed to occur more frequently in some autoimmune diseases, such as systemic lupus erythematosus and multiple sclerosis. Many autoimmune...... suspected to be caused by inflammation or brain-reactive antibodies associated with the autoimmune diseases. However, the associations could also be caused by shared genetic factors or common etiologic components such as infections. Infections can induce the development of autoimmune diseases...... and autoantibodies, possibly affecting the brain. Autoimmune diseases and brain-reactive antibodies should be considered by clinicians in the treatment of individuals with psychotic symptoms, and even if the association is not causal, treatment would probably still improve quality of life and survival....

  11. Ocular Involvement in Systemic Autoimmune Diseases.

    Science.gov (United States)

    Generali, Elena; Cantarini, Luca; Selmi, Carlo

    2015-12-01

    Eye involvement represents a common finding in patients with systemic autoimmune diseases, particularly rheumatoid arthritis, Sjogren syndrome, seronegative spondyloarthropathy, and antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. The eye is a privileged immune site but commensal bacteria are found on the ocular surface. The eye injury may be inflammatory, vascular or infectious, as well as iatrogenic, as in the case of hydroxychloroquine, chloroquine, corticosteroids, and bisphosphonates. Manifestations may affect different components of the eye, with episcleritis involving the episclera, a thin layer of tissue covering the sclera; scleritis being an inflammation of the sclera potentially leading to blindness; keratitis, referring to corneal inflammation frequently associated with scleritis; and uveitis as the inflammation of the uvea, including the iris, ciliary body, and choroid, subdivided into anterior, posterior, or panuveitis. As blindness may result from the eye involvement, clinicians should be aware of the possible manifestations and their management also independent of the ophthalmologist opinion as the therapeutic approach generally points to the underlying diseases. In some cases, the eye involvement may have a diagnostic implication, as for episcleritis in rheumatoid arthritis, or acute anterior uveitis in seronegative spondyloarthritis. Nonetheless, some conditions lack specificity, as in the case of dry eye which affects nearly 30 % of the general population. The aim of this review is to elucidate to non-ophthalmologists the major ocular complications of rheumatic diseases and their specific management and treatment options.

  12. Involvement of dendritic cells in autoimmune diseases in children

    Directory of Open Access Journals (Sweden)

    Reed Ann M

    2007-07-01

    Full Text Available Abstract Dendritic cells (DCs are professional antigen-presenting cells that are specialized in the uptake of antigens and their transport from peripheral tissues to the lymphoid organs. Over the last decades, the properties of DCs have been intensely studied and much knowledge has been gained about the role of DCs in various diseases and health conditions where the immune system is involved, particularly in cancer and autoimmune disorders. Emerging clues in autoimmune diseases, suggest that dendritic cell dysregulation might be involved in the development of various autoimmune disorders in both adults and children. However, studies investigating a possible contribution of DCs in autoimmune diseases in the pediatric population alone are scanty. The purpose of this review is to give a general overview of the current literature on the relevance of dendritic cells in the most common autoimmune conditions of childhood.

  13. Parallel Aspects of the Microenvironment in Cancer and Autoimmune Disease

    Science.gov (United States)

    Rahat, Michal A.

    2016-01-01

    Cancer and autoimmune diseases are fundamentally different pathological conditions. In cancer, the immune response is suppressed and unable to eradicate the transformed self-cells, while in autoimmune diseases it is hyperactivated against a self-antigen, leading to tissue injury. Yet, mechanistically, similarities in the triggering of the immune responses can be observed. In this review, we highlight some parallel aspects of the microenvironment in cancer and autoimmune diseases, especially hypoxia, and the role of macrophages, neutrophils, and their interaction. Macrophages, owing to their plastic mode of activation, can generate a pro- or antitumoral microenvironment. Similarly, in autoimmune diseases, macrophages tip the Th1/Th2 balance via various effector cytokines. The contribution of neutrophils, an additional plastic innate immune cell population, to the microenvironment and disease progression is recently gaining more prominence in both cancer and autoimmune diseases, as they can secrete cytokines, chemokines, and reactive oxygen species (ROS), as well as acquire an enhanced ability to produce neutrophil extracellular traps (NETs) that are now considered important initiators of autoimmune diseases. Understanding the contribution of macrophages and neutrophils to the cancerous or autoimmune microenvironment, as well as the role their interaction and cooperation play, may help identify new targets and improve therapeutic strategies. PMID:26997761

  14. Juvenile autoimmune hepatitis: Spectrum of the disease

    Institute of Scientific and Technical Information of China (English)

    Giuseppe; Maggiore; Silvia; Nastasio; Marco; Sciveres

    2014-01-01

    Juvenile autoimmune hepatitis(JAIH) is a progressive inflammatory liver disease, affecting mainly young girls, from infancy to late adolescence, characterized by active liver damage, as shown by high serum activity of aminotransferases, by elevated immunoglobulin G levels, high titers of serum non organ-specific andorgan-specific autoantibodies, and by interface hepatitis on liver biopsy. It is a multifactorial disease of unknown etiology in which environmental factors act as a trigger in genetically predisposed individuals. Two types of JAIH are identified according to the autoan-tibody panel detected at diagnosis: AIH-1, characterized by the presence of anti-smooth muscle antibody and/or antinuclear antibody and AIH-2, by anti-liver-kidney microsomal antibody type 1 and/or by the presence of anti-liver cytosol type 1 antibody. Epidemiological distribution, genetic markers, clinical presentation and pattern of serum cytokines differentiate the two types of AIH suggesting possible pathogenetic mechanisms. The most effective therapy for AIH is pharmacological suppression of the immune response. Treatment should be started as soon as the diagnosis is made to avoid severe liver damage and progression of fibrosis. The aim of this review is to outline the most significant and peculiar features of JAIH, based largely on our own personal database and on a review of current literature.

  15. Liver cirrhosis in selected autoimmune diseases: a nationwide cohort study in Taiwan.

    Science.gov (United States)

    Tung, Chien-Hsueh; Lai, Ning-Seng; Lu, Ming-Chi; Lee, Ching-Chih

    2016-02-01

    The association between autoimmune diseases and liver cirrhosis has rarely been explored in Asian populations, an endemic area of viral hepatitis. The aim of this study was to investigate the comparative risk of liver cirrhosis among a group of selective autoimmune diseases in Taiwanese patients and to identify groups of high risk. This retrospective study was a nationwide, population-based study and used Taiwan's National Health Insurance Research Database. A total of 29,856 patients with definite diagnosis of selected autoimmune diseases (Registry of Taiwan Catastrophic Illness Database, ACR classification) at the starting time point of January 1, 2005, were enrolled in this study. After tracked for a 5-year period, the endpoints were diagnosis of liver cirrhosis (in accordance with International Classification of Diseases, Ninth Revision, Clinical Modification, ICD-9-CM codes 571). The control group was composed of other patients in the same database and consisted of randomly selected 753,495 sex- and age-matched non-autoimmune disease patients. The Cox proportional hazard regression model was used to calculate the risk of liver cirrhosis after adjusting for certain variables such as comorbidity, living area, and socioeconomic status. Among the patients with selected autoimmune diseases, 1987 liver cirrhosis were observed. Patients with psoriasis had a significantly increased risk of liver cirrhosis (HR 1.87, 95 % CI 1.25-2.81) than control group without psoriasis. The risk of liver cirrhosis was significantly lower in patients with rheumatoid arthritis (HR 0.29, 95 % CI 0.19-0.44). There is a gradient of risk of liver cirrhosis among the autoimmune diseases; the specific risks need to be investigated on the basis of hypotheses. Conventional immunosuppressive drug administration should be carefully implemented by regular monitoring of liver condition in order to avoid causing an adverse effect of chronic liver fibrosis. PMID:26408009

  16. AUTOIMMUNE DISEASE DURING PREGNANCY AND THE MICROCHIMERISM LEGACY OF PREGNANCY

    OpenAIRE

    Kristina M Adams Waldorf; Nelson, J. Lee

    2008-01-01

    Pregnancy has both short-term effects and long-term consequences. For women who have an autoimmune disease and subsequently become pregnant, pregnancy can induce amelioration of the mother’s disease, such as in rheumatoid arthritis, while exacerbating or having no effect on other autoimmune diseases like systemic lupus erythematosus. That pregnancy also leaves a long-term legacy has recently become apparent by the discovery that bi-directional cell trafficking results in persistence of fetal ...

  17. Prevalence of Celiac Disease in Children with Autoimmune Hepatitis and vice versa

    OpenAIRE

    Najafi, Mehri; Sadjadei, Nooshin; Eftekhari, Kambiz; Khodadad, Ahmad; Motamed, Farzaneh; Fallahi, Gholam-Hossain; Farahmand, Fatemeh

    2014-01-01

    Objective: Celiac disease is an autoimmune disorder in which the risk of autoimmune liver disease is high. Autoimmune hepatitis is a chronic and progressive entity and the risk of its being associated with other autoimmune disorders such as celiac disease is high also. The aim of this study was to determine the prevalence of celiac disease in patients with autoimmune hepatitis and vice versa. Methods: In a cross-sectional study children with autoimmune hepatitis underwent serological screenin...

  18. T Cell Vaccination as an Immunotherapy for Autoimmune Diseases

    Institute of Scientific and Technical Information of China (English)

    JingwuZhang

    2004-01-01

    Immunization with inactivated autoreactive T cells (T cell vaccination) selected from individual's own T cellrepertoire provides a unique in vivo setting for testing immune regulation that is known to involve interactionsof a variety of related surface molecules (1). It induces regulatory immune responses that closely resemble thein vivo situation where the immune system is challenged by clonal activation and expansion of given T cellpopulations in various autoimmune diseases. T cell vaccination provides a powerful means of eliciting naturalreactions of the immune system in response to clonal expansion of T cells, which can used as a therapeuticapproach to suppress or eliminate specific pathogenic autoreactive T cells in autoimmune conditions. Clinicaltrials using T cell vaccination to deplete autoreactive T cells in human autoimmune conditions have begun toreveal the pathologic relevance of various autoimmune T cell populations in the disease processes, providing aunique opportunity to test the autoimmune theories in a clinical setting. Cellular & Molecular Immunology.2004; 1(5):321-327.

  19. Classification, disease, and diagnosis.

    Science.gov (United States)

    Jutel, Annemarie

    2011-01-01

    Classification shapes medicine and guides its practice. Understanding classification must be part of the quest to better understand the social context and implications of diagnosis. Classifications are part of the human work that provides a foundation for the recognition and study of illness: deciding how the vast expanse of nature can be partitioned into meaningful chunks, stabilizing and structuring what is otherwise disordered. This article explores the aims of classification, their embodiment in medical diagnosis, and the historical traditions of medical classification. It provides a brief overview of the aims and principles of classification and their relevance to contemporary medicine. It also demonstrates how classifications operate as social framing devices that enable and disable communication, assert and refute authority, and are important items for sociological study.

  20. Autoimmune disease: Conceptual history and contributions of ocular immunology.

    Science.gov (United States)

    Margo, Curtis E; Harman, Lynn E

    2016-01-01

    Medical historians identify the mid-20th century as the time when the scientific and medical communities acknowledged the existence of autoimmune disease. Several conditions including sympathetic ophthalmia and endophthalmitis phacoanaphylactica, however, were proposed as autoimmune disorders much earlier. During the first half of the century, autoimmune disease was viewed as biologically implausible. Paul Ehrlich coined the term horror autotoxicus to emphasize that autoimmunity would contradict nature's aversion to self-injury. The discoveries of allergy and anaphylaxis were the first clues that the immune system was capable of self-harm. A major obstacle to comprehending the pathogenesis of autoimmunity was how the immune system distinguishes foreign from self, a process eventually understood in the context of immune tolerance. Investigators of sympathetic ophthalmia and endophthalmitis phacoanaphylactica were positioned to invalidate horror autotoxicus but lacked sufficiently convincing experimental and clinical evidence to accomplish the task. Seminal studies of chronic thyroiditis and a series of clinical laboratory breakthroughs led to the general acceptance of autoimmune disease in the 1950s. The travails encountered by ophthalmic investigators offer insights into the how medical ideas take shape. We review the contributions of ocular immunology to the conceptual development of autoimmune disease and explore the reasons why the concept caught on slowly. PMID:27131478

  1. Autoimmune diseases and severe infections as risk factors for schizophrenia

    DEFF Research Database (Denmark)

    Benros, Michael E; Nielsen, Philip R; Nordentoft, Merete;

    2011-01-01

    Autoimmune diseases have been associated with an increased risk of schizophrenia. It has been suggested that brain-reactive autoantibodies are part of the mechanisms behind this association. Furthermore, an increased permeability of the blood-brain barrier has been observed during periods of...... infection and inflammation. The authors therefore investigated whether autoimmune diseases combined with exposures to severe infections may increase the risk of schizophrenia...

  2. Autoimmune diseases in pregnancy: maternal and fetal outcomes

    OpenAIRE

    Pavithra M. Vengetesh; Shripad Hebbar; Lavanya Rai

    2015-01-01

    Background: The aim of this study was to assess the impact of autoimmune connective tissue disorders on the outcomes of pregnancy and the influence of treatment on pregnancy. Methods: Thirty-seven antenatal patients with autoimmune connective tissue diseases, comprising of Systemic Lupus Erythematosus (SLE), primary antiphospholipid antibody syndrome (APS), Mixed Connective Tissue Diseases (MCTD), ankylosing spondylitis and Takayasu arteritis were analysed. Results: Multigravidas con...

  3. [Autoimmune diseases in type 1A diabetes mellitus].

    Science.gov (United States)

    Ferreira-Hermosillo, Aldo; Molina-Ayala, Mario Antonio

    2015-08-01

    Type 1A diabetes (DM1A) is an autoimmune disease that comprises 10% of patients with diabetes mellitus. Its frequency is gradually increasing in countries like Mexico. Patients with DM1A commonly have hypothyroidism, Addison disease, celiac disease and less common diseases such as polyglandular syndrome. These diseases are related to susceptibility genes such as HLA, CTLA-4 and PTPN22, which induce central and peripheral immunologic tolerance. This review article emphasizes the importance of searching other autoimmune diseases in patients with DM1A, to improve their prognosis and quality of life.

  4. Pregnancy and the risk of autoimmune disease.

    LENUS (Irish Health Repository)

    Khashan, Ali S

    2012-01-31

    Autoimmune diseases (AID) predominantly affect women of reproductive age. While basic molecular studies have implicated persisting fetal cells in the mother in some AID, supportive epidemiological evidence is limited. We investigated the effect of vaginal delivery, caesarean section (CS) and induced abortion on the risk of subsequent maternal AID. Using the Danish Civil Registration System (CRS) we identified women who were born between 1960 and 1992. We performed data linkage between the CRS other Danish national registers to identify women who had a pregnancy and those who developed AID. Women were categorised into 4 groups; nulligravida (control group), women who had 1st child by vaginal delivery, whose 1st delivery was by CS and who had abortions. Log-linear Poisson regression with person-years was used for data analysis adjusting for several potential confounders. There were 1,035,639 women aged >14 years and 25,570 developed AID: 43.4% nulligravida, 44.3% had their first pregnancy delivered vaginally, 7.6% CS and 4.1% abortions. The risk of AID was significantly higher in the 1st year after vaginal delivery (RR = 1.1[1.0, 1.2]) and CS (RR = 1.3[1.1, 1.5]) but significantly lower in the 1st year following abortion (RR = 0.7[0.6, 0.9]). These results suggest an association between pregnancy and the risk of subsequent maternal AID. Increased risks of AID after CS may be explained by amplified fetal cell traffic at delivery, while decreased risks after abortion may be due to the transfer of more primitive fetal stem cells. The increased risk of AID in the first year after delivery may also be related to greater testing during pregnancy.

  5. Pregnancy and the risk of autoimmune disease.

    Directory of Open Access Journals (Sweden)

    Ali S Khashan

    Full Text Available Autoimmune diseases (AID predominantly affect women of reproductive age. While basic molecular studies have implicated persisting fetal cells in the mother in some AID, supportive epidemiological evidence is limited. We investigated the effect of vaginal delivery, caesarean section (CS and induced abortion on the risk of subsequent maternal AID. Using the Danish Civil Registration System (CRS we identified women who were born between 1960 and 1992. We performed data linkage between the CRS other Danish national registers to identify women who had a pregnancy and those who developed AID. Women were categorised into 4 groups; nulligravida (control group, women who had 1st child by vaginal delivery, whose 1st delivery was by CS and who had abortions. Log-linear Poisson regression with person-years was used for data analysis adjusting for several potential confounders. There were 1,035,639 women aged >14 years and 25,570 developed AID: 43.4% nulligravida, 44.3% had their first pregnancy delivered vaginally, 7.6% CS and 4.1% abortions. The risk of AID was significantly higher in the 1st year after vaginal delivery (RR = 1.1[1.0, 1.2] and CS (RR = 1.3[1.1, 1.5] but significantly lower in the 1st year following abortion (RR = 0.7[0.6, 0.9]. These results suggest an association between pregnancy and the risk of subsequent maternal AID. Increased risks of AID after CS may be explained by amplified fetal cell traffic at delivery, while decreased risks after abortion may be due to the transfer of more primitive fetal stem cells. The increased risk of AID in the first year after delivery may also be related to greater testing during pregnancy.

  6. Cytokines and Cytokine Profiles in Human Autoimmune Diseases and Animal Models of Autoimmunity

    Directory of Open Access Journals (Sweden)

    Manfred Kunz

    2009-01-01

    Full Text Available The precise pathomechanisms of human autoimmune diseases are still poorly understood. However, a deepened understanding of these is urgently needed to improve disease prevention and early detection and guide more specific treatment approaches. In recent years, many new genes and signalling pathways involved in autoimmunity with often overlapping patterns between different disease entities have been detected. Major contributions were made by experiments using DNA microarray technology, which has been used for the analysis of gene expression patterns in chronic inflammatory and autoimmune diseases, among which were rheumatoid arthritis, systemic lupus erythematosus, psoriasis, systemic sclerosis, multiple sclerosis, and type-1 diabetes. In systemic lupus erythematosus, a so-called interferon signature has been identified. In psoriasis, researchers found a particular immune signalling cluster. Moreover the identification of a new subset of inflammatory T cells, so-called Th17 T cells, secreting interleukin (IL-17 as one of their major cytokines and the identification of the IL-23/IL-17 axis of inflammation regulation, have significantly improved our understanding of autoimmune diseases. Since a plethora of new treatment approaches using antibodies or small molecule inhibitors specifically targeting cytokines, cellular receptors, or signalling mechanisms has emerged in recent years, more individualized treatment for affected patients may be within reach in the future.

  7. Epigenetics and autoimmune diseases: the X chromosome-nucleolus nexus.

    Science.gov (United States)

    Brooks, Wesley H; Renaudineau, Yves

    2015-01-01

    Autoimmune diseases occur more often in females, suggesting a key role for the X chromosome. X chromosome inactivation, a major epigenetic feature in female cells that provides dosage compensation of X-linked genes to avoid overexpression, presents special vulnerabilities that can contribute to the disease process. Disruption of X inactivation can result in loss of dosage compensation with expression from previously sequestered genes, imbalance of gene products, and altered endogenous material out of normal epigenetic context. In addition, the human X has significant differences compared to other species and these differences can contribute to the frequency and intensity of the autoimmune disease in humans as well as the types of autoantigens encountered. Here a link is demonstrated between autoimmune diseases, such as systemic lupus erythematosus, and the X chromosome by discussing cases in which typically non-autoimmune disorders complicated with X chromosome abnormalities also present lupus-like symptoms. The discussion is then extended to the reported spatial and temporal associations of the inactive X chromosome with the nucleolus. When frequent episodes of cellular stress occur, the inactive X chromosome may be disrupted and inadvertently become involved in the nucleolar stress response. Development of autoantigens, many of which are at least transiently components of the nucleolus, is then described. Polyamines, which aid in nucleoprotein complex assembly in the nucleolus, increase further during cell stress, and appear to have an important role in the autoimmune disease process. Autoantigenic endogenous material can potentially be stabilized by polyamines. This presents a new paradigm for autoimmune diseases: that many are antigen-driven and the autoantigens originate from altered endogenous material due to episodes of cellular stress that disrupt epigenetic control. This suggests that epigenetics and the X chromosome are important aspects of autoimmune

  8. The role of melatonin in autoimmune and atopic diseases

    Directory of Open Access Journals (Sweden)

    J.R. Calvo

    2016-04-01

    Full Text Available Melatonin is the main secretory product synthesized and secreted by the pineal gland during the night. Melatonin is a pleitropic molecule with a wide distribution within phylogenetically distant organisms and has a great functional versatility, including the regulation of circadian and seasonal rhythms and antioxidant and anti-inflammatory properties. It also possesses the capacity to modulate immune responses by regulation of the TH1/TH2 balance and cytokine production. Immune system eradicates infecting organisms without serious injury to host tissues, but sometimes these responses are inadequately controlled, giving rise to called hypersensitivity diseases, or inappropriately targeted to host tissues, causing the autoimmune diseases. In clinical medicine, the hypersensitivity diseases include the allergic or atopic diseases and the hallmarks of these diseases are the activation of TH2 cells and the production of IgE antibody. Regarding autoimmunity, at the present time we know that the key events in the development of autoimmunity are a failure or breakdown of the mechanisms normally responsible for maintaining self-tolerance in B lymphocytes, T lymphocytes, or both, the recognition of self-antigens by autoreactive lymphocytes, the activation of these cells to proliferate and differentiate into effector cells, and the tissue injury caused by the effector cells and their products. Melatonin treatment has been investigated in atopic diseases, in several animal models of autoimmune diseases, and has been also evaluated in clinical autoimmune diseases. This review summarizes the role of melatonin in atopic diseases (atopic dermatitis and asthma and in several autoimmune diseases, such as arthritis rheumatoid, multiple sclerosis, systemic lupus erythematosus, type 1 diabetes mellitus, and inflammatory bowel diseases.

  9. 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 benef

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

    OpenAIRE

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

    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 ...

  11. Bioluminescence in vivo imaging of autoimmune encephalomyelitis predicts disease

    OpenAIRE

    Steinman Lawrence; Ho Peggy; Luo Jian; Wyss-Coray Tony

    2008-01-01

    Abstract Background Experimental autoimmune encephalomyelitis is a widely used animal model to understand not only multiple sclerosis but also basic principles of immunity. The disease is scored typically by observing signs of paralysis, which do not always correspond with pathological changes. Methods Experimental autoimmune encephalomyelitis was induced in transgenic mice expressing an injury responsive luciferase reporter in astrocytes (GFAP-luc). Bioluminescence in the brain and spinal co...

  12. Tzanck Cytology in Diagnosis of Autoimmune Bullous Diseases

    Directory of Open Access Journals (Sweden)

    Murat Durdu

    2011-06-01

    Full Text Available Tzanck smear test is a simple, rapid, repeatable, and inexpensive diagnostic method based on the investigation of characteristics of individual cells. For diagnosis of cutaneous diseases, cytology was first used by Arnault Tzanck in 1947. After this date, Tzanck cytology has been used in the diagnosis of various erosive-vesiculobullous, nodular, and tumoral skin lesions. In daily dermatology practice, the most common use areas of cytology are diagnosis of herpetic infections, cutaneous leishmaniasis, leprosy, and autoimmune bullous diseases. The purpose of cytology in autoimmune bullous diseases is to rapidly distinguish pemphigus from subepidermal bullous disease. In this review article, taking and staining methods of cytologic specimen for the diagnosis of autoimmune bullous diseases, and the cytologic findings have been reviewed.

  13. Interleukin-22: a likely target for treatment of autoimmune diseases

    Science.gov (United States)

    Yang, Xuyan; Zheng, Song Guo

    2014-01-01

    Interleukin -22 (IL-22) is a member of IL-10 family cytokines that is produced by many different types of lymphocytes including both those of the innate and adaptive immune system. This includes activated T cells, most notably Th17 and Th22 cells, and NK cells, γδ T cells, LTi cells and LTi-like cells. IL-22 mediates its effects via the IL-22-IL-22R complex and subsequent Janus Kinase-signal transduces and activators transcription (JAK-STAT) signaling pathway. Recently accumulated evidence has indicated that IL-22 also plays an important role in the pathogenesis of many autoimmune diseases. In this review, we discuss the recent findings and advancement of the role for IL-22 in several autoimmune diseases, such as psoriasis, rheumatoid arthritis (RA), hepatitis, graft versus host disease (GHVD) and allergic diseases, implicating that target IL-22 may have a therapeutic potential in those autoimmune diseases. PMID:24418299

  14. Air pollution in autoimmune rheumatic diseases: a review.

    Science.gov (United States)

    Farhat, Sylvia C L; Silva, Clovis A; Orione, Maria Angelica M; Campos, Lucia M A; Sallum, Adriana M E; Braga, Alfésio L F

    2011-11-01

    Air pollution consists of a heterogeneous mixture of gasses and particles that include carbon monoxide, nitrates, sulfur dioxide, ozone, lead, toxic by-product of tobacco smoke and particulate matter. Oxidative stress and inflammation induced by inhaled pollutants may result in acute and chronic disorders in the respiratory system, as well as contribute to a state of systemic inflammation and autoimmunity. This paper reviews the mechanisms of air contaminants influencing the immune response and autoimmunity, and it focuses on studies of inhaled pollutants triggering and/or exacerbating rheumatic diseases in cities around the world. Remarkably, environmental factors contribute to the onset of autoimmune diseases, especially smoking and occupational exposure to silica in rheumatoid arthritis and systemic lupus erythematosus. Other diseases such as scleroderma may be triggered by the inhalation of chemical solvents, herbicides and silica. Likewise, primary vasculitis associated with anti-neutrophil cytoplasmic antibody (ANCA) may be triggered by silica exposure. Only few studies showed that air pollutants could trigger or exacerbate juvenile idiopathic arthritis and systemic lupus erythematosus. In contrast, no studies of tropospheric pollution triggering inflammatory myopathies and spondyloarthropathies were carried out. In conclusion, air pollution is one of the environmental factors involved in systemic inflammation and autoimmunity. Further studies are needed in order to evaluate air pollutants and their potentially serious effects on autoimmune rheumatic diseases and the mechanisms involved in the onset and the exacerbation of these diseases.

  15. Is Tourette's syndrome an autoimmune disease?

    Science.gov (United States)

    Hoekstra, P J; Kallenberg, C G M; Korf, J; Minderaa, R B

    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 beneficial effects of immunomodulatory intervention. One of the most controversial areas in this field is the validity of the proposed PANDAS concept. Some researchers have delineated a putatively unique subgroup of patients, from the spectrum of illness encompassing Tourette's syndrome and obsessive-compulsive disorder (OCD), whose tics and obsessive-compulsive symptoms are shown to arise in response to beta-hemolytic streptococcal infections. They designated it by the term pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS). Herein we additionally present pros and cons concerning the concept of PANDAS. Finally, recommendations for future research directions are given.

  16. Collection of hematopoietic stem cells from patients with autoimmune diseases

    NARCIS (Netherlands)

    Burt, RK; Fassas, A; Snowden, JA; Kozak, T; Wulffraat, NM; Nash, RA; Dunbar, CE; Arnold, R; Prentice, G; Bingham, S; Marmont, AM; McSweeney, PA; van Laar, J.M.

    2001-01-01

    We reviewed data from 24 transplant centers in Asia, Australia, Europe, and North America to determine the outcomes of stem cell collection including methods used, cell yields, effects on disease activity, and complications in patients with autoimmune diseases. Twenty-one unprimed bone marrow harves

  17. Interferon Type I Driven Immune Activation in Generalized Autoimmune Diseases

    NARCIS (Netherlands)

    Z. Brkić (Zana)

    2013-01-01

    textabstractThis thesis describes research performed on several generalized autoimmune diseases with the main focus on primary Sjögren’s syndrome. Interferon type I has been implicated in the pathogenesis of these diseases and will be introduced in this chapter together with other important immune f

  18. DNA-abzymes in autoimmune diseases in clinic and experiment

    Directory of Open Access Journals (Sweden)

    T E Naumova

    2003-01-01

    Full Text Available DNA-abzymes enzymes in autoimmune diseases in clinic and experiment T.E. Naumova, O.M. Durova, A.G. Gabibov, Z.S. Alekberova, S. V. Suchkov DNA-hydrolyzing autoantibodies (AAB or DNA-abzymes can be found in autoimmune diseases in clinic and experiment. Technology of serum express screening for presence of DNA abzymes is described. Comparative study of DNA-hydrolising activity in patients with different forms of systemic and organ-specific autoimmune diseases was performed. Blood of clinically healthy donors was usually free of IgG DNA-abzymes. DNA-abzymes were most often revealed in patients with systemic lupus erythematosus (SLE and rheumatoid arthritis (RA less often in patients with organ-specific forms of autoimmune disturbances. The results of the study confirm the hypothesis of autoimmune origin of IgG DNA abzymes and demonstrate the possibility to use them in clinical practice for monitoring to disease activity in SLE and RA.

  19. Autoimmune Disease in First-Degree Relatives and Spouses of Individuals With Celiac Disease

    NARCIS (Netherlands)

    Emilsson, Louise; Wijmenga, Cisca; Murray, Joseph A.; Ludvigsson, Jonas F.

    2015-01-01

    BACKGROUND & AIMS: First-degree relatives of individuals with celiac disease are at increased risk for this disorder, but little is known about their risk for other autoimmune diseases. We assessed the risk of nonceliac autoimmune disease in first-degree relatives and spouses of people with celiac d

  20. Solar Radiation and Vitamin D: Mitigating Environmental Factors in Autoimmune Disease

    OpenAIRE

    Schwalfenberg, Gerry K.

    2012-01-01

    This paper looks at the environmental role of vitamin D and solar radiation as risk reduction factors in autoimmune disease. Five diseases are considered: multiple sclerosis, type 1 diabetes, rheumatoid arthritis, autoimmune disease of the thyroid, and inflammatory bowel disease. Clinical relevant studies and factors that may indicate evidence that autoimmune disease is a vitamin D-sensitive disease are presented. Studies that have resulted in prevention or amelioration of some autoimmune dis...

  1. Polymyositis and dermatomyositis: Disease spectrum and classification

    Directory of Open Access Journals (Sweden)

    Siba P Raychaudhuri

    2012-01-01

    Full Text Available Muscle inflammation and weakness are the key features of idiopathic inflammatory myopathies (IIMs. In addition IIMs are frequently associated with cutaneous and pulmonary involvement. In clinical practice the three common inflammatory myopathies we come across are polymyositis (PM, dermatomyositis (DM and inclusion body myositis (IBM. The Bohan and Peter criteria combine clinical, laboratory, and pathologic features to define PM and DM. They did not recognize inclusion body myositis (IBM or other inflammatory myopathies, such as granulomatous and eosinophilic myositis. Thus the disease spectrum is wide and IIMs are a heterogeneous group of autoimmune disorders. To address these issues in this article we have discussed the currently developing newer classifications of IIMs.

  2. Allergen-specific immunotherapy and risk of autoimmune disease

    DEFF Research Database (Denmark)

    Linneberg, Allan; Madsen, Flemming; Skaaby, Tea

    2012-01-01

    After 100 years of experience with allergen-specific immunotherapy (SIT), an issue that is still unresolved is whether SIT can act as a trigger of, or as a risk factor for, autoimmune disease. We searched the literature for evidence on this topic.......After 100 years of experience with allergen-specific immunotherapy (SIT), an issue that is still unresolved is whether SIT can act as a trigger of, or as a risk factor for, autoimmune disease. We searched the literature for evidence on this topic....

  3. Age impact on autoimmune thyroid disease in females

    Science.gov (United States)

    Stoian, Dana; Craciunescu, Mihalea; Timar, Romulus; Schiller, Adalbert; Pater, Liana; Craina, Marius

    2013-10-01

    Thyroid autoimmune disease, a widespread phenomenon in female population, impairs thyroid function during pregnancy. Identifying cases, which will develop hypothyroidism during pregnancy, is crucial in the follow-up process. The study group comprised 108 females, with ages between 20-40 years; with known inactive autoimmune thyroid disease, before pregnancy that became pregnant in the study follow-up period. They were monitored by means of clinical, hormonal and immunological assays. Supplemental therapy with thyroid hormones was used, where needed. Maternal age and level of anti-thyroid antibodies were used to predict thyroid functional impairment.

  4. Family history of autoimmune thyroid disease and childhood acute leukemia.

    Science.gov (United States)

    Perillat-Menegaux, Florence; Clavel, Jacqueline; Auclerc, Marie-Françoise; Baruchel, André; Leverger, Guy; Nelken, Brigitte; Philippe, Noël; Sommelet, Danièle; Vilmer, Etienne; Hémon, Denis

    2003-01-01

    The association between a familial history of autoimmune disease and childhood acute leukemia was investigated in a French case-control study that, overall, was designed to assess the role of perinatal, infectious, environmental, and genetic factors in the etiology of childhood acute leukemia. Familial histories of autoimmune disease in first- and second-degree relatives were compared in 279 incident cases, 240 cases of acute lymphocytic leukemia (ALL) and 39 cases of acute non-lymphoblastic leukemia (ANLL), and 285 controls. Recruitment was frequency matched by age, gender, hospital, and ethnic origin. Odds ratios (OR) were estimated using an unconditional regression model taking into account the stratification variables, socioeconomic status, and familial structure. A statistically significant association between a history of autoimmune disease in first- or second-degree relatives and ALL (OR, 1.7; 95% confidence interval (CI), 1.0-2.8) was found. A relationship between thyroid diseases overall and ALL (OR, 2.0; 95% CI, 1.0-3.9) was observed. This association was more pronounced for potentially autoimmune thyroid diseases (Grave's disease and/or hyperthyroidism and Hashimoto's disease and/or hypothyroidism) (OR, 3.5; 95% CI, 1.1-10.7 and OR, 5.6; 95% CI, 1.0-31.1, respectively for ALL and ANLL), whereas it was not statistically significant for the other thyroid diseases (thyroid goiter, thyroid nodule, and unspecified thyroid disorders) (OR, 1.6; 95% CI, 0.7-3.5 and OR, 1.3; 95% CI, 0.2-7.0, respectively, for ALL and ANLL). The results suggest that a familial history of autoimmune thyroid disease may be associated with childhood acute leukemia.

  5. Idiopathic Granulomatous Mastitis: An Autoimmune Disease?

    Directory of Open Access Journals (Sweden)

    Fatih Altintoprak

    2013-01-01

    Full Text Available Purpose. This study aimed to investigate the autoimmune basis of idiopathic granulomatous mastitis (IGM by determining the anti-nuclear antibody (ANA and extractable nuclear antigen (ENA levels of patients diagnosed with IGM. Material and Methods. Twenty-six IGM patients were evaluated. Serum samples were analyzed for autoantibodies by indirect immunofluorescence (IIF using a substrate kit that induced fluorescein-conjugated goat antibodies to human immunoglobulin G (IgG. IIF patterns were read at serum dilutions of 1 : 40 and 1 : 100 for ANA positivity. Using the immunoblot technique, the sera of patients were assayed at dilutions of 1 : 40 and 1 : 100 for human autoantibodies of the IgG class to 15 lines of highly purified ENAs. Results. In the IIF studies for ANA, positivity was identified for four different patterns in the 1 : 40 diluted preparations, for three different patients in the 1 : 100 diluted preparations and only one pattern was identified at the 1 : 320 dilution. In the ENA studies, positivity was identified for four different pattern in the 1 : 40 dilution, and only one pattern was identified at the 1 : 100 dilution. Conclusion. This study was not able to support the eventual existence of an autoimmune basis for IGM.

  6. HLA-G Molecules in Autoimmune Diseases and Infections

    Science.gov (United States)

    Rizzo, Roberta; Bortolotti, Daria; Bolzani, Silvia; Fainardi, Enrico

    2014-01-01

    Human leukocyte antigen (HLA)-G molecule, a non-classical HLA-Ib molecule, is less polymorphic when compared to classical HLA class I molecules. Human leukocyte antigen-G (HLA-G) was first detected on cytotrophoblast cells at the feto-maternal interface but its expression is prevalent during viral infections and several autoimmune diseases. HLA-G gene is characterized by polymorphisms at the 3′ un-translated region and 5′ upstream regulatory region that regulate its expression and are associated with autoimmune diseases and viral infection susceptibility, creating an unbalanced and pathologic environment. This review focuses on the role of HLA-G genetic polymorphisms, mRNA, and protein expression in autoimmune conditions and viral infections. PMID:25477881

  7. Are human endogenous retroviruses triggers of autoimmune diseases?

    DEFF Research Database (Denmark)

    Nexø, Bjørn A; Villesen, Palle; Nissen, Kari K;

    2016-01-01

    factors. Viruses including human endogenous retroviruses have long been linked to the occurrence of autoimmunity, but never proven to be causative factors. Endogenous viruses are retroviral sequences embedded in the host germline DNA and transmitted vertically through successive generations in a Mendelian...... manner. In this study by means of genetic epidemiology, we have searched for the involvement of endogenous retroviruses in three selected autoimmune diseases: multiple sclerosis, type 1 diabetes mellitus, and rheumatoid arthritis. We found that at least one human endogenous retroviral locus......Autoimmune diseases encompass a plethora of conditions in which the immune system attacks its own tissue, identifying them as foreign. Multiple factors are thought to contribute to the development of immune response to self, including differences in genotypes, hormonal milieu, and environmental...

  8. Urticarial vasculitis: an autoimmune disorder following therapy for Hodgkin's disease.

    Science.gov (United States)

    Strickland, D K; Ware, R E

    1995-09-01

    Immunological abnormalities have been described in patients with Hodgkin's disease, both associated with the malignancy itself and occurring secondary to therapy. These abnormalities often manifest as an immunodeficiency state, but can also present as immune dysregulation and autoimmune disease. We report two young patients with Hodgkin's disease who, following successful therapy, developed urticarial vasculitis (UV), a form of cutaneous autoimmune vasculitis. Both patients also had systemic symptoms including fever, an elevated erythrocyte sedimentation rate and serum copper, and abnormal in vitro studies of lymphocyte enumeration and proliferation. Distinguishing UV from recurrent Hodgkin's disease was especially difficult in one patient, and was possible only by lymph node biopsy. One patient has responded well to immunosuppressive therapy, while the other, who has more profound immune dysfunction, has developed a chronic autoimmune disorder. UV may thus occur in patients after therapy for Hodgkin's disease; we hypothesize that immune dysregulation, either associated with the malignancy or resulting from therapy, is important in the pathogenesis of this autoimmune process. PMID:7623731

  9. T Cell Vaccination as an Immunotherapy for Autoimmune Diseases

    Institute of Scientific and Technical Information of China (English)

    Jingwu Zhang

    2004-01-01

    Immunization with inactivated autoreactive T cells (T cell vaccination) selected from individual's own T cell repertoire provides a unique in vivo setting for testing immune regulation that is known to involve interactions of a variety of related surface molecules (1). It induces regulatory immune responses that closely resemble the in vivo situation where the immune system is challenged by clonal activation and expansion of given T cell populations in various autoimmune diseases. T cell vaccination provides a powerful means of eliciting natural reactions of the immune system in response to clonal expansion of T cells, which can used as a therapeutic approach to suppress or eliminate specific pathogenic autoreactive T cells in autoimmune conditions. Clinical trials using T cell vaccination to deplete autoreactive T cells in human autoimmune conditions have begun to reveal the pathologic relevance of various autoimmune T cell populations in the disease processes, providing a unique opportunity to test the autoimmune theories in a clinical setting. Cellular & Molecular Immunology.2004;1(5):321-327.

  10. Immunoglobulin G4-related disease: autoimmune pancreatitis and extrapancreatic manifestations*

    Science.gov (United States)

    Fernandes, Daniel Alvarenga; Kido, Ricardo Yoshio Zanetti; Barros, Ricardo Hoelz de Oliveira; Martins, Daniel Lahan; Penachim, Thiago José; Caserta, Nelson Marcio Gomes

    2016-01-01

    We present a case of immunoglobulin G4 (IgG4)-related disease with pancreatic and extrapancreatic involvement, including the biliary and renal systems. Given the importance of imaging methods for the diagnosis of IgG4-related disease and its differentiation from pancreatic adenocarcinoma, we emphasize important abdominal computed tomography and magnetic resonance imaging findings related to this recently recognized systemic autoimmune disease. PMID:27141136

  11. Application of latent variable models to autoimmune diseases clinimetry

    OpenAIRE

    Molano González, Nicolás

    2015-01-01

    Abstract: Clinical manifestations of autoimmune diseases often are presented as presence or absence of certain symptoms, which in the clinical context can be associated with disease severity. Classical measures like number of symptoms present have been used to assess the severity of disease, nevertheless this score does not reflect particular aspects of each symptom in the severity manifestation. In this setting latent variable models are a natural choice to address the pro...

  12. The role of parvovirus B19 in the pathogenesis of autoimmunity and autoimmune disease.

    Science.gov (United States)

    Kerr, Jonathan R

    2016-04-01

    Human parvovirus B19 is a single-stranded DNA virus which preferentially targets the erythroblasts in the bone marrow. B19 infection commonly causes erythema infectiosum, arthralgia, fetal death, transient aplastic crisis in patients with shortened red cell survival, and persistent infection in people who are immunocompromised. Less common clinical manifestations include atypical skin rashes, neurological syndromes, cardiac syndromes, and various cytopenias. B19 infection has also been associated with development of a variety of different autoimmune diseases, including rheumatological, neurological, neuromuscular, cardiovascular, haematological, nephrological and metabolic. Production of a variety of autoantibodies has been demonstrated to occur during B19 infection and these have been shown to be key to the pathogenesis of the particular disease process in a significant number of cases, for example, production of rheumatoid factor in cases of B19-associated rheumatoid arthritis and production of anti-glutamic acid decarboxylase (GAD) in patients with B19-associated type 1 diabetes mellitus. B19 infection has also been associated with the development of multiple autoimmune diseases in 12 individuals. Documented mechanisms in B19-associated autoimmunity include molecular mimicry (IgG antibody to B19 proteins has been shown to cross react with a variety of recognised human autoantigens, including collagen II, keratin, angiotensin II type 1 receptor, myelin basic protein, cardiolipin, and platelet membrane glycoprotein IIb/IIIa), B19-induced apoptosis with presentation of self-antigens to T lymphocytes, and the phospholipase activity of the B19 unique VP1 protein. PMID:26644521

  13. Toward molecular pathogenesis of an autoimmune disease: Refined genetic mapping of autoimmune polyglandular disease type I (APECED)

    Energy Technology Data Exchange (ETDEWEB)

    Aaltonen, J.; Bjoerses, P.; Peltonen, L. [National Public Health Institute, Helsinki (Finland)] [and others

    1994-09-01

    Autoimmune reactions encoupled to many human diseases are still only partially understood. Unravelling the molecular pathogenesis of inherited diseases with a strong autoimmune component in their clinical expression could help to dissect individual components in the molecular background of abnormal immune response. One such genetic disorder is autosomal recessive autoimmune polyglandular disease type I (PGD I), also known as autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED, MIM 240300). The disease is especially enriched in the genetically isolated population of Finland and we have assigned the APECED locus to human chromosome 21q22.3 in 14 Finnish families by linkage analyses. The best positional lod score of 6.49 was observed with marker D21S49. Based on the history of the Finns, the gene pool of this population clearly demonstrates the consequences of a founder effect and consequent isolation. In the Finnish population, we can take advantage of linkage disequilibrium and allelic association studies to more precisely define the critical DNA region for our disease gene of interest than would be possible by linkage analyses alone. We are now able to define the chromosomal region of interest between two flanking markers locating 1 cM apart. Linkage disequilibrium is observed with three of the markers used in the analyses and this suggests a distance of less than 500 kb to the disease locus, well approachable with molecular cloning techniques. Overlapping YAC and cosmid clones spanning our region of interest will facilitate the cloning of APECED gene in the near future.

  14. Cannabinoids and autoimmune diseases: A systematic review.

    Science.gov (United States)

    Katchan, Valeria; David, Paula; Shoenfeld, Yehuda

    2016-06-01

    Cannabinoids have shown to have a variety effects on body systems. Through CB1 and CB2 receptors, amongst other, they exert an effect by modulating neurotransmitter and cytokine release. Current research in the role of cannabinoids in the immune system shows that they possess immunosuppressive properties. They can inhibit proliferation of leucocytes, induce apoptosis of T cells and macrophages and reduce secretion of pro-inflammatory cytokines. In mice models, they are effective in reducing inflammation in arthritis, multiple sclerosis, have a positive effect on neuropathic pain and in type 1 diabetes mellitus. They are effective as treatment for fibromyalgia and have shown to have anti-fibrotic effect in scleroderma. Studies in human models are scarce and not conclusive and more research is required in this field. Cannabinoids can be therefore promising immunosuppressive and anti-fibrotic agents in the therapy of autoimmune disorders. PMID:26876387

  15. Solar Radiation and Vitamin D: Mitigating Environmental Factors in Autoimmune Disease

    Directory of Open Access Journals (Sweden)

    Gerry K. Schwalfenberg

    2012-01-01

    Full Text Available This paper looks at the environmental role of vitamin D and solar radiation as risk reduction factors in autoimmune disease. Five diseases are considered: multiple sclerosis, type 1 diabetes, rheumatoid arthritis, autoimmune disease of the thyroid, and inflammatory bowel disease. Clinical relevant studies and factors that may indicate evidence that autoimmune disease is a vitamin D-sensitive disease are presented. Studies that have resulted in prevention or amelioration of some autoimmune disease are discussed. An example of the utility of supplementing vitamin D in an unusual autoimmune disease, idiopathic thrombocytic purpura, is presented.

  16. Glassy Dynamics in the Adaptive Immune Response Prevents Autoimmune Disease

    Science.gov (United States)

    Sun, Jun; Deem, Michael

    2006-03-01

    The immune system normally protects the human host against death by infection. However, when an immune response is mistakenly directed at self antigens, autoimmune disease can occur. We describe a model of protein evolution to simulate the dynamics of the adaptive immune response to antigens. Computer simulations of the dynamics of antibody evolution show that different evolutionary mechanisms, namely gene segment swapping and point mutation, lead to different evolved antibody binding affinities. Although a combination of gene segment swapping and point mutation can yield a greater affinity to a specific antigen than point mutation alone, the antibodies so evolved are highly cross-reactive and would cause autoimmune disease, and this is not the chosen dynamics of the immune system. We suggest that in the immune system a balance has evolved between binding affinity and specificity in the mechanism for searching the amino acid sequence space of antibodies. Our model predicts that chronic infection may lead to autoimmune disease as well due to cross-reactivity and suggests a broad distribution for the time of onset of autoimmune disease due to chronic exposure. The slow search of antibody sequence space by point mutation leads to the broad of distribution times.

  17. Allergen-specific immunotherapy and risk of autoimmune disease

    DEFF Research Database (Denmark)

    Linneberg, Allan; Madsen, Flemming; Skaaby, Tea

    2012-01-01

    After 100 years of experience with allergen-specific immunotherapy (SIT), an issue that is still unresolved is whether SIT can act as a trigger of, or as a risk factor for, autoimmune disease. We searched the literature for evidence on this topic....

  18. The role of complement in autoimmune renal disease

    NARCIS (Netherlands)

    Seelen, M. A.; Daha, M. R.

    2006-01-01

    The predominance of renal involvement in autoimmune diseases can most likely be assigned to the specialised function of the kidneys filtrating over 120 ml plasma per minute. Complement activation by autoantibodies directed against planted antigens or antigens already present in renal tissue in the s

  19. Increased Prevalence of Cardiovascular and Autoimmune Diseases in Periodontitis Patients: A Cross-Sectional Study

    NARCIS (Netherlands)

    Nesse, Willem; Dijkstra, P.U.; Abbas, Frank; Spijkervet, F.K.L.; Stijger, A.; Tromp, J.A.H.; van Dijk, J.L.; Vissink, A.

    2010-01-01

    Background: Associations between periodontitis and cardiovascular and autoimmune diseases are most often assessed in patients with a particular cardiovascular or autoimmune disease. To prevent selection bias, this study assesses the existence of associations between periodontitis and cardiovascular

  20. Increased Prevalence of Cardiovascular and Autoimmune Diseases in Periodontitis Patients : A Cross-Sectional Study

    NARCIS (Netherlands)

    Nesse, Willem; Dijkstra, Pieter U.; Abbas, Frank; Spijkervet, Fred K. L.; Stijger, Astrid; Tromp, Jan A. H.; van Dijk, Johan L.; Vissink, Arjan

    2010-01-01

    Background: Associations between periodontitis and cardiovascular and autoimmune diseases are most often assessed in patients with a particular cardiovascular or autoimmune disease. To prevent selection bias, this study assesses the existence of associations between periodontitis and cardiovascular

  1. Contribution of MicroRNAs to autoimmune diseases.

    Science.gov (United States)

    Garo, Lucien P; Murugaiyan, Gopal

    2016-05-01

    MicroRNAs are a class of evolutionarily conserved, short non-coding RNAs that post-transcriptionally modulate the expression of multiple target genes. They are implicated in almost every biological process, including pathways involved in immune homeostasis, such as immune cell development, central and peripheral tolerance, and T helper cell differentiation. Alterations in miRNA expression and function can lead to major dysfunction of the immune system and mediate susceptibility to autoimmune disease. Here, we discuss the role of miRNAs in the maintenance of immune tolerance to self-antigens and the gain or loss of miRNA functions on tissue inflammation and autoimmunity. PMID:26943802

  2. Pulmonary alveolar proteinosis: another autoimmune disease associated with sarcoidosis?

    Science.gov (United States)

    Boerner, Eda Burcu; Costabel, Ulrich; Wessendorf, Thomas Ernst; Theegarten, Dirk; Hetzel, Martin; Drent, Marjolein; Bonella, Francesco

    2016-01-01

    Pulmonary alveolar proteinosis (PAP) is a rare lung disease characterized by the accumulation of surfactant phospholipids and lipoproteins within the alveoli.  Here we report on a female patient who was diagnosed with autoimmune PAP and successfully treated with whole lung lavage (WLL). 15 months after PAP diagnosis the patient developed marked fatigue. Additional tests revealed the diagnosis of sarcoidosis. We can only speculate that PAP and sarcoidosis in our patient are linked to each other based on the fact that other autoimmune disorders have also been associated with sarcoidosis. PMID:27055841

  3. Autologous hematopoietic stem cell transplantation in autoimmune diseases.

    Science.gov (United States)

    Annaloro, Claudio; Onida, Francesco; Lambertenghi Deliliers, Giorgio

    2009-12-01

    The term 'autoimmune diseases' encompasses a spectrum of diseases whose clinical manifestations and, possibly, biological features vary widely. The results of conventional treatment are considered unsatisfactory in aggressive forms, with subsets of patients having short life expectancies. Relying on wide experimental evidence and more feeble clinical data, some research groups have used autologous hematopoietic stem cell transplantation (HSCT) in the most disabling autoimmune diseases with the aim of resetting the patient's immune system. Immunoablative conditioning regimens are preferred over their myeloablative counterparts, and some form of in vivo and/or ex vivo T-cell depletion is generally adopted. Despite 15 years' experience, published controlled clinical trials are still lacking, with the evidence so far available coming from pilot studies and registry surveys. In multiple sclerosis, clinical improvement, or at least lasting disease stabilization, can be achieved in the majority of the patients; nevertheless, the worst results are observed in patients with progressive disease, where no benefit can be expected from conventional therapy. Concerning rheumatologic diseases, wide experience has been acquired in systemic sclerosis, with long-term improvements in cutaneous disease being frequently reported, although visceral involvement remains unchanged at best. Autografting has proved to be barely effective in rheumatoid arthritis and quite toxic in juvenile idiopathic arthritis, whereas it leads to clinical remission and the reversal of visceral impairment in the majority of patients with systemic lupus erythematosus. A promising indication is Crohn's disease, in which long-term endoscopic remission is frequently observed. Growing experience with autologous HCST in autoimmune diseases has progressively reduced concerns about transplant-related mortality and secondary myelodysplasia/leukemia. Therefore, a sustained complete remission seems to be within the

  4. Automated Periodontal Diseases Classification System

    Directory of Open Access Journals (Sweden)

    Aliaa A. A. Youssif

    2012-01-01

    Full Text Available This paper presents an efficient and innovative system for automated classification of periodontal diseases, The strength of our technique lies in the fact that it incorporates knowledge from the patients' clinical data, along with the features automatically extracted from the Haematoxylin and Eosin (H&E stained microscopic images. Our system uses image processing techniques based on color deconvolution, morphological operations, and watershed transforms for epithelium & connective tissue segmentation, nuclear segmentation, and extraction of the microscopic immunohistochemical features for the nuclei, dilated blood vessels & collagen fibers. Also, Feedforward Backpropagation Artificial Neural Networks are used for the classification process. We report 100% classification accuracy in correctly identifying the different periodontal diseases observed in our 30 samples dataset.

  5. Modulation of TNF receptor family members to inhibit autoimmune disease.

    Science.gov (United States)

    Weinberg, Andrew D; Montler, Ryan

    2005-04-01

    Certain members of the TNF-receptor family have shown proinflammatory function during immune activation and can be directly involved with the pathogenic effects observed during an autoimmune episode. The TNF-R family members summarized in this review includes: TNF-RI + II, OX40, and 4-1BB and they are expressed on a variety of leukocytes within the body. Studies within the last decade suggest that all of these proteins or their natural ligands can be targeted with various agents designed to diminish clinical signs of disease in autoimmune models. The data from the preclinical models specifically involving TNF-blockade have led to the development of clinical trials for patients with multiple sclerosis and rheumatoid arthritis. This review will chronicle the preclinical development of agents designed to inhibit OX40 and 4-1BB functions in autoimmunity and discuss relevant preclinical and clinical data associated with TNF-blockade. PMID:15853742

  6. Induction of Regulatory t Cells by Low Dose il2 in Autoimmune and Inflammatory Diseases

    Science.gov (United States)

    2016-04-18

    Rheumatoid Arthritis; Ankylosing Spondylitis; Systemic Lupus Erythematosus; Psoriasis; Behcet's Disease; Wegener's Granulomatosis; Takayasu's Disease; Crohn's Disease; Ulcerative Colitis; Autoimmune Hepatitis; Sclerosing Cholangitis

  7. P-Glycoprotein and Drug Resistance in Systemic Autoimmune Diseases

    Directory of Open Access Journals (Sweden)

    Andrea Picchianti-Diamanti

    2014-03-01

    Full Text Available Autoimmune diseases such as systemic lupus erythematosus (SLE, rheumatoid arthritis (RA and psoriatic arthritis (PsA are chronic inflammatory disorders of unknown etiology characterized by a wide range of abnormalities of the immune system that may compromise the function of several organs, such as kidney, heart, joints, brain and skin. Corticosteroids (CCS, synthetic and biologic immunosuppressive agents have demonstrated the capacity to improve the course of autoimmune diseases. However, a significant number of patients do not respond or develop resistance to these therapies over time. P-glycoprotein (P-gp is a transmembrane protein that pumps several drugs out of the cell, including CCS and immunosuppressants; thus, its over-expression or hyper-function has been proposed as a possible mechanism of drug resistance in patients with autoimmune disorders. Recently, different authors have demonstrated that P-gp inhibitors, such as cyclosporine A (CsA and its analogue Tacrolimus, are able to reduce P-gp expression and or function in SLE, RA and PsA patients. These observations suggest that P-gp antagonists could be adopted to revert drug resistance and improve disease outcome. The complex inter-relationship among drug resistance, P-gp expression and autoimmunity still remains elusive.

  8. Ultraviolet radiation and autoimmune disease: insights from epidemiological research

    International Nuclear Information System (INIS)

    This review examines the epidemiological evidence that suggests ultraviolet radiation (UVR) may play a protective role in three autoimmune diseases: multiple sclerosis, insulin-dependent diabetes mellitus and rheumatoid arthritis. To date, most of the information has accumulated from population studies that have studied the relationship between geography or climate and autoimmune disease prevalence. An interesting gradient of increasing prevalence with increasing latitude has been observed for at least two of the three diseases. This is most evident for multiple sclerosis, but a similar gradient has been shown for insulin-dependent diabetes mellitus in Europe and North America. Seasonal influences on both disease incidence and clinical course and, more recently, analytical studies at the individual level have provided further support for a possible protective role for UVR in some of these diseases but the data are not conclusive. Organ-specific autoimmune diseases involve Th1 cell-mediated immune processes. Recent work in photoimmunology has shown ultraviolet B (UVB) can specifically attenuate these processes through several mechanisms which we discuss. In particular, the possible contribution of an UVR-induced increase in serum vitamin D (1,25(OH)2D3) levels in the beneficial immunomodulation of these diseases is discussed

  9. Total lymphoid irradiation in autoimmune diseases and organ transplantation

    International Nuclear Information System (INIS)

    Total lymphoid irradiation, a treatment program developed for the management of Hodgkin's disease, induces profound immunologic changes. These effects have been characterized in animal systems and are now beginning to be exploited in humans for the treatment of autoimmune disease and preparation for organ transplantation. A burgeonning new era of clinical research is developing that will require multidisciplinary collaboration in order to realize its ultimate potential

  10. Low Serum Hepcidin in Patients with Autoimmune Liver Diseases

    OpenAIRE

    Lyberopoulou, Aggeliki; Chachami, Georgia; Gatselis, Nikolaos K.; Kyratzopoulou, Eleni; Saitis, Asterios; Gabeta, Stella; Eliades, Petros; Paraskeva, Efrosini; Zachou, Kalliopi; Koukoulis, George K.; Mamalaki, Avgi; Dalekos, George N; Simos, George

    2015-01-01

    Hepcidin, a liver hormone, is important for both innate immunity and iron metabolism regulation. As dysfunction of the hepcidin pathway may contribute to liver pathology, we analysed liver hepcidin mRNA and serum hepcidin in patients with chronic liver diseases. Hepcidin mRNA levels were determined in liver biopsies obtained from 126 patients with HCV (n = 21), HBV (n = 23), autoimmune cholestatic disease (primary biliary cirrhosis and primary sclerosing cholangitis; PBC/PSC; n = 34), autoimm...

  11. Low Serum Hepcidin in Patients with Autoimmune Liver Diseases.

    Directory of Open Access Journals (Sweden)

    Aggeliki Lyberopoulou

    Full Text Available Hepcidin, a liver hormone, is important for both innate immunity and iron metabolism regulation. As dysfunction of the hepcidin pathway may contribute to liver pathology, we analysed liver hepcidin mRNA and serum hepcidin in patients with chronic liver diseases. Hepcidin mRNA levels were determined in liver biopsies obtained from 126 patients with HCV (n = 21, HBV (n = 23, autoimmune cholestatic disease (primary biliary cirrhosis and primary sclerosing cholangitis; PBC/PSC; n = 34, autoimmune hepatitis (AIH; n = 16 and non-alcoholic fatty liver disease (NAFLD; n = 32. Sera sampled on the biopsy day from the same patients were investigated for serum hepcidin levels. Hepatic hepcidin mRNA levels correlated positively with ferritin and negatively with serum γ-GT levels. However, no correlation was found between serum hepcidin and either ferritin or liver hepcidin mRNA. Both serum hepcidin and the serum hepcidin/ferritin ratio were significantly lower in AIH and PBC/PSC patients' sera compared to HBV, HCV or NAFLD (P<0.001 for each comparison and correlated negatively with serum ALP levels. PBC/PSC and AIH patients maintained low serum hepcidin during the course of their two-year long treatment. In summary, parallel determination of liver hepcidin mRNA and serum hepcidin in patients with chronic liver diseases shows that circulating hepcidin and its respective ratio to ferritin are significantly diminished in patients with autoimmune liver diseases. These novel findings, once confirmed by follow-up studies involving bigger size and better-matched disease subgroups, should be taken into consideration during diagnosis and treatment of autoimmune liver diseases.

  12. Radiosensitivity of peripheral blood lymphocytes in autoimmune disease

    International Nuclear Information System (INIS)

    The proliferation of peripheral blood lymphocytes, cultured with Con A, can be inhibited by ionizing radiation. Lymphocytes from patients with conditions associated with autoimmunity, such as rheumatoid arthritis, systemic lupus erythematosus and polymyositis, are more radiosensitive than those from healthy volunteers or patients with conditions not associated with autoimmunity. Nuclear material isolated from the lymphocytes of patients with autoimmune diseases is, on average, lighter in density than the nuclear material from most healthy controls. This difference in density is not related to increased sensitivity to ionizing radiation but the degree of post-irradiation change in density (lightening) is proportional to the initial density, i.e. more dense nuclear material always shows a greater upward shift after radiation. The recovery of pre-irradiation density of nuclear material, 1 h after radiation exposure, taken as an indication of DNA repair, correlates with the radiosensitivity of lymphocyte proliferation (Con A response); failure to return to pre-irradiation density being associated with increased sensitivity of proliferative response. These results require extension but, taken with previously reported studied of the effects of DNA methylating agents, support the idea that DNA damage and its defective repair could be important in the aetio-pathogenesis of autoimmune disease. (author)

  13. Radiosensitivity of peripheral blood lymphocytes in autoimmune disease

    Energy Technology Data Exchange (ETDEWEB)

    Harris, G. (Kennedy Inst. of Rheumatology, London (UK). Div. of Experimental Pathology); Cramp, W.A.; Edwards, J.C.; George, A.M.; Sabovljev, S.A.; Hart, L.; Hughes, G.R.V. (Hammersmith Hospital, London (UK)); Denman, A.M. (Northwich Park Hospital, Harrow (UK)); Yatvin, M.B. (Wisconsin Clinical Cancer Center, Madison (USA))

    1985-06-01

    The proliferation of peripheral blood lymphocytes, cultured with Con A, can be inhibited by ionizing radiation. Lymphocytes from patients with conditions associated with autoimmunity, such as rheumatoid arthritis, systemic lupus erythematosus and polymyositis, are more radiosensitive than those from healthy volunteers or patients with conditions not associated with autoimmunity. Nuclear material isolated from the lymphocytes of patients with autoimmune diseases is, on average, lighter in density than the nuclear material from most healthy controls. This difference in density is not related to increased sensitivity to ionizing radiation but the degree of post-irradiation change in density (lightening) is proportional to the initial density, i.e. more dense nuclear material always shows a greater upward shift after radiation. The recovery of pre-irradiation density of nuclear material, 1 h after radiation exposure, taken as an indication of DNA repair, correlates with the radiosensitivity of lymphocyte proliferation (Con A response); failure to return to pre-irradiation density being associated with increased sensitivity of proliferative response. These results require extension but, taken with previously reported studied of the effects of DNA methylating agents, support the idea that DNA damage and its defective repair could be important in the aetio-pathogenesis of autoimmune disease.

  14. Autoimmune disease and risk for Parkinson disease A population-based case-control study

    DEFF Research Database (Denmark)

    Rugbjerg, K.; Friis, S.; Ritz, B.;

    2009-01-01

    Objective: Inflammatory mediators are increased in autoimmune diseases and may activate microglia and might cause an inflammatory state and degeneration of dopaminergic neurons in the brain. Thus, we evaluated whether having an autoimmune disease increases the risk for developing Parkinson disease...... do not support the hypothesis that autoimmune diseases increase the risk for Parkinson disease. The decreased risk observed among patients with rheumatoid arthritis might be explained by underdiagnosis of movement disorders such as Parkinson disease in this patient group or by a protective effect...... among inhabitants of Denmark who were alive at the date of the patient's diagnosis. The main exposure measure was a hospital diagnosis of 1 of 32 selected autoimmune diseases recorded 5 or more years before the index date in the files of the Danish Hospital Register. Results: We observed no overall...

  15. Presence of Autoimmune Diseases in Alopecia Areata Patients and Their Families and Its Effect on Prognosis

    OpenAIRE

    Hatice Ergün Duman; Afet Akdağ Köse; Halim İşsever

    2016-01-01

    Objective: We aimed to investigate the role of autoimmunity in the etiopathogenesis of alopecia areata (AA) and the effects of the coexisting autoimmune diseases on the prognosis of AA. Methods: The records of 134 AA patients diagnosed in the dermatology and venereology outpatient clinic were retrospectively analyzed for the history of concomitant autoimmune disease and the family history for autoimmune diseases. Results: Of the 134 patients, 79 were males, 55 were females. The rate of ...

  16. ANTI-B CELL THERAPY OF AUTOIMMUNE DISEASES

    Directory of Open Access Journals (Sweden)

    A. L. Masliansky

    2007-01-01

    Full Text Available Abstract. Our understanding of the multiple physiological and pathological functions of B-cells continues to expand at a fascinating rate. As pathogenic elements in the development of autoimmune diseases, B-cells have become the focus of new therapeutics. Based on the published data, rituximab, a chimeric monoclonal antibody to CD20, when used in combination with other agents (i.e., cyclophosphamide or methotrexate, appears to be a reasonable treatment option for refractory RA. There are now numerous case reports and small openlabel series using rituximab in many autoimmune diseases, others then RA. While these data must be interpreted with caution, they suggest that rituximab may be a promising addition to the therapeutic armamentarium in these diseases. However, additional controlled trials need to be conducted to confirm clinical efficacy, further define optimal dosage, response rates, comparative long-term efficacy, and treatment algorithm for rituximab in these patients.

  17. Refractive surgery in systemic and autoimmune disease

    Directory of Open Access Journals (Sweden)

    Majed AlKharashi

    2014-01-01

    Full Text Available Patients with underlying systemic disease represent challenging treatment dilemma to the refractive surgeon. The refractive error in this patient population is accompanied by a systemic disease that may have an ocular or even a corneal component. The literature is rather sparse about the use of laser refractive surgery (LRS and such procedure is not approved by the United States Food and Drug Administration (FDA in this patient population. Patients with collagen vascular disease, diabetes mellitus (DM, allergic and atopic disease, or human immunodeficiency virus (HIV are never ideal for LRS. Patients with uncontrolled systemic disease or ocular involvement of the disease should not undergo LRS. However, a patient with well-controlled and mild disease, no ocular involvement, and not on multidrug regimen may be a suitable candidate if they meet stringent criteria. There is a need for a large, multicenter, controlled trial to address the safety and efficacy of LRS in patients with systemic disease before such technology can be widely adopted by the refractive surgery community.

  18. Autoimmune hepatitis in India: profile of an uncommon disease

    Directory of Open Access Journals (Sweden)

    Baba Chalamalasetty S

    2005-08-01

    Full Text Available Abstract Background Autoimmune hepatitis (AIH has been reported to show considerable geographical variation in frequency and clinical manifestations. It is considered a rare cause of liver disease in India. The present study was undertaken to determine the incidence, clinical, biochemical and histological profile of AIH in this part of the world. Methods Patients presenting with acute or chronic liver disease between January 1999 and June 2002 were evaluated prospectively. AIH was diagnosed using the international autoimmune hepatitis group criteria. Workup included clinical, biochemical, USG, viral markers, UGI endoscopy, AI markers (ANA, SMA, Anti-LKM, AMA, RF, p-ANCA using indirect immunofluorescence and liver biopsy if possible. Results Forty-one of 2401 (1.70% patients were diagnosed to have autoimmune liver disease. Out of these, 38 had autoimmune hepatitis and the rest 3 had primary biliary cirrhosis. The mean age of the patients of autoimmune hepatitis was 36.2 (15.9 years, 34 (89.4% were females, and the duration of symptoms was 20.3 (20.5 months. Nineteen (50% of them presented with chronic hepatitis, 13 (34.2% as cirrhosis, 5 (13.1% with acute hepatitis and 1 (2.6% with cholestatic hepatitis. The presentations were jaundice in 21 (55.2%, pedal edema and hepatomegaly in 17 (44.7%, splenomegaly in 13 (34.2%, encephalopathy, abdominal pain in 9 (23.6% and fever in 8 (21%. Twelve had esophageal varices and 3 had bled. Biochemical parameters were ALT 187 (360 U/L, AST 157 (193 U/L, ALP 246 (254 U/L, globulin 4.1 (1.6 g/dL, albumin 2.8 (0.9 g/dL, bilirubin 5.2 (7.4 mg/dL, prothrombin time 17 (7 sec and ESR 47 (17 sec. The autoimmune markers were SMA (24, ANA (15, both SMA and ANA (4, AMA (1, rheumatoid factor (2, pANCA (1, and Anti-LKM in none. Thirty (79% patients had definite AIH and eight (21% had probable AI hepatitis. Associated autoimmune diseases was seen in 15/38 (39.4%, diabetes 4, hypothyroidism 3, vitiligo 2, thrombocytopenia 2

  19. Involvement of Fas/FasL system in the pathogenesis of autoimmune diseases and Wilson's disease.

    Science.gov (United States)

    Stassi, G; Di Felice, V; Todaro, M; Cappello, F; Zummo, G; Farina, F; Trucco, M; De Maria, R

    1999-01-01

    The interaction of Fas with FasL has been demonstrated to be implicated in the pathogenesis of several autoimmune and liver diseases. Recently, attention has been focused on the hypothesis that thyrocytes and beta cells undergo massive Fas/FasL-mediated apoptosis during autoimmune response. Similarly, hepatocyte cell death occurring following copper accumulation points towards the same mechanism.

  20. Autoimmune diseases in pregnancy: maternal and fetal outcomes

    Directory of Open Access Journals (Sweden)

    Pavithra M. Vengetesh

    2015-02-01

    Full Text Available Background: The aim of this study was to assess the impact of autoimmune connective tissue disorders on the outcomes of pregnancy and the influence of treatment on pregnancy. Methods: Thirty-seven antenatal patients with autoimmune connective tissue diseases, comprising of Systemic Lupus Erythematosus (SLE, primary antiphospholipid antibody syndrome (APS, Mixed Connective Tissue Diseases (MCTD, ankylosing spondylitis and Takayasu arteritis were analysed. Results: Multigravidas constituted 89.4% and were associated with bad obstetric history. Before diagnosis and treatment, serious maternal complications of eclampsia and thromboembolism were observed in patients with SLE and APS. The live birth rates were 9% and 2.4% respectively in patients with SLE and APS. With appropriate treatment- aspirin, heparin and immunosuppressant, the live birth rates were raised to 70% in SLE and 100% in APS patients. Investigation for autoimmune disease in recurrent pregnancy loss is important. A rare association between MCTD and congenital anomaly - Rhizomelic chondrodysplasia punctata was observed. Preeclampsia, gestational diabetes, fetal growth restriction and preterm labour were the common complications noted. Conclusions: Active disease at onset of pregnancy, presence of Anti-ds DNA antibodies and secondary APS were strong predictors of poor pregnancy outcomes among patients with SLE. Vigilant monitoring during pregnancy is required for favourable outcomes. [Int J Reprod Contracept Obstet Gynecol 2015; 4(1.000: 9-14

  1. Tight Junctions, Intestinal Permeability, and Autoimmunity Celiac Disease and Type 1 Diabetes Paradigms

    NARCIS (Netherlands)

    Visser, Jeroen; Rozing, Jan; Sapone, Anna; Lammers, Karen; Fasano, Alessio; Fromm, M; Schulzke, JD

    2009-01-01

    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 celiac disease (CD), an autoimmune enteropathy, and type I diabetes (TID), a hyperglycosaemia caused by a destructive autoimmune p

  2. Automated Periodontal Diseases Classification System

    OpenAIRE

    Aliaa A. A. Youssif; Abeer Saad Gawish,; Mohammed Elsaid Moussa

    2012-01-01

    This paper presents an efficient and innovative system for automated classification of periodontal diseases, The strength of our technique lies in the fact that it incorporates knowledge from the patients' clinical data, along with the features automatically extracted from the Haematoxylin and Eosin (H&E) stained microscopic images. Our system uses image processing techniques based on color deconvolution, morphological operations, and watershed transforms for epithelium & connective tissue se...

  3. Phenomics in Autoimmune and Inflammatory Diseases

    Science.gov (United States)

    2016-04-18

    Healthy Volunteer; Rheumatoid Arthritis; Ankylosing Spondylitis; Systemic Lupus Erythematosus/Antiphospholipid Syndrome; FMF; Cryopyrin-Associated Periodic Syndromes /TNF-receptor Associated Periodic Syndrome; Vasculitis; Uveitis; Myositis; Crohn's Disease; Ulcerative Rectocolitis; Type 1 Diabetes; Unclassified IAD Knee and/or Hip Arthritis, Muscular Dystrophy

  4. FOXP3+ Treg Cells and Gender Bias in Autoimmune Diseases

    OpenAIRE

    Nie, Jia; Li, Yang Yang; Zheng, Song Guo; Tsun, Andy; Li, Bin

    2015-01-01

    CD4+CD25+ regulatory T (Treg) cells play a pivotal role in the maintenance of immune homeostasis, where the X-linked master transcription factor forkhead box P3 (FOXP3) determines Treg cell development and function. Genetic deficiency of foxp3 induces dysfunction of Treg cells and immuno-dysregulation, polyendocrinopathy, enteropathy, and X-linked syndrome in humans. Functionally deficient Treg cells or the development of exTreg cells positively correlate with autoimmune diseases, such as sys...

  5. Role of soluble Fas ligand in autoimmune diseases

    Institute of Scientific and Technical Information of China (English)

    Ning-Li Li; Tong Zhou; Dong-Qing Zhang; Hong Nie; Qi-Wen Yu; Ji-Ying Zhang; An-Lun Ma; Bai-Hua Shen; Li Wang; Jun Bai; Xue-Hua Chen

    2004-01-01

    AIM: To investigate the role of soluble Fas ligand in autoimmune diseases.METHODS: RT-PCR was performed to amplify sFasL cDNA from the total RNA extracted from activated human peripheral blood lymphocytes. DNA fragments were cloned into PCR vector. After sequenced, sFasL gene fragments were inserted into pQE-31 vector and expressed in E. Coli M15respectively. Proteins were purified through affinity chromatography column with ligand of 6xHis tag and identified by SDS-PAGE and Western blot. Mice were immunized with sFasL protein and specific anti-serum was harvested 6 wk after immunization. Monoclonal anti-human FasL antibody was made from the immunized mice. Serum level of sFasL in different patients was detected using antiFasL antibodies from the immunized mice.RESULTS: The protein expressed was 24 ku by SDS-PAGE electrophrosis. The protein was specially bound to antihuman FasL antibody by Western blot analysis. The sFasL protein could induce Jurket cell apoptosis in vitro. The concentration of serum sFasL in patients with autoimmune diseases was higher than that in normal individuals. sFasL could reduce arthritis in collagen induced arthritis (CIA)mice model by subcutaneous injection.CONCLUSION: sFasL may be involved in either induction of apoptosis or autoimmune diseases. Furthermore, sFasL may have potential application in treatment of autoimmune diseases.

  6. PEG Minocycline-Liposomes Ameliorate CNS Autoimmune Disease

    OpenAIRE

    Wei Hu; Josbert Metselaar; Li-Hong Ben; Cravens, Petra D.; Mahendra P Singh; Frohman, Elliot M.; Eagar, Todd N.; Racke, Michael K.; Kieseier, Bernd C.; Olaf Stüve

    2009-01-01

    BACKGROUND: Minocycline is an oral tetracycline derivative with good bioavailability in the central nervous system (CNS). Minocycline, a potent inhibitor of matrix metalloproteinase (MMP)-9, attenuates disease activity in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). Potential adverse effects associated with long-term daily minocycline therapy in human patients are concerning. Here, we investigated whether less frequent treatment with long-circul...

  7. Association between Autoimmune Rheumatic Diseases and the Risk of Dementia

    OpenAIRE

    Kang Lu; Hao-Kuang Wang; Chih-Ching Yeh; Chih-Yuan Huang; Pi-Shan Sung; Liang-Chao Wang; Chih-Hsin Muo; Fung-Chang Sung; Han-Jung Chen; Ying-Chun Li; Li-Ching Chang; Kuen-Jer Tsai

    2014-01-01

    Aim. Autoimmune rheumatic diseases (ARD) are characterized by systemic inflammation and may affect multiple organs and cause vascular events such as ischemic stroke and acute myocardial infarction. However, the association between ARD and increased risk of dementia is uncertain. This is a retrospective cohort study to investigate and compare the risk of dementia between patients clinically diagnosed with ARD and non-ARD patients during a 5-year follow-up period. Methods. Data were obtained fr...

  8. Peripheral Nervous System Manifestations in Systemic Autoimmune Diseases

    OpenAIRE

    Cojocaru, Inimioara Mihaela; COJOCARU, Manole; SILOSI, Isabela; VRABIE, Camelia Doina

    2014-01-01

    The peripheral nervous system refers to parts of the nervous system outside the brain and spinal cord. Systemic autoimmune diseases can affect both the central and peripheral nervous systems in a myriad of ways and through a heterogeneous number of mechanisms leading to many different clinical manifestations. As a result, neurological complications of these disorders can result in significant morbidity and mortality. The most common complication of peripheral nervous system (PNS) involvement ...

  9. [Autoimmunity in pathogenesis of chronic obstructive pulmonary disease].

    Science.gov (United States)

    Urboniene, Daiva; Sakalauskas, Raimundas; Sitkauskiene, Brigita

    2005-01-01

    For years, smoking induced inflammatory reaction, comprised mainly of neutrophils and macrophages, has been accepted to be the major component in pathogenesis of chronic obstructive pulmonary disease. New developments in molecular and cell biology have provided scientists with new knowledge and understanding of inflammatory processes in lung. Recent reports have underlined the role of autoimmunity and T lymphocytes as a potential important factor, which takes place in the pathogenesis of chronic obstructive pulmonary disease. This article reviews potential mechanism of T cell mediated immune response in chronic obstructive pulmonary disease. PMID:15827384

  10. Regulatory T cells and B cells: implication on autoimmune diseases

    OpenAIRE

    Wang, Ping; Zheng, Song Guo

    2013-01-01

    The regulatory T (Treg) cells play an important role in the maintenance of homeostasis and the prevention of autoimmune diseases. Although most studies are focusing on the role of Treg cells in T cells and T cells-mediated diseases, these cells also directly affect B cells and other non-T cells. This manuscript updates the role of Treg cells on the B cells and B cell-mediated diseases. In addition, the mechanisms whereby Treg cells suppress B cell responses have been discussed.

  11. Undifferentiated vasculitis or an evolving systemic autoimmune rheumatic disease?

    Science.gov (United States)

    Fatimah, Nafeesah; Ussaid, Ahmad; Rasheed, Aflak

    2016-01-01

    Undifferentiated connective tissue diseases usually present with arthralgias, sicca symptoms, Raynaud's phenomenon and leucopenia. This case presents the atypical presentation of an undifferentiated connective tissue disease with extensive cutaneous involvement of fingers and toes leading to gangrene with absence of typical rheumatological symptoms. The autoimmune profile showed positive ANA and anti-Ro/SS-A. Thromboembolism was ruled out on the basis of transthoracic and transesophageal echo. She was treated with I/V corticosteroids and cyclophosphamide that halted the disease progression. PMID:27574560

  12. Autoimmune diseases induced by TNF-targeted therapies: analysis of 233 cases.

    Science.gov (United States)

    Ramos-Casals, Manuel; Brito-Zerón, Pilar; Muñoz, Sandra; Soria, Natalia; Galiana, Diana; Bertolaccini, Laura; Cuadrado, Maria-Jose; Khamashta, Munther A

    2007-07-01

    Tumor necrosis factor (TNF)-targeted therapies are increasingly used for a rapidly expanding number of rheumatic and autoimmune diseases. With this use and longer follow-up periods of treatment, there are a growing number of reports of the development of autoimmune processes related to anti-TNF agents. We have analyzed the clinical characteristics, outcomes, and patterns of association with the different anti-TNF agents used in all reports of autoimmune diseases developing after TNF-targeted therapy found through a MEDLINE search of articles published between January 1990 and December 2006. We identified 233 cases of autoimmune diseases (vasculitis in 113, lupus in 92, interstitial lung diseases in 24, and other diseases in 4) secondary to TNF-targeted therapies in 226 patients. The anti-TNF agents were administered for rheumatoid arthritis (RA) in 187 (83%) patients, Crohn disease in 17, ankylosing spondylitis in 7, psoriatic arthritis in 6, juvenile RA in 5, and other diseases in 3. The anti-TNF agents administered were infliximab in 105 patients, etanercept in 96, adalimumab in 21, and other anti-TNF agents in 3. We found 92 reported cases of lupus following anti-TNF therapy (infliximab in 40 cases, etanercept in 37, and adalimumab in 15). Nearly half the cases fulfilled 4 or more classification criteria for systemic lupus erythematosus (SLE), which fell to one-third after discarding preexisting lupus-like features. One hundred thirteen patients developed vasculitis after receiving anti-TNF agents (etanercept in 59 cases, infliximab in 47, adalimumab in 5, and other agents in 2). Leukocytoclastic vasculitis was the most frequent type of vasculitis, and purpura was the most frequent cutaneous lesion. A significant finding was that one-quarter of patients with vasculitis related to anti-TNF agents had extracutaneous involvement. Twenty-four cases of interstitial lung disease associated with the use of anti-TNF agents were reported. In these patients, 2 specific

  13. Biologic therapy for autoimmune diseases: an update.

    Science.gov (United States)

    Rosman, Ziv; Shoenfeld, Yehuda; Zandman-Goddard, Gisele

    2013-01-01

    Biologic therapies for rheumatologic diseases, which are targeted at molecules involved in the mechanisms of the immune system, provide an alternative to the existing treatment methods of disease-modifying anti-rheumatic drugs and other immunosuppressive medications. However, the current drawbacks of biologic therapies, including the inconvenience of intravenous administration, the high costs of these drugs, and the adverse events associated with them, prevent their wide use as first-line medications. This review provides an update of the recent literature on the new biologic therapies available. The review concentrates on nine drugs: tocilizumab, rituximab, ofatumumab, belimumab, epratuzumab, abatacept, golimumab, certolizumab, and sifalimumab, which are used as therapies for rheumatoid arthritis, spondyloarthritis, systemic lupus erythematosus, systemic sclerosis, or vasculitis. PMID:23557513

  14. Association of Addison's disease with autoimmune disorders--a long-term observation of 180 patients.

    OpenAIRE

    Kasperlik-Zaluska, A. A.; Migdalska, B.; Czarnocka, B; Drac-Kaniewska, J.; Niegowska, E.; Czech, W.

    1991-01-01

    This study aimed at evaluating the frequency of autoimmune disorders in Addison's disease. We have observed 180 patients (113 females, 67 males, aged 9-74 years) for 1 to 26 years. Tuberculosis was noted in 54 patients. Autoimmune disorders were found in 80 patients (44%); however, 125 (69%) patients were believed to have an autoimmune origin of adrenocortical insufficiency. In 20 patients two or more autoimmune disorders were found to coexist with Addison's disease.

  15. Bioluminescence in vivo imaging of autoimmune encephalomyelitis predicts disease

    Directory of Open Access Journals (Sweden)

    Steinman Lawrence

    2008-02-01

    Full Text Available Abstract Background Experimental autoimmune encephalomyelitis is a widely used animal model to understand not only multiple sclerosis but also basic principles of immunity. The disease is scored typically by observing signs of paralysis, which do not always correspond with pathological changes. Methods Experimental autoimmune encephalomyelitis was induced in transgenic mice expressing an injury responsive luciferase reporter in astrocytes (GFAP-luc. Bioluminescence in the brain and spinal cord was measured non-invasively in living mice. Mice were sacrificed at different time points to evaluate clinical and pathological changes. The correlation between bioluminescence and clinical and pathological EAE was statistically analyzed by Pearson correlation analysis. Results Bioluminescence from the brain and spinal cord correlates strongly with severity of clinical disease and a number of pathological changes in the brain in EAE. Bioluminescence at early time points also predicts severity of disease. Conclusion These results highlight the potential use of bioluminescence imaging to monitor neuroinflammation for rapid drug screening and immunological studies in EAE and suggest that similar approaches could be applied to other animal models of autoimmune and inflammatory disorders.

  16. NK Cell Subtypes as Regulators of Autoimmune Liver Disease

    Science.gov (United States)

    2016-01-01

    As major components of innate immunity, NK cells not only exert cell-mediated cytotoxicity to destroy tumors or infected cells, but also act to regulate the functions of other cells in the immune system by secreting cytokines and chemokines. Thus, NK cells provide surveillance in the early defense against viruses, intracellular bacteria, and cancer cells. However, the effecter function of NK cells must be exquisitely controlled to prevent inadvertent attack against normal “self” cells. In an organ such as the liver, where the distinction between immunotolerance and immune defense against routinely processed pathogens is critical, the plethora of NK cells has a unique role in the maintenance of homeostasis. Once self-tolerance is broken, autoimmune liver disease resulted. NK cells act as a “two-edged weapon” and even play opposite roles with both regulatory and inducer activities in the hepatic environment. That is, NK cells act not only to produce inflammatory cytokines and chemokines, but also to alter the proliferation and activation of associated lymphocytes. However, the precise regulatory mechanisms at work in autoimmune liver diseases remain to be identified. In this review, we focus on recent research with NK cells and their potential role in the development of autoimmune liver disease. PMID:27462349

  17. Th17 Cells in Autoimmune and Infectious Diseases

    Directory of Open Access Journals (Sweden)

    José Francisco Zambrano-Zaragoza

    2014-01-01

    Full Text Available The view of CD4 T-cell-mediated immunity as a balance between distinct lineages of Th1 and Th2 cells has changed dramatically. Identification of the IL-17 family of cytokines and of the fact that IL-23 mediates the expansion of IL-17-producing T cells uncovered a new subset of Th cells designated Th17 cells, which have emerged as a third independent T-cell subset that may play an essential role in protection against certain extracellular pathogens. Moreover, Th17 cells have been extensively analyzed because of their strong association with inflammatory disorders and autoimmune diseases. Also, they appear to be critical for controlling these disorders. Similar to Th1 and Th2 cells, Th17 cells require specific cytokines and transcription factors for their differentiation. Th17 cells have been characterized as one of the major pathogenic Th cell populations underlying the development of many autoimmune diseases, and they are enhanced and stabilized by IL-23. The characteristics of Th17 cells, cytokines, and their sources, as well as their role in infectious and autoimmune diseases, are discussed in this review.

  18. Celiac autoimmunity in autoimmune thyroid disease is highly prevalent with a questionable impact

    Directory of Open Access Journals (Sweden)

    Bharat Rakeshkumar Sharma

    2016-01-01

    Full Text Available Introduction: The prevalence of autoimmune thyroid disease (AITD is 10–12% in the general population worldwide. Among various disorders co-existing with AITD, the concomitance of celiac disease (CD with AITD results in poor absorption of thyroid medications and results in higher doses of the same. Institution of gluten-free diet (GFD in this cohort helps reduce medication doses. Aim: To screen patients with AITD for the presence of celiac autoimmunity (CA. Materials and Methods: A total of 280 consecutive patients with AITD attending the thyroid Out-patient Department of a tertiary care hospital were screened for the presence of tissue transglutaminase antibodies (immunoglobulin A tissue transglutaminase. Those with a positive titer (but < 10 times the upper limit of normal underwent upper gastrointestinal endoscopy and duodenal mucosal biopsy for the diagnosis of CD, followed by institution of GFD in confirmed cases. Results: Of a total of 280 (182 females and 98 males patients with AITD screened, 24 (8.6% turned out to be positive for CA. Of 24 (8.6%, 15 (8.24% females and 9 (9.18% males were positive for CA. There was no statistically significant difference in the thyroxine doses required for normalization of thyroid function and the weight of the patients in CA positive and CA negative patients. Conclusions: The prevalence of CD in patients with AITD is much greater than in the general population. This forms the basis for screening patients with AITD for presence of CD.

  19. Celiac autoimmunity in autoimmune thyroid disease is highly prevalent with a questionable impact

    Science.gov (United States)

    Sharma, Bharat Rakeshkumar; Joshi, Ameya S.; Varthakavi, Premlata K.; Chadha, Manoj D.; Bhagwat, Nikhil M.; Pawal, Pratibha S.

    2016-01-01

    Introduction: The prevalence of autoimmune thyroid disease (AITD) is 10–12% in the general population worldwide. Among various disorders co-existing with AITD, the concomitance of celiac disease (CD) with AITD results in poor absorption of thyroid medications and results in higher doses of the same. Institution of gluten-free diet (GFD) in this cohort helps reduce medication doses. Aim: To screen patients with AITD for the presence of celiac autoimmunity (CA). Materials and Methods: A total of 280 consecutive patients with AITD attending the thyroid Out-patient Department of a tertiary care hospital were screened for the presence of tissue transglutaminase antibodies (immunoglobulin A tissue transglutaminase). Those with a positive titer (but duodenal mucosal biopsy for the diagnosis of CD, followed by institution of GFD in confirmed cases. Results: Of a total of 280 (182 females and 98 males) patients with AITD screened, 24 (8.6%) turned out to be positive for CA. Of 24 (8.6%), 15 (8.24%) females and 9 (9.18%) males were positive for CA. There was no statistically significant difference in the thyroxine doses required for normalization of thyroid function and the weight of the patients in CA positive and CA negative patients. Conclusions: The prevalence of CD in patients with AITD is much greater than in the general population. This forms the basis for screening patients with AITD for presence of CD. PMID:26904476

  20. [Narcolepsy with cataplexy: an autoimmune disease?].

    Science.gov (United States)

    Jacob, Louis; Dauvilliers, Yves

    2014-12-01

    Narcolepsy type 1 (also named narcolepsy-cataplexy or hypocretin deficiency syndrome) is a rare sleep disorder characterized by excessive daytime sleepiness and cataplexy, plus frequently hypnagogic hallucinations, sleep paralysis and nocturnal sleep disturbances. Narcolepsy type 1 is an immune system-associated disease linked with the destruction of 70.000-90.000 hypocretin neurons notably involved in wakefulness. Among narcoleptic patients, 98% are positive for HLA-DQB1*06:02, a HLA class II allele, against 20-25% in general population. Individuals carrying HLA-DQB1*06:02 have an extraordinary risk to develop narcolepsy (odd ratio: 251). Other genes involved in CD4+ T cells and immune system activation as T-cell receptor α are also associated with narcolepsy. The development of the disease is linked with environmental factors such as influenza and streptococcal infections. Narcolepsy type 1 incidence also increased in Europe following the use of Pandemrix, a 2009 H1N1 AS03-adjuvanted vaccine manufactured by GlaxoSmithKline. Interestingly, such increase was not observed with Arepanrix, another vaccine developed by GSK very similar to Pandemrix.

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

    OpenAIRE

    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

    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 reg...

  2. The PD-1/PD-Ls pathway and autoimmune diseases.

    Science.gov (United States)

    Dai, Suya; Jia, Ru; Zhang, Xiao; Fang, Qiwen; Huang, Lijuan

    2014-07-01

    The programmed death (PD)-1/PD-1 ligands (PD-Ls) pathway, is a new member of the B7/CD28 family, and consists of the PD-1 receptor and its ligands PD-L1 (B7-H1, CD274) and PD-L2 (B7-DC, CD273). Recently, it is reported that PD-1, PD-L1 and PD-L2 also have soluble forms aside from their membrane bound forms. The soluble forms increase the diversity and complexity of PD-1/PD-Ls pathway in both composition and function. The PD-1/PD-Ls pathway is broadly expressed and exerts a wider range of immunoregulatory roles in T-cell activation and tolerance compared with other B7/CD28 family members. Studies show that the PD-1/PD-Ls pathway regulates the induction and maintenance of peripheral tolerance and protects tissues from autoimmune attack in physiological conditions. In addition, it is also involved in various diseases mediated by T cells, such as autoimmunity, tumor immunity, chronic viral infections, and transplantation immunity. In this review, we will summarize the relevance of the soluble forms and the latest researches on the role of PD-1/PD-Ls pathway in autoimmune diseases.

  3. Multisensory body representation in autoimmune diseases.

    Science.gov (United States)

    Finotti, Gianluca; Costantini, Marcello

    2016-02-12

    Body representation has been linked to the processing and integration of multisensory signals. An outstanding example of the pivotal role played by multisensory mechanisms in body representation is the Rubber Hand Illusion (RHI). In this paradigm, multisensory stimulation induces a sense of ownership over a fake limb. Previous work has shown high interindividual differences in the susceptibility to the RHI. The origin of this variability remains largely unknown. Given the tight and bidirectional communication between the brain and the immune system, we predicted that the origin of this variability could be traced, in part, to the immune system's functioning, which is altered by several clinical conditions, including Coeliac Disease (CD). Consistent with this prediction, we found that the Rubber Hand Illusion is stronger in CD patients as compared to healthy controls. We propose a biochemical mechanism accounting for the dependency of multisensory body representation upon the Immune system. Our finding has direct implications for a range of neurological, psychiatric and immunological conditions where alterations of multisensory integration, body representation and dysfunction of the immune system co-exist.

  4. P15: The expression of Tc17 cells in thymoma accompany with autoimmune diseases or autoimmune disorders

    Science.gov (United States)

    Zhang, Peng

    2015-01-01

    Background Thymoma is thymic epithelial cell tumor. Studies have shown that thymoma associated with autoimmune disorders and possible mechanisms of autoimmune diseases is the central immune tolerance and peripheral tolerance obstacles have resulted in the breaking of the autoimmune response activation and immune tolerance. Tc17 cells and Th17 cells have been shown play an important role in tumor and autoimmune diseases’ development process. This study test the distribution of Tc17cells in thymoma and the expression of RORγt in thymus of thymoma patients with myasthenia gravis (MG) or other autoimmune diseases, the frequency of Th17/Tc17 in PBMCs, to explore the expression of Th17/Tc17 cells in thymoma accompany with autoimmune diseases or autoimmune disorders. Methods In this study, grouped as follows: (I) thymoma non gravis group (Tm groups); (II) thymoma with MG group thymoma with MG (MG group); (III) thymoma with MG associated with other autoimmune diseases group or anti- nuclear antibodies abnormal elevation of the group (AD group), to analyze the basic differences between the groups. In this study, we examined the RT-PCR to detect RORγt in the thymoma tissue, immunohistochemical double staining method to detect Tc17 cells expression and localization in the thymoma tissue distribution expression Th17/Tc17 in PBMCs by flow cytometry [Interleukin (IL)-17-producing CD8+ cells as Thl7 cells and IL-17-producing CD4+ cells as Tcl7 cells], analysis of differential expression of three in each group thymoma; and explore of Th17/Tc17 expression. Results (I) Tm groups and AD group serum CD8+ cells was statistically significant (PTc17 cells in MG/AD group was significantly higher than that in Tm, was statistically significant (PTc17 cells have risen trend in Tm groups and MG/AD group. Conclusions (I) CD8+ cells, CD4+/CD8+ T ratio, immunoglobulin, CRP and complement C3 levels can be used as indicators of evaluation of the role of the immune status of patients with

  5. Inflammatory glycoproteins in cardiometabolic disorders, autoimmune diseases and cancer.

    Science.gov (United States)

    Connelly, Margery A; Gruppen, Eke G; Otvos, James D; Dullaart, Robin P F

    2016-08-01

    The physiological function initially attributed to the oligosaccharide moieties or glycans on inflammatory glycoproteins was to improve protein stability. However, it is now clear that glycans play a prominent role in glycoprotein structure and function and in some cases contribute to disease states. In fact, glycan processing contributes to pathogenicity not only in autoimmune disorders but also in atherosclerotic cardiovascular disease, diabetes and malignancy. While most clinical laboratory tests measure circulating levels of inflammatory proteins, newly developed diagnostic and prognostic tests are harvesting the information that can be gleaned by measuring the amount or structure of the attached glycans, which may be unique to individuals as well as various diseases. As such, these newer glycan-based tests may provide future means for more personalized approaches to patient stratification and improved patient care. Here we will discuss recent progress in high-throughput laboratory methods for glycomics (i.e. the study of glycan structures) and glycoprotein quantification by methods such as mass spectrometry and nuclear magnetic resonance spectroscopy. We will also review the clinical utility of glycoprotein and glycan measurements in the prediction of common low-grade inflammatory disorders including cardiovascular disease, diabetes and cancer, as well as for monitoring autoimmune disease activity. PMID:27312321

  6. Epstein-Barr Virus in Systemic Autoimmune Diseases

    Directory of Open Access Journals (Sweden)

    Anette Holck Draborg

    2013-01-01

    Full Text Available Systemic autoimmune diseases (SADs are a group of connective tissue diseases with diverse, yet overlapping, symptoms and autoantibody development. The etiology behind SADs is not fully elucidated, but a number of genetic and environmental factors are known to influence the incidence of SADs. Recent findings link dysregulation of Epstein-Barr virus (EBV with SAD development. EBV causes a persistent infection with a tight latency programme in memory B-cells, which enables evasion of the immune defence. A number of immune escape mechanisms and immune-modulating proteins have been described for EBV. These immune modulating functions make EBV a good candidate for initiation of autoimmune diseases and exacerbation of disease progression. This review focuses on systemic lupus erythematosus (SLE, rheumatoid arthritis (RA, and Sjögren’s syndrome (SS and sum up the existing data linking EBV with these diseases including elevated titres of EBV antibodies, reduced T-cell defence against EBV, and elevated EBV viral load. Together, these data suggest that uncontrolled EBV infection can develop diverse autoreactivities in genetic susceptible individuals with different manifestations depending on the genetic background and the site of reactivation.

  7. Is there a Common Genetic Basis for Autoimmune Diseases?

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    Juan-Manuel Anaya

    2006-01-01

    Full Text Available Autoimmune diseases (ADs represent a diverse collection of diseases in terms of their demographic profile and primary clinical manifestations. The commonality between them however, is the damage to tissues and organs that arises from the response to self-antigens. The presence of shared pathophysiological mechanisms within ADs has stimulated searches for common genetic roots to these diseases. Two approaches have been undertaken to sustain the “common genetic origin” theory of ADs. Firstly, a clinical genetic analysis showed that autoimmunity aggregates within families of probands diagnosed with primary Sjögren's (pSS syndrome or type 1 diabetes mellitus (T1D. A literature review supported the establishment of a familiar cluster of ADs depending upon the proband's disease phenotype. Secondly, in a same and well-defined population, a large genetic association study indicated that a number of polymorphic genes (i.e. HLA-DRB1, TNF and PTPN22 influence the susceptibility for acquiring different ADs. Likewise, association and linkage studies in different populations have revealed that several susceptibility loci overlap in ADs, and clinical studies have shown that frequent clustering of several ADs occurs. Thus, the genetic factors for ADs consist of two types: those which are common to many ADs (acting in epistatic pleitropy and those that are specific to a given disorder. Their identification and functional characterization will allow us to predict their effect as well as to indicate potential new therapeutic interventions. Both autoimmunity family history and the co-occurrence of ADs in affected probands should be considered when performing genetic association and linkage studies.

  8. Markers of autoimmune liver diseases in postmenopausal women with osteoporosis

    Directory of Open Access Journals (Sweden)

    Umit Secil Demirdal

    2010-01-01

    Full Text Available INTRODUCTION: Osteoporosis is a common complication of chronic liver diseases. However, there is limited information about autoimmune liver diseases as a factor of secondary osteoporosis. Therefore, we aimed to investigate the autoantibodies of autoimmune liver diseases in patients with osteoporosis. METHODS: One hundred fifty female patients with postmenopausal osteoporosis were included. Bone mineral density was measured by dual energy X-ray absorptiometry. We analysized autoantibodies including antinuclear antibodies, liver membrane antibodies, anti-liver/kidney microsomal autoantibodies1, liver-specific protein, antismooth muscle antibodies, and anti-mitochondrial antibodies by indirect immunofluorescence. Serum was assayed for the levels of aminotransferases. RESULTS: The mean age of the patients was 63,13±8,6 years. The mean values of L1-L4 T-scores and femur total T-scores were -3,08±0,58 and -1,53±0,81, respectively. Among the 150 patients with osteoporosis, 14 (9.3% were antinuclear antibodies, four (2.7% were liver membrane antibodies, three (2.0% were anti-liver/kidney microsomal autoantibodies1, and two (1.3% were liver-specific protein positive. None of the patients had anti-mitochondrial antibodies or smooth muscle antibodies positivity. The mean values of levels of aminotransferases were within normal range. CONCLUSIONS: The presence of liver membrane antibodies, liver-specific protein, and anti-liver/kidney microsomal autoantibodies1 has permitted us to see that there may be some suspicious clues of autoimmune liver diseases in patients with osteoporosis as a secondary risk factor. On the other hand, there is a need for comprehensive studies with a larger sample size and studies designed to compare the results with a normal population to understand the clinical importance of our findings.

  9. Origin of B-Cell Neoplasms in Autoimmune Disease.

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    Kari Hemminki

    Full Text Available Autoimmune diseases (ADs are associated with a number of B-cell neoplasms but the associations are selective in regard to the type of neoplasm and the conferred risks are variable. So far no mechanistic bases for these differential associations have been demonstrated. We speculate that developmental origin of B-cells might propose a mechanistic rationale for their carcinogenic response to autoimmune stimuli and tested the hypothesis on our previous studies on the risks of B-cell neoplasms after any of 33 ADs. We found that predominantly germinal center (GC-derived B-cells showed multiple associations with ADs: diffuse large B cell lymphoma associated with 15 ADs, follicular lymphoma with 7 ADs and Hodgkin lymphoma with 11 ADs. Notably, these neoplasms shared significant associations with 5 ADs (immune thrombocytopenic purpura, polymyositis/dermatomyositis, rheumatoid arthritis, Sjogren syndrome and systemic lupus erythematosis. By contrast, primarily non-GC neoplasms, acute lymphocytic leukemia, chronic lymphocytic leukemia and myeloma associated with 2 ADs only and mantle cell lymphoma with 1 AD. None of the neoplasms shared associated ADs. These data may suggest that autoimmune stimulation critically interferes with the rapid cell division, somatic hypermutation, class switch recombination and immunological selection of maturing B-cell in the GC and delivers damage contributing to transformation.

  10. Human leukocyte Antigen-DM polymorphisms in autoimmune diseases.

    Science.gov (United States)

    Alvaro-Benito, Miguel; Morrison, Eliot; Wieczorek, Marek; Sticht, Jana; Freund, Christian

    2016-08-01

    Classical MHC class II (MHCII) proteins present peptides for CD4(+) T-cell surveillance and are by far the most prominent risk factor for a number of autoimmune disorders. To date, many studies have shown that this link between particular MHCII alleles and disease depends on the MHCII's particular ability to bind and present certain peptides in specific physiological contexts. However, less attention has been paid to the non-classical MHCII molecule human leucocyte antigen-DM, which catalyses peptide exchange on classical MHCII proteins acting as a peptide editor. DM function impacts the presentation of both antigenic peptides in the periphery and key self-peptides during T-cell development in the thymus. In this way, DM activity directly influences the response to pathogens, as well as mechanisms of self-tolerance acquisition. While decreased DM editing of particular MHCII proteins has been proposed to be related to autoimmune disorders, no experimental evidence for different DM catalytic properties had been reported until recently. Biochemical and structural investigations, together with new animal models of loss of DM activity, have provided an attractive foundation for identifying different catalytic efficiencies for DM allotypes. Here, we revisit the current knowledge of DM function and discuss how DM function may impart autoimmunity at the organism level.

  11. Pervasive sharing of genetic effects in autoimmune disease.

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    Chris Cotsapas

    2011-08-01

    Full Text Available Genome-wide association (GWA studies have identified numerous, replicable, genetic associations between common single nucleotide polymorphisms (SNPs and risk of common autoimmune and inflammatory (immune-mediated diseases, some of which are shared between two diseases. Along with epidemiological and clinical evidence, this suggests that some genetic risk factors may be shared across diseases-as is the case with alleles in the Major Histocompatibility Locus. In this work we evaluate the extent of this sharing for 107 immune disease-risk SNPs in seven diseases: celiac disease, Crohn's disease, multiple sclerosis, psoriasis, rheumatoid arthritis, systemic lupus erythematosus, and type 1 diabetes. We have developed a novel statistic for Cross Phenotype Meta-Analysis (CPMA which detects association of a SNP to multiple, but not necessarily all, phenotypes. With it, we find evidence that 47/107 (44% immune-mediated disease risk SNPs are associated to multiple-but not all-immune-mediated diseases (SNP-wise P(CPMA<0.01. We also show that distinct groups of interacting proteins are encoded near SNPs which predispose to the same subsets of diseases; we propose these as the mechanistic basis of shared disease risk. We are thus able to leverage genetic data across diseases to construct biological hypotheses about the underlying mechanism of pathogenesis.

  12. MicroRNAs in Human Diseases: From Autoimmune Diseases to Skin, Psychiatric and Neurodegenerative Diseases.

    Science.gov (United States)

    Ha, Tai-You

    2011-10-01

    MicroRNAs (miRNAs) are small noncoding RNA molecules that negatively regulate gene expression via degradation or translational repression of their target messenger RNAs (mRNAs). Recent studies have clearly demonstrated that miRNAs play critical roles in several biologic processes, including cell cycle, differentiation, cell development, cell growth, and apoptosis and that miRNAs are highly expressed in regulatory T (Treg) cells and a wide range of miRNAs are involved in the regulation of immunity and in the prevention of autoimmunity. It has been increasingly reported that miRNAs are associated with various human diseases like autoimmune disease, skin disease, neurological disease and psychiatric disease. Recently, the identification of mi- RNAs in skin has added a new dimension in the regulatory network and attracted significant interest in this novel layer of gene regulation. Although miRNA research in the field of dermatology is still relatively new, miRNAs have been the subject of much dermatological interest in skin morphogenesis and in regulating angiogenesis. In addition, miRNAs are moving rapidly onto center stage as key regulators of neuronal development and function in addition to important contributions to neurodegenerative disorder. Moreover, there is now compelling evidence that dysregulation of miRNA networks is implicated in the development and onset of human neruodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, Tourette's syndrome, Down syndrome, depression and schizophrenia. In this review, I briefly summarize the current studies about the roles of miRNAs in various autoimmune diseases, skin diseases, psychoneurological disorders and mental stress.

  13. Interrelation specific autoimmune pathologies of a thyroid gland with inorganic autoimmune rheumatic diseases

    Directory of Open Access Journals (Sweden)

    O V Paramonova

    2012-03-01

    Full Text Available The problem of a pathology of a thyroid gland at rheumatic diseases, in particular at rheumatoid arthritis, remains actual and to this day. The work purpose was studying antitelogenesis to thyroid hormones at patients with mixt autoimmune pathology. In whey of blood of patients with RA and autothyroid pathology are found out antibodies (AB to Т3 and Т4, their concentration correlates with activity of pathological process. It is shown, that level AB to Т3 and Т4 authentically differs from the maintenance of the given antibodies in whey of blood of healthy faces. Level of antibodies to thyroid hormones can be considered as the criterion predicting development of pathology of a thyroid gland at patients with RA.

  14. Clustering of autoimmune diseases in patients with rosacea

    DEFF Research Database (Denmark)

    Egeberg, Alexander; Hansen, Peter Riis; Gislason, Gunnar Hilmar;

    2016-01-01

    BACKGROUND: Rosacea is a common inflammatory skin condition that shares genetic risk loci with autoimmune diseases such as type 1 diabetes mellitus (T1DM) and celiac disease. A recent genomewide association study identified 90 genetic regions associated with T1DM, celiac disease, multiple sclerosis......, and/or rheumatoid arthritis, respectively. However, a possible association with rosacea was not investigated. OBJECTIVE: We evaluated the association between rosacea and T1DM, celiac disease, multiple sclerosis, and rheumatoid arthritis, respectively. METHODS: We performed a population-based case......-control study. A total of 6759 patients with rosacea were identified and matched with 33,795 control subjects on age, sex, and calendar time. We used conditional logistic regression to calculate crude and adjusted odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: After adjustment for smoking...

  15. Single Nucleotide Polymorphism Clustering in Systemic Autoimmune Diseases

    Science.gov (United States)

    Charlon, Thomas; Bossini-Castillo, Lara; Carmona, F. David; Di Cara, Alessandro; Wojcik, Jérôme; Voloshynovskiy, Sviatoslav

    2016-01-01

    Systemic Autoimmune Diseases, a group of chronic inflammatory conditions, have variable symptoms and difficult diagnosis. In order to reclassify them based on genetic markers rather than clinical criteria, we performed clustering of Single Nucleotide Polymorphisms. However naive approaches tend to group patients primarily by their geographic origin. To reduce this “ancestry signal”, we developed SNPClust, a method to select large sources of ancestry-independent genetic variations from all variations detected by Principal Component Analysis. Applied to a Systemic Lupus Erythematosus case control dataset, SNPClust successfully reduced the ancestry signal. Results were compared with association studies between the cases and controls without or with reference population stratification correction methods. SNPClust amplified the disease discriminating signal and the ratio of significant associations outside the HLA locus was greater compared to population stratification correction methods. SNPClust will enable the use of ancestry-independent genetic information in the reclassification of Systemic Autoimmune Diseases. SNPClust is available as an R package and demonstrated on the public Human Genome Diversity Project dataset at https://github.com/ThomasChln/snpclust. PMID:27490238

  16. Autoimmune Thyroid Disease in Rheumatoid Arthritis: A Global Perspective

    Directory of Open Access Journals (Sweden)

    Jorge Cárdenas Roldán

    2012-01-01

    Full Text Available Objective. To determine the prevalence and impact of autoimmune thyroid disease (AITD in patients with rheumatoid arthritis (RA. Methods. Eight-hundred patients were included. The association between AITD and RA was analyzed was analyzed by bivariate and multivariate analysis. In addition, a literature review was done focusing on geographical variations. Results. In our cohort the prevalence of AITD was 9.8% while the presence of antibodies was 37.8% for antithyroperoxidase enzyme (TPOAb and 20.8% for antithyroglobulin protein (TgAb. The presence of type 2 diabetes, thrombosis, abnormal body mass index, and a high educational level was positively associated with AITD. The literature review disclosed a geographical variation of AITD in RA ranging from 0.5% to 27%. Autoantibody prevalence ranges from 6% to 31% for TgAb, 5% to 37% for TPOAb, and from 11.4% to 32% for the presence of either of the two. Conclusion. AITD is not uncommon in RA and should be systematically assessed since it is a risk factor for developing diabetes and cardiovascular disease. These results may help to further study the common mechanisms of autoimmune diseases, to improve patients’ outcome, and to define public health policies. An international consensus to accurately diagnose AITD is warranted.

  17. Single Nucleotide Polymorphism Clustering in Systemic Autoimmune Diseases.

    Science.gov (United States)

    Charlon, Thomas; Martínez-Bueno, Manuel; Bossini-Castillo, Lara; Carmona, F David; Di Cara, Alessandro; Wojcik, Jérôme; Voloshynovskiy, Sviatoslav; Martín, Javier; Alarcón-Riquelme, Marta E

    2016-01-01

    Systemic Autoimmune Diseases, a group of chronic inflammatory conditions, have variable symptoms and difficult diagnosis. In order to reclassify them based on genetic markers rather than clinical criteria, we performed clustering of Single Nucleotide Polymorphisms. However naive approaches tend to group patients primarily by their geographic origin. To reduce this "ancestry signal", we developed SNPClust, a method to select large sources of ancestry-independent genetic variations from all variations detected by Principal Component Analysis. Applied to a Systemic Lupus Erythematosus case control dataset, SNPClust successfully reduced the ancestry signal. Results were compared with association studies between the cases and controls without or with reference population stratification correction methods. SNPClust amplified the disease discriminating signal and the ratio of significant associations outside the HLA locus was greater compared to population stratification correction methods. SNPClust will enable the use of ancestry-independent genetic information in the reclassification of Systemic Autoimmune Diseases. SNPClust is available as an R package and demonstrated on the public Human Genome Diversity Project dataset at https://github.com/ThomasChln/snpclust. PMID:27490238

  18. Elevated Adiponectin Serum Levels in Women with Systemic Autoimmune Diseases

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    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.

  19. Development of a disease registry for autoimmune bullous diseases: initial analysis of the pemphigus vulgaris subset.

    Science.gov (United States)

    Shah, Amit Aakash; Seiffert-Sinha, Kristina; Sirois, David; Werth, Victoria P; Rengarajan, Badri; Zrnchik, William; Attwood, Kristopher; Sinha, Animesh A

    2015-01-01

    Pemphigus vulgaris (PV) is a rare, potentially life threatening, autoimmune blistering skin disease. The International Pemphigus and Pemphigoid Foundation (IPPF) has recently developed a disease registry with the aim to enhance our understanding of autoimmune bullous diseases with the long-term goal of acquiring information to improve patient care. Patients were recruited to the IPPF disease registry through direct mail, e-mail, advertisements, and articles in the IPPF-quarterly, -website, -Facebook webpage, and IPPF Peer Health Coaches to complete a 38-question survey. We present here the initial analysis of detailed clinical information collected on 393 PV patients. We report previously unrecognized gender differences in terms of lesion location, autoimmune comorbidity, and delay in diagnosis. The IPPF disease registry serves as a useful resource and guide for future clinical investigation. PMID:24691863

  20. An unusual association of three autoimmune disorders: celiac disease, systemic lupus erythematosus and Hashimoto's thyroiditis.

    Science.gov (United States)

    Boccuti, Viera; Perrone, Antonio; D'Introno, Alessia; Campobasso, Anna; Sangineto, Moris; Sabbà, Carlo

    2016-12-01

    Autoimmune disorders are known to be more frequent in women and often associated each others, but it is rare to see multiple autoimmune diseases in a single patient. Recently, the concept of multiple autoimmune syndrome has been introduced to describe patients with at least three autoimmune diseases. We describe a case of a young man with a clinical history of psychiatric symptoms and celiac disease (CD) who was diagnosed to have other two autoimmune disorders: systemic lupus erythematosus (SLE) and Hashimoto's thyroiditis. This case is unusual upon different patterns: the rare combination of the three autoimmune diseases, their appearance in a man and the atypical onset of the diseases with psychiatric symptoms likely to be related either to CD or to SLE. PMID:27383232

  1. A case of severe autoimmune hepatitis associated with Graves' disease

    Directory of Open Access Journals (Sweden)

    Samia Abdulla Bokhari

    2016-01-01

    Full Text Available Graves' disease is a common condition and is known to have a wide range of effects on a variety of organs. Hepatic dysfunction ranging from mild to severe due to direct effect of high circulating thyroid hormones as well as a deleterious effect of antithyroid medications (methimazole and propylthiouracil has been well - documented in literature. However, severe autoimmune hepatitis (AIH associated with Graves' disease is rare and limited to few case reports only. A 38-year-old woman presented with abdominal pain and yellowish discolouration of conjunctivae. On investigation, she was found to have Graves' disease and AIH. The liver histopathology showed typical features of AIH. She responded excellently to glucocorticoid therapy with normalisation of thyroid function and liver histology. The case is discussed with relevant literature review.

  2. Porous silicon biosensor for the detection of autoimmune diseases

    Science.gov (United States)

    Jane, Andrew O.; Szili, Endre J.; Reed, Joanne H.; Gordon, Tom P.; Voelcker, Nicolas H.

    2007-12-01

    Advances in porous silicon (pSi) technology have led to the development of new sensitive biosensors. The unique optical properties of pSi renders the material a perfect candidate for optical transducers exploiting photoluminescence or white light interference effects. The ability of biosensors exploiting these transduction mechanisms to quickly and accurately detect biological target molecules affords an alternative to current bioassays such as enzyme-linked immunosorbent assays (ELISAs). Here, we present a pSi biosensor that was developed to detect antibodies against the autoimmune protein La. This protein is associated with autoimmune diseases including rheumatic disorders, systematic lupus erythematosus (SLE) and Sjogren's syndrome (SS). A fast and sensitive detection platform such as the one described here can be applied to the rapid diagnosis of these debilitating autoimmune diseases. The immobilisation of the La protein onto pSi films gave a protein receptor-decorated sensor matrix. A cascade of immunological reactions was then initiated to detect anti-La antibody on the functionalised pSi surface. In the presence of o-phenylenediamine (OPD), horseradish peroxidase (HRP)/H IIO II catalysed the formation of an oxidised radical species that accelerated pSi corrosion. pSi corrosion was detected as a blue-shift in the generated interference pattern, corresponding to a decrease in the effective optical thickness (EOT) of the pSi film. Compared to an ELISA, the pSi biosensor could detect the anti-La antibody at a similar concentration (500 - 125 ng/ml). Furthermore, we found that the experimental process can be significantly shortened resulting in detection of the anti-La antibody in 80 minutes compared to a minimum of 5 hours required for ELISA.

  3. Inflammatory Bowel Disease: Autoimmune or Immune-mediated Pathogenesis?

    Directory of Open Access Journals (Sweden)

    Zhonghui Wen

    2004-01-01

    Full Text Available The pathogenesis of Crohn's disease (CD and ulcerative colitis (UC, the two main forms of inflammatory bowel disease (IBD, is still unclear, but both autoimmune and immune-mediated phenomena are involved. Autoimmune phenomena include the presence of serum and mucosal autoantibodies against intestinal epithelial cells in either form of IBD, and against human tropomyosin fraction five selectively in UC. In addition, perinuclear antineutrophil cytoplasmic antibodies (pANCA are common in UC, whereas antibodies against Saccharomyces cerevisiae (ASCA are frequently found in CD. Immune-mediate phenomena include a variety of abnormalities of humoral and cell-mediated immunity, and a generalized enhanced reactivity against intestinal bacterial antigens in both CD and UC. It is currently believed that loss of tolerance against the indigenous enteric flora is the central event in IBD pathogenesis. Various complementary factors probably contribute to the loss of tolerance to commensal bacteria in IBD. They include defects in regulatory T-cell function, excessive stimulation of mucosal dendritic cells, infections or variants of proteins critically involved in bacterial antigen recognition, such as the products of CD-associated NOD2/CARD15 mutations.

  4. Myasthenia gravis, a model of organ-specific autoimmune disease.

    Science.gov (United States)

    Berrih-Aknin, S

    1995-04-01

    Myasthenia gravis (MG) is a neuromuscular disorder of autoimmune origin. Most patients have antibodies directed against the acetylcholine receptor (AChR) that interfere with neuromuscular transmission. MG is a model of organ-specific autoimmune disease in which the autoantigen, AChR, is well characterized. However, several questions remain unanswered. Why is AChR, which is present in the thymus, not tolerized? Why does the anti-AChR antibody titre not correlate with clinical manifestations, and why do some patients not have such antibodies? What genetic elements are involved in disease susceptibility? How is the expression of AChR regulated after its attack by autoantibodies? Could MG patients benefit from new immunomodulatory treatments? At the IVth EuroMyasthenia meeting, held in Versailles in April 1994, almost 200 researchers and physicians met to discuss the pathophysiology and treatment of myasthenia gravis and to provide answers to some of these questions. The sessions covered immunological, genetic and clinical aspects of MG. PMID:7612144

  5. Encephalopathy Associated with Autoimmune Thyroid Disease: A Potentially Reversible Condition

    Directory of Open Access Journals (Sweden)

    Inês Correia

    2016-01-01

    Full Text Available Autoimmune thyroid disease may occasionally associate with unspecific neurological symptoms, which are more commonly insidious, include cognitive or behavioural symptoms, and may associate with tremor, myoclonus, or ataxia. We report a 61-year-old female patient who presented with chronic headache, insidious mood, and cognitive disturbance which evolved in a few months to dementia associated with exuberant limb myoclonus. Diagnostic workup revealed high anti-thyroid peroxidase antibody titers and an inflammatory CSF profile, and it was negative for other possible etiologies. Treatment with steroids induced significant improvement. The diagnosis of encephalopathy associated with autoimmune thyroid disease is still controversial given the fact that the clinical presentation and diagnostic workup are unspecific, the pathophysiology is still undetermined, and the diagnosis is mostly of exclusion. No direct correlation is found between anti-thyroid antibody titers and clinical presentation, and it is currently speculated that other still unrecognized antibodies may be responsible for this clinical entity. It is extremely important to recognize this entity because it is potentially treatable with immunotherapies. It is also increasingly recognized that clinical improvement with first-line treatment with steroids may be absent or incomplete, and other immunotherapies as immunosuppressants, intravenous immunoglobulin, or plasma exchange must be attempted in the clinical suspicion of EEAT.

  6. The skin in autoimmune diseases-Unmet needs.

    Science.gov (United States)

    Kuhn, A; Landmann, A; Bonsmann, G

    2016-10-01

    Treatment of skin manifestations in systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and dermatomyositis (DM) is based on the results of only few randomized controlled trials. The first-line treatment for disfiguring and widespread cutaneous involvement in SLE is antimalarials, but some patients are therapy resistant. Recently, the monoclonal antibody belimumab was approved for SLE as an adjunct therapy for patients with autoantibody-positive disease who despite standard therapy show high disease activity, intolerance of other treatments, or an unacceptably high need for corticosteroids. However, a validated skin score has not been used to confirm the efficacy of belimumab on mucocutaneous manifestations. In SSc, another multi-systemic progressive disease, involvement of the lung, kidney, and the heart is frequently treated with corticosteroids and immunosuppressives, but therapeutic modalities for cutaneous lesions, such as skin sclerosis and digital ulcers, are limited. In the past years, treatment with the endothelin-receptor antagonist bosentan has been proven to reduce the occurrence of new digital ulcers in SSc patients but has no or limited effect on healing of digital ulcers. DM is an idiopathic autoimmune disease characterized by inflammation of the muscles and skin, which is treated with immunosuppressives. Corticosteroids are the first-line treatment for muscle involvement in DM, but skin lesions often flare by reduction or discontinuation. In summary, there is a high unmet need for new therapeutic strategies focusing on skin involvement in systemic autoimmune diseases. Therefore, innovative designs of randomized controlled trials with validated skin scores are warranted to develop new therapeutic strategies for patients with cutaneous manifestations.

  7. Autoimmune hepatitis

    Science.gov (United States)

    ... Sjogren syndrome Systemic lupus erythematosus Thyroiditis Type 1 diabetes Ulcerative colitis Autoimmune hepatitis may occur in family members of people with autoimmune diseases. There may be a genetic cause. This disease is most common in young girls ...

  8. The microbiome and autoimmune disease: Report from a Noel R. Rose Colloquium.

    Science.gov (United States)

    Barin, Jobert G; Tobias, Lawrence D; Peterson, Daniel A

    2015-08-01

    Although the mechanisms by which the human microbiome influences the onset and progression of autoimmune diseases remain to be determined, established animal models of autoimmune diseases indicate that local and systemic bidirectional interactions with the microbiome play a signaling or promoting role through the immune system. Whether alterations in the microbiome are a pathogenic cause or simply an effect of inflammation and autoimmune disease remains an essential question to be addressed in disease-specific research, as well as whether particular conditions of the microbiome promote health or promote disease. Future research in this area needs to account for sex differences in microbiome composition because autoimmune diseases disproportionately affect women. Probiotic and other treatments that manipulate assemblage of the microbiome may offer methods of preventing or mitigating the effects of autoimmune disease.

  9. Pregnancy and the risk of autoimmune disease: An exploration.

    LENUS (Irish Health Repository)

    2012-01-31

    Fetal microchimerism is the study of persisting fetal cells in the mother years after pregnancy and the purported implications for her health and longevity. Due to the association between pregnancy and autoimmune disease (AID), and the preponderance of these diseases in women, laboratory studies have for years attempted to link microchimeric fetal cells with the onset of AID after pregnancy. This new study gave us the opportunity to examine for the first time if this theory could be proven clinically in a large cohort of women. By examining whether different types of delivery affected the onset of AID, we also aimed to indirectly relate this finding to fetal microchimerism. The results did suggest an association between pregnancy and the risk of subsequent maternal AID, with increased risks noted after caesarean section (CS) and decreased risks after abortion. This is the first epidemiological study on the risk of AID following pregnancy.

  10. Biomarkers of An Autoimmune Skin Disease-Psoriasis

    Institute of Scientific and Technical Information of China (English)

    Shan Jiang; Taylor E Hinchliffe; Tianfu Wu

    2015-01-01

    Psoriasis is one of the most prevalent autoimmune skin diseases. However, its etiology and pathogenesis are still unclear. Over the last decade, omics-based technologies have been exten-sively utilized for biomarker discovery. As a result, some promising markers for psoriasis have been identified at the genome, transcriptome, proteome, and metabolome level. These discoveries have provided new insights into the underlying molecular mechanisms and signaling pathways in psoriasis pathogenesis. More importantly, some of these markers may prove useful in the diagnosis of psoriasis and in the prediction of disease progression once they have been validated. In this review, we summarize the most recent findings in psoriasis biomarker discovery. In addition, we will discuss several emerging technologies and their potential for novel biomarker discovery and diagnostics for psoriasis.

  11. Determination of autoantibodies to annexin XI in systemic autoimmune diseases

    DEFF Research Database (Denmark)

    Jorgensen, C S; Levantino, G; Houen, Gunnar;

    2000-01-01

    /137), rheumatoid arthritis (1/21), and systemic lupus erythematosus (1/58). Sera from healthy donors and patients with chronic infections were negative, except for one Salmonella typhimurium antibody positive serum. Autoantibodies to annexin XI were found to relate to thrombosis, but not to other clinical......Annexin XI, a calcyclin-associated protein, has been shown to be identical to a 56,000 Da antigen recognized by antibodies found in sera from patients suffering from systemic autoimmune diseases. In this work hexahistidine-tagged recombinant annexin XI (His6- rAnn XI) was used as antigen in ELISA...... of 282 sera from patients with systemic rheumatic diseases. The highest number of annexin XI positive sera were found in primary antiphospholipid syndrome (3/17), and in subacute lupus erythematosus (1/6), while lower frequencies of positive sera were found in patients with systemic sclerosis (5...

  12. Gene expression profiling in autoimmune diseases: chronic inflammation or disease specific patterns?

    DEFF Research Database (Denmark)

    Bovin, Lone Frier; Brynskov, Jørn; Hegedüs, Laszlo;

    2007-01-01

    A central issue in autoimmune disease is whether the underlying inflammation is a repeated stereotypical process or whether disease specific gene expression is involved. To shed light on this, we analysed whether genes previously found to be differentially regulated in rheumatoid arthritis (RA...

  13. Genetic homogeneity of autoimmune polyglandular disease type I

    Energy Technology Data Exchange (ETDEWEB)

    Bjoerses, P.; Aaltonen, J.; Vikman, A. [Univ. of Helsinki (Finland)] [and others

    1996-10-01

    Autoimmune polyglandular disease type I (APECED) is an autosomal recessive autoimmune disease (MIM 240300) characterized by hypoparathyroidism, primary adrenocortical failure, and chronic mucocutaneous candidiasis. The disease is highly prevalent in two isolated populations, the Finnish population and the Iranian Jewish one. Sporadic cases have been identified in many other countries, including almost all European countries. The APECED locus has previously been assigned to chromosome 21q22.3 by linkage analyses in 14 Finnish families. Locus heterogeneity is a highly relevant question in this disease affecting multiple tissues and with great phenotypic diversity. To solve this matter, we performed linkage and haplotype analyses on APECED families rising from different populations. Six microsatellite markers on the critical chromosomal region of 2.6 cM on 21q22.3 were analyzed. Pair-wise linkage analyses revealed significant LOD scores for all these markers, maximum LOD score being 10.23. The obtained haplotype data and the geographic distribution of the great-grandparents of the Finnish APECED patients suggest the presence of one major, relatively old mutation responsible for {approximately}90% of the Finnish cases. Similar evidence for one founder mutation was also found in analyses of Iranian Jewish APECED haplotypes. These haplotypes, however, differed totally from the Finnish ones. The linkage analyses in 21 non-Finnish APECED families originating from several European countries provided independent evidence for linkage to the same chromosomal region on 21q22.3 and revealed no evidence for locus heterogeneity. The haplotype analyses of APECED chromosomes suggest that in different populations APECED is due to a spectrum of mutations in a still unknown gene on chromosome 21. 21 refs., 3 figs., 3 tabs.

  14. Prevalence of thyroid autoimmunity in children with celiac disease compared to healthy 12-year olds.

    OpenAIRE

    vanderPals, Maria; Ivarsson, Anneli; Norström, Fredrik; Högberg, Lotta; Svensson, Johan; Carlsson, Annelie

    2014-01-01

    Objectives. Studies have suggested a correlation between untreated celiac disease and risk for other autoimmune diseases. We investigated the prevalence of thyroid autoimmunity in 12-year-old children (i) with symptomatic celiac disease diagnosed and treated with a gluten-free diet, (ii) with screening-detected untreated celiac disease, and (iii) without celiac disease. Methods. Blood samples from 12632 children were collected. All celiac disease cases, previously diagnosed and newly screenin...

  15. Prevalence of Thyroid Autoimmunity in Children with Celiac Disease Compared to Healthy 12-Year Olds

    OpenAIRE

    Maria van der Pals; Anneli Ivarsson; Fredrik Norström; Lotta Högberg; Johan Svensson; Annelie Carlsson

    2014-01-01

    Objectives. Studies have suggested a correlation between untreated celiac disease and risk for other autoimmune diseases. We investigated the prevalence of thyroid autoimmunity in 12-year-old children (i) with symptomatic celiac disease diagnosed and treated with a gluten-free diet, (ii) with screening-detected untreated celiac disease, and (iii) without celiac disease. Methods. Blood samples from 12632 children were collected. All celiac disease cases, previously diagnosed and newly screenin...

  16. The Possible Future Roles for iPSC-Derived Therapy for Autoimmune Diseases

    Directory of Open Access Journals (Sweden)

    Meilyn Hew

    2015-05-01

    Full Text Available The ability to generate inducible pluripotent stem cells (iPSCs and the potential for their use in treatment of human disease is of immense interest. Autoimmune diseases, with their limited treatment choices are a potential target for the clinical application of stem cell and iPSC technology. IPSCs provide three potential ways of treating autoimmune disease; (i providing pure replacement of lost cells (immuno-reconstitution; (ii through immune-modulation of the disease process in vivo; and (iii for the purposes of disease modeling in vitro. In this review, we will use examples of systemic, system-specific and organ-specific autoimmunity to explore the potential applications of iPSCs for treatment of autoimmune diseases and review the evidence of iPSC technology in auto-immunity to date.

  17. Autoimmune diseases in Adult Life after Childhood Cancer in Scandinavia (ALiCCS)

    DEFF Research Database (Denmark)

    Holmqvist, Anna Sällfors; Olsen, Jørgen H.; Mellemkjaer, Lene;

    2015-01-01

    all autoimmune diseases combined, corresponding to an AER of 67 per 100 000 person-years. The SHRRs were significantly increased for autoimmune haemolytic anaemia (16.3), Addison's disease (13.9), polyarteritis nodosa (5.8), chronic rheumatic heart disease (4.5), localised scleroderma (3......OBJECTIVES: The pattern of autoimmune diseases in childhood cancer survivors has not been investigated previously. We estimated the risk for an autoimmune disease after childhood cancer in a large, population-based setting with outcome measures from comprehensive, nationwide health registries.......6), idiopathic thrombocytopenic purpura (3.4), Hashimoto's thyroiditis (3.1), pernicious anaemia (2.7), sarcoidosis (2.2), Sjögren's syndrome (2.0) and insulin-dependent diabetes mellitus (1.6). The SHRRs for any autoimmune disease were significantly increased after leukaemia (SHRR 1.6), Hodgkin's lymphoma (1...

  18. Long-term observations of autoimmune-prone mice treated for autoimmune disease by allogeneic bone marrow transplantation

    International Nuclear Information System (INIS)

    Long-term effects of allogeneic bone marrow transplantation (ABMT) across major histocompatibility complex barriers were studied in (NZB x NZW)F1 (B/W), BXSB, and MRL/Mr-lpr-lpr (MRL/lpr) mice with established autoimmune disease at the time of ABMT. In the BXSB or B/W mice, ABMT cured all aspects of autoimmune disease. Glomerular damage, revealed by histological study was dramatically improved. Serological abnormalities and immunologic functions also were normalized. Correction of autoimmune disease and advanced renal disease in BXSB and B/W mice regularly lasted greater than 5-6 mo and even 1 yr after ABMT. In the MRL/lpr mice, however, autoimmune and renal disease at first improved but then recurred after ABMT, apparently because of intolerance of mice for high doses of irradiation and a high degree of resistance of recipient stem cells to irradiation. In this model, H-2 typing revealed that by the time of relapse, immunocompetent cells of the chimeric mice had been replaced by host (MRL/lpr; H-2k) cells. B220+ Ly-1+ cells, present in increased numbers in untreated MRL/lpr mice, initially returned to normal levels after ABMT but then reappeared in the MRL/lpr mice that had received marrow from donors having few such lymphocytes. Thus, our results show that MRL/lpr mice possess abnormal radioresistant stem cells and provide impressive evidence that the origin of autoimmune diseases in this strain, as in the several other strains studied, resids in abnormalities present in stem cells

  19. Green tea EGCG, T cells, and T cell-mediated autoimmune diseases

    Science.gov (United States)

    One of the proposed health benefits of consuming green tea is its protective effect on autoimmune diseases. Research on the immunopathogenesis of autoimmune diseases has made significant progression in the past few years and several key concepts have been revised. T cells, particularly CD4+ T helper...

  20. Dendritic cells and veiled accessory macrophages : hormonal influences and autoimmune thyroid disease

    NARCIS (Netherlands)

    M.O. Canning (Martha)

    2005-01-01

    textabstractImmune responses to thyroid specific autoantigens form the basis of autoimmune thyroid disease pathogenesis. Two polar forms of autoimmune reactivity of the thyroid gland exist in this disease spectrum: a catabolic form characterized by gradual inflammatory destruction of thyroid parench

  1. Specific IgE positivity against inhalant allergens and development of autoimmune disease

    DEFF Research Database (Denmark)

    Skaaby, Tea; Husemoen, Lise Lotte Nystrup; Thuesen, Betina Heinsbæk;

    2015-01-01

    BACKGROUND: Allergic and autoimmune diseases have been suggested to be inversely associated. We investigated the association between atopy and development of any and specific types of autoimmune disease. METHODS: We included a total of 14,849 individuals from five population-based studies with...

  2. Rapid infusion with rituximab: short term safety in systemic autoimmune diseases

    DEFF Research Database (Denmark)

    Larsen, Janni Lisander; Jacobsen, Soren

    2013-01-01

    To describe the incidence, types and severity of adverse events, related to an accelerated regime of rituximab infusion in patients with various autoimmune diseases. Fifty-four patients with systemic autoimmune disease, to be treated with 1,000 mg of rituximab twice 2 weeks apart, participated. Pre......-medication (oral prednisolone, anti-histamine and paracetamol) was administered 1-4 h before infusion start. The first infusion was administered over a period of 195 min. The second infusion over a period of 90 min. Any adverse events were classified using the Clinical Trials Classification of Adverse Events...... (CTCAE) v. 3.0. Ten patients (18.5%) experienced at least one infusion-related reaction (IRR) ever. The first infusion was associated with reactions in 4 CTCAE categories of which rhinitis were the most frequent. The CTCAE severity grading showed six patients (11.1%) had a grade 1 reaction. One patient...

  3. Pregnancy in patients with autoimmune disease: A reality in 2016.

    Science.gov (United States)

    Tincani, A; Dall'Ara, F; Lazzaroni, M G; Reggia, R; Andreoli, L

    2016-10-01

    Autoimmune rheumatic diseases are chronic systemic conditions often affecting young women during their reproductive years, so that pregnancy is a major issue in their management. For a long time pregnancy has been discouraged in these women, mainly for two reasons: gestation could aggravate maternal disease and, vice versa, the disease could negatively influence the gestational outcome. The great improvement in the approach to pregnancy done in the past few decades has allowed a progressively increasing number of affected women to fulfill their family plan. Women should be informed about potential risks related to their disease, but they should also be reassured that a good pregnancy outcome is possible if conception occurs in a stable remission state, teratogenic medications have been properly withdrawn and "safe" drugs have been mantained to prevent disease flare. A brief excursus regarding the main issues regarding SLE/APS, Systemic Sclerosis and Systemic Vasculitis is provided, in the attempt to delineate the main risk factors for adverse pregnancy outcome, the onset of maternal complications and the role played by a close multi-specialistic monitoring.

  4. IVIG in autoimmune disease - Potential next generation biologics.

    Science.gov (United States)

    Zuercher, Adrian W; Spirig, Rolf; Baz Morelli, Adriana; Käsermann, Fabian

    2016-08-01

    Polyclonal plasma-derived IgG is a mainstay therapeutic of immunodeficiency disorders as well as of various inflammatory autoimmune diseases. In immunodeficiency the primary function of IVIG/SCIG is to replace missing antibody specificities, consequently a diverse Fab-based repertoire is critical for efficacy. Attempts to capture the Ig repertoire and express it as a recombinant IVIG product are currently ongoing. Likewise correction of the defective genes by gene therapy has also been tried. However, both approaches are far from becoming mainstream treatments. In contrast, some of the most important effector mechanisms relevant in therapy of autoimmunity are based on the Fc-portion of IgG; they include scavenging of complement and blockade/modulation of IgG receptors (Fc gamma receptor [FcγR] or the neonatal Fc receptor [FcRn]). These effects might be achieved with appropriately formulated Fc-fragments instead of full-length IgG, as suggested by a pilot study with monomeric plasma-derived Fc in children with ITP and in Kawasaki disease in the 1990s. Since then it has been proposed that structured multimerization of Fc fragments might confer efficacy at much lower doses than with IVIG. Accordingly, various molecular strategies are currently being explored to achieve controlled Fc multimerization, e.g. by fusion of IgG1 Fc to the IgG2 hinge-region or to the IgM tail-piece. Safety considerations will be crucial in the evaluation of these new entities. In a different approach, mutant Fc fragments and monoclonal antibodies have been designed for blockade of the FcRn.

  5. IVIG in autoimmune disease - Potential next generation biologics.

    Science.gov (United States)

    Zuercher, Adrian W; Spirig, Rolf; Baz Morelli, Adriana; Käsermann, Fabian

    2016-08-01

    Polyclonal plasma-derived IgG is a mainstay therapeutic of immunodeficiency disorders as well as of various inflammatory autoimmune diseases. In immunodeficiency the primary function of IVIG/SCIG is to replace missing antibody specificities, consequently a diverse Fab-based repertoire is critical for efficacy. Attempts to capture the Ig repertoire and express it as a recombinant IVIG product are currently ongoing. Likewise correction of the defective genes by gene therapy has also been tried. However, both approaches are far from becoming mainstream treatments. In contrast, some of the most important effector mechanisms relevant in therapy of autoimmunity are based on the Fc-portion of IgG; they include scavenging of complement and blockade/modulation of IgG receptors (Fc gamma receptor [FcγR] or the neonatal Fc receptor [FcRn]). These effects might be achieved with appropriately formulated Fc-fragments instead of full-length IgG, as suggested by a pilot study with monomeric plasma-derived Fc in children with ITP and in Kawasaki disease in the 1990s. Since then it has been proposed that structured multimerization of Fc fragments might confer efficacy at much lower doses than with IVIG. Accordingly, various molecular strategies are currently being explored to achieve controlled Fc multimerization, e.g. by fusion of IgG1 Fc to the IgG2 hinge-region or to the IgM tail-piece. Safety considerations will be crucial in the evaluation of these new entities. In a different approach, mutant Fc fragments and monoclonal antibodies have been designed for blockade of the FcRn. PMID:27019051

  6. PEG minocycline-liposomes ameliorate CNS autoimmune disease.

    Directory of Open Access Journals (Sweden)

    Wei Hu

    Full Text Available BACKGROUND: Minocycline is an oral tetracycline derivative with good bioavailability in the central nervous system (CNS. Minocycline, a potent inhibitor of matrix metalloproteinase (MMP-9, attenuates disease activity in experimental autoimmune encephalomyelitis (EAE, an animal model of multiple sclerosis (MS. Potential adverse effects associated with long-term daily minocycline therapy in human patients are concerning. Here, we investigated whether less frequent treatment with long-circulating polyethylene glycol (PEG minocycline liposomes are effective in treating EAE. FINDINGS: Performing in vitro time kinetic studies of PEG minocycline-liposomes in human peripheral blood mononuclear cells (PBMCs, we determined that PEG minocycline-liposome preparations stabilized with CaCl(2 are effective in diminishing MMP-9 activity. Intravenous injections of PEG minocycline-liposomes every five days were as effective in ameliorating clinical EAE as daily intraperitoneal injections of minocycline. Treatment of animals with PEG minocycline-liposomes significantly reduced the number of CNS-infiltrating leukocytes, and the overall expression of MMP-9 in the CNS. There was also a significant suppression of MMP-9 expression and proteolytic activity in splenocytes of treated animals, but not in CNS-infiltrating leukocytes. Thus, leukocytes gaining access to the brain and spinal cord require the same absolute amount of MMP-9 in all treatment groups, but minocycline decreases the absolute cell number. CONCLUSIONS: Our data indicate that less frequent injections of PEG minocycline-liposomes are an effective alternative pharmacotherapy to daily minocycline injections for the treatment of CNS autoimmune diseases. Also, inhibition of MMP-9 remains a promising treatment target in EAE and patients with MS.

  7. Inflammation is strongly associated with lupus anticoagulant positivity, indepentent of know autoimmune disease and recent venous or arterial thrombosis

    DEFF Research Database (Denmark)

    Just, Søren Andreas; Nybo, Mads; Laustrup, Helle;

    2014-01-01

    Inflammation is strongly associated with lupus anticoagulant positivity, indepentent of know autoimmune disease and recent venous or arterial thrombosis......Inflammation is strongly associated with lupus anticoagulant positivity, indepentent of know autoimmune disease and recent venous or arterial thrombosis...

  8. Challenges in Interpretation of Thyroid Function Tests in Pregnant Women with Autoimmune Thyroid Disease

    OpenAIRE

    Katharina Main; Linda Hilsted; Malene Boas; Anne-Sofie Bliddal Mortensen; Åse Krogh Rasmussen; Ulla Feldt-Rasmussen

    2011-01-01

    Physiological changes during gestation are important to be aware of in measurement and interpretation of thyroid function tests in women with autoimmune thyroid diseases. Thyroid autoimmune activity is decreasing in pregnancy. Measurement of serum TSH is the first-line screening variable for thyroid dysfunction also in pregnancy. However, using serum TSH for control of treatment of maternal thyroid autoimmunity infers a risk for compromised foetal development. Peripheral thyroid hormone value...

  9. Scientists find link between allergic and autoimmune diseases in mouse study

    Science.gov (United States)

    Scientists at the National Institutes of Health, and their colleagues, have discovered that a gene called BACH2 may play a central role in the development of diverse allergic and autoimmune diseases, such as multiple sclerosis, asthma, Crohn's disease, ce

  10. The Autoimmune Disease Database: a dynamically compiled literature-derived database

    OpenAIRE

    Mevissen Heinz-Theodor; Fluck Juliane; Karopka Thomas; Glass Änne

    2006-01-01

    Abstract Background Autoimmune diseases are disorders caused by an immune response directed against the body's own organs, tissues and cells. In practice more than 80 clinically distinct diseases, among them systemic lupus erythematosus and rheumatoid arthritis, are classified as autoimmune diseases. Although their etiology is unclear these diseases share certain similarities at the molecular level i.e. susceptibility regions on the chromosomes or the involvement of common genes. To gain an o...

  11. Some like it hot: The emerging role of spicy food (capsaicin) in autoimmune diseases.

    Science.gov (United States)

    Deng, Yaxiong; Huang, Xin; Wu, Haijing; Zhao, Ming; Lu, Qianjin; Israeli, Eitan; Dahan, Shani; Blank, Miri; Shoenfeld, Yehuda

    2016-05-01

    Autoimmune diseases refer to a spectrum of diseases characterized by an active immune response against the host, which frequently involves increased autoantibody production. The pathogenesis of autoimmune diseases is multifactorial and the exploitation of novel effective treatment is urgent. Capsaicin is a nutritional factor, the active component of chili peppers, which is responsible for the pungent component of chili pepper. As a stimuli, capsaicin selectively activate transient receptor potential vanilloid subfamily 1(TRPV1) and exert various biological effects. This review discusses the effect of capsaicin through its receptor on the development and modulation of autoimmune diseases, which may shed light upon potential therapies in capsaicin-targeted approaches. PMID:26812350

  12. The autoimmune puzzle - shared and specific genetics of immune-related diseases

    NARCIS (Netherlands)

    Zhernakova, A.P.

    2009-01-01

    Immune-mediated disorders are common diseases affecting 5-10% of the population. They include two sets of diseases: the classical autoimmune diseases, such as type 1 diabetes, rheumatoid arthritis and coeliac disease; and inflammatory diseases, such as inflammatory bowel disease, psoriasis, asthma a

  13. Autologous Peripheral Blood Stem Cell Transplantation in Patients With Life Threatening Autoimmune Diseases

    Science.gov (United States)

    2005-06-23

    Purpura, Schoenlein-Henoch; Graft Versus Host Disease; Anemia, Hemolytic, Autoimmune; Rheumatoid Arthritis; Churg-Strauss Syndrome; Hypersensitivity Vasculitis; Wegener's Granulomatosis; Systemic Lupus Erythematosus; Giant Cell Arteritis; Pure Red Cell Aplasia; Juvenile Rheumatoid Arthritis; Polyarteritis Nodosa; Autoimmune Thrombocytopenic Purpura; Takayasu Arteritis

  14. Senescence of the adaptive immune system in health and aging-associated autoimmune disease

    NARCIS (Netherlands)

    van der Geest, Kornelis Stephan Mario

    2015-01-01

    Aging of the immune system may contribute to the development of aging-associated autoimmune diseases, such as giant cell arteritis, polymyalgia rheumatica and rheumatoid arthritis. The aim of this thesis was to identify aging-dependent changes of the adaptive immune system that promote autoimmunity

  15. [AUTOIMMUNE REACTIONS IN PATIENTS WITH DISEASES OF A THYROID GLAND].

    Science.gov (United States)

    Saidova, F Kh; Shakhsuvarov, O M; Guseynov, R G; Akhmedova, L M; Aslanova, Zh B

    2015-11-01

    A state of autoimmunity was studied in 25 patients, suffering diffuse toxic goiter (DTG), and in 20--in nodular euthyroid goiter (NEG) before and after the operation. The level of circulating immune complexes, quantity of cytotoxic lymphocytes, the subpopulation index, the apoptosis marker were determined. There was established, that in NEG autoimmune disorders have occurred rarer and were less severe, than in DTG.

  16. Skin involvement and outcome measures in systemic autoimmune diseases.

    Science.gov (United States)

    Albrecht, J; Atzeni, F; Baldini, C; Bombardieri, S; Dalakas, M C; Demirkesen, C; Yazici, H; Mat, C; Werth, V P; Sarzi-Puttini, P

    2006-01-01

    This paper focuses on skin manifestations that can be observed in autoimmune diseases such as rheumatoid arthritis (RA), Sjögren syndrome (SS), dermatomyositis (DM) and Behçet syndrome (BS). In RA the most widely recognized skin lesion is the rheumatoid nodule. Other cutaneous manifestations can be observed either non-specific or related to the disease itself and/or to the commonly used drugs. Cutaneous manifestations are considered one of the most typical extraglandular features of primary SS, generally they are distinguished in vasculitic and non vasculitic lesions. Among non-vasculitc lesions, skin dryness (xerosis) has been shown to be very common in pSS while vasculitis lesions include typically flat and palpable purpura and urticarial vasculits. In DM the skin manifestations are also frequent and include a heliotrope rash (blue-purple discoloration) on the upper eyelids with edema, a flat red rash on the face and upper trunk, and erythema of the knuckles with a raised violaceous scaly eruption (Gottron rash). The most frequent mucocutaneous finding in BS is aphthous stomatitis which can not usually be differentiated from idiopatic reccurrent aphthous stomatitis on clinical grounds. The most typical skin manifestations are nodular lesions, which are commonly seen in BS and may be due to panniculitis [erythema nodosum (EN)-like lesions] or superficial thrombophlebitis. PMID:16466625

  17. Vitamin D endocrine system involvement in autoimmune rheumatic diseases.

    Science.gov (United States)

    Cutolo, Maurizio; Pizzorni, Carmen; Sulli, Alberto

    2011-12-01

    Vitamin D is synthesized from cholesterol in the skin (80-90%) under the sunlight and then metabolized into an active D hormone in liver, kidney and peripheral immune/inflammatory cells. These endocrine-immune effects include also the coordinated activities of the vitamin D-activating enzyme, 1alpha-hydroxylase (CYP27B1), and the vitamin D receptor (VDR) on cells of the immune system in mediating intracrine and paracrine actions. Vitamin D is implicated in prevention and protection from chronic infections (i.e. tubercolosis), cancer (i.e. breast cancer) and autoimmune rheumatic diseases since regulates both innate and adaptive immunity potentiating the innate response (monocytes/macrophages with antimicrobial activity and antigen presentation), but suppressing the adaptive immunity (T and B lymphocyte functions). Vitamin D has modulatory effects on B lymphocytes and Ig production and recent reports have demonstrated that 1,25(OH)2D3 does indeed exert direct effects on B cell homeostasis. A circannual rhythm of trough vitamin D levels in winter and peaks in summer time showed negative correlation with clinical status at least in rheumatoid arthritis and systemic lupus erythematosus. Recently, the onset of symptoms of early arthritis during winter or spring have been associated with greater radiographic evidence of disease progression at 12 months possibly are also related to seasonal lower vitamin D serum levels.

  18. Skin disease and thyroid autoimmunity in atopic South Italian children

    Science.gov (United States)

    Pedullà, Marcella; Fierro, Vincenzo; Marzuillo, Pierluigi; Capuano, Francesco; Miraglia del Giudice, Emanuele; Ruocco, Eleonora

    2016-01-01

    AIM To verify the prevalence of thyroid autoimmunity (TA) and the possible association between atopy and TA in children affected by skin disease. METHODS Three hundred and twenty-four children consecutively referred due to skin disease symptoms to our Pediatric Department were enrolled. One hundred and eighty-seven were diagnosed with atopic dermatitis (AD), 95 with acute urticaria, 40 with chronic urticaria (CU), and 2 with alopecia areata (AA). According to the work-up for atopy, the children were divided into two groups: Atopics and non-atopics. TA was diagnosed by serum thyroid peroxidase autoantibodies and/or thyroglobulin autoantibodies levels more than twice normal values over a period of two months by immunoassay. RESULTS In all children with skin disease, a significant prevalence of TA in atopics compared with non-atopics (13.67% vs 2.67%, P = 0.0016) and a significant association between TA and atopy (OR = 5.76, 95%CI: 1.71-19.35) were observed. These findings were confirmed as significant in children with AD: TA in atopics was 11.5%, while TA in non-atopics was 2.7% (P = 0.03, OR = 4.68, 95%CI: 1.02-21.38). In addition, atopics with CU showed a significantly higher prevalence of TA (26.9%), but none of the non-atopics showed CU (P = 0.0326). On the other hand, atopics with AA showed a 100% (2 out of 2) prevalence of TA, compared with none of the non-atopics. CONCLUSION In children with skin disease, atopy seems to be associated with an increased risk of TA. PMID:27610344

  19. Genetics of autoimmune diseases: insights from population genetics.

    Science.gov (United States)

    Ramos, Paula S; Shedlock, Andrew M; Langefeld, Carl D

    2015-11-01

    Human genetic diversity is the result of population genetic forces. This genetic variation influences disease risk and contributes to health disparities. Autoimmune diseases (ADs) are a family of complex heterogeneous disorders with similar underlying mechanisms characterized by immune responses against self. Collectively, ADs are common, exhibit gender and ethnic disparities, and increasing incidence. As natural selection is an important influence on human genetic variation, and immune function genes are enriched for signals of positive selection, it is thought that the prevalence of AD risk alleles seen in different population is partially the result of differing selective pressures (for example, due to pathogens). With the advent of high-throughput technologies, new analytical methodologies and large-scale projects, evidence for the role of natural selection in contributing to the heritable component of ADs keeps growing. This review summarizes the genetic regions associated with susceptibility to different ADs and concomitant evidence for selection, including known agents of selection exerting selective pressure in these regions. Examples of specific adaptive variants with phenotypic effects are included as an evidence of natural selection increasing AD susceptibility. Many of the complexities of gene effects in different ADs can be explained by population genetics phenomena. Integrating AD susceptibility studies with population genetics to investigate how natural selection has contributed to genetic variation that influences disease risk will help to identify functional variants and elucidate biological mechanisms. As such, the study of population genetics in human population holds untapped potential for elucidating the genetic causes of human disease and more rapidly focusing to personalized medicine.

  20. Recommendations for the use of immunoapheresis in the treatment of autoimmune bullous diseases.

    Science.gov (United States)

    Zillikens, Detlef; Derfler, Kurt; Eming, Rüdiger; Fierlbeck, Gerhard; Goebeler, Matthias; Hertl, Michael; Hofmann, Silke C; Karlhofer, Franz; Kautz, Ocko; Nitschke, Martin; Opitz, Andreas; Quist, Sven; Rose, Christian; Schanz, Stefan; Schmidt, Enno; Shimanovich, Iakov; Michael, Michael; Ziller, Fabian

    2007-10-01

    Despite the use of high-dose systemic corticosteroids in combination with other immunosuppressants, in some patients with autoimmune bullous diseases only insufficient improvement is achieved. In these cases and in acute severe disease, adjuvant immunoapheresis has been increasingly used. A consensus meeting was held in mid-2005 in Hamburg, aiming at developing guidelines for the use of immunoapheresis in the treatment of autoimmune bullous diseases. This paper summarizes the experts' recommendations. PMID:17910670

  1. Similar biotherapeutic products in Latin America. Regulation and opportunities for patients with autoimmune diseases

    OpenAIRE

    Desanvicente-Celis Z; Caro-Moreno J; Enciso-Zuluaga M; Anaya JM

    2013-01-01

    Zayrho Desanvicente-Celis, Julian Caro-Moreno, Mateo Enciso-Zuluaga, Juan-Manuel AnayaCenter for Autoimmune Diseases Research (CREA), Universidad del Rosario, Bogotá, ColombiaAbstract: Biotherapeutic products have revolutionized medicine, changing the way we can treat some chronic diseases, such as autoimmune diseases. The patent expiry and the high costs of reference biotherapeutic products, among other factors, have promoted interest in similar biotherapeutic products (SBPs), also kn...

  2. Similar biotherapeutic products in Latin America. Regulation and opportunities for patients with autoimmune diseases

    OpenAIRE

    Anaya, Juan-Manuel

    2013-01-01

    Zayrho Desanvicente-Celis, Julian Caro-Moreno, Mateo Enciso-Zuluaga, Juan-Manuel AnayaCenter for Autoimmune Diseases Research (CREA), Universidad del Rosario, Bogotá, ColombiaAbstract: Biotherapeutic products have revolutionized medicine, changing the way we can treat some chronic diseases, such as autoimmune diseases. The patent expiry and the high costs of reference biotherapeutic products, among other factors, have promoted interest in similar biotherapeutic products (SBPs), als...

  3. Autoimmune disease and the nervous system. Biochemical, molecular, and clinical update.

    OpenAIRE

    Merrill, J E; Graves, M C; Mulder, D. G.

    1992-01-01

    Autoimmunity in the central and peripheral nervous system can manifest as the result of cellular or humoral immune responses to autoantigens. There is evidence that multiple sclerosis is a cell-mediated autoimmune disease of the central nervous system in which both myelin and the cell that produces the myelin are destroyed. Diseases such as acute inflammatory demyelinating polyneuropathy (also called Guillain-Barré syndrome) and myasthenia gravis are considered antibody-mediated diseases of t...

  4. Childbirths and risk of female predominant and other autoimmune diseases in a population-based Danish cohort

    DEFF Research Database (Denmark)

    Jørgensen, Kristian Tore; Pedersen, Bo Vestergaard; Nielsen, Nete Munk;

    2012-01-01

    To evaluate the possible biological role of pregnancy on the risk of autoimmune diseases we assessed associations between reproductive history and subsequent risk of autoimmune diseases characterized by female predominance and other autoimmune diseases. Our study cohort comprised 4.6 million Danes.......14-1.24), erythema nodosum (1.15; 1.01-1.32), psoriasis (1.08; 1.01-1.15), sarcoidosis (1.17; 1.06-1.28) and systemic lupus erythematosus (0.83; 0.74-0.93). Especially the one-year postpartum period was associated with an increased risk of Hashimoto thyroiditis, Graves' disease and sarcoidosis. Overall, parity was...... associated with an 11% increased risk of female predominant autoimmune diseases. Pregnancies resulting in liveborn children therefore seem to contribute only little to the general female predominance in autoimmune diseases. However, for a number of autoimmune diseases; especially autoimmune thyroid diseases...

  5. Computer-Assisted Classification Patterns in Autoimmune Diagnostics: The AIDA Project

    Directory of Open Access Journals (Sweden)

    Amel Benammar Elgaaied

    2016-01-01

    Full Text Available Antinuclear antibodies (ANAs are significant biomarkers in the diagnosis of autoimmune diseases in humans, done by mean of Indirect ImmunoFluorescence (IIF method, and performed by analyzing patterns and fluorescence intensity. This paper introduces the AIDA Project (autoimmunity: diagnosis assisted by computer developed in the framework of an Italy-Tunisia cross-border cooperation and its preliminary results. A database of interpreted IIF images is being collected through the exchange of images and double reporting and a Gold Standard database, containing around 1000 double reported images, has been settled. The Gold Standard database is used for optimization of a CAD (Computer Aided Detection solution and for the assessment of its added value, in order to be applied along with an Immunologist as a second Reader in detection of autoantibodies. This CAD system is able to identify on IIF images the fluorescence intensity and the fluorescence pattern. Preliminary results show that CAD, used as second Reader, appeared to perform better than Junior Immunologists and hence may significantly improve their efficacy; compared with two Junior Immunologists, the CAD system showed higher Intensity Accuracy (85,5% versus 66,0% and 66,0%, higher Patterns Accuracy (79,3% versus 48,0% and 66,2%, and higher Mean Class Accuracy (79,4% versus 56,7% and 64.2%.

  6. Computer-Assisted Classification Patterns in Autoimmune Diagnostics: The AIDA Project.

    Science.gov (United States)

    Benammar Elgaaied, Amel; Cascio, Donato; Bruno, Salvatore; Ciaccio, Maria Cristina; Cipolla, Marco; Fauci, Alessandro; Morgante, Rossella; Taormina, Vincenzo; Gorgi, Yousr; Marrakchi Triki, Raja; Ben Ahmed, Melika; Louzir, Hechmi; Yalaoui, Sadok; Imene, Sfar; Issaoui, Yassine; Abidi, Ahmed; Ammar, Myriam; Bedhiafi, Walid; Ben Fraj, Oussama; Bouhaha, Rym; Hamdi, Khouloud; Soumaya, Koudhi; Neili, Bilel; Asma, Gati; Lucchese, Mariano; Catanzaro, Maria; Barbara, Vincenza; Brusca, Ignazio; Fregapane, Maria; Amato, Gaetano; Friscia, Giuseppe; Neila, Trai; Turkia, Souayeh; Youssra, Haouami; Rekik, Raja; Bouokez, Hayet; Vasile Simone, Maria; Fauci, Francesco; Raso, Giuseppe

    2016-01-01

    Antinuclear antibodies (ANAs) are significant biomarkers in the diagnosis of autoimmune diseases in humans, done by mean of Indirect ImmunoFluorescence (IIF) method, and performed by analyzing patterns and fluorescence intensity. This paper introduces the AIDA Project (autoimmunity: diagnosis assisted by computer) developed in the framework of an Italy-Tunisia cross-border cooperation and its preliminary results. A database of interpreted IIF images is being collected through the exchange of images and double reporting and a Gold Standard database, containing around 1000 double reported images, has been settled. The Gold Standard database is used for optimization of a CAD (Computer Aided Detection) solution and for the assessment of its added value, in order to be applied along with an Immunologist as a second Reader in detection of autoantibodies. This CAD system is able to identify on IIF images the fluorescence intensity and the fluorescence pattern. Preliminary results show that CAD, used as second Reader, appeared to perform better than Junior Immunologists and hence may significantly improve their efficacy; compared with two Junior Immunologists, the CAD system showed higher Intensity Accuracy (85,5% versus 66,0% and 66,0%), higher Patterns Accuracy (79,3% versus 48,0% and 66,2%), and higher Mean Class Accuracy (79,4% versus 56,7% and 64.2%). PMID:27042658

  7. The potential for induction of autoimmune disease by a randomly-mutated self-antigen

    DEFF Research Database (Denmark)

    Pedersen, Anders Elm

    2007-01-01

    The pathology of most autoimmune diseases is well described. However, the exact event that triggers the onset of the inflammatory cascade leading to disease is less certain and most autoimmune diseases are complex idiopathic diseases with no single gene known to be causative. In many cases, a...... relation to an infectious disease is described, and it is thought that microbes can play a direct role in induction of autoimmunity, for instance by molecular mimicry or bystander activation of autoreactive T cells. In contrast, less attention has been given to the possibility that modified self......-antigens can be immunogenic and lead to autoimmunity against wildtype self-antigens. In theory, modified self-antigens can arise by random errors and mutations during protein synthesis and would be recognized as foreign antigens by naïve B and T lymphocytes. Here, it is postulated that the initial auto...

  8. Surveillance of systemic autoimmune rheumatic diseases using administrative data.

    Science.gov (United States)

    Bernatsky, S; Lix, L; Hanly, J G; Hudson, M; Badley, E; Peschken, C; Pineau, C A; Clarke, A E; Fortin, P R; Smith, M; Bélisle, P; Lagace, C; Bergeron, L; Joseph, L

    2011-04-01

    There is growing interest in developing tools and methods for the surveillance of chronic rheumatic diseases, using existing resources such as administrative health databases. To illustrate how this might work, we used population-based administrative data to estimate and compare the prevalence of systemic autoimmune rheumatic diseases (SARDs) across three Canadian provinces, assessing for regional differences and the effects of demographic factors. Cases of SARDs (systemic lupus erythematosus, scleroderma, primary Sjogren's, polymyositis/dermatomyositis) were ascertained from provincial physician billing and hospitalization data. We combined information from three case definitions, using hierarchical Bayesian latent class regression models that account for the imperfect nature of each case definition. Using methods that account for the imperfect nature of both billing and hospitalization databases, we estimated the over-all prevalence of SARDs to be approximately 2-3 cases per 1,000 residents. Stratified prevalence estimates suggested similar demographic trends across provinces (i.e. greater prevalence in females-versus-males, and in persons of older age). The prevalence in older females approached or exceeded 1 in 100, which may reflect the high burden of primary Sjogren's syndrome in this group. Adjusting for demographics, there was a greater prevalence in urban-versus-rural settings. In our work, prevalence estimates had good face validity and provided useful information about potential regional and demographic variations. Our results suggest that surveillance of some rheumatic diseases using administrative data may indeed be feasible. Our work highlights the usefulness of using multiple data sources, adjusting for the error in each. PMID:20665025

  9. New Insights into the Management of Patients with Autoimmune Diseases or Inflammatory Disorders During Pregnancy.

    Science.gov (United States)

    Tavakolpour, Soheil; Rahimzadeh, Ghazal

    2016-09-01

    The treatment of autoimmune diseases remains a serious problem. Current therapies can lead to adverse effects in patients. One of the most vulnerable patient groups is pregnant women. It has been reported that different autoimmune diseases have a certain trend during pregnancy and after delivery which could be explained by maternal immune responses. Better management of pregnant women with autoimmune diseases or inflammatory disorders could be achieved by linking such alterations in immune responses and governed immune responses in different autoimmune disorders while considering various reports of autoimmune conditions during pregnancy. This study considers changing the T helper cells (Th1) and Th2 balance and suggests some new approaches for the better management of autoimmune diseases in pregnant women based on immune responses. Additionally, the possible role of Th17, alterations in some selected autoimmune diseases including rheumatoid arthritis (RA), multiple sclerosis (MS), psoriasis, systemic lupus erythematosus (SLE), atopic dermatitis (AD), asthma and pemphigus during pregnancy, and possible associated mechanisms are discussed. PMID:27300757

  10. Epstein-Barr Virus as a Trigger of Autoimmune Liver Diseases

    Directory of Open Access Journals (Sweden)

    Eirini I. Rigopoulou

    2012-01-01

    Full Text Available The pathogenesis of autoimmune diseases includes a combination of genetic factors and environmental exposures including infectious agents. Infectious triggers are commonly indicated as being involved in the induction of autoimmune disease, with Epstein-Barr virus (EBV being implicated in several autoimmune disorders. EBV is appealing in the pathogenesis of autoimmune disease, due to its high prevalence worldwide, its persistency throughout life in the host’s B lymphocytes, and its ability to alter the host’s immune response and to inhibit apoptosis. However, the evidence in support of EBV in the pathogenesis varies among diseases. Autoimmune liver diseases (AiLDs, including autoimmune hepatitis (AIH, primary biliary cirrhosis (PBC, and primary sclerosing cholangitis (PSC, have a potential causative link with EBV. The data surrounding EBV and AiLD are scarce. The lack of evidence surrounding EBV in AiLD may also be reflective of the rarity of these conditions. EBV infection has also been linked to other autoimmune conditions, which are often found to be concomitant with AiLD. This paper will critically examine the literature surrounding the link between EBV infection and AiLD development. The current evidence is far from being conclusive of the theory of a link between EBV and AiLD.

  11. Same-sex marriage, autoimmune thyroid gland dysfunction and other autoimmune diseases in Denmark 1989-2008.

    Science.gov (United States)

    Frisch, Morten; Nielsen, Nete Munk; Pedersen, Bo Vestergaard

    2014-01-01

    Autoimmune diseases have been little studied in gay men and lesbians. We followed 4.4 million Danes, including 9,615 same-sex married (SSM) persons, for 47 autoimmune diseases in the National Patient Registry between 1989 and 2008. Poisson regression analyses provided first hospitalization rate ratios (RRs) comparing rates between SSM individuals and persons in other marital status categories. SSM individuals experienced no unusual overall risk of autoimmune diseases. However, the risk of autoimmune thyroid dysfunction was increased, notably Hashimoto's thyroiditis (women(SSM), RR = 2.92; 95% confidence interval (CI) 1.74-4.55) and Graves' disease (men(SSM), RR = 1.88; 95% CI 1.08-3.01). There was also an excess of primary biliary cirrhosis (women(SSM), RR = 4.09; 95% CI 1.01-10.7), and of psoriasis (men(SSM), RR = 2.48; 95% CI 1.77-3.36), rheumatic fever (men(SSM), RR = 7.55; 95% CI 1.87-19.8), myasthenia gravis (men(SSM), RR = 5.51; 95% CI 1.36-14.4), localized scleroderma (men(SSM), RR = 7.16; 95% CI 1.18-22.6) and pemphigoid (men(SSM), RR = 6.56; 95% CI 1.08-20.6), while Dupuytren's contracture was reduced (men(SSM), RR = 0.64; 95% CI 0.39-0.99). The excess of psoriasis was restricted to same-sex married men with HIV/AIDS (men(SSM), RR = 10.5; 95% CI 6.44-15.9), whereas Graves' disease occurred in excess only among same-sex married men without HIV/AIDS (men(SSM), RR = 1.99; 95% CI 1.12-3.22). Lesbians and immunologically competent gay men in same-sex marriage face no unusual overall risk of autoimmune diseases. However, the observed increased risk of thyroid dysfunction in these lesbians and gay men deserves further study.

  12. Same-sex marriage, autoimmune thyroid gland dysfunction and other autoimmune diseases in Denmark 1989-2008.

    Science.gov (United States)

    Frisch, Morten; Nielsen, Nete Munk; Pedersen, Bo Vestergaard

    2014-01-01

    Autoimmune diseases have been little studied in gay men and lesbians. We followed 4.4 million Danes, including 9,615 same-sex married (SSM) persons, for 47 autoimmune diseases in the National Patient Registry between 1989 and 2008. Poisson regression analyses provided first hospitalization rate ratios (RRs) comparing rates between SSM individuals and persons in other marital status categories. SSM individuals experienced no unusual overall risk of autoimmune diseases. However, the risk of autoimmune thyroid dysfunction was increased, notably Hashimoto's thyroiditis (women(SSM), RR = 2.92; 95% confidence interval (CI) 1.74-4.55) and Graves' disease (men(SSM), RR = 1.88; 95% CI 1.08-3.01). There was also an excess of primary biliary cirrhosis (women(SSM), RR = 4.09; 95% CI 1.01-10.7), and of psoriasis (men(SSM), RR = 2.48; 95% CI 1.77-3.36), rheumatic fever (men(SSM), RR = 7.55; 95% CI 1.87-19.8), myasthenia gravis (men(SSM), RR = 5.51; 95% CI 1.36-14.4), localized scleroderma (men(SSM), RR = 7.16; 95% CI 1.18-22.6) and pemphigoid (men(SSM), RR = 6.56; 95% CI 1.08-20.6), while Dupuytren's contracture was reduced (men(SSM), RR = 0.64; 95% CI 0.39-0.99). The excess of psoriasis was restricted to same-sex married men with HIV/AIDS (men(SSM), RR = 10.5; 95% CI 6.44-15.9), whereas Graves' disease occurred in excess only among same-sex married men without HIV/AIDS (men(SSM), RR = 1.99; 95% CI 1.12-3.22). Lesbians and immunologically competent gay men in same-sex marriage face no unusual overall risk of autoimmune diseases. However, the observed increased risk of thyroid dysfunction in these lesbians and gay men deserves further study. PMID:24306355

  13. The many faces of Mac-1 in autoimmune disease.

    Science.gov (United States)

    Rosetti, Florencia; Mayadas, Tanya N

    2016-01-01

    Mac-1 (CD11b/CD18) is a β2 integrin classically regarded as a pro-inflammatory molecule because of its ability to promote phagocyte cytotoxic functions and enhance the function of several effector molecules such as FcγR, uPAR, and CD14. Nevertheless, recent reports have revealed that Mac-1 also plays significant immunoregulatory roles, and genetic variants in ITGAM, the gene that encodes CD11b, confer risk for the autoimmune disease systemic lupus erythematosus (SLE). This has renewed interest in the physiological roles of this integrin and raised new questions on how its seemingly opposing biological functions may be regulated. Here, we provide an overview of the CD18 integrins and how their activation may be regulated as this may shed light on how the opposing roles of Mac-1 may be elicited. We then discuss studies that exemplify Mac-1's pro-inflammatory versus regulatory roles particularly in the context of IgG immune complex-mediated inflammation. This includes a detailed examination of molecular mechanisms that could explain the risk-conferring effect of rs1143679, a single nucleotide non-synonymous Mac-1 polymorphism associated with SLE.

  14. Bartonella henselae Infection: An Uncommon Mimicker of Autoimmune Disease

    Directory of Open Access Journals (Sweden)

    Despoina N. Maritsi

    2013-01-01

    Full Text Available We present a case of a seven-year-old immunocompetent female patient who developed systemic symptoms mimicking an autoimmune rather than an infectious disease. The patient presented with rash, biquotidian fever, night sweats, and arthralgias. There was no antecedent history of cat contact. Investigations showed increased inflammatory markers, leukocytosis, thrombocytosis, hypercalcemia, and raised angiotensin-converting enzyme. Interferon-gamma releasing assay for tuberculosis infection was negative. Abdominal imaging demonstrated multifocal lesions of the liver and spleen (later proved to be granulomata, chest X-ray showed enlarged hilar lymph nodes, and ophthalmology review revealed uveitis. Clinical, laboratory, and imaging features pointed towards sarcoidosis. Subsequently, raised titers (IgM 1 : 32, IgG 1 : 256 against Bartonella confirmed the diagnosis of B. henselae infection. She was treated with gentamycin followed by ciprofloxacin; repeat investigations showed complete resolution of findings. The presence of hepatic and splenic lesions in children with bartonellosis is well documented. Our case, however, exhibited certain unusual findings such as the coexistence of acute ocular and systemic involvement in an immunocompetent host. Serological testing is an inexpensive and effective way to diagnose bartonellosis in immunocompetent patients; we suggest that bartonella serology is included in the baseline tests performed on children with prolonged fever even in the absence of contact with cats in countries where bartonellosis is prevalent.

  15. Etanercept (SB4): A Review in Autoimmune Inflammatory Diseases.

    Science.gov (United States)

    Burness, Celeste B; Duggan, Sean T

    2016-08-01

    Etanercept (SB4) [Benepali(®)], a tumour necrosis factor inhibitor that is a biosimilar of reference etanercept (Enbrel(®)), is approved in the EU for use in all adult indications for which reference etanercept is approved, namely rheumatoid arthritis, axial spondyloarthritis (ankylosing spondylitis and non-radiographic axial spondyloarthritis), psoriatic arthritis, and plaque psoriasis. The approval of etanercept (SB4) was based on the results of stringent comparability exercises designed to demonstrate similarity to reference etanercept in terms of quality, biological activity, efficacy, safety, and immunogenicity. In two well-designed clinical trials, etanercept (SB4) was equivalent to reference etanercept with regard to pharmacokinetic properties in healthy volunteers and in terms of efficacy in patients with moderate to severe rheumatoid arthritis despite methotrexate therapy. Longer-term efficacy (up to 52 weeks) was also similar in both treatment groups. Etanercept (SB4) was generally well tolerated, with a similar safety profile to that of reference etanercept. Preliminary results of the open-label extension period (100 weeks) suggest that transitioning from reference etanercept to etanercept (SB4) was associated with sustained efficacy and no change in the adverse event profile or immunogenicity. In conclusion, etanercept (SB4) provides therapeutically equivalent alternative in adult patients with autoimmune inflammatory diseases requiring treatment with etanercept. PMID:27455991

  16. Association between Autoimmune Rheumatic Diseases and the Risk of Dementia

    Directory of Open Access Journals (Sweden)

    Kang Lu

    2014-01-01

    Full Text Available Aim. Autoimmune rheumatic diseases (ARD are characterized by systemic inflammation and may affect multiple organs and cause vascular events such as ischemic stroke and acute myocardial infarction. However, the association between ARD and increased risk of dementia is uncertain. This is a retrospective cohort study to investigate and compare the risk of dementia between patients clinically diagnosed with ARD and non-ARD patients during a 5-year follow-up period. Methods. Data were obtained from the Longitudinal Health Insurance Database 2000 (LHID2000. We included 1221 patients receiving ambulatory or hospitalization care and 6105 non-ARD patients; patients were matched by sex, age, and the year of index use of health care. Each patient was studied for 5 years to identify the subsequent manifestation of dementia. The data obtained were analyzed by Cox proportional hazard regression. Results. During the 5-year follow-up period, 30 ARD (2.48% and 141 non-ARD patients (2.31% developed dementia. During the 5-year follow-up period, there were no significant differences in the risks of any type of dementia (adjusted hazard ratio (HR, 1.18; 95% CI, 0.79–1.76 in the ARD group after adjusting for demographics and comorbidities. Conclusions. Within the 5-year period, patients with and without ARD were found to have similar risks of developing dementia.

  17. The use of stem cells for the treatment of autoimmune diseases

    Directory of Open Access Journals (Sweden)

    S.B. Rosa

    2007-12-01

    Full Text Available Autoimmune diseases constitute a heterogeneous group of conditions commonly treated with anti-inflammatory, immunosuppressant and immunomodulating drugs, with satisfactory results in most cases. Nevertheless, some patients become resistant to conventional therapy. The use of high doses of drugs in such cases results in the need for bone marrow reconstitution, a situation which has stimulated research into the use of hematopoietic stem cells in autoimmune disease therapy. Stem cell transplantation in such diseases aims to destroy the self-reacting immune cells and produce a new functional immune system, as well as substitute cells for tissue damaged in the course of the disease. Significant results, such as the reestablishment of tolerance and a decrease in the recurrence of autoimmune disease, have been reported following stem cell transplantation in patients with autoimmune disease in Brazil and throughout the world. These results suggest that stem cell transplantation has the potential to become an important therapeutic approach to the treatment of various autoimmune diseases including rheumatoid arthritis, juvenile idiopathic arthritis, systemic lupus erythematosus, multiple sclerosis, systemic sclerosis, Crohn's disease, autoimmune blood cytopenias, and type I diabetes mellitus.

  18. Sex bias in paediatric autoimmune disease - Not just about sex hormones?

    Science.gov (United States)

    Chiaroni-Clarke, Rachel C; Munro, Jane E; Ellis, Justine A

    2016-05-01

    Autoimmune diseases affect up to 10% of the world's population, and approximately 80% of those affected are female. The majority of autoimmune diseases occur more commonly in females, although some are more frequent in males, while others show no bias by sex. The mechanisms leading to sex biased disease prevalence are not well understood. However, for adult-onset autoimmune disease, at least some of the cause is usually ascribed to sex hormones. This is because levels of sex hormones are one of the most obvious physiological differences between adult males and females, and their impact on immune system function is well recognised. While for paediatric-onset autoimmune diseases a sex bias is not as common, there are several such diseases for which one sex predominates. For example, the oligoarticular subtype of juvenile idiopathic arthritis (JIA) occurs in approximately three times more girls than boys, with a peak age of onset well before the onset of puberty, and at a time when levels of androgen and oestrogen are low and not strikingly different between the sexes. Here, we review potential explanations for autoimmune disease sex bias with a particular focus on paediatric autoimmune disease, and biological mechanisms outside of sex hormone differences.

  19. Immunogenicity and safety of the human papillomavirus vaccine in patients with autoimmune diseases: A systematic review.

    Science.gov (United States)

    Pellegrino, Paolo; Radice, Sonia; Clementi, Emilio

    2015-07-01

    Whereas safety and efficacy of HPV vaccines in healthy women have been shown in several randomised controlled clinical trials and in post marketing analyses, only few data exist in patients affected by autoimmune diseases. These issues are significant as autoimmune conditions are recognised as a risk factor for the persistence of HPV infection. Herein we review and systematise the existing literature to assess immunogenicity and safety of HPV vaccination in patients with autoimmune diseases, including systemic lupus erythematosus and juvenile idiopathic arthritis. The results of our literature revision suggest that the HPV vaccines are efficacious and safe in most of the patients affected by autoimmune diseases. Yet, some points of concern remain to be tackled, including the effects of concomitant therapies, the risk of disease exacerbation and the cost-effectiveness of such immunisation programmes in these populations. PMID:26036945

  20. CLINICAL DIAGNOSTIC VALUE OF AUTOANTIBODIES IN THE DIAGNOSIS OF AUTOIMMUNE LIVER DISEASES

    Directory of Open Access Journals (Sweden)

    V. V. Bazarnyi

    2015-01-01

    Full Text Available We are studied the 15 patients with autoimmune liver diseases and 36 patients without autoimmune pathology found the diagnostic value of antinuclear and antimitochondrial autoantibodies (AMA-M2 tests, and antibodies to asialoglycoprotein receptor (anti-ASGPR. Based on the ROC analysis showed that the diagnostic sensitivity and diagnostic specificity of AMA-M2 was 73% and 100% and for anti-ASGPR – 60% and 77%, respectively. Therefore, the test for anti-ASGPR in autoimmune diseases of the liver showed no advantages over standart tests, and its using in clinical practice requires clarification. 

  1. Review of the diagnosis,classification and management of autoimmune pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Derek; A; O’Reilly; Deep; J; Malde; Trish; Duncan; Madhu; Rao; Rafik; Filobbos

    2014-01-01

    Autoimmune pancreatitis(AIP)is a rare form of chronic pancreatitis,with as yet undetermined incidence and prevalence in the general population.Our understanding of it continues to evolve.In the last few years,2separate subtypes have been identified:type 1 AIP has been recognised as the pancreatic manifestation of a multiorgan disease,named immunoglobulin G4(IgG4)-related disease while type 2 AIP is a pancreas specific disorder not associated with IgG4.International criteria for the diagnosis of AIP have been defined:the HISORt criteria from the Mayo clinic,the Japan consensus criteria and,most recently,the international association of pancreatology"International Consensus Diagnostic Criteria".Despite this,in clinical practice it can still be very difficult to confirm the diagnosis and differenti-ate AIP from a pancreatic cancer.There are no large studies into the long-term prognosis and management of relapses of AIP,and there is even less information at present regarding the Type 2 AIP subtype.Further studies are necessary to clarify the pathogenesis,treatment and long-term outcomes of this disease.Critically for clinicians,making the correct diagnosis and differentiating the disease from pancreatic cancer is of the utmost importance and the greatest challenge.

  2. Obesity as a risk and severity factor in rheumatic diseases (Autoimmune Chronic inflammatory diseases-ACIDs

    Directory of Open Access Journals (Sweden)

    Elisa eGremese

    2014-11-01

    Full Text Available The growing body of evidence recognizing the adipose tissue as an active endocrine organ secreting bioactive mediators involved in metabolic and inflammatory disorders, together with the global epidemic of overweight and obesity, rise obesity as a hot topic of current research. The chronic state of low grade inflammation present in the obese condition and the multiple pleiotropic effects of adipokines on the immune system has been implicated in the pathogenesis of several inflammatory conditions including rheumatic autoimmune and inflammatory diseases. We will discuss the main relevant evidences on the role of the adipose tissue on immune and inflammatory networks and the more recent evidences regarding the effects of obesity on the incidence and outcomes of the major autoimmune chronic inflammatory diseases.

  3. Possible Role of Human Herpesvirus 6 as a Trigger of Autoimmune Disease

    OpenAIRE

    Francesco Broccolo; Lisa Fusetti; Luca Ceccherini-Nelli

    2013-01-01

    Human herpesvirus 6 (HHV-6) infection is common and has a worldwide distribution. Recently, HHV-6A and HHV-6B have been reclassified into two distinct species based on different biological features (genetic, antigenic, and cell tropism) and disease associations. A role for HHV-6A/B has been proposed in several autoimmune disorders (AD), including multiple sclerosis (MS), autoimmune connective tissue diseases, and Hashimoto's thyroiditis. The focus of this review is to discuss the above-mentio...

  4. The use of stem cells for the treatment of autoimmune diseases

    OpenAIRE

    S.B. Rosa; J.C. Voltarelli; J.A.B. Chies; Pranke, P.

    2007-01-01

    Autoimmune diseases constitute a heterogeneous group of conditions commonly treated with anti-inflammatory, immunosuppressant and immunomodulating drugs, with satisfactory results in most cases. Nevertheless, some patients become resistant to conventional therapy. The use of high doses of drugs in such cases results in the need for bone marrow reconstitution, a situation which has stimulated research into the use of hematopoietic stem cells in autoimmune disease therapy. Stem cell transplanta...

  5. The hygiene hypothesis revisited: autoimmune diseases, intestinal microbiota and vitamin D's role

    OpenAIRE

    Clark, Allison

    2016-01-01

    The hygiene hypothesis postulates that higher levels of hygiene and improper exposure to microorganisms early in childhood could disturb the intestinal microbiome functions resulting in abnormal immune responses that can later lead to allergies and autoimmune diseases. Additionally, vitamin D deficiency and vitamin D receptor (VDR) polymorphisms and function might also trigger abnormal immune responses that can lead to an autoimmune disease. Therefore, this review explores the role Western li...

  6. On the classification of diseases.

    Science.gov (United States)

    Smart, Benjamin

    2014-08-01

    Identifying the necessary and sufficient conditions for individuating and classifying diseases is a matter of great importance in the fields of law, ethics, epidemiology, and of course, medicine. In this paper, I first propose a means of achieving this goal, ensuring that no two distinct disease-types could correctly be ascribed to the same disease-token. I then posit a metaphysical ontology of diseases-that is, I give an account of what a disease is. This is essential to providing the most effective means of interfering with disease processes. Following existing work in the philosophy of medicine and epidemiology (primarily Christopher Boorse; Caroline Whitbeck; Alexander Broadbent), philosophy of biology (Joseph LaPorte; D.L. Hull), conditional analyses of causation (J.L. Mackie; David Lewis), and recent literature on dispositional essentialism (Stephen Mumford and Rani Anjum; Alexander Bird), I endorse a dispositional conception of disease. Following discussion of various conceptions of disease-identity, their relations to the clinical and pathological effects of the diseases in question, and how diseases are treated, I conclude (i) that diseases should be individuated by their causes, and (ii) that diseases are causal processes best seen as simultaneously acting sequences of mutually manifesting dispositions.

  7. Organic solvents as risk factor for autoimmune diseases: a systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Carolina Barragán-Martínez

    Full Text Available BACKGROUND: Genetic and epigenetic factors interacting with the environment over time are the main causes of complex diseases such as autoimmune diseases (ADs. Among the environmental factors are organic solvents (OSs, which are chemical compounds used routinely in commercial industries. Since controversy exists over whether ADs are caused by OSs, a systematic review and meta-analysis were performed to assess the association between OSs and ADs. METHODS AND FINDINGS: The systematic search was done in the PubMed, SCOPUS, SciELO and LILACS databases up to February 2012. Any type of study that used accepted classification criteria for ADs and had information about exposure to OSs was selected. Out of a total of 103 articles retrieved, 33 were finally included in the meta-analysis. The final odds ratios (ORs and 95% confidence intervals (CIs were obtained by the random effect model. A sensitivity analysis confirmed results were not sensitive to restrictions on the data included. Publication bias was trivial. Exposure to OSs was associated to systemic sclerosis, primary systemic vasculitis and multiple sclerosis individually and also to all the ADs evaluated and taken together as a single trait (OR: 1.54; 95% CI: 1.25-1.92; p-value<0.001. CONCLUSION: Exposure to OSs is a risk factor for developing ADs. As a corollary, individuals with non-modifiable risk factors (i.e., familial autoimmunity or carrying genetic factors should avoid any exposure to OSs in order to avoid increasing their risk of ADs.

  8. Vitamin D or hormone D deficiency in autoimmune rheumatic diseases, including undifferentiated connective tissue disease

    OpenAIRE

    Cutolo, Maurizio

    2008-01-01

    Epidemiological evidence indicates a significant association between vitamin D deficiency and an increased incidence of autoimmune diseases. The presence of vitamin D receptors in the cells of the immune system and the fact that several of these cells produce the vitamin D hormone suggested that vitamin D could have immunoregulatory properties, and now potent immuno-mudulatory activities on dendritic cells, Th1 and Th17 cells, as well as B cells have been confirmed. Patients with undifferenti...

  9. Regulation of IL-17 in autoimmune diseases by transcriptional factors and microRNAs

    Directory of Open Access Journals (Sweden)

    Deena eKhan

    2015-07-01

    Full Text Available In recent years, IL-17A (IL-17, a pro-inflammatory cytokine, has received intense attention of researchers and clinicians alike with documented effects in inflammation and autoimmune diseases. IL-17 mobilizes, recruits and activates different cells to increase inflammation. Although protective in infections, overproduction of IL-17 promotes inflammation in autoimmune diseases such as multiple sclerosis, rheumatoid arthritis, psoriasis, among others. Regulating IL-17 levels or action by using IL-17-blocking antibodies or IL-17R antagonist has shown to attenuate experimental autoimmune diseases. It is now known that in addition to IL-17-specific transcription factor, RORγt, several other transcription factors and select microRNAs (miRNA regulate IL-17. Given that miRNAs are dysregulated in autoimmune diseases, a better understanding of transcriptional factors and miRNA regulation of IL-17 expression and function will be essential for devising potential new therapies. In this review, we will overview IL-17 induction and function in relation to autoimmune diseases. In addition, current findings on transcriptional regulation of IL-17 induction and plausible interplay between IL-17 and miRNA in autoimmune diseases are highlighted.

  10. Reengineering chimeric antigen receptor T cells for targeted therapy of autoimmune disease.

    Science.gov (United States)

    Ellebrecht, Christoph T; Bhoj, Vijay G; Nace, Arben; Choi, Eun Jung; Mao, Xuming; Cho, Michael Jeffrey; Di Zenzo, Giovanni; Lanzavecchia, Antonio; Seykora, John T; Cotsarelis, George; Milone, Michael C; Payne, Aimee S

    2016-07-01

    Ideally, therapy for autoimmune diseases should eliminate pathogenic autoimmune cells while sparing protective immunity, but feasible strategies for such an approach have been elusive. Here, we show that in the antibody-mediated autoimmune disease pemphigus vulgaris (PV), autoantigen-based chimeric immunoreceptors can direct T cells to kill autoreactive B lymphocytes through the specificity of the B cell receptor (BCR). We engineered human T cells to express a chimeric autoantibody receptor (CAAR), consisting of the PV autoantigen, desmoglein (Dsg) 3, fused to CD137-CD3ζ signaling domains. Dsg3 CAAR-T cells exhibit specific cytotoxicity against cells expressing anti-Dsg3 BCRs in vitro and expand, persist, and specifically eliminate Dsg3-specific B cells in vivo. CAAR-T cells may provide an effective and universal strategy for specific targeting of autoreactive B cells in antibody-mediated autoimmune disease. PMID:27365313

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

    Directory of Open Access Journals (Sweden)

    Regina M. Innocencio

    2004-06-01

    Full Text Available 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 patients with antiphospholipid syndrome to a control group of 113 healthy individuals. Evaluation included a thorough clinical examination with particular attention to thyroid disease and a serologic immune profile including rheumatoid factor, antinuclear and anticardiolipin antibody measurements. Subclinical hypothyroidism (4.2Ciertas anormalidades en la función tiroidea y anticuerpos antitiroideos han sido frecuentemente descriptos en pacientes con enfermedades autoinmunes, y más raramente en pacientes con el síndrome antifosfolipídico. Para determinar la prevalencía de anormalidades en la función tiroidea y de autoinmunidad, comparamos los niveles séricos de tirotropina (TSH tiroxina libre en suero (T4 anticuerpos antitiroglobulina (TgAb y antitiroperoxidasa (TPOAb en 25 pacientes con esclerosis sistémica, 25 pacientes con artritis reumatoidea y 13 pacientes con el síndrome antifosfolipídico con un grupo control de 113 individuos aparentemente sanos. La evaluación incluyó un completo examen clínico con particular atención para las enfermedades de la tiroides y una evaluación inmunológica incluyendo dosaje del factor reumatoideo, anticuerpos antinucleares y anticardiolipina. Hipotiroidismo subclínico (4.2

  12. The increased risk for autoimmune diseases in patients with eating disorders.

    Directory of Open Access Journals (Sweden)

    Anu Raevuori

    Full Text Available OBJECTIVE: Research suggests autoimmune processes to be involved in psychiatric disorders. We aimed to address the prevalence and incidence of autoimmune diseases in a large Finnish patient cohort with anorexia nervosa, bulimia nervosa, and binge eating disorder. METHODS: Patients (N = 2342 treated at the Eating Disorder Unit of Helsinki University Central Hospital between 1995 and 2010 were compared with general population controls (N = 9368 matched for age, sex, and place of residence. Data of 30 autoimmune diseases from the Hospital Discharge Register from 1969 to 2010 were analyzed using conditional and Poisson regression models. RESULTS: Of patients, 8.9% vs. 5.4% of control individuals had been diagnosed with one or more autoimmune disease (OR 1.7, 95% CI 1.5-2.0, P<0.001. The increase in endocrinological diseases (OR 2.4, 95% CI 1.8-3.2, P<0.001 was explained by type 1 diabetes, whereas Crohn's disease contributed most to the risk of gastroenterological diseases (OR 1.8, 95% CI 1.4-2.5, P<0.001. Higher prevalence of autoimmune diseases among patients with eating disorders was not exclusively due to endocrinological and gastroenterological diseases; when the two categories were excluded, the increase in prevalence was seen in the patients both before the onset of the eating disorder treatment (OR 1.5, 95% CI 1.1-2.1, P = 0.02 and at the end of the follow-up (OR 1.4, 95% CI 1.1-1.8, P = 0.01. CONCLUSIONS: We observed an association between eating disorders and several autoimmune diseases with different genetic backgrounds. Our findings support the link between immune-mediated mechanisms and development of eating disorders. Future studies are needed to further explore the risk of autoimmune diseases and immunological mechanisms in individuals with eating disorders and their family members.

  13. Frequency of autoimmune thyroid disease in chronic urticaria

    International Nuclear Information System (INIS)

    To determine the frequency of autoimmune thyroid disease in diagnosed cases of chronic urticaria (CU) and the association between hypothyroidism and chronic urticaria if any. Study Design: Non-interventional, descriptive study. Place and Duration of Study: Department of Physiology, Dow University of Health Sciences, Karachi, from December 2004 to January 2006. Methodology: The patients were selected from Department of Dermatology and Medical Units of Civil Hospital, Jinnah Postgraduate Medical Centre, the Aga Khan Hospital and community clinics. A total number of 60 patients were enrolled in this study. In all patients, serum antithyroid autoantibodies (anti thyroglobulin and anti microsomal/thyroperoxidase), thyroid profile (serum TSH, T3 and FT4), complete blood count, erythrocyte sedimentation rate and IgE levels were carried out. The proportions were compared using chi-square test with significance at p < 0.05. Results: Forty seven (78%) patients were found to have chronic urticaria (history and laboratory reports). Out of 47 patients with diagnosis of CU, elevated titres of anti thyroglobulin (TGA) and anti microsomal antibodies (TMA) were found to be present in 20 (42.6%) and 27 (57.4%) patients respectively. Serum TSH level (thyroid stimulating hormone) was increased and T3, FT4 were decreased in 20 (42.6%) patients (p < 0.001). A total number of 20 (42.5%) patients were found to be hypothyroid with chronic urticaria of greater than 6 weeks duration. Conclusion: This study shows a statistically significant association between hypothyroidism and chronic urticaria. Full thyroid profile (serum thyroid autoantibodies, serum TSH, T3 and FT4) is highly recommended in patients with diagnosis of chronic urticaria. (author)

  14. Plasticity of Th17 Cells in Autoimmune Kidney Diseases.

    Science.gov (United States)

    Krebs, Christian F; Turner, Jan-Eric; Paust, Hans-Joachim; Kapffer, Sonja; Koyro, Tobias; Krohn, Sonja; Ufer, Friederike; Friese, Manuel A; Flavell, Richard A; Stockinger, Brigitta; Steinmetz, Oliver M; Stahl, Rolf A K; Huber, Samuel; Panzer, Ulf

    2016-07-15

    The ability of CD4(+) T cells to differentiate into pathogenic Th1 and Th17 or protective T regulatory cells plays a pivotal role in the pathogenesis of autoimmune diseases. Recent data suggest that CD4(+) T cell subsets display a considerable plasticity. This plasticity seems to be a critical factor for their pathogenicity, but also for the potential transition of pathogenic effector T cells toward a more tolerogenic phenotype. The aim of the current study was to analyze the plasticity of Th17 cells in a mouse model of acute crescentic glomerulonephritis and in a mouse chronic model of lupus nephritis. By transferring in vitro generated, highly purified Th17 cells and by using IL-17A fate reporter mice, we demonstrate that Th17 cells fail to acquire substantial expression of the Th1 and Th2 signature cytokines IFN-γ and IL-13, respectively, or the T regulatory transcription factor Foxp3 throughout the course of renal inflammation. In an attempt to therapeutically break the stability of the Th17 phenotype in acute glomerulonephritis, we subjected nephritic mice to CD3-specific Ab treatment. Indeed, this treatment induced an immunoregulatory phenotype in Th17 cells, which was marked by high expression of IL-10 and attenuated renal tissue damage in acute glomerulonephritis. In summary, we show that Th17 cells display a minimum of plasticity in acute and chronic experimental glomerulonephritis and introduce anti-CD3 treatment as a tool to induce a regulatory phenotype in Th17 cells in the kidney that may be therapeutically exploited.

  15. Ionizing radiation and autoimmunity: Induction of autoimmune disease in mice by high dose fractionated total lymphoid irradiation and its prevention by inoculating normal T cells

    International Nuclear Information System (INIS)

    Ionizing radiation can functionally alter the immune system and break self-tolerance. High dose (42.5 Gy), fractionated (2.5 Gy 17 times) total lymphoid irradiation (TLI) on mice caused various organ-specific autoimmune diseases, such as gastritis, thyroiditis, and orchitis, depending on the radiation dosages, the extent of lymphoid irradiation, and the genetic background of the mouse strains. Radiation-induced tissue damage is not the primary cause of the autoimmune disease because irradiation of the target organs alone failed to elicit the autoimmunity and shielding of the organs from irradiation was unable to prevent it. In contrast, irradiation of both the thymus and the peripheral lymphoid organs/tissues was required for efficient induction of autoimmune disease by TLI. TLI eliminated the majority of mature thymocytes and the peripheral T cells for 1 mo, and inoculation of spleen cell, thymocyte, or bone marrow cell suspensions (prepared from syngeneic nonirradiated mice) within 2 wk after TLI effectively prevented the autoimmune development. Depletion of T cells from the inocula abrogated the preventive activity. CD4+ T cells mediated the autoimmune prevention but CD8+ T cells did not. CD4+ T cells also appeared to mediate the TLI-induced autoimmune disease because CD4+ T cells from disease-bearing TLI mice adoptively transferred the autoimmune disease to syngeneic naive mice. Taken together, these results indicate that high dose, fractionated ionizing radiation on the lymphoid organs/tissues can cause autoimmune disease by affecting the T cell immune system, rather than the target self-Ags, presumably by altering T cell-dependent control of self-reactive T cells. 62 refs., 9 figs., 2 tabs

  16. Environmental chemicals and autoimmune disease: cause and effect

    International Nuclear Information System (INIS)

    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

  17. IMMUNOHISTOCHEMISTRY VERSUS IMMUNOFLUORESENCE IN THE DIAGNOSIS OF AUTOIMMUNE BLISTERING DISEASES

    Directory of Open Access Journals (Sweden)

    Ana Maria Abreu Velez

    2013-11-01

    Full Text Available Introduction: In patients with autoimmune skin blistering diseases (ABDs, the diagnostic gold standard has classically been direct and indirect immunofluorescence (DIF and IIF, despite inherent technical problems of autofluorescence. Aim: We sought to overcome autofluorescence issues and compare the reliability of immunofluorescence versus immunohistochemistry (IHC staining in the diagnoses of these diseases. Methods: We tested via IHC for anti-human IgG, IgM, IgA, IgD, IgE, Kappa light chains, Lambda light chains, Complement/C3c, Complement/C1q, Complement/C3d, albumin and fibrinogen in 30 patients affected by a new variant of endemic pemphigus foliaceus in El Bagre, Colombia (El Bagre-EPF, and 30 control biopsies from the endemic area. We also tested archival biopsies from patients with ABDs whose diagnoses were made clinically, histopathologically and by DIF/IIF studies from 2 independent dermatopathology laboratories in the USA. Specifically, we tested 34 patients with bullous pemphigoid (BP, 18 with pemphigus vulgaris (PV, 8 with pemphigus foliaceus (PF, 14 with dermatitis herpetiformis (DH and 30 control skin samples from plastic esthetic surgery reduction surgeries. Results: The diagnostic correlation between IHC and DIF-IIF was almost 98% in most cases. IHC revealed evidence of autofluorescence around dermal blood vessels, dermal eccrine glands and neurovascular packages feeding skin appendices in ABDs; this autofluorescence may represent a non-specific immune response. Strong patterns of positivity were seen also in endothelial-mesenchymal cell junction-like structures, as well as between dermal fibrohistiocytic cells. In PV, we noted strong reactivity to neurovascular packages supplying sebaceous glands, as well as apocrine glands with edematous changes. Conclusions: We suggest that IHC is as reliable as DIF or IIF for the diagnosis of ABDs; our findings further suggest that what has previously been considered DIF/IIF autofluorescence

  18. Diagnostic utility of IgG and IgM immunohistochemistry in autoimmune liver disease

    Institute of Scientific and Technical Information of China (English)

    Roger; Klein; Moreira; Frank; Revetta; Elizabeth; Koehler; Mary; Kay; Washington

    2010-01-01

    AIM:To assess the role of IgM and IgG immunohistochemistry(IHC) in the evaluation of autoimmune liver conditions-autoimmune hepatitis(AIH),primary biliary cirrhosis(PBC),and primary sclerosing cholangitis(PSC).METHODS:Forty one biopsies from untreated patients diagnosed with autoimmune liver disease(AIH,n = 20;PBC,n = 13;PSC,n = 8) and fourteen biopsies of patients with chronic hepatitis C were selected.IgM and IgG-positive plasma cells were counted in each sample.RESULTS:A predominance of IgG-positive plas...

  19. Immunohistochemistry of human Hsp60 in health and disease: from autoimmunity to cancer.

    Science.gov (United States)

    Cappello, Francesco; de Macario, Everly Conway; Zummo, Giovanni; Macario, Alberto J L

    2011-01-01

    Hsp60 (also called Cpn60) is a chaperonin with essential functions for cell physiology and survival. Additionally, its involvement in the pathogenesis of a number of diseases (e.g., some autoimmune disorders and cancer) is becoming evident with new research. For example, the distribution and levels of Hsp60 in cells and tissues have been found altered in many pathologic conditions, and the significance of these alterations is being investigated in a number of laboratories. The aim of this ongoing research is to determine the meaning of these Hsp60 alterations with regard to pathogenetic mechanisms, diagnosis, classification of lesions, and assessing of prognosis and response to treatment. Hsp60 occurs in the mitochondria, i.e., its typical residence according to classic knowledge, and also in other locales, such as the cytosol, the cell membrane, the intercellular space, and biological fluids (e.g., blood and cerebrospinal fluid). Detection and quantitative determinations in all these locations are becoming essential components of laboratory pathology in clinics and research. Consequently, immunohistochemistry targeting Hsp60 is also becoming essential for pathologists and researchers interested in disorders involving this chaperonin. In this chapter, we briefly summarize some recent discoveries on the participation of Hsp60 in the pathogenesis of human diseases and describe in detail how to perform immunohistochemical reactions for detecting the chaperonin, determining its location, and measuring its levels of expression.

  20. Human parvovirus B19 and autoimmune diseases. Review of the literature and pathophysiological hypotheses.

    Science.gov (United States)

    Page, Cyril; François, Catherine; Goëb, Vincent; Duverlie, Gilles

    2015-11-01

    A number of arguments support the role played by PVB19 in autoimmunity, in the broad sense of the term essentially derived from numerous clinical case reports and/or small series over the past 20-30 years in the medical literature. PVB19 can induce a very broad spectrum of autoantibody production, especially including: anti-soluble nuclear antigen antibodies, antiphospholipid antibodies anti-native DNA antibodies, antilymphocyte antibody, anticardiolipin antibodies, antinuclear antibodies and rheumatoid factor. Notably acute PVB19 infection can mimic or stimulate autoimmune systemic diseases as rheumatoid arthritis or systemic lupus erythematosus. However, at the present time, there is no formal scientific evidence demonstrating a direct role of PVB19 in autoimmunity, bearing in mind that there are also no formal arguments against it. Further large studies are needed to understand the eventual role of PVB19 in autoimmune diseases. PMID:26433772

  1. Challenges in Interpretation of Thyroid Function Tests in Pregnant Women with Autoimmune Thyroid Disease

    Directory of Open Access Journals (Sweden)

    Ulla Feldt-Rasmussen

    2011-01-01

    Full Text Available Physiological changes during gestation are important to be aware of in measurement and interpretation of thyroid function tests in women with autoimmune thyroid diseases. Thyroid autoimmune activity is decreasing in pregnancy. Measurement of serum TSH is the first-line screening variable for thyroid dysfunction also in pregnancy. However, using serum TSH for control of treatment of maternal thyroid autoimmunity infers a risk for compromised foetal development. Peripheral thyroid hormone values are highly different among laboratories, and there is a need for laboratory-specific gestational age-related reference ranges. Equally important, the intraindividual variability of the thyroid hormone measurements is much narrower than the interindividual variation (reflecting the reference interval. The best laboratory assessment of thyroid function is a free thyroid hormone estimate combined with TSH. Measurement of antithyroperoxidase and/or TSH receptor antibodies adds to the differential diagnosis of autoimmune and nonautoimmune thyroid diseases.

  2. Autoimmune diseases — connecting risk alleles with molecular traits of the immune system

    Science.gov (United States)

    Gutierrez-Arcelus, Maria; Rich, Stephen S.; Raychaudhuri, Soumya

    2016-01-01

    Genome-wide strategies have driven the discovery of more than 300 susceptibility loci for autoimmune diseases. However, for almost all loci, understanding of the mechanisms leading to autoimmunity remains limited, and most variants that are likely to be causal are in non-coding regions of the genome. A critical next step will be to identify the in vivo and ex vivo immunophenotypes that are affected by risk variants. To do this, key cell types and cell states that are implicated in autoimmune diseases will need to be defined. Functional genomic annotations from these cell types and states can then be used to resolve candidate genes and causal variants. Together with longitudinal studies, this approach may yield pivotal insights into how autoimmunity is triggered. PMID:26907721

  3. Contrasting the Genetic Background of Type 1 Diabetes and Celiac Disease Autoimmunity

    NARCIS (Netherlands)

    Gutierrez-Achury, Javier; Romanos, Jihane; Bakker, Sjoerd F.; Magadi Gopalaiah, Vinod Kumar; de Haas, Esther C.; Trynka, Gosia; Ricano-Ponce, Isis; Steck, Andrea; Chen, Wei-Min; Onengut-Gumuscu, Suna; Simsek, Suat; Rewers, Marian; Mulder, Chris J.; Liu, Ed; Rich, Stephen S.; Wijmenga, Cisca

    2015-01-01

    Type 1 diabetes (T1D) and celiac disease (CeD) cluster in families and can occur in the same individual. Genetic loci have been associated with susceptibility to both diseases. Our aim was to explore the genetic differences between individuals developing both these diseases (double autoimmunity) ver

  4. 76 FR 13111 - Compassionate Allowances for Autoimmune Disease, Office of the Commissioner; Hearing

    Science.gov (United States)

    2011-03-10

    ... Alzheimer's disease and related dementias, schizophrenia, and cardiovascular disease and multiple organ... methods of identifying and implementing compassionate allowances for both adults and children with... respect to adults and children with autoimmune diseases, as well as topics covered at the hearing by:...

  5. Mast cells are important modifiers of autoimmune disease: With so much evidence, why is there controversy?

    Directory of Open Access Journals (Sweden)

    Melissa Ann Brown

    2012-06-01

    Full Text Available There is abundant evidence that mast cells are active participants in events that mediate tissue damage in autoimmune disease. Disease-associated increases in mast cell numbers accompanied by mast cell degranulation and elaboration of numerous mast cell mediators at sites of inflammation are commonly observed in many human autoimmune diseases including multiple sclerosis, rheumatoid arthritis and bullous pemphigoid. In animal models, treatment with mast cell stabilizing drugs or mast cell ablation can result in diminished disease. A variety of receptors including those engaged by antibody, complement, pathogens and intrinsic danger signals are implicated in mast cell activation in disease. Similar to their role as first responders in infection settings, mast cells likely orchestrate early recruitment of immune cells, including neutrophils, to the sites of autoimmune destruction. This co-localization promotes cellular crosstalk and activation and results in the amplification of the local inflammatory response thereby promoting and sustaining tissue damage. Despite the evidence, there is still a debate regarding the relative role of mast cells in these processes. However, by definition, mast cells can only act as accessory cells to the self-reactive T and/or antibody driven autoimmune responses. Thus, when evaluating mast cell involvement using existing and somewhat imperfect animal models of disease, their importance is sometimes obscured. However, these potent immune cells are undoubtedly major contributors to autoimmunity and should be considered as important targets for therapeutic disease intervention.

  6. Unresolved issues in theories of autoimmune disease using myocarditis as a framework.

    Science.gov (United States)

    Root-Bernstein, Robert; Fairweather, DeLisa

    2015-06-21

    Many theories of autoimmune disease have been proposed since the discovery that the immune system can attack the body. These theories include the hidden or cryptic antigen theory, modified antigen theory, T cell bypass, T cell-B cell mismatch, epitope spread or drift, the bystander effect, molecular mimicry, anti-idiotype theory, antigenic complementarity, and dual-affinity T cell receptors. We critically review these theories and relevant mathematical models as they apply to autoimmune myocarditis. All theories share the common assumption that autoimmune diseases are triggered by environmental factors such as infections or chemical exposure. Most, but not all, theories and mathematical models are unifactorial assuming single-agent causation of disease. Experimental and clinical evidence and mathematical models exist to support some aspects of most theories, but evidence/models that support one theory almost invariably supports other theories as well. More importantly, every theory (and every model) lacks the ability to account for some key autoimmune disease phenomena such as the fundamental roles of innate immunity, sex differences in disease susceptibility, the necessity for adjuvants in experimental animal models, and the often paradoxical effect of exposure timing and dose on disease induction. We argue that a more comprehensive and integrated theory of autoimmunity associated with new mathematical models is needed and suggest specific experimental and clinical tests for each major theory that might help to clarify how they relate to clinical disease and reveal how theories are related.

  7. Classification rules for Indian Rice diseases

    Directory of Open Access Journals (Sweden)

    A. Nithya

    2011-01-01

    Full Text Available Many techniques have been developed for learning rules and relationships automatically from diverse data sets, to simplify the often tedious and error-prone process of acquiring knowledge from empirical data. Decision tree is one of learning algorithm which posses certain advantages that make it suitable for discovering the classification rule for data mining applications. Normally Decision trees widely used learning method and do not require any prior knowledge of data distribution, works well on noisy data .It has been applied to classify Rice disease based on the symptoms. This paper intended to discover classification rules for the Indian rice diseases using the c4.5 decision trees algorithm. Expert systems have been used in agriculture since the early 1980s. Several systems have been developed in different countries including the USA, Europe, and Egypt for plant-disorder diagnosis, management and other production aspects. This paper explores what Classification rule can do in the agricultural domain.

  8. Management of rheumatic and autoimmune blistering disease in pregnancy and postpartum.

    Science.gov (United States)

    Wan, Joy; Imadojemu, Sotonye; Werth, Victoria P

    2016-01-01

    The treatment of rheumatic and autoimmune skin disease in women who are pregnant or of childbearing potential can present challenges to the dermatologist. We discuss the current approaches to treating lupus erythematosus, antiphospholipid antibody syndrome, dermatomyositis, morphea and systemic sclerosis, mixed connective tissue disease, rheumatoid arthritis, and autoimmune blistering disease in such patients. In the appropriate setting, topical and systemic corticosteroids, hydroxychloroquine, dapsone, azathioprine, and ultraviolet B phototherapy may be safely and cautiously used during pregnancy. Considerations about contraception, planned conception, therapeutic options, and disease control are paramount in optimizing pregnancy outcomes and minimizing risks to both mother and fetus. PMID:27265072

  9. Is vitamin D a player or not in the pathophysiology of autoimmune thyroid diseases?

    Science.gov (United States)

    D'Aurizio, Federica; Villalta, Danilo; Metus, Paolo; Doretto, Paolo; Tozzoli, Renato

    2015-05-01

    1,25-Dihydroxyvitamin D is a steroid hormone derived from vitamin D, playing an important role in maintaining an adequate serum level of calcium and phosphorus. It is now clear that vitamin D exerts an endocrine action on the cells of the immune system, generating anti-inflammatory and immunoregulatory effects. The mechanisms underlying the role of vitamin D in autoimmunity are not completely understood. Lower vitamin D levels have been found in several autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, type 1 diabetes mellitus, multiple sclerosis, inflammatory bowel diseases, autoimmune thyroid diseases (i.e. Hashimoto's thyroiditis and Graves' disease) and autoimmune gastritis. Several genetic studies have demonstrated an association between thyroid autoimmunity susceptibility and gene polymorphisms of vitamin D receptor, vitamin D binding protein, 1-alpha-hydroxylase and 25-hydroxylase. Of note, some papers do not confirm this connection. With regard to the role of vitamin D in autoimmune thyroid diseases, available data remain controversial. Only few reports have analyzed the supposed association between autoimmune thyroid diseases and vitamin D concentration with inconclusive results. In our experience, low serum levels of vitamin D do not correlate either with Hashimoto's thyroiditis or with Graves' disease. The inability to achieve an unambiguous conclusion is in part due to the limitations in study design. In fact, most of the studies are cross-sectional surveys with a small number of subjects. In addition, the heterogeneity of the study population, seasonal variation of blood sampling, inter-method analytical variability of vitamin D assays and different definitions of vitamin D deficiency/insufficiency contribute to contradicting results. Therefore, further randomized, controlled, prospective trials are needed in order to demonstrate the causality of vitD in AITD and consequently the role of vitamin D

  10. Is vitamin D a player or not in the pathophysiology of autoimmune thyroid diseases?

    Science.gov (United States)

    D'Aurizio, Federica; Villalta, Danilo; Metus, Paolo; Doretto, Paolo; Tozzoli, Renato

    2015-05-01

    1,25-Dihydroxyvitamin D is a steroid hormone derived from vitamin D, playing an important role in maintaining an adequate serum level of calcium and phosphorus. It is now clear that vitamin D exerts an endocrine action on the cells of the immune system, generating anti-inflammatory and immunoregulatory effects. The mechanisms underlying the role of vitamin D in autoimmunity are not completely understood. Lower vitamin D levels have been found in several autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, type 1 diabetes mellitus, multiple sclerosis, inflammatory bowel diseases, autoimmune thyroid diseases (i.e. Hashimoto's thyroiditis and Graves' disease) and autoimmune gastritis. Several genetic studies have demonstrated an association between thyroid autoimmunity susceptibility and gene polymorphisms of vitamin D receptor, vitamin D binding protein, 1-alpha-hydroxylase and 25-hydroxylase. Of note, some papers do not confirm this connection. With regard to the role of vitamin D in autoimmune thyroid diseases, available data remain controversial. Only few reports have analyzed the supposed association between autoimmune thyroid diseases and vitamin D concentration with inconclusive results. In our experience, low serum levels of vitamin D do not correlate either with Hashimoto's thyroiditis or with Graves' disease. The inability to achieve an unambiguous conclusion is in part due to the limitations in study design. In fact, most of the studies are cross-sectional surveys with a small number of subjects. In addition, the heterogeneity of the study population, seasonal variation of blood sampling, inter-method analytical variability of vitamin D assays and different definitions of vitamin D deficiency/insufficiency contribute to contradicting results. Therefore, further randomized, controlled, prospective trials are needed in order to demonstrate the causality of vitD in AITD and consequently the role of vitamin D

  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. The Increased Risk for Autoimmune Diseases in Patients with Eating Disorders

    OpenAIRE

    Anu Raevuori; Jari Haukka; Outi Vaarala; Suvisaari, Jaana M.; Mika Gissler; Marjut Grainger; Milla S Linna; Suokas, Jaana T

    2014-01-01

    OBJECTIVE: Research suggests autoimmune processes to be involved in psychiatric disorders. We aimed to address the prevalence and incidence of autoimmune diseases in a large Finnish patient cohort with anorexia nervosa, bulimia nervosa, and binge eating disorder. METHODS: Patients (N = 2342) treated at the Eating Disorder Unit of Helsinki University Central Hospital between 1995 and 2010 were compared with general population controls (N = 9368) matched for age, sex, and place of residence. Da...

  13. Google-driven search for big data in autoimmune geoepidemiology: analysis of 394,827 patients with systemic autoimmune diseases.

    Science.gov (United States)

    Ramos-Casals, Manuel; Brito-Zerón, Pilar; Kostov, Belchin; Sisó-Almirall, Antoni; Bosch, Xavier; Buss, David; Trilla, Antoni; Stone, John H; Khamashta, Munther A; Shoenfeld, Yehuda

    2015-08-01

    Systemic autoimmune diseases (SADs) are a significant cause of morbidity and mortality worldwide, although their epidemiological profile varies significantly country by country. We explored the potential of the Google search engine to collect and merge large series (>1000 patients) of SADs reported in the Pubmed library, with the aim of obtaining a high-definition geoepidemiological picture of each disease. We collected data from 394,827 patients with SADs. Analysis showed a predominance of medical vs. administrative databases (74% vs. 26%), public health system vs. health insurance resources (88% vs. 12%) and patient-based vs. population-based designs (82% vs. 18%). The most unbalanced gender ratio was found in primary Sjögren syndrome (pSS), with nearly 10 females affected per 1 male, followed by systemic lupus erythematosus (SLE), systemic sclerosis (SSc) and antiphospholipid syndrome (APS) (ratio of nearly 5:1). Each disease predominantly affects a specific age group: children (Kawasaki disease, primary immunodeficiencies and Schonlein-Henoch disease), young people (SLE Behçet disease and sarcoidosis), middle-aged people (SSc, vasculitis and pSS) and the elderly (amyloidosis, polymyalgia rheumatica, and giant cell arteritis). We found significant differences in the geographical distribution of studies for each disease, and a higher frequency of the three SADs with available data (SLE, inflammatory myopathies and Kawasaki disease) in African-American patients. Using a "big data" approach enabled hitherto unseen connections in SADs to emerge. PMID:25842074

  14. 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.

  15. 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.

  16. Clinical indications and biological mechanisms of splenic irradiation in autoimmune diseases

    International Nuclear Information System (INIS)

    Background: Splenic irradiation (SI) is a fairly unknown treatment modality in autoimmune disorders like autoimmune thrombocytopenia (AIT) or autoimmune hemolytic anemia (AIHA), which may provide an effective, low toxic and cost-effective treatment for selected patients. Patients, Materials and Methods: This article reviews the limited experiences on splenic irradiation in autoimmune thrombocytopenia by analyzing the current studies including 71 patients and some preliminary reports on splenic irradiation in autoimmune hemolytic anemia. Results: In autoimmune thrombocytopenia between 40 and 90% of all patients responded, but most of them relapsed within 4 to 6 months after splenic irradiation. Between 10 and 20% of all patients had a sustained response. The efficacy of splenic irradiation in HIV-associated cases of thrombocytopenia is probably lower than in other forms of autoimmune thrombocytopenia, but especially in this group immunosuppressive drug treatment of autoimmune thrombocytopenia exposes some problems. In autoimmune hemolytic anemia there are some case reports about efficacy of splenic irradiation. Toxicity of splenic irradiation in both diseases was very moderate. Conclusions: For HIV patients, for elderly patients or patients at high risk for complications following splenectomy splenic irradiation might be a treatment option. Splenic irradiation as preoperative treatment in patients not responding to or not suitable for immunosuppressive drugs prior to splenectomy may be a promising new application of splenic irradiation to reduce adverse effects of splenectomy in thrombocytopenic patients. A further analysis of the biological mechanisms underlying splenic irradiation may help to improve patient selection, to optimize dose concepts and treatment schedules and will improve understanding of radiotherapy as an immunomodulatory treatment modality. (orig.)

  17. Thyroid volume in hypothyroidism due to autoimmune disease follows a unimodal distribution: evidence against primary thyroid atrophy and autoimmune thyroiditis being distinct diseases

    DEFF Research Database (Denmark)

    Carlé, Allan; Pedersen, Inge Bülow; Knudsen, Nils;

    2009-01-01

    dispersed distribution of thyroid volumes compared with controls (P distribution in both males and females with no bimodal pattern. Nearly all patients had measurable thyroid autoantibodies, but with increasing thyroid volume (quartile I, II, III, and IV......CONTEXT: Primary overt autoimmune hypothyroidism is often divided into primary idiopathic hypothyroidism with thyroid atrophy (Ord's disease) and hypothyroidism with goitre (Hashimoto's disease). OBJECTIVE: The aim of the present study was to characterize the two subtypes of disease. DESIGN...... before hypothyroidism was diagnosed. CONCLUSIONS: In primary autoimmune hypothyroidism, thyroid volume follows a normal distribution. Cases with thyroid atrophy and goiter are only extremes within this distribution and do not represent separate disorders. However, patients with low vs. high thyroid...

  18. Pendrin and NIS antibodies are absent in healthy individuals and are rare in autoimmune thyroid disease

    DEFF Research Database (Denmark)

    Brix, Thomas H; Hegedüs, Laszlo; Weetman, Anthony P;

    2014-01-01

    OBJECTIVE: Antibodies against thyroglobulin, thyroid peroxidase and the TSH receptor are accepted as pathophysiological and diagnostic biomarkers in autoimmune thyroid disease (AITD). In contrast, the prevalence, aetiology and clinical relevance of autoantibodies against the human sodium-iodine s......OBJECTIVE: Antibodies against thyroglobulin, thyroid peroxidase and the TSH receptor are accepted as pathophysiological and diagnostic biomarkers in autoimmune thyroid disease (AITD). In contrast, the prevalence, aetiology and clinical relevance of autoantibodies against the human sodium...... prevalence than the controls: NISAb: 17% vs 0% (P disease (GD) and 14% (5/37) of patients with Hashimoto's thyroiditis (HT) had NISAb, (P

  19. Classification of chest wall diseases.

    Science.gov (United States)

    Pozzi, E; Gulotta, C

    1993-01-01

    Several disorders of the thoracic cage are known to cause respiratory failure, by means of relatively simple mechanisms, such as the increased work of breathing, which results in alveolar hypoventilation. A variety of pathogenic mechanisms may be considered, as functions of the types of thoracic disorders present. As causes of these additional potential mechanisms, we considered the following: 1) ventilation-perfusion (V/Q) inhomogeneity; 2) inability to cough; 3) malformation or acquired defect of the respiratory centres; and 4) excess blood volume and fluid retention, which aggravate work of breathing and V/Q inhomogeneity. All of these disorders can be grouped into two major categories (which nevertheless have some of the pathophysiology in common): the mechanical syndrome and the neuromuscular or paralytic syndrome. In this paper we discuss chest wall diseases falling into the first category; namely, kyphoscoliosis, fibrothorax, thoracoplasty, ankylosing spondylitis and obesity-hypoventilation. Congenital deformities of the thoracic cage, which do not have important effects on ventilatory apparatus (e.g. pectus excavatum and pectus carinatum), were also considered. PMID:8472068

  20. Vitiligo vulgaris and autoimmune diseases in Japan: A report from vitiligo clinic in Kyoto University Hospital.

    Science.gov (United States)

    Tanioka, Miki; Yamamoto, Yosuke; Katoh, Mayumi; Takahashi, Kenzo; Miyachi, Yoshiki

    2009-01-01

    We reviewed the causes of "loss of skin color" in 144 patients, who visited Vitiligo Clinic of Kyoto University Hospital between April 2005 and August 2008. The numbers of patients with generalized and segmental Vitiligo vulgaris were 98 (68.1%) and 26 (18.1%), respectively. Small numbers of the patients suffered from Vogt-Koyanagi-Harada disease, piebaldism, congenital albinism, Hypomelanosis of Ito, post-inflammatory hypopigmentation, white leaf-shaped macules associated with tuberous sclerosis and nevus hypopigmentosus. One forth of the patients with generalized vitiligo had complications, while no complications were found in the patients with segmental vitiligo. Among the complications, autoimmune diseases dominated 43% (10 of 23 cases). Autoimmune thyroid diseases explained for the most of the complicated autoimmune diseases and were associated with 7.4% of the patients with generalized vitiligo. Minor autoimmune complications include myasthenia gravis, Sjogren syndrome and autoimmune nephritis. Reflecting the condition that our clinic is located in a university hospital, vitiligo patients with end-stage non-melanoma cancers of internal organs accounted for 8.4% of the patients of generalized vitiligo. PMID:20046588

  1. [Classification of gastroesophageal reflux disease and gastritis].

    Science.gov (United States)

    Vukobrat-Bijedic, Zora

    2002-01-01

    The gastroesophageal reflux disease (GORD) is frequent and causes by retrograde flow of the gastric content through incompetent gastroesophageal junction. Epidemiological studies have proved that GORD is associated with hearburn in high prevalence. In western countries several studies reported that 20-40% of adult population experience heartburn symptoms at least once in the year, approximately 10% have symptoms weekly and 5% daily. Esophagitis was objectively defined as a mucosal damage and it was endoscopically verificated in 25% of patients. Indeed, GORD symptoms and esophagitis are in poor correlation and less than half of patients with heartburn symptoms had esophagitis on endoscopy. From 1989, Savary Monniér and Metaplasia-Ulcer-Stricture-Erosion (MUSE) endoscopically classification is in use. From 1994, LA (Los Angeles) classification of reflux disease is also in use by endoscopists. During its life cycle, gastric mucosa is exposed to different harmful agents and its response is restitution "ad integrum" on the beginning and at the end of process. First line defence is mucuse barrier which prevent contact between epithelial cell and possible irritant. Important role in mucuse layer plays prostaglandins. After several classification systems previously used, in 1991 Price introduced Sydney system gradation and gastritis classification. Pointing out importance of topographical differences in gastritis distribution, system has introduced 5 histological variations in its Morphological section: chronic inflammation, neutrophylic activity, glandular atrophy, intestinal metaplasy and H. pylori colonisation, with 4 points grading. PMID:12055715

  2. High prevalence of systemic autoimmune diseases in patients with Meniere's disease.

    Directory of Open Access Journals (Sweden)

    Irene Gazquez

    Full Text Available BACKGROUND: Autoimmunity appears to be associated with the pathophysiology of Meniere's disease (MD, an inner ear disorder characterized by episodes of vertigo associated with hearing loss and tinnitus. However, the prevalence of autoimmune diseases (AD in patients with MD has not been studied in individuals with uni or bilateral sensorineural hearing loss (SNHL. METHODS AND FINDINGS: We estimated the prevalence of AD in 690 outpatients with MD with uni or bilateral SNHL from otoneurology clinics at six tertiary referral hospitals by using clinica criteria and an immune panel (lymphocyte populations, antinuclear antibodies, C3, C4 and proinflammatory cytokines TNFα, INFγ. The observed prevalence of rheumatoid arthritis (RA, systemic lupus erythematosus (SLE and ankylosing spondylitis (AS was higher than expected for the general population (1.39 for RA, 0.87 for SLE and 0.70 for AS, respectively. Systemic AD were more frequently observed in patients with MD and diagnostic criteria for migraine than cases with MD and tension-type headache (p = 0.007. There were clinical differences between patients with uni or bilateral SNHL, but no differences were found in the immune profile. Multiple linear regression showed that changes in lymphocytes subpopulations were associated with hearing loss and persistence of vertigo, suggesting a role for the immune response in MD. CONCLUSIONS: Despite some limitations, MD displays an elevated prevalence of systemic AD such as RA, SLE and AS. This finding, which suggests an autoimmune background in a subset of patients with MD, has important implications for the treatment of MD.

  3. [MEDICAL CANNABIS - A SOURCE FOR A NEW TREATMENT FOR AUTOIMMUNE DISEASE?].

    Science.gov (United States)

    Katz, Daphna; Katz, Itay; Golan, Amir

    2016-02-01

    Medical uses of Cannabis sativa have been known for over 6,000 years. Nowadays, cannabis is mostly known for its psychotropic effects and its ability to relieve pain, even though there is evidence of cannabis use for autoimmune diseases like rheumatoid arthritis centuries ago. The pharmacological therapy in autoimmune diseases is mainly based on immunosuppression of diffefent axes of the immune system while many of the drugs have major side effects. In this review we set out to examine the rule of Cannabis sativa as an immunomodulator and its potential as a new treatment option. In order to examine this subject we will focus on some major autoimmune diseases such as diabetes type I and rheumatoid arthritis.

  4. How Does Age at Onset Influence the Outcome of Autoimmune Diseases?

    Directory of Open Access Journals (Sweden)

    Manuel J. Amador-Patarroyo

    2012-01-01

    Full Text Available The age at onset refers to the time period at which an individual experiences the first symptoms of a disease. In autoimmune diseases (ADs, these symptoms can be subtle but are very relevant for diagnosis. They can appear during childhood, adulthood or late in life and may vary depending on the age at onset. Variables like mortality and morbidity and the role of genes will be reviewed with a focus on the major autoimmune disorders, namely, systemic lupus erythematosus (SLE, rheumatoid arthritis (RA, multiple sclerosis (MS, type 1 diabetes mellitus (T1D, Sjögren's syndrome, and autoimmune thyroiditis (AITD. Early age at onset is a worst prognostic factor for some ADs (i.e., SLE and T1D, while for others it does not have a significant influence on the course of disease (i.e., SS or no unanimous consensus exists (i.e., RA and MS.

  5. Induced Foxp3+ regulatory T cells: a potential new weapon to treat autoimmune and inflammatory diseases?

    Institute of Scientific and Technical Information of China (English)

    Qin Lan; Huimin Fan; Valerie Quesniaux; Bernhard Ryffel; Zhongmin Liu; Song Guo Zheng

    2012-01-01

    Foxp3+ T regulatory cells (Tregs) consisting of natural and induced Treg subsets play a crucial role in the maintenance of immune homeostasis against self-antigen.The actions designed to correct defects in numbers or functions of Tregs may be therapeutic in the treatment of autoimmune diseases.While recent studies demonstrated that natural Tregs are instable and dysfunctional in the inflammatory condition,induced Tregs (iTregs) may have a different feature.Here we review the progress of iTregs,particularly focus on their stability and function in the established autoimmune diseases.The advantage of iTregs as therapeutics used under inflammatory conditions is highlighted.Proper generation and manipulation of iTregs used for cellular therapy may provide a promise for the treatment of many autoimmune and inflammatory diseases.

  6. The autoimmune tautology

    OpenAIRE

    Anaya, Juan-Manuel

    2010-01-01

    Although autoimmune diseases exhibit contrasting epidemiological features, pathology, and clinical manifestations, three lines of evidence demonstrate that these diseases share similar immunogenetic mechanisms (that is, autoimmune tautology). First, clinical evidence highlights the co-occurrence of distinct autoimmune diseases within an individual (that is, polyautoimmunity) and within members of a nuclear family (that is, familial autoimmunity). Second, physiopathologic evidence indicates th...

  7. Clinical characteristics and the incidence of extrahepatic autoimmune disease and malignant tumor in primary biliary cirrhosis-autoimmune hepatitis overlap syndrome

    Institute of Scientific and Technical Information of China (English)

    杨蜜蜜

    2013-01-01

    Objective To analyze clinical pathologic characteristics of patients with primary biliary cirrhosis-autoimmune hepatitis overlap syndrome (PBC-AIH OS) ,the incidence of extrahepatic autoimmune disease,malignant tumor and the abdominal lymph node enlargement.Methods From January 2000 to January 2012,the clinical data of 49 patients with PBC-AIH OS were retrospectively analyzed,which included general information,clinical manifestations,biochemical parameters,immu-

  8. Periodic Acid-Schiff Staining Parallels the Immunoreactivity Seen By Direct Immunofluorescence in Autoimmune Skin Diseases

    Science.gov (United States)

    Abreu Velez, Ana Maria; Upegui Zapata, Yulieth Alexandra; Howard, Michael S

    2016-01-01

    Background: In many countries and laboratories, techniques such as direct immunofluorescence (DIF) are not available for the diagnosis of skin diseases. Thus, these laboratories are limited in the full diagnoses of autoimmune skin diseases, vasculitis, and rheumatologic diseases. In our experience with these diseases and the patient's skin biopsies, we have noted a positive correlation between periodic acid-Schiff (PAS) staining and immunofluorescence patterns; however, these were just empiric observations. In the current study, we aim to confirm these observations, given the concept that the majority of autoantibodies are glycoproteins and should thus be recognized by PAS staining. Aims: To compare direct immunofluorescent and PAS staining, in multiple autoimmune diseases that are known to exhibit specific direct immunofluorescent patterns. Materials and Methods: We studied multiple autoimmune skin diseases: Five cases of bullous pemphigoid, five cases of pemphigus vulgaris, ten cases of cutaneous lupus, ten cases of autoimmune vasculitis, ten cases of lichen planus (LP), and five cases of cutaneous drug reactions (including one case of erythema multiforme). In addition, we utilized 45 normal skin control specimens from plastic surgery reductions. Results: We found a 98% positive correlation between DIF and PAS staining patterns over all the disease samples. Conclusion: We recommend that laboratories without access to DIF always perform PAS staining in addition to hematoxylin and eosin (H&E) staining, for a review of the reactivity pattern. PMID:27114972

  9. Vitamin D Actions on CD4+ T cells in Autoimmune Disease

    Directory of Open Access Journals (Sweden)

    Colleen Elizabeth Hayes

    2015-03-01

    Full Text Available This review summarizes and integrates research on vitamin D and CD4+ T lymphocyte biology to develop new mechanistic insights into the molecular etiology of autoimmune disease. A deep understanding of molecular mechanisms relevant to gene-environment interactions is needed to deliver etiology-based autoimmune disease prevention and treatment strategies. Evidence linking sunlight, vitamin D, and the risk of multiple sclerosis and type 1 diabetes is summarized to develop the thesis that vitamin D is the environmental factor that most strongly influences autoimmune disease development. Evidence for CD4+ T cell involvement in autoimmune disease pathogenesis and for paracrine calcitriol signaling to CD4+ T lymphocytes is summarized to support the thesis that calcitriol is sunlight’s main protective signal transducer in autoimmune disease risk. Animal modeling and human mechanistic data to support the view that vitamin D probably influences thymic negative selection, effector Th1 and Th17 pathogenesis and responsiveness to extrinsic cell death signals, FoxP3+CD4+ Treg cell and CD4+ Tr1 cell functions, and a Th1-Tr1 switch. The proposed Th1-Tr1 switch appears to bridge two stable, self-reinforcing immune states, pro- and anti-inflammatory, each with a characteristic gene regulatory network. The bi-stable switch would enable T cells to integrate signals from pathogens, hormones, cell-cell interactions, and soluble mediators and respond in a biologically appropriate manner. Finally, we highlight unanswered questions that potentially informative future research directions that may speed delivery of etiology-based strategies to reduce autoimmune disease.

  10. HLA-B27 associated spondyloarthropathy, an autoimmune disease based on crossreactivity between bacteria and HLA-B27?

    OpenAIRE

    Ringrose, J.H.

    1999-01-01

    Most autoimmune diseases are associated with certain HLA types. Therefore, spondyloarthropathies (SpA) strongly associated with HLA-B27, are also often classified as autoimmune diseases. This study questions whether SpA indeed fulfils the criteria of an autoimmune disease. The Medline database was searched for all reports between 1966 and April 1998 on the presence of autoimmune reactivity in SpA patients. This search yielded 45 articles on this subject. Only eight articles study T cell react...

  11. Selenium status and over-expression of interleukin-15 in celiac disease and autoimmune thyroid diseases

    Directory of Open Access Journals (Sweden)

    Anna Velia Stazi

    2010-12-01

    Full Text Available In celiac disease (CD, for its multifactorial nature, the target organs are not limited to the gut, but include thyroid, liver, skin and reproductive and nervous systems. Between the extraintestinal symptoms associated with CD, autoimmune thyroid diseases (AITDs are more evident, underlining as CD-related autoimmune alterations can be modulated not only by gluten but also by various concurrent endogenous (genetic affinity, over-expression of cytokines and exogenous (environment, nutritional deficiency factors. In their pathogenesis a central role for over-expression of interleukin-15 (IL-15 is shown, by inhibiting apoptosis, leading to the perpetuation of inflammation and tissue destruction. Thyroid is particularly sensitive to selenium deficiency because selenoproteins are significant in biosynthesis and activity of thyroid hormones; besides, some selenoproteins as glutathione peroxidase are involved in inhibiting apoptosis. Thus, selenium malabsorption in CD can be thought as a key factor directly leading to thyroid and intestinal damage. Considering the complexity of this interaction and on the basis of available evidence, the aim of this review is to assess as preventive and therapeutic target the role of IL-15 and selenium in the pathogeneses of both CD and AITD.

  12. Autoimmune diseases and celiac disease which came first: genotype or gluten?

    Science.gov (United States)

    Diamanti, Antonella; Capriati, Teresa; Bizzarri, Carla; Ferretti, Francesca; Ancinelli, Monica; Romano, Francesca; Perilli, Alessia; Laureti, Francesca; Locatelli, Mattia

    2016-01-01

    Celiac disease (CD) is associated with several autoimmune diseases (ADs) and, in particular, thyroid autoimmunity (TA) and Type 1 diabetes (T1D). TA and T1D are defined as 'associated conditions' to CD (conditions at increased prevalence in CD but not directly related to gluten ingestion). The diagnosis of CD may precede or follow that of TA/T1D. To date, the available evidence suggests that the common genetic background is the main factor determining the high prevalence of the association. Conversely, no conclusive findings clarify whether extrinsic gluten-related factors (age at the first introduction, concomitant breastfeeding, length of gluten exposure and gluten-free diet) may link CD to the ADs. The aim of this review is to evaluate whether genetic background alone could explain the association between CD and ADs or if gluten-related factors ought to be considered. The pathophysiological links clarifying how the gluten-related factors could predispose to ADs will also be discussed.

  13. From Single Nucleotide Polymorphisms to Constant Immunosuppression: Mesenchymal Stem Cell Therapy for Autoimmune Diseases

    Directory of Open Access Journals (Sweden)

    Raghavan Chinnadurai

    2013-01-01

    Full Text Available The regenerative abilities and the immunosuppressive properties of mesenchymal stromal cells (MSCs make them potentially the ideal cellular product of choice for treatment of autoimmune and other immune mediated disorders. Although the usefulness of MSCs for therapeutic applications is in early phases, their potential clinical use remains of great interest. Current clinical evidence of use of MSCs from both autologous and allogeneic sources to treat autoimmune disorders confers conflicting clinical benefit outcomes. These varied results may possibly be due to MSC use across wide range of autoimmune disorders with clinical heterogeneity or due to variability of the cellular product. In the light of recent genome wide association studies (GWAS, linking predisposition of autoimmune diseases to single nucleotide polymorphisms (SNPs in the susceptible genetic loci, the clinical relevance of MSCs possessing SNPs in the critical effector molecules of immunosuppression is largely undiscussed. It is of further interest in the allogeneic setting, where SNPs in the target pathway of MSC's intervention may also modulate clinical outcome. In the present review, we have discussed the known critical SNPs predisposing to disease susceptibility in various autoimmune diseases and their significance in the immunomodulatory properties of MSCs.

  14. The clinical value of detection of serum TGAb and TPOAb level in autoimmune thyroid diseases

    International Nuclear Information System (INIS)

    To study the clinical value of serum TGAb and TPOAb levels in the diagnosis of patients with autoimmune thyroid diseases (AITD), the serum levels of TGAb and TPOAb in 175 patients with AITD and 64 non-AITD patients and 57 health controls were measured by RIA. The results showed that the serum levels of TGAb and TPOAb in AITD patients with GD and HT were significantly higher than that of control group (P0.05). The detection of serum TGAb and TPOAb levels may have clinical value in the diagnosis, treatment and prognosis of autoimmune thyroid diseases. (authors)

  15. Restoring the balance: immunotherapeutic combinations for autoimmune disease

    OpenAIRE

    Smilek, Dawn E.; Ehlers, Mario R.; Nepom, Gerald T.

    2014-01-01

    Autoimmunity occurs when T cells, B cells or both are inappropriately activated, resulting in damage to one or more organ systems. Normally, high-affinity self-reactive T and B cells are eliminated in the thymus and bone marrow through a process known as central immune tolerance. However, low-affinity self-reactive T and B cells escape central tolerance and enter the blood and tissues, where they are kept in check by complex and non-redundant peripheral tolerance mechanisms. Dysfunction or im...

  16. Encephalopathy associated with autoimmune thyroid disease in patients with Graves' disease: clinical manifestations, follow-up, and outcomes

    LENUS (Irish Health Repository)

    Tamagno, Gianluca

    2010-04-28

    Abstract Background The encephalopathy associated with autoimmune thyroid disease (EAATD) is characterized by neurological\\/psychiatric symptoms, high levels of anti-thyroid antibodies, increased cerebrospinal fluid protein concentration, non-specific electroencephalogram abnormalities, and responsiveness to the corticosteroid treatment in patients with an autoimmune thyroid disease. Almost all EAATD patients are affected by Hashimoto\\'s thyroiditis (HT), although fourteen EAATD patients with Graves\\' disease (GD) have been also reported. Methods We have recorded and analyzed the clinical, biological, radiological, and electrophysiological findings and the data on the therapeutic management of all GD patients with EAATD reported so far as well as the clinical outcomes in those followed-up in the long term. Results Twelve of the fourteen patients with EAATD and GD were women. The majority of GD patients with EAATD presented with mild hyperthyroidism at EAATD onset or shortly before it. Active anti-thyroid autoimmunity was detected in all cases. Most of the patients dramatically responded to corticosteroids. The long term clinical outcome was benign but EAATD can relapse, especially at the time of corticosteroid dose tapering or withdrawal. GD and HT patients with EAATD present with a similar clinical, biological, radiological, and electrophysiological picture and require an unaffected EAATD management. Conclusions GD and HT equally represent the possible background condition for the development of EAATD, which should be considered in the differential diagnosis of all patients with encephalopathy of unknown origin and an autoimmune thyroid disease, regardless of the nature of the underlying autoimmune thyroid disease.

  17. Encephalopathy associated with autoimmune thyroid disease in patients with Graves' disease: clinical manifestations, follow-up, and outcomes.

    LENUS (Irish Health Repository)

    Tamagno, Gianluca

    2010-01-01

    BACKGROUND: The encephalopathy associated with autoimmune thyroid disease (EAATD) is characterized by neurological\\/psychiatric symptoms, high levels of anti-thyroid antibodies, increased cerebrospinal fluid protein concentration, non-specific electroencephalogram abnormalities, and responsiveness to the corticosteroid treatment in patients with an autoimmune thyroid disease. Almost all EAATD patients are affected by Hashimoto\\'s thyroiditis (HT), although fourteen EAATD patients with Graves\\' disease (GD) have been also reported. METHODS: We have recorded and analyzed the clinical, biological, radiological, and electrophysiological findings and the data on the therapeutic management of all GD patients with EAATD reported so far as well as the clinical outcomes in those followed-up in the long term. RESULTS: Twelve of the fourteen patients with EAATD and GD were women. The majority of GD patients with EAATD presented with mild hyperthyroidism at EAATD onset or shortly before it. Active anti-thyroid autoimmunity was detected in all cases. Most of the patients dramatically responded to corticosteroids. The long term clinical outcome was benign but EAATD can relapse, especially at the time of corticosteroid dose tapering or withdrawal. GD and HT patients with EAATD present with a similar clinical, biological, radiological, and electrophysiological picture and require an unaffected EAATD management. CONCLUSIONS: GD and HT equally represent the possible background condition for the development of EAATD, which should be considered in the differential diagnosis of all patients with encephalopathy of unknown origin and an autoimmune thyroid disease, regardless of the nature of the underlying autoimmune thyroid disease.

  18. Encephalopathy associated with autoimmune thyroid disease in patients with Graves' disease: clinical manifestations, follow-up, and outcomes.

    LENUS (Irish Health Repository)

    Tamagno, Gianluca

    2012-02-01

    BACKGROUND: The encephalopathy associated with autoimmune thyroid disease (EAATD) is characterized by neurological\\/psychiatric symptoms, high levels of anti-thyroid antibodies, increased cerebrospinal fluid protein concentration, non-specific electroencephalogram abnormalities, and responsiveness to the corticosteroid treatment in patients with an autoimmune thyroid disease. Almost all EAATD patients are affected by Hashimoto\\'s thyroiditis (HT), although fourteen EAATD patients with Graves\\' disease (GD) have been also reported. METHODS: We have recorded and analyzed the clinical, biological, radiological, and electrophysiological findings and the data on the therapeutic management of all GD patients with EAATD reported so far as well as the clinical outcomes in those followed-up in the long term. RESULTS: Twelve of the fourteen patients with EAATD and GD were women. The majority of GD patients with EAATD presented with mild hyperthyroidism at EAATD onset or shortly before it. Active anti-thyroid autoimmunity was detected in all cases. Most of the patients dramatically responded to corticosteroids. The long term clinical outcome was benign but EAATD can relapse, especially at the time of corticosteroid dose tapering or withdrawal. GD and HT patients with EAATD present with a similar clinical, biological, radiological, and electrophysiological picture and require an unaffected EAATD management. CONCLUSIONS: GD and HT equally represent the possible background condition for the development of EAATD, which should be considered in the differential diagnosis of all patients with encephalopathy of unknown origin and an autoimmune thyroid disease, regardless of the nature of the underlying autoimmune thyroid disease.

  19. Regulatory T-Cells in Chronic Lymphocytic Leukemia and Autoimmune Diseases

    Science.gov (United States)

    D’Arena, Giovanni; Rossi, Giovanni; Vannata, Barbara; Deaglio, Silvia; Mansueto, Giovanna; D’Auria, Fiorella; Statuto, Teodora; Simeon, Vittorio; De Martino, Laura; Marandino, Aurelio; Del Poeta8, Giovanni; De Feo, Vincenzo; Musto, Pellegrino

    2012-01-01

    Regulatory T-cells (Tregs) constitute a small subset of cells that are actively involved in maintaining self-tolerance, in immune homeostasis and in antitumor immunity. They are thought to play a significant role in the progression of cancer and are generally increased in patient with chronic lymphocytic leukemia (CLL). Their number correlates with more aggressive disease status and is predictive of the time to treatment, as well. Moreover, it is now clear that dysregulation in Tregs cell frequency and/or function may result in a plethora of autoimmune diseases, including multiple sclerosis, type 1 diabetes mellitus, myasthenia gravis, systemic lupus erythematosus, autoimmune lymphoproliferative disorders, rheumatoid arthritis, and psoriasis. Efforts are made aiming to develop approaches to deplete Tregs or inhibit their function in cancer and autoimmune disorders, as well. PMID:22973497

  20. Autoantigens as Partners in Initiation and Propagation of Autoimmune Rheumatic Diseases.

    Science.gov (United States)

    Rosen, Antony; Casciola-Rosen, Livia

    2016-05-20

    Systemic autoimmune diseases are characterized by specific targeting of a limited group of ubiquitously expressed autoantigens by the immune system. This review examines the mechanisms underlying their selection as immune targets. Initiation of autoimmune responses likely reflects the presentation of antigens with a distinct structure not previously encountered by the immune system, in a proimmune context (injury, malignancy, or infection). Causes of modified structure include somatic mutation and posttranslational modifications (including citrullination and proteolysis). Many autoantigens are components of multimolecular complexes, and some of the other components may provide adjuvant activity. Propagation of autoimmune responses appears to reflect a bidirectional interaction between the immune response and the target tissues in a mutually reinforcing cycle: Immune effector pathways generate additional autoantigen, which feeds further immune response. We propose that this resonance may be a critical principle underlying disease propagation, with specific autoantigens functioning as the hubs around which amplification occurs. PMID:26907212

  1. Sniping the scout: Targeting the key molecules in dendritic cell functions for treatment of autoimmune diseases.

    Science.gov (United States)

    Li, Xing; Han, Yanping; Sun, Erwei

    2016-05-01

    Dendritic cells (DCs) are a power tool for manipulating immune system. They play important roles in the induction of immunity as well as inducing intrathymic and peripheral tolerance. After generated from stem cells in the bone marrow, DCs traffic to the peripheral tissues, where they capture and process antigens, express lymphocyte co-stimulators, migrate to the secondary lymph organs and present the processed antigen to naive T cells to either activate or tolerize them. These processes are modulated subtly and influenced by various factors. Aberrant regulation of the processes may cause autoimmunity. Investigation into the biology of DCs and the molecules and mechanisms that regulate them helps us understanding the pathogenesis of autoimmune diseases and reveals numerous steps for pharmacological manipulation. In this review, we made a sketch line of the critical events of DC biology that are potential pharmacologic targets for the treatment of autoimmune diseases. PMID:26931618

  2. Clinical Significance of Autoantibodies to P53 Protein in Patients with Autoimmune Liver Diseases

    Directory of Open Access Journals (Sweden)

    Takashi Himoto

    2012-01-01

    Full Text Available Mutations in the p53 gene leading to conformational changes in the p53 protein have been well established in many human cancers. Conformational changes and/or cellular accumulation of the protein may induce an immune response, resulting in circulating autoantibodies to p53, which have been documented in several types of cancers. Although rarely associated with autoimmune disease, a few reports have documented titres of anti-p53 autoantibodies in patients with autoimmune hepatitis and primary biliary cirrhosis. The clinical relevance of circulating autoantibodies to p53, therefore, remains unclear. Accordingly, this study aimed to examine the prevalence and clinical relevance of anti-p53 autoantibodies in patients with selected autoimmune liver diseases.

  3. Liver biopsy interpretation in the differential diagnosis of autoimmune liver disease in children

    Directory of Open Access Journals (Sweden)

    Clara Gerosa

    2013-06-01

    Full Text Available Autoimmune liver disease  (AILD represents a group of complex inflammatory liver diseases, all characterized by an aberrant autoreactivity against hepatocytes and/or biliary structures. AILD may be subclassified into four major diseases: autoimmune hepatitis (AIH, primary biliary cirrhosis (PBC, primary sclerosing cholangitis (PSC, and autoimmune cholangitis (AIC. Recently a new entity frequently associated with autoimmune pancreatitis and defined IgG4-related cholangitis (IgG4-RC,  has been added to the spectrum of AILD. The most frequent autoimmune liver diseases  of the AILD spectrum occurring in children and in young adults are  AIH  and PSC, overlap syndrome between AIH and PSC, also defined as autoimmune sclerosing cholangitis (ASC, representing a frequent finding in pediatric patients. Here,  the morphological findings that may help liver pathologists in the differential diagnosis of AILD in pediatric patients are reviewed, underlying the frequency in liver biopsy interpretation of complex cases in which a precise diagnosis may remain controversial, due to overlap of hepatocytic and bile duct cell lesions. Among the multiple morphological changes typical of AILD,  the detection of an high number of plasma cell clusters in the portal and periportal regions is generally considered one of the main clue for the diagnosis of AIH. The recent report in a 13-year old  boy of IgG4-associated cholangitis, induces  pathologists when detecting a huge number of plasmacells, to consider the differential diagnosis between AIH and IgG4-RC.Proceedings of the 9th International Workshop on Neonatology · Cagliari (Italy · October 23rd-26th, 2013 · Learned lessons, changing practice and cutting-edge research

  4. Non-infectious environmental antigens as a trigger for the initiation of an autoimmune skin disease.

    Science.gov (United States)

    Qian, Ye; Culton, Donna A; Jeong, Joseph S; Trupiano, Nicole; Valenzuela, Jesus G; Diaz, Luis A

    2016-09-01

    Pemphigus represents a group of organ specific autoimmune blistering disorders of the skin mediated by pathogenic autoantibodies with well-defined antigenic targets. While most of these diseases are sporadic, endemic forms of disease do exist. The endemic form of pemphigus foliaceus (also known as fogo selvagem, FS) exhibits epidemiological features that suggest exposure to hematophagous insect bites are a possible precipitating factor of this autoimmune disease, and provides a unique opportunity to study how environmental factors contribute to autoimmune disease development. FS patients and healthy individuals from endemic regions show an autoreactive IgM response that starts in early childhood and becomes restricted to IgG4 autoantibodies in FS patients. In searching for triggering environmental antigens, we have found that IgG4 and IgE autoantibodies from FS patients cross-react with a salivary antigen from sand flies. The presence of these cross-reactive antibodies and antibody genetic analysis confirming that these antibodies evolve from the same naïve B cells provides compelling evidence that this non-infectious environmental antigen could be the initial target of the autoantibody response in FS. Consequently, FS serves as an ideal model to study the impact of environmental antigens in the development of autoimmune disease.

  5. Holmes-Adie syndrome, autoimmune hepatitis and celiac disease: A case report

    Institute of Scientific and Technical Information of China (English)

    Timea Csak; Aniko Folhoffer; Andrea Horvath; Judit Halász; Csaba Diczházi; Zsuzsa Schaff; Ferenc Szalay

    2006-01-01

    A 35-year-old female patient presented with the following symptoms of Holmes-Adie syndrome: photophobia,enlargement of the left pupil unresponsive to light,Achilles areflexia. The pilocarpine test was positive. No tumor or other neurological abnormality was found. She had a 19-year history of autoimmune hepatitis. Flares up were observed following each 3 deliveries. At age of 31she presented with diarrhea and weight loss. Abdominal tumor was detected by ultrasound. The surgically removed tumor was histologically a benign mesenteric multicystic lymphangioma. Simultaneously, celiac disease was diagnosed. Gluten-free diet resulted in a significant improvement of celiac disease, but not of autoimmune hepatitis. Autonomic neuropathy was proven by standard cardiovascular tests. The patient was a homozygous carrier for HLA DQ2 antigen characteristic for celiac disease and heterozygous for HLA DR3 B8 frequent in autoimmune liver diseases. Our novel observation on association of Holmes-Adie syndrome with autoimmune hepatitis and celiac disease is suggestive for a common immunological background for all three entities present in a patient with mesenteric multicystic lymphangioma.

  6. Challenges in interpretation of thyroid function tests in pregnant women with autoimmune thyroid disease

    DEFF Research Database (Denmark)

    Feldt-Rasmussen, Ulla; Bliddal, Sofie; Rasmussen, Åse Krogh;

    2011-01-01

    Physiological changes during gestation are important to be aware of in measurement and interpretation of thyroid function tests in women with autoimmune thyroid diseases. Thyroid autoimmune activity is decreasing in pregnancy. Measurement of serum TSH is the first-line screening variable for thyr......Physiological changes during gestation are important to be aware of in measurement and interpretation of thyroid function tests in women with autoimmune thyroid diseases. Thyroid autoimmune activity is decreasing in pregnancy. Measurement of serum TSH is the first-line screening variable...... for thyroid dysfunction also in pregnancy. However, using serum TSH for control of treatment of maternal thyroid autoimmunity infers a risk for compromised foetal development. Peripheral thyroid hormone values are highly different among laboratories, and there is a need for laboratory-specific gestational age......-related reference ranges. Equally important, the intraindividual variability of the thyroid hormone measurements is much narrower than the interindividual variation (reflecting the reference interval). The best laboratory assessment of thyroid function is a free thyroid hormone estimate combined with TSH...

  7. Activation-induced cytidine deaminase deficiency causes organ-specific autoimmune disease.

    Directory of Open Access Journals (Sweden)

    Koji Hase

    Full Text Available Activation-induced cytidine deaminase (AID expressed by germinal center B cells is a central regulator of somatic hypermutation (SHM and class switch recombination (CSR. Humans with AID mutations develop not only the autosomal recessive form of hyper-IgM syndrome (HIGM2 associated with B cell hyperplasia, but also autoimmune disorders by unknown mechanisms. We report here that AID-/- mice spontaneously develop tertiary lymphoid organs (TLOs in non-lymphoid tissues including the stomach at around 6 months of age. At a later stage, AID-/- mice develop a severe gastritis characterized by loss of gastric glands and epithelial hyperplasia. The disease development was not attenuated even under germ-free (GF conditions. Gastric autoantigen -specific serum IgM was elevated in AID-/- mice, and the serum levels correlated with the gastritis pathological score. Adoptive transfer experiments suggest that autoimmune CD4+ T cells mediate gastritis development as terminal effector cells. These results suggest that abnormal B-cell expansion due to AID deficiency can drive B-cell autoimmunity, and in turn promote TLO formation, which ultimately leads to the propagation of organ-specific autoimmune effector CD4+ T cells. Thus, AID plays an important role in the containment of autoimmune diseases by negative regulation of autoreactive B cells.

  8. Autoimmune epilepsy.

    Science.gov (United States)

    Greco, Antonio; Rizzo, Maria Ida; De Virgilio, Armando; Conte, Michela; Gallo, Andrea; Attanasio, Giuseppe; Ruoppolo, Giovanni; de Vincentiis, Marco

    2016-03-01

    Despite the fact that epilepsy is the third most common chronic brain disorder, relatively little is known about the processes leading to the generation of seizures. Accumulating data support an autoimmune basis in patients with antiepileptic drug-resistant seizures. Besides, recent studies show that epilepsy and autoimmune disease frequently co-occur. Autoimmune epilepsy is increasingly recognized in the spectrum of neurological disorders characterized by detection of neural autoantibodies in serum or spinal fluid and responsiveness to immunotherapy. An autoimmune cause is suspected based on frequent or medically intractable seizures and the presence of at least one neural antibody, inflammatory changes indicated in serum or spinal fluid or on MRI, or a personal or family history of autoimmunity. It is essential that an autoimmune etiology be considered in the initial differential diagnosis of new onset epilepsy, because early immunotherapy assures an optimal outcome for the patient. PMID:26626229

  9. Clinical indications and biological mechanisms of splenic irradiation in autoimmune diseases

    Energy Technology Data Exchange (ETDEWEB)

    Weinmann, M.; Becker, G. [Tuebingen Univ. (Germany). Abt. fuer Strahlenonkologie; Einsele, H.; Bamberg, M. [Tuebingen Univ. (Germany). Abt. fuer Innere Medizin 2

    2001-02-01

    Background: Splenic irradiation (SI) is a fairly unknown treatment modality in autoimmune disorders like autoimmune thrombocytopenia (AIT) or autoimmune hemolytic anemia (AIHA), which may provide an effective, low toxic and cost-effective treatment for selected patients. Patients, Materials and Methods: This article reviews the limited experiences on splenic irradiation in autoimmune thrombocytopenia by analyzing the current studies including 71 patients and some preliminary reports on splenic irradiation in autoimmune hemolytic anemia. Results: In autoimmune thrombocytopenia between 40 and 90% of all patients responded, but most of them relapsed within 4 to 6 months after splenic irradiation. Between 10 and 20% of all patients had a sustained response. The efficacy of splenic irradiation in HIV-associated cases of thrombocytopenia is probably lower than in other forms of autoimmune thrombocytopenia, but especially in this group immunosuppressive drug treatment of autoimmune thrombocytopenia exposes some problems. In autoimmune hemolytic anemia there are some case reports about efficacy of splenic irradiation. Toxicity of splenic irradiation in both diseases was very moderate. Conclusions: For HIV patients, for elderly patients or patients at high risk for complications following splenectomy splenic irradiation might be a treatment option. Splenic irradiation as preoperative treatment in patients not responding to or not suitable for immunosuppressive drugs prior to splenectomy may be a promising new application of splenic irradiation to reduce adverse effects of splenectomy in thrombocytopenic patients. A further analysis of the biological mechanisms underlying splenic irradiation may help to improve patient selection, to optimize dose concepts and treatment schedules and will improve understanding of radiotherapy as an immunomodulatory treatment modality. (orig.) [German] Hintergrund: Die Bestrahlung der Milz zur Behandlung von haematologischen

  10. Total lymphoid irradiation as an immunosuppressive agent for transplantation and the treatment of 'autoimmune' disease

    International Nuclear Information System (INIS)

    Total lymphoid irradiation (TLI) is a powerful immunosuppressive agent. This immunosuppression has the potential for clinical application in certain selected situations. In this review, the immunological changes produced by TLI and its potential applications in organ transplantation and the treatment of certain 'autoimmune' diseases are discussed. (author)

  11. Autoimmune Diseases in Parents of Children with Infantile Autism: A Case--Control Study

    Science.gov (United States)

    Mouridsen, Svend Erik; Rich, Bente; Isager, Torben; Nedergaard, Niels Jorgen

    2007-01-01

    This register study compared the rates and types of autoimmune disease in the parents of 111 patients (82 males, 29 females; mean age at diagnosis 5y 5mo [SD 2y 6mo]) with infantile autism (IA) with a matched control group of parents of 330 children from the general population. All parents were screened through the nationwide Danish National…

  12. Altered BCR signalling quality predisposes to autoimmune disease and a pre-diabetic state

    OpenAIRE

    Königsberger, Sebastian; Prodöhl, Jan; Stegner, David; Weis, Vanessa; Andreas, Martin; Stehling, Martin; Schumacher, Theresa; Böhmer, Ruben; Thielmann, Ina; van Eeuwijk, Judith M M; Nieswandt, Bernhard; Kiefer, Friedemann

    2012-01-01

    The related tyrosine kinases Syk and Zap-70 are key signalling proteins downstream of antigen receptors. A knock-in strategy reveals that the two kinases differentially affect BCR signalling, leading to aberrant B cell section and increased risk of autoimmune disease.

  13. Tc-99m-labeled Rituximab for Imaging B Lymphocyte Infiltration in Inflammatory Autoimmune Disease Patients

    NARCIS (Netherlands)

    Malviya, G.; Anzola, K. L.; Podesta, E.; Lagana, B.; Del Mastro, C.; Dierckx, R. A.; Scopinaro, F.; Signore, A.

    2012-01-01

    The rationale of the present study was to radiolabel rituximab with 99m-technetium and to image B lymphocytes infiltration in the affected tissues of patients with chronic inflammatory autoimmune diseases, in particular, the candidates to be treated with unlabelled rituximab, in order to provide a r

  14. Widespread non-additive and interaction effects within HLA loci modulate the risk of autoimmune diseases

    NARCIS (Netherlands)

    Lenz, Tobias L; Deutsch, Aaron J; Han, Buhm; Hu, Xinli; Okada, Yukinori; Eyre, Stephen; Knapp, Michael; Zhernakova, Alexandra; Huizinga, Tom W J; Abecasis, Gonçalo; Becker, Jessica; Boeckxstaens, Guy E; Chen, Wei-Min; Franke, Andre; Gladman, Dafna D; Gockel, Ines; Gutierrez-Achury, Javier; Martin, Javier; Nair, Rajan P; Nöthen, Markus M; Onengut-Gumuscu, Suna; Rahman, Proton; Rantapää-Dahlqvist, Solbritt; Stuart, Philip E; Tsoi, Lam C; van Heel, David A; Worthington, Jane; Wouters, Mira M; Klareskog, Lars; Elder, James T; Gregersen, Peter K; Schumacher, Johannes; Rich, Stephen S; Wijmenga, Cisca; Sunyaev, Shamil R; de Bakker, Paul I W; Raychaudhuri, Soumya

    2015-01-01

    Human leukocyte antigen (HLA) genes confer substantial risk for autoimmune diseases on a log-additive scale. Here we speculated that differences in autoantigen-binding repertoires between a heterozygote's two expressed HLA variants might result in additional non-additive risk effects. We tested the

  15. Serum Resistin Level and Progression of Atherosclerosis during Glucocorticoid Therapy for Systemic Autoimmune Diseases

    Directory of Open Access Journals (Sweden)

    Nahoko Tanaka

    2016-09-01

    Full Text Available Adipokines are important regulators of several processes, including inflammation and atherosclerosis. In patients with systemic autoimmune diseases, atherosclerosis is accelerated with higher cardiovascular morbidity and mortality. We prospectively investigated the association of adipokines and glucocorticoid therapy with progression of premature atherosclerosis in 38 patients starting glucocorticoid therapy for systemic autoimmune diseases. To detect premature atherosclerosis, carotid ultrasonography was performed at initiation of glucocorticoid therapy and after a mean three-year follow-up period. The ankle-brachial pressure index and cardio-ankle vascular index (CAVI were measured. Serum adipokine levels were determined with enzyme-linked immunosorbent assay kits. Twenty-three patients (60.5% had carotid artery plaque at baseline. The carotid artery intima-media thickness (IMT increased significantly during follow-up. Glucocorticoids reduced the serum resistin level, while increasing serum leptin and high molecular weight-adiponectin. There was slower progression of atherosclerosis (carotid IMT and CAVI at follow-up in patients with greater reduction of serum resistin and with higher cumulative prednisolone dose. In conclusion, progression of premature atherosclerosis occurred at an early stage of systemic autoimmune diseases before initiation of glucocorticoid therapy. Since resistin, an inflammation and atherosclerosis related adipokine, is reduced by glucocorticoids, glucocortidoid therapy may not accelerate atherosclerosis in patients with systemic autoimmune diseases.

  16. Serum Resistin Level and Progression of Atherosclerosis during Glucocorticoid Therapy for Systemic Autoimmune Diseases.

    Science.gov (United States)

    Tanaka, Nahoko; Masuoka, Shotaro; Kusunoki, Natsuko; Nanki, Toshihiro; Kawai, Shinichi

    2016-09-16

    Adipokines are important regulators of several processes, including inflammation and atherosclerosis. In patients with systemic autoimmune diseases, atherosclerosis is accelerated with higher cardiovascular morbidity and mortality. We prospectively investigated the association of adipokines and glucocorticoid therapy with progression of premature atherosclerosis in 38 patients starting glucocorticoid therapy for systemic autoimmune diseases. To detect premature atherosclerosis, carotid ultrasonography was performed at initiation of glucocorticoid therapy and after a mean three-year follow-up period. The ankle-brachial pressure index and cardio-ankle vascular index (CAVI) were measured. Serum adipokine levels were determined with enzyme-linked immunosorbent assay kits. Twenty-three patients (60.5%) had carotid artery plaque at baseline. The carotid artery intima-media thickness (IMT) increased significantly during follow-up. Glucocorticoids reduced the serum resistin level, while increasing serum leptin and high molecular weight-adiponectin. There was slower progression of atherosclerosis (carotid IMT and CAVI) at follow-up in patients with greater reduction of serum resistin and with higher cumulative prednisolone dose. In conclusion, progression of premature atherosclerosis occurred at an early stage of systemic autoimmune diseases before initiation of glucocorticoid therapy. Since resistin, an inflammation and atherosclerosis related adipokine, is reduced by glucocorticoids, glucocortidoid therapy may not accelerate atherosclerosis in patients with systemic autoimmune diseases.

  17. Neuromyelitis optica (NMO) - an autoimmune disease of the central nervous system (CNS)

    DEFF Research Database (Denmark)

    Asgari, N; Owens, T; Frøkiaer, J;

    2010-01-01

    Asgari N, Owens T, Frøkiaer J, Stenager E, Lillevang ST, Kyvik KO. Neuromyelitis optica (NMO) - an autoimmune disease of the central nervous system (CNS).
Acta Neurol Scand: DOI: 10.1111/j.1600-0404.2010.01416.x.
© 2010 John Wiley & Sons A/S. In the past 10 years, neuromyelitis optica (NMO) has...

  18. Vaccination of patients with auto-immune inflammatory rheumatic diseases requires careful benefit-risk assessment

    NARCIS (Netherlands)

    Bijl, M.; Agmon-Levin, N.; Dayer, J. -M.; Israeli, E.; Gatto, M.; Shoenfeld, Y.

    2012-01-01

    Will vaccination raise the incidence of autoimmune diseases, what is the impact of increasingly crowded vaccination schedules, the vaccination in age groups and the risk of coincidental temporal association? All these issues are still under debate. However, for the time being, to avoid confusion in

  19. Residual Salivary Secretion Ability May Be a Useful Marker for Differential Diagnosis in Autoimmune Diseases

    Directory of Open Access Journals (Sweden)

    Etsuko Maeshima

    2014-01-01

    Full Text Available Background. We have elucidated decreased resting salivary flow in approximately 60% of patients with autoimmune diseases not complicated by Sjögren syndrome (SjS. In this study, salivary stimulation tests using capsaicin were performed to examine residual salivary secretion ability in patients with autoimmune diseases. Materials and Methods. Fifty-eight patients were divided into three groups: patients with primary or secondary SjS (SjS group, patients with systemic sclerosis not complicated by SjS (SSc group, and patients with other autoimmune diseases (non-SjS/non-SSc group. Simple filter paper and filter paper containing capsaicin were used to evaluate salivary flow rates. Results. Resting salivary flow rates were significantly lower in the SjS and SSc groups than in the non-SjS/non-SSc group but did not differ significantly between the SjS and SSc groups. Capsaicin-stimulated salivary flow rates were significantly lower in the SjS and SSc groups than in the non-SjS/non-SSc group, but not significantly different between the SjS and SSc groups. In the non-SjS/non-SSc group, salivary flow rates increased after capsaicin stimulation to the threshold level for determination of salivary gland dysfunction, whereas no improvement was observed in the SjS and SSc groups. Conclusion. Residual salivary secretion ability may be a useful marker for differential diagnosis in autoimmune diseases.

  20. Beta-endorphin and the immune system--possible role in autoimmune diseases

    DEFF Research Database (Denmark)

    Mørch, H; Pedersen, B K

    1995-01-01

    The immune system and the neuroendocrine system are closely interconnected having such means of bidirectional communication and regulation. In this review, a hypothesis is put forward regarding the possible role of beta-endorphins in the pathogenesis of autoimmune diseases: It is suggested...

  1. Autoimmune diseases in parents of children with infantile autism: a case-control study

    DEFF Research Database (Denmark)

    Mouridsen, Svend Erik; Rich, Bente; Isager, Torben;

    2007-01-01

    This register study compared the rates and types of autoimmune disease in the parents of 111 patients (82 males, 29 females; mean age at diagnosis 5y 5mo [SD 2y 6mo]) with infantile autism (IA) with a matched control group of parents of 330 children from the general population. All parents were...

  2. Primary biliary cirrhosis and autoimmune cholangitis are not associated with coeliac disease in Crete

    Directory of Open Access Journals (Sweden)

    Dimoulios Philippos

    2002-03-01

    Full Text Available Abstract Background An increased prevalence of coeliac disease in patients with primary biliary cirrhosis has been recently reported. However, in other studies the association has not been confirmed. There have been no formal attempts to systematically evaluate patients with autoimmune cholangitis for coeliac disease. Methods Sera from 62 patients with primary biliary cirrhosis, 17 with autoimmune cholangitis and 100 blood donors were screened for anti-gliadin, anti-endomysial, anti-reticulin, and IgA class antibodies to guinea pig liver-derived tissue transglutaminase. Eighteen untreated coeliacs served as methodological controls. Analyses were performed by using the χ2 and Fischer's exact tests. Results Anti-gliadin antibodies were detected in 21% of patients with primary biliary cirrhosis, 35% of patients with autoimmune cholangitis, and 3% of controls (p Conclusions We were unable to demonstrate an increased risk of coeliac disease in patients with primary biliary cirrhosis and autoimmune cholangitis. Our results confirm the previously reported high prevalence of false-positive anti-gliadin and guinea pig liver-derived anti-tissue transglutaminase antibodies in patients with chronic liver disease.

  3. Therapeutic dosing of an orally active, selective cathepsin S inhibitor suppresses disease in models of autoimmunity

    NARCIS (Netherlands)

    Baugh, Mark; Black, Darcey; Westwood, Paul; Kinghorn, Emma; McGregor, Kieran; Bruin, John; Hamilton, William; Dempster, Maureen; Claxton, Christopher; Cai, Jiaqiang; Bennett, Jonathan; Long, Clive; Mckinnon, Heather; Vink, Paul; den Hoed, Leontien; Gorecka, Monika; Vora, Kalpit; Grant, Ethan; Percival, M. David; Boots, A. Mieke H.; van Lierop, Marie-Jose; Boots, Annemieke

    2011-01-01

    The purpose of the study was to examine the potential of inhibition of cathepsin S as a treatment for autoimmune diseases. A highly selective cathepsin S inhibitor, CSI-75, was shown to upregulate levels of the cathepsin S substrate, invariant chain Lip10, in vitro as well as in vivo in C57Bl/6 mice

  4. Recent advancement on autoantigens, autoantibodies and inflammatory cells in subepidermal autoimmune bullous diseases

    Institute of Scientific and Technical Information of China (English)

    Jianguo Huang; Qiying Gong; Guiming Li

    2007-01-01

    Subepidermal autoimmune bullous diseases (SABD) are some autoimmune skin diseases that can present in a variety of forms and can be a challenging disease to treat. An overview of the different forms of SABD are discussed including bullous pemphigoid (BP), epidermolysis bullosa acquisita (EBA), cicatricial pemphigoid (CP), bullous systemic lupus erythematosus (BSLE), and Anti-p200 pemphigoid. Emphasis on recent advancement is presented. In recent years, improved Knowledge of the mechanisms of intercellular and cell-matrix adhesion has led to better understanding of the blistering process in some SABD. Defects of such structures cause the subepidermal bullous diseases and have also led to the discovery of new diseases (e.g. anti-p200-pemphigoid). Recent studies have outlined the important role of autoantibodies, mast cell lymphocytes and their cytokines in pathogenesis of SABD.

  5. Dysbiosis may trigger autoimmune diseases via inappropriate posttranslational modification of host proteins

    Directory of Open Access Journals (Sweden)

    Aaron eLerner

    2016-02-01

    Full Text Available The gut ecosystem with myriads of microorganisms and the high concentration of immune system cells can be considered as a separate organ on its own. The balanced interaction between the host and microbial cells has been shaped during the long co-evolutionary process. In dysbiotic conditions, however, this balance is compromised and results in abnormal interaction between the host and microbiota. It is hypothesize here that the changed spectrum of microbial enzymes involved in posttranslational modification of proteins may contribute to the aberrant modification of host proteins thus generating autoimmune responses by the host, resulting in autoimmune diseases.

  6. Systemic Autoimmune, Rheumatic Diseases and Coinciding Psoriasis: Data from a Large Single-Centre Registry and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Anna Bazsó

    2015-01-01

    Full Text Available Psoriasis is a systemic immune-inflammatory disease characterized by chronic or recurrent skin symptoms, psoriatic arthritis, enthesopathy, and uveitis. Psoriasis has recently been published to appear with various autoimmune disorders, but the coexistence has been systematically reviewed by only few studies until now. In the present study, charts and electronic database of 4344 patients with various systemic autoimmune disorders, under regular medical control at our department, were reviewed retrospectively searching for association with psoriasis. Hereby, we demonstrate 25 psoriatic patients coinciding with various systemic autoimmune diseases. The coexistence of psoriasis and autoimmune diseases resulted in the worsening of the clinical outcome of the autoimmune diseases as indicated by higher frequency and dosages of glucocorticoid use, need for biologicals, and other comorbidities. These results suggest common environmental and genetic background as well as therapeutic possibilities in the future.

  7. Challenges in interpretation of thyroid function tests in pregnant women with autoimmune thyroid disease

    DEFF Research Database (Denmark)

    Feldt-Rasmussen, Ulla; Bliddal, Sofie; Rasmussen, Åse Krogh;

    2011-01-01

    Physiological changes during gestation are important to be aware of in measurement and interpretation of thyroid function tests in women with autoimmune thyroid diseases. Thyroid autoimmune activity is decreasing in pregnancy. Measurement of serum TSH is the first-line screening variable for...... thyroid dysfunction also in pregnancy. However, using serum TSH for control of treatment of maternal thyroid autoimmunity infers a risk for compromised foetal development. Peripheral thyroid hormone values are highly different among laboratories, and there is a need for laboratory-specific gestational age......-related reference ranges. Equally important, the intraindividual variability of the thyroid hormone measurements is much narrower than the interindividual variation (reflecting the reference interval). The best laboratory assessment of thyroid function is a free thyroid hormone estimate combined with TSH...

  8. Presumed Isotretinoin-Induced, Concomitant Autoimmune Thyroid Disease and Ocular Myasthenia Gravis: A Case Report

    Directory of Open Access Journals (Sweden)

    Huseyin Gursoy

    2012-11-01

    Full Text Available Introduction: There are many adverse effects that have been described for isotretinoin. To the best of our knowledge, this is the first report of a possible association of oral isotretinoin intake with autoimmune thyroiditis and ocular myasthenia gravis (OMG. Case Presentation: A 19-year-old Caucasian male, who had used oral isotretinoin for severe acne disease for the previous six months, was referred to our clinic. He had a three-week history of diplopia and variable bilateral ptosis. Physical examination showed moderate periorbital edema and limitations of up- and down-gaze in the left eye. Laboratory findings and thyroid ultrasound were consistent with autoimmune thyroiditis. Antithyroid therapy did not relieve the clinical symptoms. Concomitant OMG was suspected. Variable ptosis and a positive response to oral prednisolone of 40 mg/day and pyridostigmine of 360 mg/day supported the diagnosis of concomitant autoimmune thyroiditis and OMG. Conclusion: Autoimmune disorders may be triggered by oral isotretinoin treatment. Clinicians prescribing isotretinoin should be aware of the possible association between isotretinoin intake and concomitant autoimmune thyroiditis and OMG.

  9. Mesenchymal stem cells and their application in autoimmune disease treatment: review article

    Directory of Open Access Journals (Sweden)

    Mehrnaz Tayebi Kamardi

    2014-09-01

    Full Text Available Mesenchymal Stem Cells (MSCs are well known as the regulator of the immune system. These multipotent non-hematopoietic progenitor cells have been originally isolated from bone marrow, and later on found in several other tissues, such as skeletal muscle, umbilical cord blood, adipose and fetal liver tissues. Immunomodulatory effects of MSCs on a variety of immune cells such as T and B lymphocytes, Natural Killer cells (NK, neutrophils, macrophages and dendritic cells, has made a good candidate of them for the treatment of inflammatory disorders, particularly autoimmune diseases such as multiple sclerosis and rheumatoid arthritis. In addition, several studies have indicated mechanisms by which MSCs could reduce immune cell proliferation and activation leading to immune tolerance induction. Since T lymphocytes are considered as the most important immune cells, effect of MSCs on the activity of these cells has a very special significance to direct immune response. Under various conditions, T-lymphocytes have different phenotype and performance and can be differentiated into particular subtype such as regulatory T cells. Both in vitro and in vivo studies have indicated that MSCs modulate innate and adaptive immune system by promoting generation of CD4+CD25+ T regulatory cells which have important role in immune tolerance induction and autoimmune disease prevention. MSCs are able to block pro-inflammatory and increase anti-inflammatory cytokines secretion. So such unique immunomodulatory features make MSCs ideal candidates for clinical application as immunosuppressants which can be considered for autoimmune diseases treatment. Therefore, in this short-review, we attempt to focus mainly on the existing information about MSCs in association with immunomodulatory function of them on the immune system. In addition, the possible mechanisms and the performance impact of MSCs in autoimmune diseases improvement are discussed here. However, increasing

  10. Prevalence of coeliac disease in patients with autoimmune thyroiditis in a Turkish population

    Institute of Scientific and Technical Information of China (English)

    Sefa Guliter; Fahri Yakaryilmaz; Zubeyde Ozkurt; Reyhan Ersoy; Derya Ucardag; Osman Caglayan; Pinar Atasoy

    2007-01-01

    AIM: To investigate the prevalence of coeliac disease in a series of Turkish patients with autoimmune thyroiditis.METHODS: Sera from 136 consecutive patients with newly diagnosed autoimmune thyroiditis and 119 healthy blood donors were tested for IgA tissue transglutaminase antibody with enzyme-linked immunosorbent assay. Endoscopic mucosal biopsy from the second part of duodenum was performed in patients with positive antibody test.RESULTS: Eight patients (5.9%) and one control subject (0.8%) were positive for IgA tissue transglutaminase antibody (OR: 7.38, 95% CI: 0.91-59.85, P = 0.04). Six patients and one control agreed to take biopsies. Histopathological examination revealed changes classified as Marsh ma in one, Marsh n in one, Marsh I in two, and Marsh 0 in two patients with autoimmune throiditis, and Marsh I in one blood donor.CONCLUSION: Turkish patients with autoimmune thyroiditis have an increased risk of coeliac disease and serological screening may be useful for early detection of coeliac disease in these patients. Our findings need to be confirmed in a larger series of patients.

  11. Autoimmune Hepatitis and Celiac Disease: Case Report Showing an Entero-Hepatic Link

    Directory of Open Access Journals (Sweden)

    Francesco Tovoli

    2010-10-01

    Full Text Available Celiac disease is an autoimmune disorder primarily targeting the small bowel, although extraintestinal extensions have been reported. The autoimmune processes can affect the liver with manifestations such as primary biliary cirrhosis and autoimmune hepatitis. We describe a 61-year-old woman with celiac disease and an increased levels of aminotransferases. The persistence of increased levels of aminotransferases after 1 year of gluten-free diet and the positivity for an anti-nuclear and anti-double-strand DNA antibodies led to a misdiagnosis of systemic lupus erythematosus-related hepatitis. Based on these findings the patient was placed on steroids, which after a few months were stopped because of the onset of diabetes mellitus. Soon after steroid withdrawal, the patient had a marked increase in aminotransferases and γ-globulins, and a liver biopsy revealed chronic active hepatitis. A course of three months of steroids and azathioprine normalized both biochemical and clinical parameters. Currently the patient is symptom-free and doing well. In conclusion, a hypertransaminasemia persisting after a gluten-free diet should be interpreted as a sign of coexisting autoimmune liver disease. Any autoantibody positivity (in this case to ANA and anti-dsDNA should be carefully considered in order to avoid misdiagnosis delaying appropriate clinical management.

  12. Recurrence of autoimmune liver disease and inflammatory bowel disease after pediatric liver transplantation.

    Science.gov (United States)

    Liberal, Rodrigo; Vergani, Diego; Mieli-Vergani, Giorgina

    2016-09-01

    Approximately 10% of children with autoimmune hepatitis (AIH) and 30% of those with sclerosing cholangitis (SC) require liver transplantation (LT). LT is indicated in patients who present with fulminant hepatic failure (ie, with encephalopathy) and in those who develop end-stage liver disease despite treatment. After LT, recurrent AIH is reported in approximately 30% of patients and recurrent SC in up to 50%. Diagnosis of recurrence is based on biochemical abnormalities, seropositivity for autoantibodies, interface hepatitis on histology, steroid dependence, and, for SC, presence of cholangiopathy. Recurrence of SC after LT is often associated with poorly controlled inflammatory bowel disease (IBD). Recurrence may even appear years after LT; therefore, steroid-based immunosuppression should be maintained at a higher dose than that used for patients transplanted for nonautoimmune liver diseases. Although the impact of recurrent disease on graft function is controversial, it seems that in pediatric LT recipients recurrence of AIH or SC is associated with compromised graft survival. Exacerbation of preexistent IBD may be observed after LT for SC or AIH, and IBD appears to have a more aggressive course than before LT. In addition, IBD can develop de novo following LT. Liver Transplantation 22 1275-1283 2016 AASLD. PMID:27257963

  13. Dietary metabolites and the gut microbiota: an alternative approach to control inflammatory and autoimmune diseases.

    Science.gov (United States)

    Richards, James L; Yap, Yu Anne; McLeod, Keiran H; Mackay, Charles R; Mariño, Eliana

    2016-05-01

    It is now convincingly clear that diet is one of the most influential lifestyle factors contributing to the rise of inflammatory diseases and autoimmunity in both developed and developing countries. In addition, the modern 'Western diet' has changed in recent years with increased caloric intake, and changes in the relative amounts of dietary components, including lower fibre and higher levels of fat and poor quality of carbohydrates. Diet shapes large-bowel microbial ecology, and this may be highly relevant to human diseases, as changes in the gut microbiota composition are associated with many inflammatory diseases. Recent studies have demonstrated a remarkable role for diet, the gut microbiota and their metabolites-the short-chain fatty acids (SCFAs)-in the pathogenesis of several inflammatory diseases, such as asthma, arthritis, inflammatory bowel disease, colon cancer and wound-healing. This review summarizes how diet, microbiota and gut microbial metabolites (particularly SCFAs) can modulate the progression of inflammatory diseases and autoimmunity, and reveal the molecular mechanisms (metabolite-sensing G protein-coupled receptor (GPCRs) and inhibition of histone deacetylases (HDACs)). Therefore, considerable benefit could be achieved simply through the use of diet, probiotics and metabolites for the prevention and treatment of inflammatory diseases and autoimmunity. PMID:27350881

  14. A novel mutation in NCF2 associated with autoimmune disease and a solitary late-onset infection.

    Science.gov (United States)

    Chou, Janet; Hsu, Joyce T; Bainter, Wayne; Al-Attiyah, Raja'a; Al-Herz, Waleed; Geha, Raif S

    2015-12-01

    Chronic granulomatous disease (CGD) is typically characterized by recurrent infections, granulomatous disease, and an increased susceptibility to autoimmune disease. We report a novel homozygous mutation in NCF2 that permits residual expression of an alternatively spliced variant in a patient with duodenitis and systemic lupus erythematosus (SLE), followed by a late-onset, single pulmonary infection in the setting of immunosuppressive medications. This report highlights the importance of considering CGD in patients who present initially exclusively with autoimmune disease. PMID:26272171

  15. Multiple Sclerosis and autoimmune diseases: clinical cases and review of the literature

    Directory of Open Access Journals (Sweden)

    A. Protti

    2011-09-01

    Full Text Available Multiple sclerosis (MS, the most frequent demyelinating disease in adults, is thought to be an autoimmune disease. Symptoms and signs observed in MS reflect lesions present mainly in the white matter of the central nervous system (CNS. The diagnosis remains difficult, at least concerning presenting symptoms, because of their low specificity. Diagnosis criteria are usually based on dissemination of signs in time and space, evoked potentials, findings of magnetic resonance imaging, results of cerebrospinal fluid examination, and the exclusion of other diagnosis possibly explaining the clinical signs. However, no clinical and paraclinical investigation can distinguish with certainity MS from other conditions such as autoimmune or inflammatory diseases predominantly affecting the central nervous system. These other disorders include systemic lupus erythematosus, antiphospholipid syndrome, Behcet disease, Sjogren syndrome, sarcoidosis and vasculitides. We present four clinical cases showing the difficulty in reaching a proper diagnosis...

  16. The U1-snRNP complex: structural properties relating to autoimmune pathogenesis in rheumatic diseases

    OpenAIRE

    Kattah, Nicole H.; Kattah, Michael G.; Utz, Paul J.

    2010-01-01

    The U1 small nuclear ribonucleoprotein particle (snRNP) is a target of autoreactive B cells and T cells in several rheumatic diseases including systemic lupus erythematosus (SLE) and mixed connective tissue disease (MCTD). We propose that inherent structural properties of this autoantigen complex, including common RNA-binding motifs, B and T-cell epitopes, and a unique stimulatory RNA molecule, underlie its susceptibility as a target of the autoimmune response. Immune mechanisms that may cont...

  17. Evolutionary dynamics of human autoimmune disease genes and malfunctioned immunological genes

    Directory of Open Access Journals (Sweden)

    Podder Soumita

    2012-01-01

    Full Text Available Abstract Background One of the main issues of molecular evolution is to divulge the principles in dictating the evolutionary rate differences among various gene classes. Immunological genes have received considerable attention in evolutionary biology as candidates for local adaptation and for studying functionally important polymorphisms. The normal structure and function of immunological genes will be distorted when they experience mutations leading to immunological dysfunctions. Results Here, we examined the fundamental differences between the genes which on mutation give rise to autoimmune or other immune system related diseases and the immunological genes that do not cause any disease phenotypes. Although the disease genes examined are analogous to non-disease genes in product, expression, function, and pathway affiliation, a statistically significant decrease in evolutionary rate has been found in autoimmune disease genes relative to all other immune related diseases and non-disease genes. Possible ways of accumulation of mutation in the three steps of the central dogma (DNA-mRNA-Protein have been studied to trace the mutational effects predisposed to disease consequence and acquiring higher selection pressure. Principal Component Analysis and Multivariate Regression Analysis have established the predominant role of single nucleotide polymorphisms in guiding the evolutionary rate of immunological disease and non-disease genes followed by m-RNA abundance, paralogs number, fraction of phosphorylation residue, alternatively spliced exon, protein residue burial and protein disorder. Conclusions Our study provides an empirical insight into the etiology of autoimmune disease genes and other immunological diseases. The immediate utility of our study is to help in disease gene identification and may also help in medicinal improvement of immune related disease.

  18. Fusing Heterogeneous Data for Alzheimer's Disease Classification.

    Science.gov (United States)

    Pillai, Parvathy Sudhir; Leong, Tze-Yun

    2015-01-01

    In multi-view learning, multimodal representations of a real world object or situation are integrated to learn its overall picture. Feature sets from distinct data sources carry different, yet complementary, information which, if analysed together, usually yield better insights and more accurate results. Neuro-degenerative disorders such as dementia are characterized by changes in multiple biomarkers. This work combines the features from neuroimaging and cerebrospinal fluid studies to distinguish Alzheimer's disease patients from healthy subjects. We apply statistical data fusion techniques on 101 subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. We examine whether fusion of biomarkers helps to improve diagnostic accuracy and how the methods compare against each other for this problem. Our results indicate that multimodal data fusion improves classification accuracy. PMID:26262148

  19. Possible role of histamine in pathogenesis of autoimmune diseases: implications for immunotherapy with histamine-2 receptor antagonists

    DEFF Research Database (Denmark)

    Nielsen, Hans Jørgen; Hammer, J H

    1992-01-01

    The immunosuppressive chemical drugs cyclosporine A (CsA) and methotrexate (Mx) have recently been shown to be of benefit in several different diseases of autoimmune origin. Cellular immune responses may play a major role in autoimmunity as autoreactive T lymphocytes appear to recognize autoantig......The immunosuppressive chemical drugs cyclosporine A (CsA) and methotrexate (Mx) have recently been shown to be of benefit in several different diseases of autoimmune origin. Cellular immune responses may play a major role in autoimmunity as autoreactive T lymphocytes appear to recognize...... the possibility, that histamine is one of the molecules involved in pathogenesis of autoimmune diseases. T cell mediated regulation and suppression of autoreactive T cells seem to be ineffective in controlling the enhanced immune reaction in patients where the discrimination between self and non-self is changed...

  20. The autoimmune tautology.

    Science.gov (United States)

    Anaya, Juan-Manuel

    2010-01-01

    Although autoimmune diseases exhibit contrasting epidemiological features, pathology, and clinical manifestations, three lines of evidence demonstrate that these diseases share similar immunogenetic mechanisms (that is, autoimmune tautology). First, clinical evidence highlights the co-occurrence of distinct autoimmune diseases within an individual (that is, polyautoimmunity) and within members of a nuclear family (that is, familial autoimmunity). Second, physiopathologic evidence indicates that the pathologic mechanisms may be similar among autoimmune diseases. Lastly, genetic evidence shows that autoimmune phenotypes might represent pleiotropic outcomes of the interaction of non-specific disease genes.

  1. Autoimmune thyroid diseases and Helicobacter pylori: The correlation is present only in Graves's disease

    Institute of Scientific and Technical Information of China (English)

    Vincenzo Bassi; Gennaro Marino; Alba Iengo; Olimpia Fattoruso; Crescenzo Santinelli

    2012-01-01

    AIM:To investigate the correlation between autoimmune thyroid diseases (ATDs) and the prevalence of Cag-A positive strains of Helicobacter pylori (H.pylon)in stool samples.METHODS:Authors investigated 112 consecutive Caucasian patients (48 females and 4 males with Graves' disease and 54 females and 6 males with Hashimoto's thyroiditis HT),at their first diagnosis of ATDs.Authors tested for H.pylori in stool samples using an amplified enzyme immunoassay and Cag-A in serum samples using an enzyme-linked immunoassay method (ELISA).The results were analyzed using the two-sided Fisher's exact test and the respective odds ratio (OR) was calculated.RESULTS:A marked correlation was found between the presence of H.pylori (P ≤ 0.0001,OR 6.3) and,in particular,Cag-A positive strains (P ≤ 0.005,OR 5.3)in Graves' disease,but not in Hashimoto's thyroiditis,where authors found only a correlation with Cag-A strains (P ≤ 0.005,OR 8.73) but not when H.pylori was present.CONCLUSION:The marked correlation between H.pylori and Cag-A,found in ATDs,could be dependent on the different expression of adhesion molecules in the gastric mucosa.

  2. Ribosomal protein s6-ps240 is expressed in lesional skin from patients with autoimmune skin blistering diseases

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    Ana Maria Abreu Velez

    2013-01-01

    Full Text Available Background: The in situ signaling transduction within skin biopsies from patients affected by autoimmune skin blistering diseases is not well-characterized. Aim : In autoimmune skin blistering diseases, autoantibodies seem to trigger several intracellular signaling pathways and we investigated the presence of the phosphorylated form of ribosomal protein S6-pS240 within autoimmune skin blistering diseases biopsies. Materials and Methods: We utilized immunohistochemistry to evaluate the presence of S6-pS240 in lesional skin biopsies of patients affected by autoimmune skin blistering diseases including patients with an endemic and nonendemic pemphigus foliaceus (non EPF, with bullous pemphigoid (BP, pemphigus vulgaris (PV, dermatitis herpetiformis (DH, and the respective controls. Results: Most autoimmune bullous skin diseases biopsies stained positive for S6-pS240 around lesional blisters, including adjacent areas of the epidermis; and within upper dermal inflammatory infiltrates, and/or mesenchymal-endothelial cell junctions within the dermis. Conclusions: We document that S6-pS240 is expressed in lesional areas of skin biopsies from patients with autoimmune skin blistering diseases, as well as on eccrine glands and piloerector muscles. Thus, the role of this molecule in autoimmune skin blistering diseases warrants further study.

  3. Autoimmune BSEP disease: disease recurrence after liver transplantation for progressive familial intrahepatic cholestasis.

    Science.gov (United States)

    Kubitz, Ralf; Dröge, Carola; Kluge, Stefanie; Stross, Claudia; Walter, Nathalie; Keitel, Verena; Häussinger, Dieter; Stindt, Jan

    2015-06-01

    Severe cholestasis may result in end-stage liver disease with the need of liver transplantation (LTX). In children, about 10 % of LTX are necessary because of cholestatic liver diseases. Apart from bile duct atresia, three types of progressive familial intrahepatic cholestasis (PFIC) are common causes of severe cholestasis in children. The three subtypes of PFIC are defined by the involved genes: PFIC-1, PFIC-2, and PFIC-3 are due to mutations of P-type ATPase ATP8B1 (familial intrahepatic cholestasis 1, FIC1), the ATP binding cassette transporter ABCB11 (bile salt export pump, BSEP), or ABCB4 (multidrug resistance protein 3, MDR3), respectively. All transporters are localized in the canalicular membrane of hepatocytes and together mediate bile salt and phospholipid transport. In some patients with PFIC-2 disease, recurrence has been observed after LTX, which mimics a PFIC phenotype. It could be shown by several groups that inhibitory anti-BSEP antibodies emerge, which most likely cause disease recurrence. The prevalence of severe BSEP mutations (e.g., splice site and premature stop codon mutations) is very high in this group of patients. These mutations often result in the complete absence of BSEP, which likely accounts for an insufficient auto-tolerance against BSEP. Although many aspects of this "new" disease are not fully elucidated, the possibility of anti-BSEP antibody formation has implications for the pre- and posttransplant management of PFIC-2 patients. This review will summarize the current knowledge including diagnosis, pathomechanisms, and management of "autoimmune BSEP disease." PMID:25342496

  4. Possible Role of Human Herpesvirus 6 as a Trigger of Autoimmune Disease

    Directory of Open Access Journals (Sweden)

    Francesco Broccolo

    2013-01-01

    Full Text Available Human herpesvirus 6 (HHV-6 infection is common and has a worldwide distribution. Recently, HHV-6A and HHV-6B have been reclassified into two distinct species based on different biological features (genetic, antigenic, and cell tropism and disease associations. A role for HHV-6A/B has been proposed in several autoimmune disorders (AD, including multiple sclerosis (MS, autoimmune connective tissue diseases, and Hashimoto's thyroiditis. The focus of this review is to discuss the above-mentioned AD associated with HHV-6 and the mechanisms proposed for HHV-6A/B-induced autoimmunity. HHV-6A/B could trigger autoimmunity by exposing high amounts of normally sequestered cell antigens, through lysis of infected cells. Another potential trigger is represented by molecular mimicry, with the synthesis of viral proteins that resemble cellular molecules, as a mechanism of immune escape. The virus could also induce aberrant expression of histocompatibility molecules thereby promoting the presentation of autoantigens. CD46-HHV-6A/B interaction is a new attractive mechanism proposed: HHV-6A/B (especially HHV-6A could participate in neuroinflammation in the context of MS by promoting inflammatory processes through CD46 binding. Although HHV-6A/B has the ability to trigger all the above-mentioned mechanisms, more studies are required to fully elucidate the possible role of HHV-6A/B as a trigger of AD.

  5. Pathogenic functions of B cells in autoimmune diseases: IFN-γ production joins the criminal gang.

    Science.gov (United States)

    Fillatreau, Simon

    2015-04-01

    B-cell depletion therapy has emerged as a powerful strategy to intercept the progression of T-cell-mediated autoimmune diseases such as rheumatoid arthritis, type 1 diabetes, or relapsing remitting multiple sclerosis. However, its mode of action remains incompletely defined, reflecting our incomplete understanding of the pathogenic functions of B cells in such pathologies. B cells can contribute to immune responses through the production of antibodies, presentation of antigen to T cells, and production of cytokines. In this issue of the European Journal of Immunology [Eur. J. Immunol. 2015. 45: 988-998], Olalekan et al. demonstrate that IFN-γ production by B cells is essential for the development of arthritis in mice. Lack of IFN-γ expression in B cells results in reduced autoimmune T-cell responses and autoantibody levels, impacting the arthritogenic reaction akin to that in B-cell depletion therapy. Together with other reports, the article by Olalekan et al. emphasizes the importance of cytokine-producing B cells in the pathogenesis of autoimmune diseases. In this commentary, I discuss how these findings shed new light on the roles of B cells as drivers of autoimmune pathogenesis, and how they more generally contribute to our understanding of the role of B cells in immunity.

  6. Anterior Hypopituitarism is Rare and Autoimmune Disease is Common in Adults with Idiopathic Central Diabetes Insipidus.

    LENUS (Irish Health Repository)

    2012-02-01

    Objective: Central diabetes insipidus is a rare clinical condition with a heterogenous aetiology. Up to 40% of cases are classified as idiopathic, though many of these are thought to have an autoimmune basis. Published data has suggested that anterior hypopituitarism is common in childhood onset idiopathic diabetes insipidus. We aimed to assess the incidence of anterior hypopituitarism in a cohort of adult patients with idiopathic diabetes insipidus. Design and Patients: We performed a retrospective review of the databases of two pituitary investigation units. This identified 39 patients with idiopathic diabetes insipidus. All had undergone MRI scanning and dynamic pituitary testing (either insulin tolerance testing or GHRH\\/arginine and short synacthen testing) to assess anterior pituitary function. Results: One patient had partial growth hormone deficiency; no other anterior pituitary hormonal deficits were found. 33% had at least one autoimmune disease in addition to central diabetes insipidus. Conclusions: Our data suggest that anterior hypopituitarism is rare in adult idiopathic diabetes insipidus. Routine screening of these patients for anterior hypopituitarism may not therefore be indicated. The significant prevalence of autoimmune disease in this cohort supports the hypothesis that idiopathic diabetes insipidus may have an autoimmune aetiology.

  7. Control of autoimmune diseases by the B7-CD28 family molecules.

    Science.gov (United States)

    Anand, Sudarshan; Chen, Lieping

    2004-01-01

    The roles of B7-CD28 family molecules in the regulation of immune responses have been intensively studied over the past decade. The findings resulting from these studies not only broaden our understanding in the control of immune responses at the molecular level, but also lead to identification of molecular targets for future manipulation and potential treatment of human diseases. There is convincing evidence that the B7-CD28 family molecules play critical roles in the control of initiation, progression and pathogenesis of autoimmune diseases, which is the focus of this review. Currently, five molecular pathways within this family have been identified and each of them appears to overlap but have distinct functions in the control of priming, activation, maturation and amplification of cellular and humoral immune responses. Rationale-based design of intervention, targeting on multiple pathways should lead to new methods and approaches for management of autoimmune diseases. PMID:14754392

  8. Effect of Associated Autoimmune Diseases on Type 1 Diabetes Mellitus Incidence and Metabolic Control in Children and Adolescents

    Science.gov (United States)

    2016-01-01

    Type 1 diabetes mellitus (T1DM) is one of the most common chronic diseases developing in childhood. The incidence of the disease in children increases for unknown reasons at a rate from 3 to 5% every year worldwide. The background of T1DM is associated with the autoimmune process of pancreatic beta cell destruction, which leads to absolute insulin deficiency and organ damage. Complex interactions between environmental and genetic factors contribute to the development of T1DM in genetically predisposed patients. The T1DM-inducing autoimmune process can also affect other organs, resulting in development of additional autoimmune diseases in the patient, thereby impeding diabetes control. The most common T1DM comorbidities include autoimmune thyroid diseases, celiac disease, and autoimmune gastritis; additionally, diabetes can be a component of PAS (Polyglandular Autoimmune Syndrome). The aim of this review is to assess the prevalence of T1DM-associated autoimmune diseases in children and adolescents and their impact on the course of T1DM. We also present suggestions concerning screening tests. PMID:27525273

  9. Widespread non-additive and interaction effects within HLA loci modulate the risk of autoimmune diseases

    Science.gov (United States)

    Lenz, Tobias L.; Deutsch, Aaron J.; Han, Buhm; Hu, Xinli; Okada, Yukinori; Eyre, Stephen; Knapp, Michael; Zhernakova, Alexandra; Huizinga, Tom W.J.; Abecasis, Goncalo; Becker, Jessica; Boeckxstaens, Guy E.; Chen, Wei-Min; Franke, Andre; Gladman, Dafna D.; Gockel, Ines; Gutierrez-Achury, Javier; Martin, Javier; Nair, Rajan P.; Nöthen, Markus M.; Onengut-Gumuscu, Suna; Rahman, Proton; Rantapää-Dahlqvist, Solbritt; Stuart, Philip E.; Tsoi, Lam C.; Van Heel, David A.; Worthington, Jane; Wouters, Mira M.; Klareskog, Lars; Elder, James T.; Gregersen, Peter K.; Schumacher, Johannes; Rich, Stephen S.; Wijmenga, Cisca; Sunyaev, Shamil R.; de Bakker, Paul I.W.; Raychaudhuri, Soumya

    2015-01-01

    Human leukocyte antigen (HLA) genes confer strong risk for autoimmune diseases on a log-additive scale. Here we speculated that differences in autoantigen binding repertoires between a heterozygote’s two expressed HLA variants may result in additional non-additive risk effects. We tested non-additive disease contributions of classical HLA alleles in patients and matched controls for five common autoimmune diseases: rheumatoid arthritis (RA, Ncases=5,337), type 1 diabetes (T1D, Ncases=5,567), psoriasis vulgaris (Ncases=3,089), idiopathic achalasia (Ncases=727), and celiac disease (Ncases=11,115). In four out of five diseases, we observed highly significant non-additive dominance effects (RA: P=2.5×1012; T1D: P=2.4×10−10; psoriasis: P=5.9×10−6; celiac disease: P=1.2×10−87). In three of these diseases, the dominance effects were explained by interactions between specific classical HLA alleles (RA: P=1.8×10−3; T1D: P=8.6×1027; celiac disease: P=6.0×10−100). These interactions generally increased disease risk and explained moderate but significant fractions of phenotypic variance (RA: 1.4%, T1D: 4.0%, and celiac disease: 4.1%, beyond a simple additive model). PMID:26258845

  10. Similar biotherapeutic products in Latin America. Regulation and opportunities for patients with autoimmune diseases

    Directory of Open Access Journals (Sweden)

    Desanvicente-Celis Z

    2013-01-01

    Full Text Available Zayrho Desanvicente-Celis, Julian Caro-Moreno, Mateo Enciso-Zuluaga, Juan-Manuel AnayaCenter for Autoimmune Diseases Research (CREA, Universidad del Rosario, Bogotá, ColombiaAbstract: Biotherapeutic products have revolutionized medicine, changing the way we can treat some chronic diseases, such as autoimmune diseases. The patent expiry and the high costs of reference biotherapeutic products, among other factors, have promoted interest in similar biotherapeutic products (SBPs, also known as biosimilars. The objective of developing an SBP is to manufacture a “highly similar” molecule to a reference biotherapeutic product, by conducting a comparability exercise that can demonstrate similar quality, safety, and efficacy. Regulations like those of the World Health Organization, the European Medicines Agency, and the Food and Drug Administration are international reference standards. Herein, we aim to point out the current status in Latin America on SBPs, focusing on regulatory issues within the context of autoimmune diseases. The regulations of Argentina, Peru, Chile, Guatemala, Panama and Costa Rica follow the World Health Organization guidelines. Other countries, such as Cuba, Mexico, Venezuela, and Brazil have regulations that take into account international standards combined with local features. In Colombia, a draft decree is under revision and the debate is ongoing. Some countries have already approved SBPs. Mexico, Chile, Ecuador, Bolivia, and Peru market SBPs of rituximab, and Colombia markets an SBP of etanercept. The advent of SBPs is definitely beneficial. Safety and efficacy must be ensured following clear and comprehensive regulations.Keywords: biological therapy, biotechnology, similar biotherapeutic product, autoimmune disease, Latin America

  11. Clinical manifestations of autoimmune disease-related non-Hodgkin lymphoma: a Korean single-center, retrospective clinical study

    Science.gov (United States)

    Jeon, Young-Woo; Yoon, Jae-Ho; Lee, Sung-Eun; Eom, Ki-Seong; Kim, Yoo-Jin; Kim, Hee-Je; Lee, Seok; Min, Chang-Ki; Lee, Jong Wook; Min, Woo-Sung; Cho, Seok-Goo

    2016-01-01

    Background/Aims: Recently, large cohort studies regarding associations between autoimmune disease and lymphomas have been reported in a few Western countries. However, Asian data concerning autoimmune-related lymphomas are limited. Therefore, we evaluated the clinical characteristics and prognostic factors of patients with autoimmune disease-related non-Hodgkin lymphoma (NHL) in a single center in Korea. Methods: We analyzed the data from 11 patients with autoimmune-related NHL. Patients were categorized into two groups, those with rheumatoid arthritis (RA) and those with non-RA-related NHL. Then patients were re-categorized into a group with methotrexate (MTX) usage and a MTX non-usage group. Histological subtype, MTX duration, autoimmune disease duration, treatment modalities, and other data were collected and analyzed. Results: Our study revealed that older RA patients have a greater likelihood of occurrence of NHL (p = 0.042). We confirmed that MTX duration and cumulative dose of MTX have no significant correlation with autoimmune disease and NHL (p = 0.073). In the management of autoimmune disease-related NHL, all patients were directly treated with systemic chemotherapy instead of employing a wait and watch approach. Overall survival (OS) and progression-free survival (PFS) in all autoimmune disease-related NHL were 100% and 87.5%, with no treatment-related mortality during the 2-year follow-up period of our study. Conclusions: Our study suggests that patients with RA-NHL are characterized by older age at onset compared to those with non-RA-NHL. Also considering of OS and PFS, intensive treatment strategy instead of delayed watchful managements may be required for autoimmune disease-related NHL including of old age group. PMID:27384438

  12. Association of subcutaneous allergen-specific immunotherapy with incidence of autoimmune disease, ischemic heart disease, and mortality

    DEFF Research Database (Denmark)

    Linneberg, Allan; Jacobsen, Rikke Kart; Jespersen, Lasse;

    2012-01-01

    Subcutaneous allergen-specific immunotherapy (SCIT) is a well-documented treatment of IgE-mediated allergic disease. Little is known about potential effects of SCIT on the risk of other chronic immune-related diseases. Over the years, a few casuistic reports have caused concern that SCIT might ac...... as a trigger of autoimmune disease.......Subcutaneous allergen-specific immunotherapy (SCIT) is a well-documented treatment of IgE-mediated allergic disease. Little is known about potential effects of SCIT on the risk of other chronic immune-related diseases. Over the years, a few casuistic reports have caused concern that SCIT might act...

  13. Pathogenic role of platelets in rheumatoid arthritis and systemic autoimmune diseases. Perspectives and therapeutic aspects.

    Science.gov (United States)

    Harifi, Ghita; Sibilia, Jean

    2016-04-01

    Well-recognized for their role in vascular homoeostasis, platelets may play a major role in inflammation and immunomodulation. Substantial data are emerging on the pathogenic involvement of platelets in inflammatory arthritis and autoimmune diseases, indicating the existence of crosstalk between the coagulation and inflammation system. Upon activation, platelets release pro-inflammatory platelets microparticles, which interact with leucocytes leading to joint and systemic inflammation in rheumatoid arthritis. Platelets activation by immune complexes activate dendritic cells promoting the secretion of interferon alpha, which has a key role in the development of systemic lupus erythematous. In this review, we discuss the current data on the role of platelets in the pathophysiology of inflammatory arthritis and various autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis. PMID:27052277

  14. Autoimmune Pancreatitis and IgG4 Related Disease in Three Children

    Science.gov (United States)

    Chong, Sze Yee; Coleman, Lee; MacGregor, Duncan; Hardikar, Winita; Oliver, Mark R.

    2016-01-01

    We report 3 children who presented with fever and abdominal pain, deranged liver function tests, and on abdominal ultrasound were found to have an enlarged pancreas, substantial abdominal lymphadenopathy, and extrahepatic biliary duct dilatation. After ruling out malignancy, probable immunoglobulin G4-related disease (IgG4RD) associated with autoimmune pancreatitis was considered. This condition was first described in the adults and often mimics pancreatic cancer. It can involve multiple organs, either synchronously or metachronously, and is rarely reported in children. The disorder mostly responds to corticosteroid therapy and other immune suppression. We highlight the difficulty in diagnosing autoimmune pancreatitis/IgG4-related disease in children and illustrate the difference between pediatric and adult presentation. PMID:27622194

  15. POSSIBLE ROLE OF PROBIOTIC MICROORGANISMS OF BIFIDOBACTERIUM AND LACTOBACILLUS GENUS IN PATHOGENESIS OF AUTOIMMUNE THYROID DISEASES

    Directory of Open Access Journals (Sweden)

    E. P. Kiseleva

    2010-01-01

    Full Text Available It was revealed, that, in blood samples of the patients with autoimmune thyroid diseases, serum antibodies against cell-free fraction of Bifidobacterium bifidum 791 and Lactobacillus plantarum B-01 were detected, respectively, in 71 and 63% of cases, that being two-fold higher than appropriate frequencies in healthy blood donors. An evidence was obtained that presence of some components specifically reacting with autoantibodies against thyroid peroxidase and thyroglobulin on the surface of the microorganisms cells and competing for binding of these immunoglobulins with thyroid antigens. One may also suggest a presence of bacterial components, interacting with thyroid peroxidase. The data obtained let us suggest that probiotic microorganisms of Bifidobacterium and Lactobacillus genus could take part in pathogenesis of autoimmune thyroid diseases, by means of molecular mimicry mechanisms.

  16. Pathogenic role of platelets in rheumatoid arthritis and systemic autoimmune diseases

    Science.gov (United States)

    Harifi, Ghita; Sibilia, Jean

    2016-01-01

    Well-recognized for their role in vascular homoeostasis, platelets may play a major role in inflammation and immunomodulation. Substantial data are emerging on the pathogenic involvement of platelets in inflammatory arthritis and autoimmune diseases, indicating the existence of crosstalk between the coagulation and inflammation system. Upon activation, platelets release pro-inflammatory platelets microparticles, which interact with leucocytes leading to joint and systemic inflammation in rheumatoid arthritis. Platelets activation by immune complexes activate dendritic cells promoting the secretion of interferon alpha, which has a key role in the development of systemic lupus erythematous. In this review, we discuss the current data on the role of platelets in the pathophysiology of inflammatory arthritis and various autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis. PMID:27052277

  17. Autoimmune Pancreatitis and IgG4 Related Disease in Three Children.

    Science.gov (United States)

    Bolia, Rishi; Chong, Sze Yee; Coleman, Lee; MacGregor, Duncan; Hardikar, Winita; Oliver, Mark R

    2016-07-01

    We report 3 children who presented with fever and abdominal pain, deranged liver function tests, and on abdominal ultrasound were found to have an enlarged pancreas, substantial abdominal lymphadenopathy, and extrahepatic biliary duct dilatation. After ruling out malignancy, probable immunoglobulin G4-related disease (IgG4RD) associated with autoimmune pancreatitis was considered. This condition was first described in the adults and often mimics pancreatic cancer. It can involve multiple organs, either synchronously or metachronously, and is rarely reported in children. The disorder mostly responds to corticosteroid therapy and other immune suppression. We highlight the difficulty in diagnosing autoimmune pancreatitis/IgG4-related disease in children and illustrate the difference between pediatric and adult presentation. PMID:27622194

  18. Perspectives of ofatumumab as CD20 targeted therapy in rheumatoid arthritis and other autoimmune diseases.

    Science.gov (United States)

    Pers, Yves Marie; Jorgensen, Christian

    2016-09-01

    Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune condition viewed as a severe destructive disease. The treatment strategies include anti-CD20 monoclonal antibody (mAb)-targeting B cells. Ofatumumab specifically targets a membrane-proximal epitope on the CD20 molecule distinct from other anti-CD20 antibodies including rituximab and ocrelizumab, and bind the epitope located on the large loop of CD20. This explains a more durable B-cell depletion and a different pharmacodynamic. We review the pharmacodynamic of B-cell depletion and analyze the results in RA and other B-cell-mediated autoimmune diseases. The randomized trial in RA showed clinical efficacy comparable to rituximab at week 24. However, structural impact has not been demonstrated. Studies including RA patients refractory to rituximab would be useful to define the optimal strategy of ofatumumab therapy. PMID:27485081

  19. Autoimmune liver disease and the Canadian First Nations Aboriginal Communities of British Columbia's Pacific Northwest

    Institute of Scientific and Technical Information of China (English)

    Eric M Yoshida; Mark Riley; Laura T Arbour

    2006-01-01

    Primary biliary cirrhosis (PBC) is a well-known but uncommon chronic liver disease that is presumed to be of autoimmune etiology. Recently, investigations in British Columbia (BC), a province of Canada situated along the Pacific North-West of North America, have suggested that PBC is not a rare disease amongst BC's Aboriginal (i.e. First Nations) communities. Geographically, BC is adjacent to South East Alaska, an American state that has also reported an increased prevalence of PBC amongst its Aboriginal communities. In this article, the medical evidence supporting a hypothesis of increased risk of PBC amongst BC's First Nations communities is reviewed. Evidence suggesting that autoimmune hepatitis is also more likely amongst BC's First Nations communities is also presented.(C)2006 The WJG Press. All rights reserved.

  20. Mixed connective tissue disease associated with autoimmune hepatitis and thyroiditis.

    OpenAIRE

    Tomsic, M.; Ferlan-Marolt, V.; Kveder, T; Hojker, S; Rozman, B.

    1992-01-01

    The case is reported of a 27 year old woman who had mixed connective tissue disease (MCTD) associated with chronic active hepatitis and thyroiditis. Although hepatomegaly is sometimes observed in MCTD, only four cases of MCTD and chronic active hepatitis have been described. It is thought that this is the first report of an association between MCTD, chronic active hepatitis and thyroiditis.

  1. Body mass index and risk of autoimmune diseases

    DEFF Research Database (Denmark)

    Harpsøe, Maria C; Basit, Saima; Andersson, Mikael;

    2014-01-01

    .57) and type 1 diabetes mellitus (HR 2.67; 95% CI, 1.71 to 4.17). Risk of dermatitis herpetiformis increased by 14% (95% CI, 1% to 30%) per BMI unit. Conversely, risk of celiac disease and Raynaud's phenomenon decreased by 7% (95% CI, 1% to 13%) and 12% (95% CI, 4% to 19%) per BMI unit, respectively. Further...

  2. IL-35-producing B cells are critical regulators of immunity during autoimmune and infectious diseases.

    Science.gov (United States)

    Shen, Ping; Roch, Toralf; Lampropoulou, Vicky; O'Connor, Richard A; Stervbo, Ulrik; Hilgenberg, Ellen; Ries, Stefanie; Dang, Van Duc; Jaimes, Yarúa; Daridon, Capucine; Li, Rui; Jouneau, Luc; Boudinot, Pierre; Wilantri, Siska; Sakwa, Imme; Miyazaki, Yusei; Leech, Melanie D; McPherson, Rhoanne C; Wirtz, Stefan; Neurath, Markus; Hoehlig, Kai; Meinl, Edgar; Grützkau, Andreas; Grün, Joachim R; Horn, Katharina; Kühl, Anja A; Dörner, Thomas; Bar-Or, Amit; Kaufmann, Stefan H E; Anderton, Stephen M; Fillatreau, Simon

    2014-03-20

    B lymphocytes have critical roles as positive and negative regulators of immunity. Their inhibitory function has been associated primarily with interleukin 10 (IL-10) because B-cell-derived IL-10 can protect against autoimmune disease and increase susceptibility to pathogens. Here we identify IL-35-producing B cells as key players in the negative regulation of immunity. Mice in which only B cells did not express IL-35 lost their ability to recover from the T-cell-mediated demyelinating autoimmune disease experimental autoimmune encephalomyelitis (EAE). In contrast, these mice displayed a markedly improved resistance to infection with the intracellular bacterial pathogen Salmonella enterica serovar Typhimurium as shown by their superior containment of the bacterial growth and their prolonged survival after primary infection, and upon secondary challenge, compared to control mice. The increased immunity found in mice lacking IL-35 production by B cells was associated with a higher activation of macrophages and inflammatory T cells, as well as an increased function of B cells as antigen-presenting cells (APCs). During Salmonella infection, IL-35- and IL-10-producing B cells corresponded to two largely distinct sets of surface-IgM(+)CD138(hi)TACI(+)CXCR4(+)CD1d(int)Tim1(int) plasma cells expressing the transcription factor Blimp1 (also known as Prdm1). During EAE, CD138(+) plasma cells were also the main source of B-cell-derived IL-35 and IL-10. Collectively, our data show the importance of IL-35-producing B cells in regulation of immunity and highlight IL-35 production by B cells as a potential therapeutic target for autoimmune and infectious diseases. This study reveals the central role of activated B cells, particularly plasma cells, and their production of cytokines in the regulation of immune responses in health and disease.

  3. The Clinical Usefulness of 18F FDG PET/CT in Patients with Systemic Autoimmune Disease

    International Nuclear Information System (INIS)

    Individuals with systemic autoimmune disease have an increased susceptibility to both inflammation and malignancy. The aim of this study was to evaluate the clinical usefulness of 18F FDG PET/CT in patients with systemic autoimmune disease. Forty patients diagnosed with systemic autoimmune disease were enrolled. Diagnostic accuracy of FDG PET/CT for detecting malignancy was assessed. FDG PET/CT findings, including maximum standardized uptake (SUVmax) of lymphadenopathy (LAP), liver, bone marrow, spleen, joint and muscles, were considered for the characterization of LAPs. FDG PET/CT could detect metabolically activated lesions in 36 out of 40 patients (90%) including inflammatory lesions in 28 out of 32 patients (88%). The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of FDG PET/CT for the detection of malignancy were 100, 67, 70, 25, and 100%, respectively. Multiple LAPs were found in 25 of 40 patients (63%), and comprised three malignancies, four cases of tuberculosis, and 18 reactive changes. A SUVmax ratio of bone marrow to liver below 0.78 could distinguish malignancy from tuberculosis + reactive change (AUC=1.000, sensitivity: 100%, specificity: 100%). The SUVmax ratio of spleen to liver in the reactive group was also significantly higher than that in the malignancy group (P=0.014). SUVmax of LAP in the TB group was significantly higher than that in the reactive group (P=0.040). PET/CT is useful in detecting and differentiating inflammation and malignancy in patients with systemic autoimmune disease. Frequent false positive interpretations can be minimized by consideration of FDG uptake in bone marrow and spleen.

  4. Idiopathic CD4+ T lymphopenia without autoimmunity or granulomatous disease in the slipstream of RAG mutations

    OpenAIRE

    Kuijpers, Taco W.; IJspeert, Hanna; Leeuwen, Ester; Jansen, Machiel H.; Mette D Hazenberg; Weijer, Kees; Van Lier, Rene A. W.; van der Burg, Mirjam

    2011-01-01

    textabstractA girl presented during childhood with a single course of extensive chickenpox and moderate albeit recurrent pneumonia in the presence of idiopathic CD4+T lymphocytopenia (ICL). Her clinical condition remained stable over the past 10 years without infections, any granulomatous disease, or autoimmunity. Immunophenotyping demonstrated strongly reduced naive T and B cells with intact proliferative capacity. Antibody reactivity on in vivo immunizations was normal. T-cell receptor-Vβ r...

  5. Generation and characterization of integration-free induced pluripotent stem cells from patients with autoimmune disease

    OpenAIRE

    Son, Mi-Young; Lee, Mi-Ok; Jeon, Hyejin; Seol, Binna; Kim, Jung Hwa; Chang, Jae-Suk; Cho, Yee Sook

    2016-01-01

    Autoimmune diseases (AIDs), a heterogeneous group of immune-mediated disorders, are a major and growing health problem. Although AIDs are currently treated primarily with anti-inflammatory and immunosuppressive drugs, the use of stem cell transplantation in patients with AIDs is becoming increasingly common. However, stem cell transplantation therapy has limitations, including a shortage of available stem cells and immune rejection of cells from nonautologous sources. Induced pluripotent stem...

  6. Rare Variants in the TREX1 Gene and Susceptibility to Autoimmune Diseases

    OpenAIRE

    Nadia Barizzone; Sara Monti; Simona Mellone; Michela Godi; Maurizio Marchini; Raffaella Scorza; Danieli, Maria G.; Sandra D’Alfonso

    2013-01-01

    TREX1 (DNase III) is an exonuclease involved in response to oxidative stress and apoptosis. Heterozygous mutations in TREX1 were previously observed in patients with systemic lupus erythematosus (SLE) and Sjögren's syndrome (SS). We performed a mutational analysis of the TREX1 gene on three autoimmune diseases: SLE (210 patients) and SS (58 patients), to confirm a TREX1 involvement in the Italian population, and systemic sclerosis (SSc, 150 patients) because it shares similarities with SLE (p...

  7. Complement in Experimental Autoimmune Encephalomyelitis Revisited: C3 is Required for Development of Maximal Disease

    OpenAIRE

    Szalai, Alexander J.; Hu, Xianzhen; Adams, Jillian E.; Barnum, Scott R.

    2007-01-01

    Complement per se has been shown to play an important role in demyelinating disease but controversy remains regarding the role of C3 in the development and progression of experimental autoimmune encephalomyelitis (EAE), the animal model for multiple sclerosis. In this study we used C3-/- mice to confirm previous findings that C3 is required for full development of EAE. Furthermore, C3+/- mice (with serum C3 levels 50% that of wild type mice) developed EAE with a severity intermediate between ...

  8. Somatostatin and substance P analogues: applications in autoimmune and haematological diseases

    OpenAIRE

    Van Hagen, Martin

    1995-01-01

    textabstractSomatostatin has been extensively studied in relation to the endocrine and nervous systems. Many reports on the role of somatostatin receptor imaging and somatostatin treatment of neuroendocrine tumours have been published. The relation between somatostatin and other neuropeptides and the immune system is less explored. The aim of this study was to investigate the diagnostic applications of somatostatin and substance P analogues in autoimmune and haematological diseases. Both in v...

  9. Mesenchymal stem cells in the treatment of inflammatoryand autoimmune diseases in experimental animal models

    Institute of Scientific and Technical Information of China (English)

    Matthew W Klinker; Cheng-Hong Wei

    2015-01-01

    Multipotent mesenchymal stromal cells [also known asmesenchymal stem cells (MSCs)] are currently beingstudied as a cell-based treatment for inflammatorydisorders. Experimental animal models of humanimmune-mediated diseases have been instrumental inestablishing their immunosuppressive properties. Inthis review, we summarize recent studies examiningthe effectiveness of MSCs as immunotherapy in severalwidely-studied animal models, including type 1 diabetes,experimental autoimmune arthritis, experimentalautoimmune encephalomyelitis, inflammatory boweldisease, graft-vs -host disease, and systemic lupuserythematosus. In addition, we discuss mechanismsidentified by which MSCs mediate immune suppressionin specific disease models, and potential sources offunctional variability of MSCs between studies.

  10. Imaging of pulmonary involvement in autoimmune rheumatic diseases

    International Nuclear Information System (INIS)

    Conjunctive tissue pathology obtains special aspect, by affecting most workable contingent - young and middle-age persons. In clinical practice special value has early diagnostic of these processes that permits to use in time adequate methods of treatment. In connection with appearance of new methods of imaging diagnostic, appears necessity of estimation of its diagnostic possibilities with main aim to optimize early diagnostic of these diseases. (authors)

  11. Autoimmunity in chronic obstructive pulmonary disease: clinical and experimental evidence

    OpenAIRE

    Kheradmand, Farrah; Shan, Ming; Xu, Chuang; Corry, David B.

    2012-01-01

    Over the past few decades, neutrophils and macrophages had co-occupied center stage as the critical innate immune cells underlying the pathobiology of cigarette smoke-induced chronic obstructive pulmonary disease and lung parenchymal destruction (i.e., emphysema). While chronic exposure to smoke facilitates the recruitment of innate immune cells into the lung, a clear role for adaptive immunity in emphysema has emerged. Evidence from human studies specifically point to a role for recruitment ...

  12. Genes, autoimmunity and pathogenesis of rheumatic heart disease

    OpenAIRE

    Guilherme L.; Köhler K; Postol E; Kalil J

    2011-01-01

    Pathogenesis of rheumatic heart disease (RHD) remains incompletely understood. Several genes associated with RHD have been described; most of these are involved with immune responses. Single nucleotide polymorphisms in a number of genes affect patients with RHD compared to controls. Molecular mimicry between streptococcal antigens and human proteins, including cardiac myosin epitopes, vimentin and other intracellular proteins is central to the pathogenesis of RHD. Autoreactive T cells migrate...

  13. Autoimmunity in Rheumatic Diseases Is Induced by Microbial Infections via Crossreactivity or Molecular Mimicry

    Directory of Open Access Journals (Sweden)

    Taha Rashid

    2012-01-01

    Full Text Available A general consensus supports fundamental roles for both genetic and environmental, mainly microbial, factors in the development of autoimmune diseases. One form of autoimmune rheumatic diseases is confined to a group of nonpyogenic conditions which are usually preceded by or associated with either explicit or occult infections. A previous history of clinical pharyngitis, gastroenteritis/urethritis, or tick-borne skin manifestation can be obtained from patients with rheumatic fever, reactive arthritis, or Lyme disease, respectively, whilst, other rheumatic diseases like rheumatoid arthritis (RA, ankylosing spondylitis (AS, and Crohn’s disease (CD are usually lacking such an association with a noticeable microbial infection. A great amount of data supports the notion that RA is most likely caused by Proteus asymptomatic urinary tract infections, whilst AS and CD are caused by subclinical bowel infections with Klebsiella microbes. Molecular mimicry is the main pathogenetic mechanism that can explain these forms of microbe-disease associations, where the causative microbes can initiate the disease with consequent productions of antibacterial and crossreactive autoantibodies which have a great impact in the propagation and the development of these diseases.

  14. Rare Variants in the TREX1 Gene and Susceptibility to Autoimmune Diseases

    Directory of Open Access Journals (Sweden)

    Nadia Barizzone

    2013-01-01

    Full Text Available TREX1 (DNase III is an exonuclease involved in response to oxidative stress and apoptosis. Heterozygous mutations in TREX1 were previously observed in patients with systemic lupus erythematosus (SLE and Sjögren's syndrome (SS. We performed a mutational analysis of the TREX1 gene on three autoimmune diseases: SLE (210 patients and SS (58 patients, to confirm a TREX1 involvement in the Italian population, and systemic sclerosis (SSc, 150 patients because it shares similarities with SLE (presence of antinuclear antibodies and connective tissue damage. We observed 7 variations; two of these are novel nonsynonymous variants (p.Glu198Lys and p.Met232Val. They were detected in one SS and in one SSc patient, respectively, and in none of the 200 healthy controls typed in this study and of the 1712 published controls. In silico analysis predicts a possibly damaging role on protein function for both variants. The other 5 variations are synonymous and only one of them is novel (p.Pro48Pro. This study contributes to the demonstration that TREX1 is involved in autoimmune diseases and proposes that the spectrum of involved autoimmune diseases can be broader and includes SSc. We do not confirm a role of TREX1 variants in SLE.

  15. Rare variants in the TREX1 gene and susceptibility to autoimmune diseases.

    Science.gov (United States)

    Barizzone, Nadia; Monti, Sara; Mellone, Simona; Godi, Michela; Marchini, Maurizio; Scorza, Raffaella; Danieli, Maria G; D'Alfonso, Sandra

    2013-01-01

    TREX1 (DNase III) is an exonuclease involved in response to oxidative stress and apoptosis. Heterozygous mutations in TREX1 were previously observed in patients with systemic lupus erythematosus (SLE) and Sjögren's syndrome (SS). We performed a mutational analysis of the TREX1 gene on three autoimmune diseases: SLE (210 patients) and SS (58 patients), to confirm a TREX1 involvement in the Italian population, and systemic sclerosis (SSc, 150 patients) because it shares similarities with SLE (presence of antinuclear antibodies and connective tissue damage). We observed 7 variations; two of these are novel nonsynonymous variants (p.Glu198Lys and p.Met232Val). They were detected in one SS and in one SSc patient, respectively, and in none of the 200 healthy controls typed in this study and of the 1712 published controls. In silico analysis predicts a possibly damaging role on protein function for both variants. The other 5 variations are synonymous and only one of them is novel (p.Pro48Pro). This study contributes to the demonstration that TREX1 is involved in autoimmune diseases and proposes that the spectrum of involved autoimmune diseases can be broader and includes SSc. We do not confirm a role of TREX1 variants in SLE. PMID:24224166

  16. Cytotoxic T lymphocyte antigen-4 (CTLA-4 A49G polymorphism and autoimmune blood diseases

    Directory of Open Access Journals (Sweden)

    Faruk Aktürk

    2010-06-01

    Full Text Available Objective: The cytotoxic T lymphocyte associated antigen-4 (CTLA-4 is expressed on T lymphocytes, and inhibits the T-cell responses. In animal models, it has been shown that complete CTLA-4 deficiency was lethal due to massive infiltration of tissues by polyclonally proliferating lymphocytes. CTLA-4 A49G polymorphism, which has been suggested to reduce the inhibitory function of the CTLA-4 molecule, was found to be associated with various autoimmune diseases in recent studies. Material and Methods: In this study, we evaluated the frequency of CTLA-4 A49G polymorphism in 46 patients with autoimmune hemolytic anemia (AIHA, 62 patients with immune thrombocytopenic purpura (ITP, and 150 healthy individuals. Results: Allele frequencies and genotype distributions were similar in both ITP and AIHA patients compared to healthy individuals. In subgroup analysis, however, we found that in chronic lymphocytic leukemia (CLL patients with AIHA (n=4, all patients had CTLA-4 A49G polymorphism (3 had AG, 1 had GG. There was no significant statistical association between G allele and systemic lupus erythematosus (SLE or AIHA.Conclusion: These data suggest that CTLA-4 A49G polymorphism does not contribute to the pathogenesis of lymphoproliferative diseases itself, nor does it increase the risk of autoimmune complications in patients with lymphoproliferative disease.

  17. Immunomodulatory effects and mechanisms of plant alkaloid tetrandrine in autoimmune diseases

    Institute of Scientific and Technical Information of China (English)

    LAI Jenn-Haung

    2002-01-01

    Autoimmune diseases characterized by activation of immune effector cells and damage of target organs are currently treated with a combination of several disease-modifying antirheumatic drugs (DMARDs) that preserve different immunomodulatory mechanisms. Such a combination treatment strategy not only provides synergistic effects but also reduces side effects from individual drug. Tetrandrine (Tet), purified from a creeper Stephania tetrandra S Moore, is a bis-benzylisoquinoline alkaloid and has been used to treat patients with silicosis, autoimmune disorders, and hypertension in Mainland China for decades. The accumulated studies both in vitro and in vivo reveal that Tet preserves a wide variety of immunosuppressive effects. Importantly, the Tet-mediated immunosuppressive mechanisms are evidently different from some known DMARDs. The synergistic effects have also been demonstrated between Tet and other DMARDs like FK506 and cyclosporin. These results highlight Tet a very potential candidate to be considered as one of DMARDs in the treatment of autoimmune diseases, especially rheumatoid arthritis. This review summarizes evidence-based in vivo and in vitro studies on this potential Chinese immunosuppressive herb.

  18. Peripheral blood and intrathyroidal T cell clones from patients with thyroid autoimmune diseases.

    Science.gov (United States)

    Massart, C; Caroff, G; Maugendre, D; Genetet, N; Gibassier, J

    1999-01-01

    For a better understanding of the pathogenesis of thyroid autoimmune diseases, we have studied morphological and functional properties of T clones from peripheral blood lymphocytes (PBL) and from intrathyroidal lymphocytes (ITL) obtained from 3 patients with Graves' disease or 1 Hashimoto's thyroiditis. Investigations were carried out on clones cultured alone or cocultured with autologous thyrocytes. Clonage efficiency ranged from 30% to 33% for PBL and 10% to 36% for ITL. A predominance of CD4-positive clones was observed whatever the origin of the lymphocytes or the autoimmune pathology. Gamma interferon (IFN-gamma) was detected in the majority (17/19) of the clones tested. Intracytoplasmic interleukin (IL-4) was secreted in 7/19 clones and both cytokines were produced in 5/19 clones. In coculture a proliferative response and tumour necrosis factor (TNF-alpha) production were observed with 6 clones (4 from Graves thyrocytes and 2 from thyroiditis). No cytotoxic clone was derived from Graves or thyroiditis tissues. These data demonstrate that the large majority of T clones are principally CD4-T cells; all the clones secreted TNF-alpha and a large majority produced IFN-gamma. Only a few clones produced IL-4 alone or associated with IFN-gamma. Six T clones induced proliferative response and of TNF-alpha secretion in coculture. Further investigations must be performed on these antigen-reactive T clones to analyse their role in the pathogenesis of the human thyroid autoimmune diseases. PMID:10739333

  19. Inhibition of SLPI ameliorates disease activity in experimental autoimmune encephalomyelitis

    Directory of Open Access Journals (Sweden)

    Müller André

    2012-03-01

    Full Text Available Abstract Background The secretory leukocyte protease inhibitor (SLPI exerts wide ranging effects on inflammatory pathways and is upregulated in EAE but the biological role of SLPI in EAE, an animal model of multiple sclerosis is unknown Methods To investigate the pathophysiological effects of SLPI within EAE, we induced SLPI-neutralizing antibodies in mice and rats to determine the clinical severity of the disease. In addition we studied the effects of SLPI on the anti-inflammatory cytokine TGF-β. Results The induction of SLPI neutralizing antibodies resulted in a milder disease course in mouse and rat EAE. SLPI neutralization was associated with increased serum levels of TGF-β and increased numbers of FoxP3+ CD4+ T cells in lymph nodes. In vitro, the addition of SLPI significantly decreased the number of functional FoxP3+ CD25hi CD4+ regulatory T cells in cultures of naive human CD4+ T cells. Adding recombinant TGF-β to SLPI-treated human T cell cultures neutralized SLPI's inhibitory effect on regulatory T cell differentiation. Conclusion In EAE, SLPI exerts potent pro-inflammatory actions by modulation of T-cell activity and its neutralization may be beneficial for the disease.

  20. 重症肌无力合并自身免疫病的临床研究%Associated autoimmune diseases in myasthenia gravis

    Institute of Scientific and Technical Information of China (English)

    管宇宙; 崔丽英

    2012-01-01

    patients were included. One or more autoimmune diseases were diagnosed in 28 patients (9. 18%) , who were 9 Males and 19 females, there were no sex ratio difference compared with the non-autoimmune diseases group (F >0. 05). Twelve patients developed autoimmune diseases 69. 6 ± 35. 3 months before MG symptoms onset. Fourteen patients developed autoimmune diseases 72. 4 ± 38. 4 months after MG symptoms onset, 2 patients simultaneously. (1) The mean onset age of MG symptoms in autoimmune diseases group was 33. 9±9. 4 years, which have no difference with non-autoimmune diseases group (35. 3 ± 12. 2 years, P>0. 05). The mean onset age in MG associated hyperthyroidism was 27. 4 ± 12. 5 years, which was younger than other autoimmune diseases group (41.6 Ⅱ10.3 years, P<0. 05) and non-autoimmune diseases group (35.3+12.2 years, P< 0. 05). (2) Hyperthyroidism was most frequently found in autoimmune diseases group (13 patients), rheumatoid arthritis was found in 5 patients, Hashimoto's thyroiditis in 4 patients, Guillain-Barre syndrome in 3 patients. Two autoimmune diseases were diagnosed together in 3 MG patients, and three in one MG patient. (3) Osserman classification in autoimmune diseases group: Thirteen cases were diagnosed as type I, 3 cases as type Ⅱa, 10 cases as type Ⅱb, 2 cases as type HI. Cases of Type I were more frequently diagnosed in MG group complicated with hyperthyroidism than other autoimmune diseases group (P<0. 05). Conclusions One or more autoimmune diseases developed in MG patients, which could develop before or after MG onset, among which hyperthyroidism was most frequently diagnosed. The onset age of MG symptoms in patients complicated hyperthyroidism was younger than other groups. Ocular type was more frequently found in this group.

  1. Computational Modelling Approaches on Epigenetic Factors in Neurodegenerative and Autoimmune Diseases and Their Mechanistic Analysis

    Directory of Open Access Journals (Sweden)

    Afroza Khanam Irin

    2015-01-01

    Full Text Available Neurodegenerative as well as autoimmune diseases have unclear aetiologies, but an increasing number of evidences report for a combination of genetic and epigenetic alterations that predispose for the development of disease. This review examines the major milestones in epigenetics research in the context of diseases and various computational approaches developed in the last decades to unravel new epigenetic modifications. However, there are limited studies that systematically link genetic and epigenetic alterations of DNA to the aetiology of diseases. In this work, we demonstrate how disease-related epigenetic knowledge can be systematically captured and integrated with heterogeneous information into a functional context using Biological Expression Language (BEL. This novel methodology, based on BEL, enables us to integrate epigenetic modifications such as DNA methylation or acetylation of histones into a specific disease network. As an example, we depict the integration of epigenetic and genetic factors in a functional context specific to Parkinson’s disease (PD and Multiple Sclerosis (MS.

  2. Autoimmune diseases and severe infections as risk factors for schizophrenia: a 30-year population-based register study

    DEFF Research Database (Denmark)

    Benros, Michael E; Nielsen, Philip Finn Rising; Nordentoft, Merete;

    2011-01-01

    Autoimmune diseases have been associated with an increased risk of schizophrenia. It has been suggested that brain-reactive autoantibodies are part of the mechanisms behind this association. Furthermore, an increased permeability of the blood-brain barrier has been observed during periods...... of infection and inflammation. The authors therefore investigated whether autoimmune diseases combined with exposures to severe infections may increase the risk of schizophrenia...

  3. Activation of Blood Coagulation in Two Prototypic Autoimmune Skin Diseases: A Possible Link with Thrombotic Risk.

    Directory of Open Access Journals (Sweden)

    Massimo Cugno

    Full Text Available Coagulation activation has been demonstrated in two prototypic autoimmune skin diseases, chronic autoimmune urticaria and bullous pemphigoid, but only the latter is associated with increased thrombotic risk. Two markers of coagulation activation (prothrombin fragment F1+2 and fibrin fragment D-dimer were measured by immunoenzymatic methods in plasma samples from 30 patients with active chronic autoimmune urticaria, positive for autologous serum skin test, 30 patients with active bullous pemphigoid and 30 healthy subjects. In skin biopsies, tissue factor expression was evaluated by both immunohistochemistry and in situ hybridization. F1+2 and D-dimer levels were higher in active chronic autoimmune urticaria (276.5±89.8 pmol/L and 5.56±4.40 nmol/L, respectively than in controls (145.2±38.0 pmol/L and 1.06±0.25 nmol/L; P=0.029 and P=0.011 and were much higher in active bullous pemphigoid (691.7±318.7 pmol/L and 15.24±9.09 nmol/L, respectively (P<0.0001. Tissue factor positivity was evident in skin biopsies of both disorders with higher intensity in bullous pemphigoid. F1+2 and D-dimer, during remission, were markedly reduced in both disorders. These findings support the involvement of coagulation activation in the pathophysiology of both diseases. The strong systemic activation of coagulation in bullous pemphigoid may contribute to increase the thrombotic risk and provides the rationale for clinical trials on anticoagulant treatments in this disease.

  4. Impact of Aging on Liver Histological Findings of Autoimmune Liver Diseases

    Directory of Open Access Journals (Sweden)

    Yuki Haga

    2014-11-01

    Full Text Available Our aim is to investigate the recent liver biopsy findings of autoimmune liver diseases at a university hospital located in an urban area of Japan. The study included 259 patients (mean age 56.8 ± 12.5; male/female, 46/213 who underwent a liver biopsy for primary biliary cirrhosis (PBC or autoimmune hepatitis (AIH. We analyzed their liver biopsy findings according to age and gender. Among 127 PBC patients, Scheuer stages 1, 2, 3, and 4 were 42, 54, 18, and 13, respectively. Among 101 AIH patients, fibrosis stages F1, F2, F3, and F4 were 37, 32, 19, and 13, respectively, and inflammatory activity grades A1, A2, and A3 were 22, 25, and 54, respectively. Among PBC aged ≥65 years, Scheuer stages 1–3 and 4 patients were 27 and 6, respectively. The proportion of Scheuer stage 4 patients in PBC aged ≥65 years tended to be higher than that in PBC aged <65 years (p = 0.0659. Of interest, the proportion of AIH patients with moderate or severe activity (A2 or A3 in males was higher than in females (p = 0.0311. From the point of view of fibrosis stage or inflammatory activity grade of the liver, the proportion of AIH patients aged ≥65 years was similar to that aged <65 years. Although we identified six older cirrhotic patients with AIH, three of them were male. The progression of fibrosis and inflammatory activity of the liver should be noted when we treat older patients suffering from autoimmune liver diseases. Liver biopsy plays an important role in obtaining accurate information on autoimmune liver diseases in older patients.

  5. Epigenetic Modulation as a Therapeutic Prospect for Treatment of Autoimmune Rheumatic Diseases.

    Science.gov (United States)

    Ciechomska, Marzena; O'Reilly, Steven

    2016-01-01

    Systemic inflammatory rheumatic diseases are considered as autoimmune diseases, meaning that the balance between recognition of pathogens and avoidance of self-attack is impaired and the immune system attacks and destroys its own healthy tissue. Treatment with conventional Disease Modifying Antirheumatic Drugs (DMARDs) and/or Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) is often associated with various adverse reactions due to unspecific and toxic properties of those drugs. Although biologic drugs have largely improved the outcome in many patients, such drugs still pose significant problems and fail to provide a solution to all patients. Therefore, development of more effective treatments and improvements in early diagnosis of rheumatic diseases are badly needed in order to increase patient's functioning and quality of life. The reversible nature of epigenetic mechanisms offers a new class of drugs that modulate the immune system and inflammation. In fact, epigenetic drugs are already in use in some types of cancer or cardiovascular diseases. Therefore, epigenetic-based therapeutics that control autoimmunity and chronic inflammatory process have broad implications for the pathogenesis, diagnosis, and management of rheumatic diseases. This review summarises the latest information about potential therapeutic application of epigenetic modification in targeting immune abnormalities and inflammation of rheumatic diseases. PMID:27594771

  6. Epigenetic Modulation as a Therapeutic Prospect for Treatment of Autoimmune Rheumatic Diseases

    Directory of Open Access Journals (Sweden)

    Marzena Ciechomska

    2016-01-01

    Full Text Available Systemic inflammatory rheumatic diseases are considered as autoimmune diseases, meaning that the balance between recognition of pathogens and avoidance of self-attack is impaired and the immune system attacks and destroys its own healthy tissue. Treatment with conventional Disease Modifying Antirheumatic Drugs (DMARDs and/or Nonsteroidal Anti-Inflammatory Drugs (NSAIDs is often associated with various adverse reactions due to unspecific and toxic properties of those drugs. Although biologic drugs have largely improved the outcome in many patients, such drugs still pose significant problems and fail to provide a solution to all patients. Therefore, development of more effective treatments and improvements in early diagnosis of rheumatic diseases are badly needed in order to increase patient’s functioning and quality of life. The reversible nature of epigenetic mechanisms offers a new class of drugs that modulate the immune system and inflammation. In fact, epigenetic drugs are already in use in some types of cancer or cardiovascular diseases. Therefore, epigenetic-based therapeutics that control autoimmunity and chronic inflammatory process have broad implications for the pathogenesis, diagnosis, and management of rheumatic diseases. This review summarises the latest information about potential therapeutic application of epigenetic modification in targeting immune abnormalities and inflammation of rheumatic diseases.

  7. Alzheimer's Disease: A Pathogenetic Autoimmune Disorder Caused by Herpes Simplex in a Gene-Dependent Manner

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    C. J. Carter

    2010-01-01

    Full Text Available Herpes simplex is implicated in Alzheimer's disease and viral infection produces Alzheimer's disease like pathology in mice. The virus expresses proteins containing short contiguous amino acid stretches (5–9aa “vatches” = viralmatches homologous to APOE4, clusterin, PICALM, and complement receptor 1, and to over 100 other gene products relevant to Alzheimer's disease, which are also homologous to proteins expressed by other pathogens implicated in Alzheimer's disease. Such homology, reiterated at the DNA level, suggests that gene association studies have been tracking infection, as well as identifying key genes, demonstrating a role for pathogens as causative agents. Vatches may interfere with the function of their human counterparts, acting as dummy ligands, decoy receptors, or via interactome interference. They are often immunogenic, and antibodies generated in response to infection may target their human counterparts, producing protein knockdown, or generating autoimmune responses that may kill the neurones in which the human homologue resides, a scenario supported by immune activation in Alzheimer's disease. These data may classify Alzheimer's disease as an autoimmune disorder created by pathogen mimicry of key Alzheimer's disease-related proteins. It may well be prevented by vaccination and regular pathogen detection and elimination, and perhaps stemmed by immunosuppression or antibody adsorption-related therapies.

  8. Genes, autoimmunity and pathogenesis of rheumatic heart disease

    International Nuclear Information System (INIS)

    Pathogenesis of rheumatic heart disease (RHD) remains incompletely understood. Several genes associated with RHD have been described; most of these are involved with immune responses. Single nucleotide polymorphisms in a number of genes affect patients with RHD compared to controls. Molecular mimicry between streptococcal antigens and human proteins, including cardiac myosin epitopes, vimentin and other intracellular proteins is central to the pathogenesis of RHD. Autoreactive T cells migrate from the peripheral blood to the heart and proliferate in the valves in response to stimulation with specific cytokines. The types of cells involved in the inflammation as well as different cytokine profiles in these patients are being investigated. High TNF alpha, interferon gamma, and low IL4 are found in the rheumatic valve suggesting an imbalance between Th1 and Th2 cytokines and probably contributing to the progressive and permanent valve damage. Animal model of ARF in the Lewis rat may further contribute towards understanding the ARF

  9. USE OF RITUXIMAB IN AUTOIMMUNE DISEASES: NEW ASPECTS

    Directory of Open Access Journals (Sweden)

    Dmitry Evgenyevich Karateyev

    2010-01-01

    Full Text Available It has been noted that off-label indication for Rituximab (RTX in rheumatological care indubitably requires its confirmation in the randomized clinical trials. A particular cautious approach should be taken in extending the indications for therapy with gene-engineering biologicals because of the intricacy and interaction of different immunoregulatory mechanisms. Nonetheless, it is stated that much clinical experience with RTX used in most severely ill therapy-resistant patients may serve as a basis for its prescription in a number of most complex inflammatory rheumatic diseases (RDs. There is new evidence for the use of RTX in various RDs differing in their clinical picture, course, and pathogenesis, such as spondyloarthritis, systemic lupus erythematosus, systemic vasculitis.

  10. The Role of IL-17 and Th17 Lymphocytes in Autoimmune Diseases.

    Science.gov (United States)

    Tabarkiewicz, Jacek; Pogoda, Katarzyna; Karczmarczyk, Agnieszka; Pozarowski, Piotr; Giannopoulos, Krzysztof

    2015-12-01

    The end of twentieth century has introduced some changes into T helper (Th) cells division. The identification of the new subpopulation of T helper cells producing IL-17 modified model of Th1-Th2 paradigm and it was named Th17. High abilities to stimulate acute and chronic inflammation made these cells ideal candidate for crucial player in development of autoimmune disorders. Numerous publications based on animal and human models confirmed their pivotal role in pathogenesis of human systemic and organ-specific autoimmune diseases. These findings made Th17 cells and pathways regulating their development and function a good target for therapy. Therapies based on inhibition of Th17-dependent pathways are associated with clinical benefits, but on the other hand are frequently inducing adverse effects. In this review, we attempt to summarize researches focused on the importance of Th17 cells in development of human autoimmune diseases as well as effectiveness of targeting IL-17 and its pathways in pre-clinical and clinical studies.

  11. 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.

  12. APO-1/Fas gene: Structural and functional characteristics in systemic lupus erythematosus and other autoimmune diseases

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    Singh Richa

    2009-01-01

    Full Text Available Systemic lupus erythematosus (SLE is an autoimmune disorder affecting multiple organ systems. It is characterized by the presence of autoantibodies reactive against various self-antigens. Susceptibility to SLE is found to be associated with many major histocompatibility complex (MHC and non-MHC genes, one of which is APO-1/Fas gene, which is present on chromosome 10 in humans. The APO-1/Fas promoter contains consensus sequences for binding of several transcription factors that affect the intensity of Fas expression in cells. The mutations in the APO-1/Fas promoter are associated with risk and severity in various autoimmune diseases and other malignancies. The APO-1/Fas receptor is expressed by many cell types. Two forms of APO-1/Fas protein that are involved in regulation of apoptosis have been identified. Fas receptor-mediated apoptosis plays a physiological and pathological role in killing of infected cell targets. In this review, we have focused on APO-1/Fas gene structure, promoter variants and its association with SLE and other autoimmune diseases. Functional aspects of Fas receptor in apoptosis are also discussed.

  13. The CREB/CRTC2 Pathway Modulates Autoimmune Disease by Promoting Th17 Differentiation

    Science.gov (United States)

    Hernandez, Jeniffer B.; Chang, Christina; LeBlanc, Mathias; Grimm, David; Le Lay, John; Kaestner, Klaus H.; Zheng, Ye; Montminy, Marc

    2015-01-01

    Following their activation in response to inflammatory signals, innate immune cells secrete T cell polarizing cytokines that promote the differentiation of naïve CD4 T cells into T helper (Th) cell subsets. Amongst these, Th17 cells play a prominent role in the development of a number of autoimmune diseases. Although regarded primarily as an immunosuppressant signal, cAMP has been found to mediate pro-inflammatory effects of macrophage-derived prostaglandin E2 (PGE2) on Th17 cells. Here we show that PGE2 enhances Th17 cell differentiation via the activation of the CREB co-activator CRTC2. Following its dephosphorylation, CRTC2 stimulates the expression of the cytokines IL-17A and IL-17F by binding to CREB over both promoters. CRTC2 mutant mice have decreased Th17 cell numbers, and they are protected from experimental autoimmune encephalitis, a model for multiple sclerosis. Our results suggest that small molecule inhibitors of CRTC2 may provide therapeutic benefit to individuals with autoimmune disease. PMID:26031354

  14. Activation of Helicobacter pylori causes either autoimmune thyroid diseases or carcinogenesis in the digestive tract.

    Science.gov (United States)

    Astl, J; Šterzl, I

    2015-01-01

    Helicobacter pylori has been implicated in stimulation of immune system, development of autoimmune endocrinopathies as autoimmune thyroiditis (AT) and on other hand induction of immunosupresion activates gastric and extra-gastric diseases such as gastric ulcer or cancer. It causes persistent lifelong infection despite local and systemic immune response. Our results indicate that Helicobacter pylori might cause inhibition of the specific cellular immune response in Helicobacter pylori-infected patients with or without autoimmune diseases such as AT. We cannot also declare the carcinogenic effect in oropharynx. However the association of any infection agents and cancerogenesis exists. The adherence of Helicobacter pylori expression and enlargement of benign lymphatic tissue and the high incidence of the DNA of Helicobacter pylori in laryngopharyngeal and oropharyngeal cancer is reality. LTT appears to be a good tool for detection of immune memory cellular response in patients with Helicobacter pylori infection and AT. All these complications of Helicobacter pylori infection can be abrogated by successful eradication of Helicobacter pylori.

  15. Possible Implication of Fcγ Receptor-Mediated Trogocytosis in Susceptibility to Systemic Autoimmune Disease

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    Sakiko Masuda

    2013-01-01

    Full Text Available Leukocytes can “gnaw away” the plasma membrane of other cells. This phenomenon, called trogocytosis, occurs subsequent to cell-to-cell adhesion. Currently, two mechanisms of trogocytosis, adhesion molecule-mediated trogocytosis and Fcγ receptor-(FcγR- mediated trogocytosis, have been identified. In our earlier study, we established an in vitro model of FcγR-mediated trogocytosis, namely, CD8 translocation model from T cells to neutrophils. By using this model, we demonstrated that the molecules transferred to neutrophils via FcγR-mediated trogocytosis were taken into the cytoplasm immediately. This result suggests that the chance of molecules transferred via FcγR-mediated trogocytosis to play a role on the cell surface could be time-limited. Thus, we consider the physiological role of FcγR-mediated trogocytosis as a means to remove antibodies (Abs that bind with self-molecules rather than to extract molecules from other cells. This concept means that FcγR-mediated trogocytosis can be a defense mechanism to Ab-mediated autoimmune response. Moreover, the activity of FcγR-mediated trogocytosis was revealed to be parallel to the endocytotic activity of neutrophils, which was critically related to the susceptibility to systemic autoimmune diseases. The collective findings suggest that FcγR-mediated trogocytosis could physiologically play a role in removal of Abs bound to self-antigens and prevent autoimmune diseases.

  16. Statistical Colocalization of Genetic Risk Variants for Related Autoimmune Diseases in the Context of Common Controls

    Science.gov (United States)

    Fortune, Mary D.; Guo, Hui; Burren, Oliver; Schofield, Ellen; Walker, Neil M.; Ban, Maria; Sawcer, Stephen J.; Bowes, John; Worthington, Jane; Barton, Ann; Eyre, Steve; Todd, John A.; Wallace, Chris

    2015-01-01

    Identifying whether potential causal variants for related diseases are shared can identify overlapping etiologies of multifactorial disorders. Colocalization methods disentangle shared and distinct causal variants. However, existing approaches require independent datasets. Here we extend two colocalization methods to allow for the shared control design commonly used in comparison of genome-wide association study results across diseases. Our analysis of four autoimmune diseases, type 1 diabetes (T1D), rheumatoid arthritis, celiac disease and multiple sclerosis, revealed 90 regions that were associated with at least one disease, 33 (37%) of which with two or more disorders. Nevertheless, for 14 of these 33 shared regions there was evidence that causal variants differed. We identified novel disease associations in 11 regions previously associated with one or more of the other three disorders. Four of eight T1D-specific regions contained known type 2 diabetes candidate genes: COBL, GLIS3, RNLS and BCAR1, suggesting a shared cellular etiology. PMID:26053495

  17. Seropositive myasthenia and autoimmune autonomic ganglionopathy: cross reactivity or subclinical disease?

    Science.gov (United States)

    Miglis, Mitchell G; Racela, Rikki; Kaufmann, Horacio

    2011-10-28

    Autoimmune autonomic ganglionopathy (AAG) and myasthenia gravis (MG) are both autoimmune channelopathies mediated by antibodies directed against nicotinic acetylcholine receptors. While both diseases target acetylcholine receptors, skeletal muscle and ganglionic receptor subtypes have key immunologic and genetic distinctions, and reports of patients with both AAG and MG are rare. We report a patient with antibody-confirmed AAG and elevated levels of ACh binding antibodies that did not meet clinical or electrodiagnostic criteria for MG. We presume that his skeletal muscle nAChR seropositivity was a false positive, perhaps due to the cross reactivity of the patient's ganglionic nAChR antibodies with skeletal nAChR subtypes. PMID:21745762

  18. Brazilian society of hepatology recommendations for the diagnosis and management of autoimmune diseases of the liver.

    Science.gov (United States)

    Bittencourt, Paulo Lisboa; Cançado, Eduardo Luiz Rachid; Couto, Cláudia Alves; Levy, Cynthia; Porta, Gilda; Silva, Antônio Eduardo Benedito; Terrabuio, Debora Raquel Benedita; Carvalho Filho, Roberto José de; Chaves, Dalton Marques; Miura, Irene Kazue; Codes, Liana; Faria, Luciana Costa; Evangelista, Andreia Silva; Farias, Alberto Queiroz; Gonçalves, Luciana Lofêgo; Harriz, Michele; Lopes Neto, Edmundo Pessoa A; Luz, Gustavo Oliveira; Oliveira, Patrícia; Oliveira, Elze Maria Gomes de; Schiavon, Janaina Luz Narciso; Seva-Pereira, Tiago; Parise, Edison Roberto

    2015-12-01

    In order to draw evidence-based recommendations concerning the management of autoimmune diseases of the liver, the Brazilian Society of Hepatology has sponsored a single-topic meeting in October 18th, 2014 at São Paulo. An organizing committee comprised of seven investigators was previously elected by the Governing Board to organize the scientific agenda as well as to select twenty panelists to make a systematic review of the literature and to present topics related to the diagnosis and treatment of autoimmune hepatitis, primary sclerosing cholangitis, primary biliary cirrhosis and their overlap syndromes. After the meeting, all panelists gathered together for the discussion of the topics and the elaboration of those recommendations. The text was subsequently submitted for suggestions and approval of all members of the Brazilian Society of Hepatology through its homepage. The present paper is the final version of the reviewed manuscript organized in topics, followed by the recommendations of the Brazilian Society of Hepatology. PMID:26959804

  19. Treatment of autoimmune disease with total lymphoid irradiation. Cellular and humoral mechanisms

    International Nuclear Information System (INIS)

    The rationale for using total lymphoid irradiation (TLI) as an immunosuppressive treatment originated from studies of patients with lymphoid malignancies. TLI has been an accepted form of therapy for Hodgkin's disease and non-Hodgkin's lymphoma for over 15 years. This radiotherapy regimen induced profound immunologic abnormalities in these patients; however, it has proven to be relatively safe and well tolerated with few long-term side effects. More recent studies in both experimental animals and humans have further documented the profound long-lasting immunosuppression and relative lack of toxicity. The authors review here the development of TLI as an immunosuppressive treatment in autoimmune disease

  20. Repetitive pertussis toxin promotes development of regulatory T cells and prevents central nervous system autoimmune disease.

    Directory of Open Access Journals (Sweden)

    Martin S Weber

    Full Text Available Bacterial and viral infections have long been implicated in pathogenesis and progression of multiple sclerosis (MS. Incidence and severity of its animal model experimental autoimmune encephalomyelitis (EAE can be enhanced by concomitant administration of pertussis toxin (PTx, the major virulence factor of Bordetella pertussis. Its adjuvant effect at the time of immunization with myelin antigen is attributed to an unspecific activation and facilitated migration of immune cells across the blood brain barrier into the central nervous system (CNS. In order to evaluate whether recurring exposure to bacterial antigen may have a differential effect on development of CNS autoimmunity, we repetitively administered PTx prior to immunization. Mice weekly injected with PTx were largely protected from subsequent EAE induction which was reflected by a decreased proliferation and pro-inflammatory differentiation of myelin-reactive T cells. Splenocytes isolated from EAE-resistant mice predominantly produced IL-10 upon re-stimulation with PTx, while non-specific immune responses were unchanged. Longitudinal analyses revealed that repetitive exposure of mice to PTx gradually elevated serum levels for TGF-β and IL-10 which was associated with an expansion of peripheral CD4(+CD25(+FoxP3(+ regulatory T cells (Treg. Increased frequency of Treg persisted upon immunization and thereafter. Collectively, these data suggest a scenario in which repetitive PTx treatment protects mice from development of CNS autoimmune disease through upregulation of regulatory cytokines and expansion of CD4(+CD25(+FoxP3(+ Treg. Besides its therapeutic implication, this finding suggests that encounter of the immune system with microbial products may not only be part of CNS autoimmune disease pathogenesis but also of its regulation.

  1. Differential Expression of Glucocorticoid Receptor Noncoding RNA Repressor Gas5 in Autoimmune and Inflammatory Diseases.

    Science.gov (United States)

    Mayama, T; Marr, A K; Kino, T

    2016-08-01

    Glucocorticoids have strong regulatory actions on the immune system and act as potent therapeutic compounds for autoimmune and inflammatory diseases. We previously reported that the long noncoding RNA growth arrest-specific 5 (Gas5), which accumulates inside the cells in response to cellular starvation/growth arrest, functions as a potent repressor of the glucocorticoid receptor (GR) through its RNA "glucocorticoid response element (GRE)". To evaluate potential roles of Gas5 in immune-related disorders, we examined Gas5 RNA levels in various autoimmune, inflammatory, and infectious diseases using the microarray data available in the Gene Expression Omnibus. We found that Gas5 levels were altered in whole blood or leukocytes of the patients with rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, and sarcoidosis. Gas5 levels were also altered in infectious diseases, such as by the human immunodeficiency virus type-1 and influenza virus, and bacterial sepsis. In our experimental analysis using mice, Gas5 levels were kept at high basal levels and did not respond to fasting in immune organs, such as spleen and thymus, while its levels in metabolic organs, including liver, fat, and skeletal muscles, were low at baseline and were highly elevated upon this treatment, possibly through suppression of the mTOR pathway. These results suggest that Gas5 plays a role in the regulation of immune functions and pathogenesis/pathophysiology of autoimmune, inflammatory, and infectious diseases in part through modulation of the GR transcriptional activity via its decoy RNA "GRE". Changes in the Gas5 levels may also influence disease response to immunosuppressive glucocorticoid therapy. PMID:27214311

  2. Current practice in laboratory diagnostics of autoimmune diseases in Croatia. 
Survey of the Working group for laboratory diagnostics of autoimmune diseases of the Croatian Society of Medical Biochemistry and Laboratory Medicine

    Science.gov (United States)

    Kuna, Andrea Tešija; Đerek, Lovorka; Kozmar, Ana; Drvar, Vedrana

    2016-01-01

    Introduction With the trend of increasing incidence of autoimmune diseases, laboratories are faced with exponential growth of the requests for tests relating the diagnosis of these diseases. Unfortunately, the lack of laboratory personnel experienced in this specific discipline of laboratory diagnostic, as well as an unawareness of a method limitation often results in confusion for clinicians. The aim was to gain insight into number and type of Croatian laboratories that perform humoral diagnostics with the final goal to improve and harmonize laboratory diagnostics of autoimmune diseases in Croatia. Materials and methods In order to get insight into current laboratory practice two questionnaires, consisting of 42 questions in total, were created. Surveys were conducted using SurveyMonkey application and were sent to 88 medical biochemistry laboratories in Croatia for the first survey. Out of 33 laboratories that declared to perform diagnostic from the scope, 19 were selected for the second survey based on the tests they pleaded to perform. The survey comprised questions regarding autoantibody hallmarks of systemic autoimmune diseases while regarding organ-specific autoimmune diseases was limited to diseases of liver, gastrointestinal and nervous system. Results Response rate was high with 80 / 88 (91%) laboratories which answered the first questionnaire, and 19 / 19 (1.0) for the second questionnaire. Obtained results of surveys indicate high heterogeneity in the performance of autoantibody testing among laboratories in Croatia. Conclusions Results indicate the need of creating recommendations and algorithms in order to harmonize the approach to laboratory diagnostics of autoimmune diseases in Croatia.

  3. [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. PMID:26575109

  4. Prospective population-based study of the association between vitamin D status and incidence of autoimmune disease.

    Science.gov (United States)

    Skaaby, Tea; Husemoen, Lise Lotte Nystrup; Thuesen, Betina Heinsbæk; Linneberg, Allan

    2015-09-01

    Beside its traditional role in skeletal health, vitamin D is believed to have multiple immunosuppressant properties, and low vitamin D status has been suggested to be a risk factor in the development of autoimmune disease. We investigated the association between vitamin D status and development of autoimmune disease. We included a total of 12,555 individuals from three population-based studies with measurements of vitamin D status (25-hydroxy vitamin D). We followed the participants by linkage to the Danish National Patient Register (median follow-up time 10.8 years). Relative risks of autoimmune disease were estimated by Cox regression and expressed as hazard ratios, HRs (95 % confidence intervals CIs). There were 525 cases of incident autoimmune disease. The risk for a 10 nmol/l higher vitamin D was: for any autoimmune disease (HR = 0.94 % CI 0.90, 0.98); thyrotoxicosis (HR = 0.83, 95 % CI 0.72, 0.96); type 1 diabetes (HR = 0.95, 95 % CI 0.88, 1.02), multiple sclerosis (HR = 0.89, 95 % CI 0.74, 1.07), iridocyclitis (HR = 1.00, 95 % CI 0.86, 1.17); Crohn's disease (HR = 0.95, 95 % CI 0.80, 1.13), ulcerative colitis (HR = 0.88, 95 % CI 0.75, 1.04); psoriasis vulgaris (HR = 0.99, 95 % CI 0.86, 1.13); seropositive rheumatoid arthritis (HR = 0.97, 95 % CI 0.89, 1.07), and polymyalgia rheumatica (HR = 0.94, 95 % CI 0.83, 1.06). We found statistically significant inverse associations between vitamin D status and development of any autoimmune disease and thyrotoxicosis in particular. Our findings suggest a possible protective role of a higher vitamin D status on autoimmune disease but warrant further studies to clarify causality. PMID:25666936

  5. [Pathogenesis of thyroid eye disease - does autoimmunity against the TSH receptor explain all cases?].

    Science.gov (United States)

    Wall, Jack R; Lahooti, Hooshang

    2011-01-01

    Thyroid associated ophthalmopathy, or thyroid eye disease (TED), is a complex inflammatory disorder of the eye that, as its name implies, is usually associated with thyroid disease. Clinical observation supports the existence of three main TED subtypes, namely ocular myopathy, congestive myopathy, and mixed congestive and myopathic ophthalmopathy. Although the precise pathophysiology of TED remains unclear, it is likely to reflect an autoimmune reaction involving sensitised T lymphocytes and autoantibodies directed against a specific orbital or thyroid-and-orbital shared antigen(s). One well-studied candidate in this immune reaction is the thyroid-stimulating hormone receptor (TSHR), which is also expressed in the orbital fibroblast and preadipocyte. Most patients with ophthalmopathy have associated Graves' disease, 10% have Hashimoto's thyroiditis in which the eye changes are often mild and expressed mainly as upper eyelid retraction (UER), and 10% have no apparent associated thyroid disease - so-called "euthyroid Graves' disease". Ophthalmopathy can also occur in some patients with transient thyroiditis, thyroid cancer, and Graves' disease many years after treatment of the hyperthyroidism - situations where TSHR antibodies are not expected to be present, suggesting that the relationship between TSHR antibodies and the eye disorder has not been established for all cases. In our studies of TED we have investigated the nature and significance of antibodies targeting other eye muscle and orbital connective tissue (OCT) antigens, in particular the calcium binding protein calsequestrin (CASQ1) and the orbital fibroblast membrane antigen collagen XIII. Our working hypotheses for the pathogenesis of TED are: i) the initial reaction in the orbit is antibody and T lymphocyte targeting of the TSHR in the OCT compartment, and ii) the associated extra ocular and upper eyelid muscle inflammation reflects either autoimmunity against primary skeletal muscle antigens such as CASQ

  6. The autoimmune tautology with a focus on antiphospholipid syndrome.

    Science.gov (United States)

    Franco, J-S; Anaya, J-M

    2014-10-01

    Autoimmune diseases (ADs) are often diagnosed according to classification criteria; however, they share similar subphenotypes including signs and symptoms, non-specific autoantibodies and other immune changes, which are prone to taxonomic problems. Polyautoimmunity is defined as the presence of more than one AD in a single patient. The close relationship between antiphospholipid syndrome (APS) and systemic lupus erythematosus has been studied throughout the years. However, APS may coexist with several other ADs confirming polyautoimmunity in this systemic disease. Herein, we summarized the common characteristics shared between APS and others ADs in light of the autoimmune tautology (that is, common mechanisms of autoimmune diseases).

  7. 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 1...

  8. Identification of antigenic proteins associated with trichloroethylene-induced autoimmune disease by serological proteome analysis

    International Nuclear Information System (INIS)

    Although many studies indicated that trichloroethylene (TCE) could induce autoimmune diseases and some protein adducts were detected, the proteins were not identified and mechanisms remain unknown. To screen and identify autoantigens which might be involved in TCE-induced autoimmune diseases, three groups of sera were collected from healthy donors (I), patients suffering from TCE-induced exfoliative dermatitis (ED) (II), and the healed ones (III). Serological proteome analysis (SERPA) was performed with total proteins of TCE-treated L-02 liver cells as antigen sources and immunoglobins of the above sera as probes. Highly immunogenic spots (2-fold or above increase compared with group I) in group II and III were submitted to matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and tandem mass spectrometry sequencing. Western blot analysis was followed using commercial antibodies and individual serum. Six proteins were identified. Among them, Enoyl Coenzyme A hydratase peroxisoma 1 and lactate dehydrogenase B only showed stronger immunogenicity for group II sera, while Purine nucleoside phosphorylase, ribosomal protein P0 and proteasome activator subunit1 isoform1 also showed stronger immunogenicity for group III sera. Noteworthy, NM23 reacted only with group II sera. Western blot analysis of NM23 expression indicated that all of the individual serum of group II showed immune activity, which confirmed the validity of SERPA result. These findings revealed that there exist autoantibodies in group II and III sera. Besides, autoantibodies of the two stages of disease course were different. These autoantigens might serve as biomarkers to elucidate mechanisms underlying TCE toxicity and are helpful for diagnosis, therapy and prognosis of TCE-induced autoimmune diseases.

  9. Possible deletion of a developmentally regulated heavy-chain variable region gene in autoimmune diseases

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Pei-Ming; Olee, Tsaiwei; Kozin, F.; Carson, D.A.; Chen, P.P. (Research Institute of Scripps Clinic, La Jolla, CA (USA)); Olsen, N.J. (Vanderbilt Univ., Nashville, TN (USA)); Siminovitch, K.A. (Univ. of Toronto (Canada))

    1990-10-01

    Several autoantibody-associated variable region (V) genes are preferentially expressed during early ontogenic development, suggesting strongly that they are of developmental and physiological importance. As such, it is possible that polymorphisms in one or more of these genes may alter susceptibility to autoimmune disease. The authors have searched extensively for a probe related to a developmentally regulated V gene that has the power to differentiate among highly homologous V genes in human populations. Using such a probe (i.e., Humhv3005/P1) related to both anti-DNA and anti-IgG autoantibodies, they studied restriction fragment length polymorphisms in patients with rheumatoid arthritis and systemic lupus erythematosus and found an apparent heavy-chain V (V{sub H}) gene deletion that was nearly restricted to the autoimmune patients. These data suggest that deletions of physiologically important V{sub H} genes may increase the risk of autoimmunity through indirect effects on the development and homeostasis of the B-cell repertoire.

  10. Vitamin D metabolites as clinical markers in autoimmune and chronic disease.

    Science.gov (United States)

    Blaney, Greg P; Albert, Paul J; Proal, Amy D

    2009-09-01

    Recent research has implicated vitamin D deficiency (serum levels of 25-hydroxyvitamin D fibromyalgia and chronic fatigue syndrome. It has been assumed that low levels of 25-hydroxyvitamin D (25-D) accurately indicate vitamin D storage and vitamin D receptor (VDR)-mediated control of calcium metabolism and innate immunity. To evaluate this assumption, 25-D and 1,25-dihydroxyvitamin D3 (1,25-D) levels were measured in 100 Canadian patients with these conditions. Additionally, other inflammatory markers (CK, CRP) were measured. Results showed a strong positive association between these autoimmune conditions and levels of 1,25-D >110 pmol/L. However, there was little association with vitamin D deficiency or the other inflammatory markers, meaning that the results challenge the assumption that serum levels of 25-D are a sensitive measure of the autoimmune disease state. Rather, these findings support the use of 1,25-D as a clinical marker in autoimmune conditions. High levels of 1,25-D may result when dysregulation of the VDR by bacterial ligands prevents the receptor from expressing enzymes necessary to keep 1,25-D in a normal range. PMID:19758177

  11. What caused the increase of autoimmune and allergic diseases: A decreased or an increased exposure to luminal microbial components?

    Institute of Scientific and Technical Information of China (English)

    Xiaofa Qin

    2007-01-01

    @@ TO THE EDITOR The dramatic increase of allergic and autoimmune diseases such as asthma, atopic dermatitis (eczema), allergic rhinitis, inflammatory bowel disease (IBD, including both Crohn's disease and ulcerative colitis), multiple sclerosis,and insulin-dependent diabetes mellitus (type Ⅰ diabetes)in the developed countries in the last century[1-3] is a big puzle.

  12. Childbirths and risk of female predominant and other autoimmune diseases in a population-based Danish cohort

    DEFF Research Database (Denmark)

    Jørgensen, Kristian Tore; Pedersen, Bo Vestergaard; Nielsen, Nete Munk;

    2012-01-01

    .14-1.24), erythema nodosum (1.15; 1.01-1.32), psoriasis (1.08; 1.01-1.15), sarcoidosis (1.17; 1.06-1.28) and systemic lupus erythematosus (0.83; 0.74-0.93). Especially the one-year postpartum period was associated with an increased risk of Hashimoto thyroiditis, Graves' disease and sarcoidosis. Overall, parity......To evaluate the possible biological role of pregnancy on the risk of autoimmune diseases we assessed associations between reproductive history and subsequent risk of autoimmune diseases characterized by female predominance and other autoimmune diseases. Our study cohort comprised 4.6 million Danes...... were at a relative risk of 1.04 (1.02-1.06) for any autoimmune diseases, 1.11 (1.08-1.14) for female predominant and 0.97 (0.95-1.00) for other autoimmune diseases. Possibly biologically related associations with parity were found for Hashimoto thyroiditis (1.11; 1.00-1.24), Graves' disease (1.19; 1...

  13. Histone Posttranslational Modifications of CD4⁺ T Cell in Autoimmune Diseases.

    Science.gov (United States)

    Wang, Zijun; Yin, Heng; Lau, Chak Sing; Lu, Qianjin

    2016-01-01

    The complexity of immune system is tempered by precise regulation to maintain stabilization when exposed to various conditions. A subtle change in gene expression may be magnified when drastic changes are brought about in cellular development and function. Posttranslational modifications (PTMs) timely alter the functional activity of immune system, and work proceeded in these years has begun to throw light upon it. Posttranslational modifications of histone tails have been mentioned in a large scale of biological developments and disease progression, thereby making them a central field to investigate. Conventional assessments of these changes are centered on the transcription factors and cytokines in T cells regulated by variable histone codes to achieve chromatin remodeling, as well as involved in many human diseases, especially autoimmune diseases. We here put forward an essential review of core posttranslational modulations that regulate T cell function and differentiation in the immune system, with a special emphasis on histone modifications in different T helper cell subsets as well as in autoimmune diseases. PMID:27669210

  14. Role of soluble and cell surface molecules in the pathogenesis of autoimmune skin diseases.

    Science.gov (United States)

    Drosera, M; Facchetti, F; Landolfo, S; Mondini, M; Nyberg, F; Parodi, A; Santoro, A; Zampieri, S; Doria, A

    2006-01-01

    The skin is one of the most commonly involved tissue in rheumatic autoimmune diseases. Different mechanisms are thought to be implicated in the pathogenesis of skin lesions. In genetically predisposed individuals, ultraviolet (UV) light can contribute to the induction of skin lesions via an inflammatory process. UV light promotes the release of cytokines by keratinocytes and the induction of adhesion molecules on the surface of epidermal cells initiating a cascade of inflammatory events and recruiting immunoinflammatory cells into the skin. In this review data regarding the expression of TNF-alpha in lesional skin tissue from subacute cutaneous lupus erythematosus patients and the role of interferons in the pathogenesis of skin manifestations of rheumatic autoimmune diseases are reported. In addition, an overview on the expression of cellular adhesion molecules in these diseases is provided.UV light can also induce apoptosis in keratinocytes. During this cell death several enzymes became activated. Among them, desoxyribonuclease (DNase) is an enzyme involved in degrading DNA during apoptosis. Data regarding the activity of DNAse in patients with cutaneous lupus erythematosus as a possible risk factor for the development of systemic disease are here reported. PMID:16466628

  15. Regulations of Gene Expression in Medullary Thymic Epithelial Cells Required for Preventing the Onset of Autoimmune Diseases

    OpenAIRE

    Akiyama, Taishin; Shinzawa, Miho; Qin, Junwen; Akiyama, Nobuko

    2013-01-01

    Elimination of potential self-reactive T cells in the thymus is crucial for preventing the onset of autoimmune diseases. Epithelial cell subsets localized in thymic medulla [medullary thymic epithelial cells (mTECs)] contribute to this process by supplying a wide range of self-antigens that are otherwise expressed in a tissue-specific manner (TSAs). Expression of some TSAs in mTECs is controlled by the autoimmune regulator (AIRE) protein, of which dysfunctional mutations are the causative fac...

  16. Antinuclear antibodies in rheumatic disease: a proposal for a function-based classification.

    Science.gov (United States)

    Pisetsky, D S

    2012-09-01

    Antinuclear antibodies (ANAs) are a diverse group of autoantibodies that bind macromolecular components of the cell nucleus. While some ANAs occur in normal individuals, others are expressed almost exclusively in patients with rheumatic disease and serve as markers for diagnosis and prognosis. Despite the clinical associations of ANAs, the relationship of these antibodies to specific disease manifestations is often unknown because the target antigens are intracellular molecules that are ubiquitously expressed. In systemic lupus erythematosus, the role of ANAs in disease manifestations is better understood, especially for antibodies to DNA and related nucleosomal antigens. These antibodies can promote nephritis by the formation of immune complexes that are deposited in the kidney. In addition, anti-DNA, along with antibodies to RNA-binding proteins such as anti-Sm, can induce non-specific immune abnormalities based on the induction of type interferon 1 by plasmacytoid dendritic cells. Despite ANA expression in rheumatic disease, studies in animal models of inflammation and tissue injury indicate that antibodies to certain nuclear molecules such as HMGB1 have protective effects. Together, these considerations suggest a function-based classification of ANAs based on their expression in normal and autoimmune individuals as well as their capacity to induce or attenuate immunological disturbances. This classification provides a framework to elucidate the serological features of rheumatic disease and the often uncertain relationship between ANA expression and disease manifestations.

  17. Autoimmune disease

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    2008016 Clinicopathological study of two subtypes of diffuse proliferative lupus nephritis. ZHENG Zhaohui(郑朝晖),et al. Dept Nephrol, 1st Affili Hosp, Zhengzhou Univ , Zhengzhou 450052. Chin J Nephrol 2007;23(11):696-699. Objective To investigate the clinicopathological characteristics and outcome of two subtypes of class Ⅳ lupus nephritis (LN).

  18. Autoimmune disease

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    2010294 A study of T cell recombination excision circles levels in peripheral blood mononuclear cells of systemic lupus erythematosus patients. DU Zhenyan(杜臻雁),et al.Dept Rheumatol,PUMC & CAMS,Beijing 100032. Chin J Intern Med 2010;49(6):500-503. Objective To

  19. Autoimmune Disease

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    2009154 Expression of cellular FLICE inhibitory proteins in peripheral blood B lymphocytes in patients with systemic lupus erythematosus.DONG Jing(董婧),et al.Dept Dermatol,Wuhan 1st Hospital,Wuhan 430030.Chin J Dermatol,2009;42(4):226-229.

  20. Autoimmune disease

    Institute of Scientific and Technical Information of China (English)

    1997-01-01

    970238 Determination and significance of glucocorti-cold receptor level of leukocyte in patients with sys-temic lupus erythematosus. ZHANG xian(张献), etal. 1st Affili Hosp, Henan Med Univ, Zhengzhou,450052. Chin J Nephrol 1997; 13(1):37-39. Objective: To study the level of glucocorticoid recep-tor(GCR)in patients with systemic lupus erythemato-

  1. Autoimmune Disease

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    2007159 Acute kidney injury of systemic sclerosis: scleroderma renal crisis and crescentic glomerulonephritis. LIU Dongyan(刘冬妍), et al. Dept Nephrol, PUMC Hosp, CAMS & PUMC, Beijin 100730. Chin J Nephrol 2007;23(4):209-203. Objective To explore the clinicopathological characteristics of acute kidney injury (AKI) of systemic sclerosis (SSc). Methods A retrospective study was performed on 11 SSc patients with AKI. The clinical data were analyzed and the patients were divided into antineutrophil cytoplasmic antibodies (ANCA) negative group(n=9) and ANCA positive(n=2) group. Results In the ANCA negative group, 2 cases were without malignant hypertension, 1 was acute tubular necrosis(ATN) caused by herbs, 6 were scleroderma renal crisis(SRC), including 4 with renal biopsy, indicating hypertrophic arterial media, edema, thickened intima, onion-skin lesion in interlobular arteries and afferent arterioles, as well as ischemic lesion in glomeruli. In the MPO-ANCA positive group, 1 was crescentic glomerulonephritis. Malignant hypertension was not noticed. All patients were given steroid, 8 of them received CTX in addition. Nine patients received dialysis, and 8 cases progressed to permanent hemodialysis. Six cases with SRC were given high dose ACEI and / or ARB. Six patients resulted in early death. Conclusion Scleroderma renal crisis and ANCA associated vasculitis may cause AKI in SSc patients. Patients with positive ANCA differ from those with negative ANCA in terms of clinical manifestation, pathology and treatment. Survival and prognosis of SSc patient were bad. High dose corticosteroids increases the risk of scleroderma renal crisis, so it is thereby recommended that the dose above 15 rog/day should be avoided if possible.

  2. Autoimmune disease

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    2008249 Role of gonadotropin releasing hormone analogues for ovarian protection in systemic lupus erythematosus patients treated with cyclophosphamide.LIANG Liuqin(梁柳琴),et al.Dept Rheumatol Clin Immunol,1st Affili Hosp Sun Yat-sen Univ,Guangzhou 510080.Natl Med J Chin 2008;88(15):1009-1011.Objective To evaluate the effectiveness of gonadotropin releasing hormone analogues(GnRH-a)in protection against premature ovarian failure during cyclophosphamide(CTX)

  3. The influence of cyclosporin A on experimental autoimmune thyroid disease in the rat

    International Nuclear Information System (INIS)

    Female PVG/c rats, thymectomised on weaning and given 4 courses of whole body irradiation to a total dose of 1000 rads, developed experimental autoimmune thyroid disease (EAITD) as assessed by histological evidence of thyroiditis and circulating levels of antithyroglobulin antibodies. Hypothyroidism resulted. Induction of the disease was associated with a highly significant fall in T lymphocyte numbers. Eight weeks after their last dose of irradiation the animals commenced treatment with cyclosporin A (10 mg/kg rat/day, intragastrically) and were treated for varying time intervals thereafter. The reversal of the T lymphocyte helper: suppressor ratio on cyclosporin A therapy was associated with a significant improvement in the disease process. The alterations in the T cell subsets and in the disease lasted only as long as the drug was administered and thereafter reverted towards that seen in the control groups of animals receiving no treatment

  4. Autoimmune synaptopathies.

    Science.gov (United States)

    Crisp, Sarah J; Kullmann, Dimitri M; Vincent, Angela

    2016-02-01

    Autoantibodies targeting proteins at the neuromuscular junction are known to cause several distinct myasthenic syndromes. Recently, autoantibodies targeting neurotransmitter receptors and associated proteins have also emerged as a cause of severe, but potentially treatable, diseases of the CNS. Here, we review the clinical evidence as well as in vitro and in vivo experimental evidence that autoantibodies account for myasthenic syndromes and autoimmune disorders of the CNS by disrupting the functional or structural integrity of synapses. Studying neurological and psychiatric diseases of autoimmune origin may provide new insights into the cellular and circuit mechanisms underlying a broad range of CNS disorders. PMID:26806629

  5. Childhood malignancy and maternal diabetes or other auto-immune disease during pregnancy

    OpenAIRE

    Westbom, L; Åberg, A; Källén, B

    2002-01-01

    Among 4380 children born in 1987–1997 of women with a diagnosis of diabetes and alive at the age of one, 10 were registered in the Swedish Cancer Registry before the end of 1998. The odds ratio for having a childhood cancer after maternal diabetes, stratified for year of birth, maternal age, parity, multiple birth, and 500 g birth weight class was 2.25 (95%CI 1.22–4.15). Among 5842 children born during the period 1973–1997 whose mothers had other auto-immune diseases (SLE, rheumatoid arthriti...

  6. Association between STAT4 Gene Polymorphisms and Autoimmune Thyroid Diseases in a Chinese Population

    Directory of Open Access Journals (Sweden)

    Ni Yan

    2014-07-01

    Full Text Available The STAT4 gene encodes a transcriptional factor that transmits signals induced by several key cytokines which play important roles in the development of autoimmune diseases. The aim of this study was to explore the association of STAT4 polymorphism with Graves’ disease (GD and Hashimoto’s thyroiditis (HT. A total of 1048 autoimmune thyroid diseases (AITDs patients (693 with GD and 355 with HT and 909 age- and gender-matched controls were examined. STAT4 polymorphisms (rs7574865/rs10181656/ rs7572482 were genotyped by multiplex polymerase chain reaction (PCR and ligase detection reaction (LDR. The results indicated that the frequencies of rs7574865 genotypes in patients with GD differed significantly from the controls (p = 0.028, the T allele frequency of GD patients was also significantly higher than the controls (p = 0.020. The genotypes of rs10181656 differed significantly in GD patients from controls (p = 0.012; G allele frequencies were significantly higher in AITD patients than the controls (p = 0.014 and 0.031, respectively. The frequencies of haplotype GC with GD and HT patients were significantly lower than their controls (p = 0.015 and 0.030, respectively. In contrast, the frequencies of haplotype TG with GD and HT patients were significantly higher than their controls (p = 0.016 and 0.048, respectively. These findings strongly suggest that STAT4 rs7574865/rs10181656 polymorphisms increase the risk of AITD in a Chinese population.

  7. Oxidative post-translational modifications and their involvement in the pathogenesis of autoimmune diseases

    Directory of Open Access Journals (Sweden)

    Brent J. Ryan

    2014-01-01

    Full Text Available Tissue inflammation results in the production of numerous reactive oxygen, nitrogen and chlorine species, in addition to the products of lipid and sugar oxidation. Some of these products are capable of chemically modifying amino acids. This in turn results in changes to the structure and function of proteins. Increasing evidence demonstrates that such oxidative post-translational modifications result in the generation of neo-epitopes capable of eliciting both innate and adaptive immune responses. In this paper, we focus on how free radicals and related chemical species generated in inflammatory environments modulate the antigenicity of self-proteins, resulting in immune responses which involve the generation of autoantibodies against key autoantigens in autoimmune diseases. As examples, we will focus on Ro-60 and C1q in systemic lupus erythematosus, along with type-II collagen in rheumatoid arthritis. This review also covers some of the emerging literature which demonstrates that neo-epitopes generated by oxidation are conserved, as exemplified by the evolutionarily conserved pathogen-associated molecular patterns (PAMPs. We discuss how these observations relate to the pathogenesis of both human autoimmune diseases and inflammatory disease, such as atherosclerosis. The potential for these neo-epitopes and the immune responses against them to act as biomarkers or therapeutic targets is also discussed.

  8. Comparative assessment of the prevalence of periodontal disease in subjects with and without systemic autoimmune diseases: A case–control study

    Directory of Open Access Journals (Sweden)

    S G Ramesh Kumar

    2016-01-01

    Full Text Available Background: Immune mechanism shares a common pathway both for systemic autoimmune diseases and periodontal diseases. Scientific exploration of literature revealed limited studies on the association between systemic autoimmune diseases and periodontal diseases in India. Aim: The aim of the study is to find whether the presence of systemic autoimmune diseases in an individual is a risk factor for the development of periodontal disease. Settings and Design: This was a hospital-based case–control study. Materials and Methods: A sample of 253 patients with systemic autoimmune diseases, attending the Rheumatology Department of Government General Hospital, Chennai-3, and 262 patients without systemic autoimmune diseases, attending the outpatient department of the Tamil Nadu Government Dental College and Hospital, Chennai-3, constituted the case and control groups, respectively. Age, gender, and oral hygiene status matching was done. Oral hygiene status was assessed using oral hygiene index (OHI and periodontal status was assessed using community periodontal index (CPI and loss of attachment (LOA index. Statistical Analysis: Statistical analysis was done using SPSS version 15 (SPSS Inc, 2006, Chicago. Results: Results showed 99.2% and 73.9% prevalence of gingivitis and periodontitis, respectively, in the case group as compared to 85.5% and 14.9%, respectively, in the control group. There is no linear relationship between OHI scores and prevalence of periodontitis (CPI and LOA scores in the case group. Patients suffering from systemic autoimmune diseases showed more prevalence of periodontal diseases irrespective of oral hygiene scores. Conclusion: It is postulated that the presence of systemic autoimmune diseases may pose a risk for the development of periodontal diseases.

  9. Enterocolitis induced by autoimmune targeting of enteric glial cells: A possible mechanism in Crohn's disease?

    Science.gov (United States)

    Cornet, Anne; Savidge, Tor C.; Cabarrocas, Julie; Deng, Wen-Lin; Colombel, Jean-Frederic; Lassmann, Hans; Desreumaux, Pierre; Liblau, Roland S.

    2001-11-01

    Early pathological manifestations of Crohn's disease (CD) include vascular disruption, T cell infiltration of nerve plexi, neuronal degeneration, and induction of T helper 1 cytokine responses. This study demonstrates that disruption of the enteric glial cell network in CD patients represents another early pathological feature that may be modeled after CD8+ T cell-mediated autoimmune targeting of enteric glia in double transgenic mice. Mice expressing a viral neoself antigen in astrocytes and enteric glia were crossed with specific T cell receptor transgenic mice, resulting in apoptotic depletion of enteric glia to levels comparable in CD patients. Intestinal and mesenteric T cell infiltration, vasculitis, T helper 1 cytokine production, and fulminant bowel inflammation were characteristic hallmarks of disease progression. Immune-mediated damage to enteric glia therefore may participate in the initiation and/or the progression of human inflammatory bowel disease.

  10. Autoimmune diseases, gastrointestinal disorders and the microbiome in schizophrenia: more than a gut feeling.

    Science.gov (United States)

    Severance, Emily G; Yolken, Robert H; Eaton, William W

    2016-09-01

    Autoimmunity, gastrointestinal (GI) disorders and schizophrenia have been associated with one another for a long time. This paper reviews these connections and provides a context by which multiple risk factors for schizophrenia may be related. Epidemiological studies strongly link schizophrenia with autoimmune disorders including enteropathic celiac disease. Exposure to wheat gluten and bovine milk casein also contribute to non-celiac food sensitivities in susceptible individuals. Co-morbid GI inflammation accompanies humoral immunity to food antigens, occurs early during the course of schizophrenia and appears to be independent from antipsychotic-generated motility effects. This inflammation impacts endothelial barrier permeability and can precipitate translocation of gut bacteria into systemic circulation. Infection by the neurotropic gut pathogen, Toxoplasma gondii, will elicit an inflammatory GI environment. Such processes trigger innate immunity, including activation of complement C1q, which also functions at synapses in the brain. The emerging field of microbiome research lies at the center of these interactions with evidence that the abundance and diversity of resident gut microbiota contribute to digestion, inflammation, gut permeability and behavior. Dietary modifications of core bacterial compositions may explain inefficient gluten digestion and how immigrant status in certain situations is a risk factor for schizophrenia. Gut microbiome research in schizophrenia is in its infancy, but data in related fields suggest disease-associated altered phylogenetic compositions. In summary, this review surveys associative and experimental data linking autoimmunity, GI activity and schizophrenia, and proposes that understanding of disrupted biological pathways outside of the brain can lend valuable information regarding pathogeneses of complex, polygenic brain disorders. PMID:25034760

  11. Evaluation of shared genetic susceptibility loci between autoimmune diseases and schizophrenia based on genome-wide association studies

    DEFF Research Database (Denmark)

    Hoeffding, Louise K; Rosengren, Anders; Thygesen, Johan H;

    2016-01-01

    BACKGROUND: Epidemiological studies have documented higher than expected comorbidity (or, in some cases, inverse comorbidity) between schizophrenia and several autoimmune disorders. It remains unknown whether this comorbidity reflects shared genetic susceptibility loci. AIMS: The present study...... aimed to investigate whether verified genome wide significant variants of autoimmune disorders confer risk of schizophrenia, which could suggest a common genetic basis. METHODS: Seven hundred and fourteen genome wide significant risk variants of 25 autoimmune disorders were extracted from the NHGRI GWAS...... catalogue and examined for association to schizophrenia in the Psychiatric Genomics Consortium schizophrenia GWAS samples (36,989 cases and 113,075 controls). RESULTS: Two independent loci at 4q24 and 6p21.32-33 originally identified from GWAS of autoimmune diseases were found genome wide associated...

  12. Prevalence of collagen VII-specific autoantibodies in patients with autoimmune and inflammatory diseases

    Directory of Open Access Journals (Sweden)

    Licarete Emilia

    2012-04-01

    Full Text Available Abstract Background Autoimmunity to collagen VII is typically associated with the skin blistering disease epidermolysis bullosa acquisita (EBA, but also occurs occasionally in patients with systemic lupus erythematosus or inflammatory bowel disease. The aim of our present study was to develop an accurate immunoassay for assessing the presence of autoantibodies against collagen VII in large cohorts of patients and healthy donors. Methods Based on in silico antigenic analysis and previous wetlab epitope mapping data, we designed a chimeric collagen VII construct containing all collagen VII epitopes with higher antigenicity. ELISA was performed with sera from patients with EBA (n = 50, Crohn's disease (CD, n = 50, ulcerative colitis (UC, n = 50, bullous pemphigoid (BP, n = 76, and pemphigus vulgaris (PV, n = 42 and healthy donors (n = 245. Results By ELISA, the receiver operating characteristics analysis yielded an area under the curve of 0.98 (95% CI: 0.9638-1.005, allowing to set the cut-off at 0.32 OD at a calculated specificity of 98% and a sensitivity of 94%. Running the optimized test showed that serum IgG autoantibodies from 47 EBA (94%; 95% CI: 87.41%-100%, 2 CD (4%; 95% CI: 0%-9.43%, 8 UC (16%; 95% CI: 5.8%-26%, 2 BP (2.63%; 95% CI: 0%-6.23%, and 4 PV (9.52%; 95% CI: 0%-18.4% patients as well as from 4 (1.63%; 95% CI: 0%-3.21% healthy donors reacted with the chimeric protein. Further analysis revealed that in 34%, 37%, 16% and 100% of sera autoantibodies of IgG1, IgG2, IgG3, and IgG4 isotype, respectively, recognized the recombinant autoantigen. Conclusions Using a chimeric protein, we developed a new sensitive and specific ELISA to detect collagen specific antibodies. Our results show a low prevalence of collagen VII-specific autoantibodies in inflammatory bowel disease, pemphigus and bullous pemphigoid. Furthermore, we show that the autoimmune response against collagen VII is dominated by IgG4 autoantibodies. The new immunoassay should

  13. AKT isoforms modulate Th1-like Treg generation and function in human autoimmune disease.

    Science.gov (United States)

    Kitz, Alexandra; de Marcken, Marine; Gautron, Anne-Sophie; Mitrovic, Mitja; Hafler, David A; Dominguez-Villar, Margarita

    2016-08-01

    Foxp3(+) regulatory T cells (Tregs) exhibit plasticity, which dictates their function. Secretion of the inflammatory cytokine IFNγ, together with the acquisition of a T helper 1 (Th1)-like effector phenotype as observed in cancer, infection, and autoimmune diseases, is associated with loss of Treg suppressor function through an unknown mechanism. Here, we describe the signaling events driving the generation of human Th1-Tregs. Using a genome-wide gene expression approach and pathway analysis, we identify the PI3K/AKT/Foxo1/3 signaling cascade as the major pathway involved in IFNγ secretion by human Tregs. Furthermore, we describe the opposing roles of AKT isoforms in Th1-Treg generation ex vivo Finally, we employ multiple sclerosis as an in vivo model with increased but functionally defective Th1-Tregs. We show that the PI3K/AKT/Foxo1/3 pathway is activated in ex vivo-isolated Tregs from untreated relapsing-remitting MS patients and that blockade of the pathway inhibits IFNγ secretion and restores the immune suppressive function of Tregs. These data define a fundamental pathway regulating the function of human Tregs and suggest a novel treatment paradigm for autoimmune diseases. PMID:27312110

  14. Autoimmune blistering diseases of the pemphigus group = Enfermedades ampollosas autoinmunes del grupo de los pénfigos

    Directory of Open Access Journals (Sweden)

    Juliana Calle Isaza

    2014-07-01

    Full Text Available Autoimmune blistering diseases of the pemphigus group Blisters may appear in many dermatological diseases, but they are not necessarily of autoimmune etiology. For the study of blistering diseases, it is necessary to take into account the clinical aspects, the history of when and how blisters appeared, the epidemiological and histological information (for instance, the skin level at which blisters are located, and whether inflammatory infiltrates are present. In order to corroborate the autoimmune etiology of blisters, it is important to have the results of confirmatory tests such as direct and indirect immunofluorescence, immune blotting, enzyme-linked immune-assay (ELISA, immune precipitation, and electronic microscopy. Information on autoantibodies serum titers may help to conduct a more precise immunosuppressive therapy.

  15. Alterations of TH1/TH2 reactivity by heavy metals: possible consequences include induction of autoimmune diseases.

    Science.gov (United States)

    Hemdan, Nasr Y A; Emmrich, Frank; Faber, Sonya; Lehmann, Joerg; Sack, Ulrich

    2007-08-01

    Heavy metal pollution still represents a primary concern regarding human health. Recently, it become evident that the contribution of heavy metals extends far beyond their accepted role in allergic diseases, and that they may play a more extensive role in a variety of other diseases. Several lines of evidence indicate that heavy metals have a key role in the induction or exacerbation of several autoimmune diseases (AD). Moreover, the association between exposure to heavy metals and the signs of autoimmunity are supported by some studies. The mechanisms by which heavy metals induce the development of AD are not yet fully understood. Our objective here is to highlight the association of exposure to some heavy metals and AD. In addition, we present recent results showing the possible alterations in Th1/Th2 reactivity by some heavy metals, which may constitute the trigger for the incidence of autoimmunity in susceptible individuals.

  16. Involvement of endocrine system in a patient affected by glycogen storage disease 1b: speculation on the role of autoimmunity.

    Science.gov (United States)

    Melis, Daniela; Della Casa, Roberto; Balivo, Francesca; Minopoli, Giorgia; Rossi, Alessandro; Salerno, Mariacarolina; Andria, Generoso; Parenti, Giancarlo

    2014-03-19

    Glycogen storage disease type 1b (GSD1b) is an inherited metabolic defect of glycogenolysis and gluconeogenesis due to mutations of the SLC37A4 gene and to defective transport of glucose-6-phosphate. The clinical presentation of GSD1b is characterized by hepatomegaly, failure to thrive, fasting hypoglycemia, and dyslipidemia. Patients affected by GSD1b also show neutropenia and/or neutrophil dysfunction that cause increased susceptibility to recurrent bacterial infections. GSD1b patients are also at risk for inflammatory bowel disease. Occasional reports suggesting an increased risk of autoimmune disorders in GSD1b patients, have been published. These complications affect the clinical outcome of the patients. Here we describe the occurrence of autoimmune endocrine disorders including thyroiditis and growth hormone deficiency, in a patient affected by GSD1b. This case further supports the association between GSD1b and autoimmune diseases.

  17. A Classification System for Peri-implant Diseases and Conditions.

    Science.gov (United States)

    Sarmiento, Hector L; Norton, Michael R; Fiorellini, Joseph P

    2016-01-01

    Peri-implant bone levels are influenced by pathologic and nonpathologic conditions. The understanding of peri-implant disease has evolved over the past several decades, and the classification of peri-implantitis has been limited to descriptions of disease progression or those involving soft and/or hard tissues (peri-implant mucositis or peri-implantitis). However, no classification system has been established based on etiology. The objective of this study was to identify various etiologies for peri-implantitis and to establish a classification system based on the pathogenesis. The results indicate that the majority of bone loss was related to biofilm, followed by iatrogenic factors, exogenous irritants, absence of keratinized tissue, and extrinsic pathology. The proposed classification system will allow the clinician to properly diagnose peri-implant diseases in relation to etiology. These conditions may respond differently to applied therapies. PMID:27560674

  18. 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...

  19. Perspectives on autoimmunity

    Energy Technology Data Exchange (ETDEWEB)

    Cohen, I.R.

    1987-01-01

    The contents of this book are: HLA and Autoimmunity; Self-Recognition and Symmetry in the Immune System; Immunology of Insulin Dependent Diabetes Mellitus; Multiple Sclerosis; Autoimmunity and Immune Pathological Aspects of Virus Disease; Analyses of the Idiotypes and Ligand Binding Characteristics of Human Monoclonal Autoantibodies to DNA: Do We Understand Better Systemic Lupus Erythematosus. Autoimmunity and Rheumatic Fever; Autoimmune Arthritis Induced by Immunization to Mycobacterial Antigens; and The Interaction Between Genetic Factors and Micro-Organisms in Ankylosing Spondylitis: Facts and Fiction.

  20. Time for the endocrinologists to expand their awareness of and contribution to the diagnosis and management of encephalopathy associated with autoimmune thyroid disease.

    LENUS (Irish Health Repository)

    Tamagno, Gianluca

    2011-01-01

    Encephalopathy associated with autoimmune thyroid disease is a rare condition presenting in the setting of autoimmune thyroid disease and characterized by unspecific neurological and\\/or psychiatric symptoms. Bearing in mind the currently prevailing lack of consensus on the most appropriate nomenclature and diagnostic criteria for this condition and the implications that this lack undeniably has on clinical practice, it is obvious that an international and multidisciplinary agreement among clinicians should arrive at the most appropriate definition and terminology of encephalopathy occurring in patients with autoimmune thyroid disease. Concomitantly, efforts must be made to uncover the pathogenetic link between thyroid autoimmunity and the occurrence of encephalopathy.

  1. Time for the endocrinologists to expand their awareness of and contribution to the diagnosis and management of encephalopathy associated with autoimmune thyroid disease.

    LENUS (Irish Health Repository)

    Tamagno, Gianluca

    2012-02-01

    Encephalopathy associated with autoimmune thyroid disease is a rare condition presenting in the setting of autoimmune thyroid disease and characterized by unspecific neurological and\\/or psychiatric symptoms. Bearing in mind the currently prevailing lack of consensus on the most appropriate nomenclature and diagnostic criteria for this condition and the implications that this lack undeniably has on clinical practice, it is obvious that an international and multidisciplinary agreement among clinicians should arrive at the most appropriate definition and terminology of encephalopathy occurring in patients with autoimmune thyroid disease. Concomitantly, efforts must be made to uncover the pathogenetic link between thyroid autoimmunity and the occurrence of encephalopathy.

  2. A nationwide study on the risk of autoimmune diseases in individuals with a personal or a family history of schizophrenia and related psychosis

    DEFF Research Database (Denmark)

    Benros, Michael E; Pedersen, Marianne G; Rasmussen, Helle;

    2014-01-01

    -like psychosis and 142,328 individuals with autoimmune disease. Data were analyzed using survival analysis and adjusted for calendar year, age, and sex. RESULTS: Individuals with schizophrenia had an elevated risk of subsequent autoimmune diseases, with an incidence rate ratio of 1.53 (95% CI=1.46-1.62). Among...... persons without hospital contacts for infections, the effect of having schizophrenia was smaller, with an increased incidence rate ratio of 1.32 (95% CI=1.22-1.43) for autoimmune diseases. For individuals with schizophrenia as well as hospital contacts for infections, the combined risk of autoimmune...

  3. A case of cholestatic autoimmune hepatitis and acute liver failure: an unusual hepatic manifestation of mixed connective tissue disease and Sjögren's syndrome.

    OpenAIRE

    Min, J. K.; Han, N. I.; Kim, J. A; Lee, Y. S.; Cho, C.S.; Kim, H. Y.

    2001-01-01

    Although hepatomegaly is reported to occur occasionally in patients with mixed connective tissue disease (MCTD) or Sjögren's syndrome (SS), autoimmune liver diseases such as primary biliary cirrhosis, sclerosing cholangitis, and autoimmune hepatitis in association with MCTD or SS have rarely been described. We report a case of severe cholestatic autoimmune hepatitis presenting with acute liver failure in a 40-yr-old female patient suffering from MCTD and SS. The diagnosis of MCTD and SS was m...

  4. Prevalence of celiac disease autoimmunity in children with type 1 diabetes

    DEFF Research Database (Denmark)

    Adlercreutz, Emma H; Svensson, Jannet; Hansen, Dorthe;

    2015-01-01

    OBJECTIVES: The aim was to determine the prevalence of celiac disease autoimmunity in children with type 1 diabetes (T1D) diagnosed in Denmark and Sweden. METHODS: A total of 662 Swedish children with T1D were matched with 1080 Danish children with T1D and 309 healthy children from Sweden and 283...... was equally distributed among 89 children with T1D positive for both IgAG-DGP/tTG and IgG-tTG. CONCLUSION: The discrepancy in levels of IgAG-DGP/tTG and IgG-tTG between Swedish and Danish T1D cohorts was independent of HLA and suggests that regional variations in comorbidity of celiac disease in T1D is caused...

  5. Autoimmune pulmonary proteinosis in a Chilean teenager, a rare aetiology of interstitial lung disease.

    Science.gov (United States)

    Strickler, Alexis; Boza, Maria Lina; Koppmann, Andres; Gonzalez, Sergio

    2014-05-23

    Interstitial lung disease (ILD) is rare and encompasses a heterogeneous group of diseases, and is even rarer in children than in adults. ILDs compromise more than 100 different entities, including pulmonary alveolar proteinosis (PAP). There are many causes of PAP in children, including surfactant protein gene mutations (SFTPB, SFTPC, ABCA3, TTF-1), GMCSF receptor mutations and antigranulocyte-macrophage colony-stimulating factor autoantibodies. We report a case of a 13-year-old Chilean girl who presented with an 8-month history of progressive exercise intolerance, fatigability and diminished school performance. Physical examination revealed resting tachypnoea, a few basal bilateral inspiratory crackles, and hypoxaemia on minimal exertion. Clinical suspicion and evaluation, including international collaboration, led to the diagnosis of autoimmune PAP and specific therapy for the condition.

  6. Design of a Computer-Assisted System to Automatically Detect Cell Types Using ANA IIF Images for the Diagnosis of Autoimmune Diseases.

    Science.gov (United States)

    Cheng, Chung-Chuan; Lu, Chun-Feng; Hsieh, Tsu-Yi; Lin, Yaw-Jen; Taur, Jin-Shiuh; Chen, Yung-Fu

    2015-10-01

    Indirect immunofluorescence technique applied on HEp-2 cell substrates provides the major screening method to detect ANA patterns in the diagnosis of autoimmune diseases. Currently, the ANA patterns are mostly inspected by experienced physicians to identify abnormal cell patterns. The objective of this study is to design a computer-assisted system to automatically detect cell patterns of IIF images for the diagnosis of autoimmune diseases in the clinical setting. The system simulates the functions of modern flow cytometer and provides the diagnostic reports generated by the system to the technicians and physicians through the radar graphs, box-plots, and tables. The experimental results show that, among the IIF images collected from 17 patients, 6 were classified as coarse-speckled, 3 as diffused, 2 as discrete-speckled, 1 as fine-speckled, 2 as nucleolar, and 3 as peripheral patterns, which were consistent with the patterns determined by the physicians. In addition to recognition of cell patterns, the system also provides the function to automatically generate the report for each patient. The time needed for the whole procedure is less than 30 min, which is more efficient than the manual operation of the physician after inspecting the ANA IIF images. Besides, the system can be easily deployed on many desktop and laptop computers. In conclusion, the designed system, containing functions for automatic detection of ANA cell pattern and generation of diagnostic report, is effective and efficient to assist physicians to diagnose patients with autoimmune diseases. The limitations of the current developed system include (1) only a unique cell pattern was considered for the IIF images collected from a patient, and (2) the cells during the process of mitosis were not adopted for cell classification. PMID:26289629

  7. Induction of Graves' disease in patients with non-autoimmune hyperthyroidism or nontoxic goiter after radioiodine treatment

    International Nuclear Information System (INIS)

    Thyrotropin receptors antibodies may occur and induce Graves' disease (GD) several months after radioiodine therapy in a small number of patients with non-autoimmune hyperthyroidism or nontoxic goiter. The prevalence of radiation-induced GD is between 0.05% and 5%. The hypothesis of this disease includes induction by autoimmune reaction and others. Detection of the thyroid autoantibodise or of 99mTc pertechnetate scan can forecast the appearance of GD. Antithyroid drugs, again radioiodine therapy and surgery are the treatments. (authors)

  8. Successful treatment with Ipilimumab and Interleukin‑2 in two patients with metastatic melanoma and systemic autoimmune disease

    DEFF Research Database (Denmark)

    Pedersen, Magnus; Andersen, Rikke; Larsen, Peter Nørgaard;

    2014-01-01

    Two patients were treated with immunotherapy for metastatic malignant melanoma (MM) despite suffering from systemic autoimmune disease, i.e., ulcerative colitis (UC) and Behcets disease (BD), respectively. Both patients benefitted from the treatment. The patient with UC achieved partial remission...... exclusion criterion for treatment of MM with immunotherapy. Consequently, given the poor prognosis of refractory MM, immunotherapies need to be taken into consideration even in cases of autoimmune comorbidity due to the potential long-term benefit that these therapies offer to MM patients....

  9. High prevalence of hypovitaminosis D of patients with autoimmune rheumatic diseases in China

    Science.gov (United States)

    Zheng, Zhao-Hui; Gao, Cong-Cong; Wu, Zhen-Zhen; Liu, Sheng-Yun; Li, Tian-Fang; Gao, Guan-Min; Liu, Zhang-Suo

    2016-01-01

    We aimed to determine the prevalence of hypovitaminosis D in patients with autoimmune rheumatic diseases (ARDs) in China and its association with demographic characteristics of the patients. We recruited 384 patients in this cross-sectional study including 121 cases of systemic lupus erythematosus (SLE), 131 rheumatoid arthritis (RA), 102 spondyloarthritis (SpA) and 30 other ARDs. For each patient, demographic information was collected and serum concentration of 25OHD3 was measured by electrochemiluminescence immunoassay (ECLIA). The multivariate logistic regression model was used to investigate the association between vitamin D deficiency and patient characteristics. The mean serum vitamin D level of the 384 patients was 18.91 (8.12) ng/mL, and the median age was 37.33 (12.01) yrs. Among these patients, 222 (57.81%) and 127 (33.07%) were found to be vitamin D deficiency and insufficiency, respectively. From the disease perspective, the percentages of insufficiency and deficiency were as follow: 97.52% and 84.30% in SLE, 87.02% and 48.85% in RA, 88.24% and 40.20% in SpA, 90.89% and 57.81% in other ARDs patients. The causative factors for vitamin D deficiency included SLE per se (OR 12.54, P vitamin D deficiency (OR 0.95, P = 0.005). No correlation was disclosed between vitamin D deficiency and gender or disease duration. Hypovitaminosis D is highly prevalent among autoimmune rheumatic diseases population in China. The SLE per se and the obesity are the risk factors for vitamin D deficiency. Clinicians are advised to supplement vitamin D in these patients. PMID:27335701

  10. A PILOT TRIAL FOR SEVERE,REFRACTORY SYSTEMIC AUTOIMMUNE DISEASE WITH STEM CELL TRANSPLANTATION

    Institute of Scientific and Technical Information of China (English)

    Xiao-mei Leng; Yi Dong; Fu-lin Tang; Yan Zhao; Dao-bing Zhou; Huifen Situ; Tai-sheng Li; Ti Shen; Yong-qiang Zhao; Xiao-feng Zeng; Feng-chun Zhang

    2005-01-01

    Objective To evaluate the feasibility, efficacy, and safety of high dose immunosuppressive therapy (HDIT) and autolo gous hemopoietic stem cell transplantation (HSCT) with CD34+ cell selection in patients with severe, refractory autoim mune diseases.Methods Twenty-six patients with persistent systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), primary Sjogren's syndrome (Pss), or systemic sclerosis (SSc) who had been treated unsuccessfully with conventional treatment were enrolled in the trial in Peking Union Medical College Hospital from September 1999 to June 2004. The patients received HDIT with 200 mg/kg cyclophosphamide followed by an infusion of autologous stem cells that were CD34 selected. Disease activity, adverse effect, hemopoietic and immune reconstitution, and time to recurrence of disease were monitored. Results Overall treatment related mortality was 7.7% (2/26) with 1 patient died of cytomegalovirus infection and an other of severe pneumonia. Relapse occurred in 3 SLE patients (17.6%) in 37, 26, and 19 months posttransplantation respectively, and 1 RA patient in 15 months posttransplantation. SLE Disease Activity Index (SLEDAI) scores of SLE survivors decreased significantly (P < 0.01). RA patients recorded a drop of Disease Activity Score 28 (DAS 28). The pSS patient remained symptoms free up to now, more than 50 months after the transplantation.Conclusion HSCT can be performed relative safely in patients with severe autoimmune disease. Short-term effect of HSCT is promising. However treatment related mortality and relapse were observed in a subset of patients.

  11. Performance of the Montreal classification for inflammatory bowel diseases

    NARCIS (Netherlands)

    Spekhorst, Lieke M.; Visschedijk, Marijn C.; Alberts, Rudi; Festen, Eleonora A.; van der Wouden, Egbert-Jan; Dijkstra, Gerard; Weersma, Rinse K.

    2014-01-01

    AIM: To validate the Montreal classification system for Crohn's disease (CD) and ulcerative colitis (UC) within the Netherlands. METHODS: A selection of 20 de-identified medical records with an appropriate representation of the inflammatory bowel disease (IBD) sub phenotypes were scored by 30 observ

  12. 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 1...... 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....

  13. Circulating macrophage activation markers, CD163 and CD206, are associated with disease severity and treatment response in patients with autoimmune hepatitis

    DEFF Research Database (Denmark)

    Grønbæk, Henning; Kazankov, Konstantin; Jessen, Niels;

    Circulating macrophage activation markers, CD163 and CD206, are associated with disease severity and treatment response in patients with autoimmune hepatitis......Circulating macrophage activation markers, CD163 and CD206, are associated with disease severity and treatment response in patients with autoimmune hepatitis...

  14. Circulating activated T cell subsets in autoimmune thyroid diseases: differences between untreated and treated patients.

    Science.gov (United States)

    Ohashi, H; Okugawa, T; Itoh, M

    1991-11-01

    To investigate the relationships between lymphocyte subsets and thyroid function, peripheral blood lymphocytes were analysed with cell surface antigens of activated (HLA-DR+) T, helper T (CD4+ 2H4-, CD4+ 4B4+) and suppressor-inducer T (CD4+ 2H4+, CD4+ 4B4-) cells subsets in 56 patients with Graves' disease, 16 patients with Hashimoto's thyroiditis, 7 patients with typical subacute thyroiditis and 2 patients with the thyrotoxic phase of autoimmune thyroiditis. Both patients with Graves' disease and Hashimoto's thyroiditis had increased percentages of HLA-DR+ T (Ia+ CD3+) cells as well as HLA-DR+ helper-inducer T (Ia+ CD4+) cells, which seemed to be independent of treatments. The percentage of HLA-DR+ suppressor-cytotoxic T (Ia+ CD8+) cells was increased in euthyroid or hypothyroid patients with Graves' disease following treatment, but was normal in hyperthyroid patients. The percentages of Ia+ CD4+ cells and Ia+ CD8+ were also increased in patients with thyroiditis, whereas these abnormal values normalized in the remission phase. These findings suggest that an increase in Ia+ CD4+ cells characteristically occurs during immune system activation in patients with hyperthyroid Graves' disease, Hashimoto's thyroiditis and the thyrotoxic phase of subacute thyroiditis, whereas the activated CD8+ cells in Graves' disease are induced by antithyroidal therapy. PMID:1684685

  15. Immunopathological events initiated and maintained by pathogenic IgG autoantibodies in an experimental autoimmune kidney disease.

    Science.gov (United States)

    Barabas, Arpad Zsigmond; Cole, Chad Douglas; Lafreniere, Rene; Weir, Donald Mackay

    2012-11-01

    The experimental models of Heymann nephritis (HN) and slowly progressive Heymann nephritis (SPHN) give us rare opportunities to investigate the etiologies and pathogenesis of two immunopathological processes in rats leading to: (1) autoimmune disease, where the autoimmune disease HN and SPHN is initiated and maintained by cross-reactive pathogenic IgG autoantibodies (aabs) directed against the renal proximal convoluted tubules' brush border (BB) cells - where the nephritogenic antigen (ag) is produced and localized - damaging and releasing BB associated nephritogenic ag into the circulation which in turn contributes to continuation of the autoimmune disease; and (2) immune complex glomerulonephritis, where the glomerular injury is initiated, proceeding into a chronic progressive disease by depositing immune complexes (ICs) - made up of a glomerular epithelial cell produced endogenous nephritogenic ag and the developing pathogenic IgG aab directed against the nephritogenic ag, and complement components - on the epithelial side of the glomerular basement membrane. We also observed how the normally functioning immune system is able to avert autoimmune disease developments by circulating specific non-pathogenic IgM aabs clearing the system of intracytoplasmic ags released from cells at the end of their life spans or following damage by toxic agents. We also described how an autoimmune disease SPHN can be prevented and when present terminated by the implementation of a new vaccination technique we have developed and call modified vaccination technique. By increasing the specific IgM aab production against the native nephritogenic ag - by injecting ICs made up of: [nephritogenic ag X homologous anti-nephritogenic ag IgM ab] in slight ag excess into SPHN rats - pathogenic IgG aab producing native and modified nephritogenic ags were removed from the circulation and termination of the autoimmune disease causing immune events was achieved. Even though HN and SPHN are not

  16. The innate immune response affects the development of the autoimmune response in Theiler’s virus- induced demyelinating disease

    OpenAIRE

    Olson, Julie K.; Miller, Stephen D.

    2009-01-01

    Multiple sclerosis (MS) is a human CNS autoimmune demyelinating disease. Epidemiological evidence has suggested a role for virus infection in the initiation and/or exacerbation of MS. Theiler’s murine encephalomyelitis virus (TMEV)- induced demyelinating disease serves as a relevant mouse model for MS. TMEV- infected mice develop a demyelinating disease with clinical symptoms beginning around 35 days post infection which is associated with development of myelin- specific, PLP139–151, CD4+ T c...

  17. Thyrotropin - Binding Inhibiting Immunoglobulin (TBII) in Patients with Autoimmune Thyroid Diseases

    International Nuclear Information System (INIS)

    In order to evaluate the significance of thyrotropin-binding inhibiting immunoglobulin (TBII) in the patients with autoimmune thyroid diseases, the authors investigated 402 cases of Graves' disease and 230 cases of Hashimoto's thyroiditis comparing 30 cases of normal healthy adult at Kyung Pook University Hospital from February 1993 to August 1994. The TBII was tested by radioimmunoassay and assessed on the dynamic change with the disease course, thyroid functional parameters, and other thyroid autoantibodies; antithyroglobulin antibody(ATAb) and antimicrosomal antibody(AMAb) including thyroglobulin. The serum level of TBII was 40.82 ± 21.651(mean ± SD)% in hyperthyroid Graves' disease and 8.89 ± 14.522% in Hashimoto's thyroiditis and both were significant different from normal control of which was 3.21 ± 2.571%. The frequency of abnormally increased TBII level was 92.2% in hyperthyroid Craves' disease, 46.7% in euthyroid Graves' disease or remission state of hyperthyroidism, and 23.9% in Hashimoto's thyroiditis. The serum levels of increased TBII in Graves' disease were positively correlated with RAIU, serum T3, T4, and FT4, but negatively correlated with serum TSH(each p<0.001). The TBII in Graves' disease had significant positive correlation with serum thyroglobulin and AMAb, but no significant correlation with ATAb. In the Hashimoto's thyroiditis, the serum levels of TBII were positively correlated with RAIU, serum T3, TSH and AMAb, but not significantly correlated with serum T4, FT4, thyroglobulin and ATAb. Therefore serum level of TBII seemed to be a useful mean of assessing the degree of hyperthyroidism in Graves' disease and correlated well with thyroidal stimulation. The serum level of TBII in Hashimoto's thyroiditis is meaningful for the degree of both functional abnormality reflecting either hyperfunction or hypofunction and the immunologic abnormality.

  18. Primary sclerosing cholangitis, autoimmune hepatitis and overlap syndromes in inflammatory bowel disease

    Institute of Scientific and Technical Information of China (English)

    Rebecca Saich; Roger Chapman

    2008-01-01

    Primary sclerosing cholangitis (PSC) is a chronic progressive disorder of unknown aetiology characterised by chronic inflammation and stricture formation of the biliary tree. Symptoms include itch and lethargy and in advanced cases cholangitis and end-stage liver disease, however increasing numbers of asymptomatic individuals are being identified. The disease is rare in the general population but is strongly associated with inflammatory bowel disease (IBD) affecting up to 5% of patients with Ulcerative Colitis, with a slightly lower prevalence (up to 3.6%) in Crohns disease. The strength of this association means that the vast majority (> 90%) of patients with PSC also have IBD, although many may have only mild gastro-intestinal symptoms. Usually IBD presents before PSC, although vice-versa can occur and the onset of both conditions can be separated in some cases by many years. Mean age of diagnosis of PSC is in the fifth decade of life with a strong male predominance.Risk is increased in those with a family history of PSC, suggesting a genetic predisposition and the disease is almost exclusive to non-smokers. The ulcerative colitis associated with PSC is characteristically mild, runs a quiescent course, is associated with rectal sparing, more severe right sided disease, backwash ilieitis and has a high risk of pouchiUs post-colectomy. Most worrisome is the high risk of colorectal malignancy which necessitates routine colonoscopic surveillance. Cholangiocarcinoma is also a frequent complication of PSC with a 10%-15% lifetime risk of developing this condition. Treatment with high dose ursodeoxycholic acid offers some chemoprotective effects against colorectal malignancy and may decrease symptoms, biochemical and histological progression of liver disease. Small duct PSC patients characteristically have normal cholangiography, and liver biopsy is required for diagnosis, it appears to have a more favourable prognosis. Autoimmune Hepatitis (AIH) is also more prevalent

  19. Exploring the genetics underlying autoimmune diseases with network analysis and link prediction

    KAUST Repository

    Alanis Lobato, Gregorio

    2014-02-01

    Ever since the first Genome Wide Association Study (GWAS) was carried out we have seen an important number of discoveries of biological and clinical relevance. However, there are some scientists that consider that these research outcomes and their utility are far from what was expected from this experimental design. We instead believe that the thousands of genetic variants associated with complex disorders by means of GWASs are an extremely valuable source of information that needs to be mined in a different way. Based on this philosophy, we followed a holistic perspective to analyze GWAS data and explored the structural properties of the network representation of one of these datasets with the aim to advance our understanding of the genetic intricacies underlying autoimmune human diseases. The simplicity, computational efficiency and precision of the tools proposed in this paper represent a new means to address GWAS data and contribute to the better exploitation of these rich sources of information. © 2014 IEEE.

  20. Autoimmune encephalitis mimicking sporadic Creutzfeldt-Jakob disease: A retrospective study.

    Science.gov (United States)

    Chen, Yu; Xing, Xiao-Wei; Zhang, Jia-Tang; Wang, Ruo-Xi; Zhao, Wei; Tan, Qing-Che; Liu, Ruo-Zhuo; Wang, Xiang-Qing; Huang, Xu-Sheng; Yu, Sheng-Yuan

    2016-06-15

    Autoimmune encephalitis associated with anti-voltage-gated potassium channel antibodies are most likely to be misdiagnosed as sporadic Creutzfeldt-Jakob disease (sCJD). Our goal was to delineate patients who were initially suspected to have CJD but were later found to have AE. We performed a retrospective clinical review of cases of individuals and made a comparison between groups of patients diagnosed with sCJD and AE. Patients who had rapidly progressing dementia and focal neurological impairment, such as aphasia, gait disturbance, visual disturbance, and depression, at onset were diagnosed with sCJD, whereas epilepsy, hyponatremia and dysautonomia were strong hints for AE. Fluoroscope-positron emission tomography (PET) of patients with AE revealed variable metabolism and normative and long-term immunosuppression were less likely to relapse. PMID:27235341