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Sample records for acquired autoimmune disease

  1. Understanding Autoimmune Diseases

    MedlinePlus

    ... Autoimmune Diseases Progress and Promise Key Words The Immune System Your immune system is the network of cells and tissues throughout ... having two parts: the acquired and the innate immune systems. The acquired (or adaptive) immune system develops as ...

  2. The autoimmune diseases

    SciTech Connect

    Rose, N.R.; Mackay, I.R.

    1985-01-01

    This book contains 25 chapters. Some of the chapter titles are: Genetic Predisposition to Autoimmune Diseases; Systemic Lupus Erythematosus; Autoimmune Aspects of Rheumatoid Arthritis; Immunology of Insulin-Dependent Diabetes; and Adrenal Autoimmunity and Autoimmune Polyglandular Syndromes.

  3. Autoimmune liver disease panel

    MedlinePlus

    Liver disease test panel - autoimmune ... Autoimmune disorders are a possible cause of liver disease. The most common of these diseases are autoimmune hepatitis and primary biliary cirrhosis. This group of tests helps your health care provider ...

  4. Autoimmune Inner Ear Disease

    MedlinePlus

    ... Find an ENT Doctor Near You Autoimmune Inner Ear Disease Autoimmune Inner Ear Disease Patient Health Information ... with a hearing loss. How Does the Healthy Ear Work? The ear has three main parts: the ...

  5. Acquired hemophilia A associated with IgG4-related lung disease in a patient with autoimmune pancreatitis.

    PubMed

    Sugino, Keishi; Gocho, Kyoko; Ishida, Fumiaki; Kikuchi, Naoshi; Hirota, Nao; Sato, Keita; Sano, Go; Isobe, Kazutoshi; Sakamoto, Susumu; Takai, Yujiro; Hata, Yoshinobu; Shibuya, Kazutoshi; Uekusa, Toshimasa; Kurosaki, Atsuko; Homma, Sakae

    2012-01-01

    Immunoglobulin G4 (IgG4)-related lung diseases can occur in patients with autoimmune pancreatitis (AIP). However, the causal relationship between AIP and acquired hemophilia A (AH) is unknown. We herein report the first case of AH associated with IgG4-related lung disease that developed in a patient with AIP. A 65-year-old asymptomatic man with a history of AIP and sclerosing cholangitis diagnosed at the age of 57 was admitted to our hospital due to an abnormal reticulonodular shadow on chest X-ray. An examination of lung biopsy specimens revealed IgG4-positive plasma cell infiltration in the interstitium. The serum IgG4 level was elevated. One year later, the patient developed a progressive severe hematoma in the left femoral muscle. On admission, laboratory examinations revealed severe anemia with a markedly prolonged activated partial prothrombin time, a decreased level of factor VIII (FVIII) activity, and the existence of anti-FVIII antibodies. These findings were consistent with a diagnosis of AH. No relapse has been observed over the past 25 months, during which time, corticosteroid therapy has been continuously administered.

  6. [Interferons and autoimmune diseases].

    PubMed

    Niino, Masaaki; Miyazaki, Yusei

    2013-11-01

    Interferons are widely expressed cytokines that have potent antiviral, antiproliferative, and immunomodulatory effects. Type I interferons show complex biology; in some cases, they promote autoimmunity and inflammation, and in other cases, exhibit homeostatic functions by controlling inflammation and tissue destruction. This complexity is exemplified in the 2 major autoimmune diseases: systemic lupus erythematosus, in which type I interferons play an important role in the pathogenesis, and multiple sclerosis, in which interferon beta, a type I interferon, exhibits protective and therapeutic roles. This article reviews the basic clinical data on type I interferons in autoimmune diseases and type I interferons as potential targets for therapies in autoimmune diseases.

  7. American Autoimmune Related Diseases Association

    MedlinePlus

    ... With #25FOR25 Campaign During National Autoimmune Disease Awareness Month AARDA officially kicks of National Autoimmune Disease Awareness ... Click here to read more. Autoimmune Disease Awareness Month AARDA and the NCAPG held two important events ...

  8. Autoimmune diseases and vaccinations.

    PubMed

    Vial, Thierry; Descotes, Jacques

    2004-01-01

    The potential association between vaccination and autoimmune diseases has been largely questioned in the past few years, but this assumption has mostly been based on case reports. The available evidence derived from several negative epidemiological studies is reassuring and at least indicates that vaccines are not a major cause of autoimmune diseases. However, there are still uncertainties as to whether a susceptible subpopulation may be at a higher risk of developing an autoimmune disease without causing an overall increase in the disease incidence. Based on selected examples, this review highlights the difficulties in assessing this issue. We suggest that a potential link between vaccines and autoimmune diseases cannot be definitely ruled out and should be carefully explored during the development of new candidate vaccines. PMID:15196997

  9. Autoimmune disease and pregnancy.

    PubMed

    Jones, W R

    1994-06-01

    Autoimmune diseases are relatively common in women, and tend to occur in the childbearing years. These disorders fall broadly into two groups: (i) Multisystem diseases such as systemic lupus erythematosus (SLE) and related connective tissue disorders (CTD). This group includes the 'pre-clinical' antiphospholipid or lupus obstetric syndrome which may first manifest itself as a pregnancy disorder causing recurrent abortion, fetal death, fetal growth retardation and early onset severe pre-eclampsia. (ii) Tissue- or organ-specific disorders such as autoimmune thrombocytopaenic purpura (ATP), autoimmune thyroid disease (Graves' disease, Hashimoto's autoimmune thyroiditis, and post-postum thyroiditis), autoimmune haemolytic anaemia, and the very rare myasthenia gravis. The study of autoimmune diseases against the background of pregnancy as an experimental system of nature has provided important insights into the nature of the disease processes and the relevance or otherwise of circulating autoantibodies to pathological effects. Thus, for example, if neonatal manifestations of adult disease are causally related to the transfer of autoantibodies across the placenta, they will disappear over a time course consistent with the catabolism of IgG, providing no permanent damage is produced. Conversely, if autoantibodies are demonstrable in the neonate, in the absence of clinical effects, they may only be an epiphenomenon of the maternal disease. In addition, on occasions, disease manifestations may be seen in the baby when the mother shows none. This may occur when the mother is in remission, but still has circulating antibodies, or when she has an occult form of the disease.(ABSTRACT TRUNCATED AT 250 WORDS)

  10. Sirolimus for Autoimmune Disease of Blood Cells

    ClinicalTrials.gov

    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

  11. Epigenomics of autoimmune diseases.

    PubMed

    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. Galectin-3 in autoimmunity and autoimmune diseases

    PubMed Central

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

    2015-01-01

    Galectin-3 (gal-3) is a β-galactoside-binding lectin, which regulates cell–cell and extracellular interactions during self/non-self-antigen recognition and cellular activation, proliferation, differentiation, migration and apoptosis. It plays a significant role in cellular and tissue pathophysiology by organizing niches that drive inflammation and immune responses. Gal-3 has some therapeutic potential in several diseases, including chronic inflammatory disorders, cancer and autoimmune diseases. Gal-3 exerts a broad spectrum of functions which differs according to its intra- or extracellular localization. Recombinant gal-3 strategy has been used to identify potential mode of action of gal-3; however, exogenous gal-3 may not reproduce the functions of the endogenous gal-3. Notably, gal-3 induces monocyte–macrophage differentiation, interferes with dendritic cell fate decision, regulates apoptosis on T lymphocytes and inhibits B-lymphocyte differentiation into immunoglobulin secreting plasma cells. Considering the influence of these cell populations in the pathogenesis of several autoimmune diseases, gal-3 seems to play a role in development of autoimmunity. Gal-3 has been suggested as a potential therapeutic agent in patients affected with some autoimmune disorders. However, the precise role of gal-3 in driving the inflammatory process in autoimmune or immune-mediated disorders remains elusive. Here, we reviewed the involvement of gal-3 in cellular and tissue events during autoimmune and immune-mediated inflammatory diseases. PMID:26142116

  13. Rituximab in autoimmune diseases

    PubMed Central

    Randall, Katrina L

    2016-01-01

    SUMMARY Rituximab is a monoclonal antibody that depletes B cells from the circulation. It was originally used to treat lymphoma but is increasingly used for the treatment of autoimmune diseases. Rituximab was found to be effective in randomised controlled trials for rheumatoid arthritis, granulomatosis with polyangiitis and other antineutrophil cytoplasmic antibody-associated vasculitides. However, evidence of efficacy is very limited for many other autoimmune conditions. Before starting rituximab, it is important to check the patient’s baseline immunoglobulins and immunisation status. Patients should also be screened for latent infections and other contraindications. PMID:27756976

  14. Endothelial damage and autoimmune diseases.

    PubMed

    Kaplan, Mariana J

    2009-11-01

    This issue of Autoimmunity reviews the mechanisms that lead to vascular damage in systemic autoimmune diseases. In addition, this issue explores recent advances in the understanding of how abnormalities in angiogenesis present in autoimmune diseases may lead to tissue damage and/or to premature vascular disease.

  15. Autoimmune thyroid disease: an expanding spectrum.

    PubMed

    Fisher, D A; Pandian, M R; Carlton, E

    1987-08-01

    Autoimmune thyroid disease classically has included Hashimoto's thyroiditis and Graves' disease. Hashimoto's thyroiditis probably also includes focal thyroiditis, fibrous thyroiditis, primary myxedema, and Hashitoxicosis as variants. Graves' disease is associated with ophthalmopathy and dermopathy, and recent evidence suggests that these manifestations are autoimmune phenomena as well. Other associated autoimmune disorders include idiopathic thrombocytopenic purpura and antigen-antibody complex nephritis. Nonthyroid endocrine autoimmune deficiency disorders also have been classified as part of the spectrum of thyroid autoimmune disease. With the recent recognition of the spectrum of autoimmune mechanisms and antibody types and methods to distinguish antibody functions or types, our understanding of postpartum and neonatal thyroid disorders has been advanced considerably. The spectrum of neonatal thyroid disorders in the infants of women with autoimmune disease relates to the levels and types of antithyroid antibodies acquired from the mother. Finally, there is suggestive evidence that nonspecific goiter, including simple adolescent goiter and multinodular goiter as well as some cases of sporadic cretinism, may be part of an even more expanded spectrum of autoimmune thyroid disease.

  16. Autoimmune Addison's disease.

    PubMed

    Napier, Catherine; Pearce, Simon H S

    2012-12-01

    Addison's disease is a rare autoimmune disorder. In the developed world, autoimmune adrenalitis is the commonest cause of primary adrenal insufficiency, where the majority of patients have circulating antibodies against the key steroidogenic enzyme 21-hydroxylase. A complex interplay of genetic, immunological and environmental factors culminates in symptomatic adrenocortical insufficiency, with symptoms typically developing over months to years. Biochemical evaluation and further targeted investigations must confirm primary adrenal failure and establish the underlying aetiology. The diagnosis of adrenocortical insufficiency will necessitate lifelong glucocorticoid and mineralocorticoid replacement therapy, aiming to emulate physiological patterns of hormone secretion to achieve well-being and good quality of life. Education of patients and healthcare professionals is essential to minimise the risk of a life-threatening adrenal crisis, which must be promptly recognised and aggressively managed when it does occur. This article provides an overview of our current understanding of the natural history and underlying genetic and immunological basis of this condition. Future research may reveal novel therapeutic strategies for patient management. Until then, optimisation of pharmacological intervention and continued emphasis on education and empowerment of patients should underpin the management of individuals with autoimmune Addison's disease.

  17. [Hydroxychloroquine for autoimmune diseases].

    PubMed

    Danza, Álvaro; Graña, Diego; Goñi, Mabel; Vargas, Andrea; Ruiz-Irastorza, Guillermo

    2016-02-01

    Hydroxychloroquine (HCQ) is by far the most frequently used antimalarial for the management of Systemic Autoimmune Diseases. It has immunomodulatory, hypolipidemic, hypoglycemic and antithrombotic properties and it diminishes the risk of malignancies. The most important mechanisms to explain the immunomodulatory actions are its ability to reduce inflammatory pathways and Toll-like receptors activation. The safety profile is favorable. In spite of its low frequency, retinal toxicity is potentially severe. In systemic lupus erythematous HCQ therapy reduces activity, the accrual of organ damage, risk of infections and thrombosis and improves the cardiometabolic profile. It contributes to induce lupus nephritis remission, spares steroid use and increases survival rates. In rheumatoid arthritis, it improves cardiometabolic risk and has a favorable effect in joint inflammation. In Sjögren's syndrome, an increased lacrimal quality as well as an improvement in objective and subjective inflammatory markers has been demonstrated with HCQ. In Antiphospholipid Syndrome, HCQ is effective in primary and secondary thrombosis prevention. The effectiveness of the drug in other systemic autoimmune diseases is less established. HCQ therapy may improve dermatological manifestations in Dermatomyositis and may have a positive effects in the treatment of Sarcoidosis and Still disease. PMID:27092678

  18. Autoimmune muscle disease.

    PubMed

    Mammen, Andrew

    2016-01-01

    Patients with polymyositis (PM), dermatomyositis (DM), and immune-mediated necrotizing myopathy (IMNM) present with the subacute onset of symmetric proximal muscle weakness, elevated muscle enzymes, myopathic findings on electromyography, and autoantibodies. DM patients are distinguished by their cutaneous manifestations. Characteristic features on muscle biopsy include the invasion of nonnecrotic muscle fibers by T cells in PM, perifascicular atrophy in DM, and myofiber necrosis without prominent inflammation in IMNM. Importantly, these are regarded as autoimmune diseases and most patients respond partially, if not completely, to immunosuppressive therapy. Patients with inclusion body myositis (IBM) usually present with the insidious onset of asymmetric weakness in distal muscles (e.g., wrist flexors, and distal finger flexors), often when more proximal muscle groups are relatively preserved. Although IBM muscle biopsies usually have focal invasion of myofibers by lymphocytes, the majority of IBM biopsies also include rimmed vacuoles. While most IBM patients do have autoantibodies, treatment with immunosuppressive agents does not improve their clinical course. Along with the presence of abnormally aggregated proteins on muscle biopsy, the refractory nature and relentless course of IBM suggest that the underlying pathophysiology may include a dominant myodegenerative component. This chapter will focus on the epidemiology, clinical presentation, and treatment of the autoimmune myopathies and IBM. An emphasis will be placed on recent advances, indicating that these are a diverse family of diseases and that each of more than a dozen myositis autoantibodies is associated with a distinct clinical phenotype. PMID:27112692

  19. Autoimmunity and dysmetabolism of human acquired immunodeficiency syndrome.

    PubMed

    Huang, Yan-Mei; Hong, Xue-Zhi; Xu, Jia-Hua; Luo, Jiang-Xi; Mo, Han-You; Zhao, Hai-Lu

    2016-06-01

    Acquired immunodeficiency syndrome (AIDS) remains ill-defined by lists of symptoms, infections, tumors, and disorders in metabolism and immunity. Low CD4 cell count, severe loss of body weight, pneumocystis pneumonia, and Kaposi's sarcoma are the major disease indicators. Lines of evidence indicate that patients living with AIDS have both immunodeficiency and autoimmunity. Immunodeficiency is attributed to deficits in the skin- and mucosa-defined innate immunity, CD4 T cells and regulatory T cells, presumably relating human immunodeficiency virus (HIV) infection. The autoimmunity in AIDS is evident by: (1) overproduction of autoantibodies, (2) impaired response of CD4 cells and CD8 cells, (3) failure of clinical trials of HIV vaccines, and (4) therapeutic benefits of immunosuppression following solid organ transplantation and bone marrow transplantation in patients at risk of AIDS. Autoantibodies are generated in response to antigens such as debris and molecules de novo released from dead cells, infectious agents, and catabolic events. Disturbances in metabolic homeostasis occur at the interface of immunodeficiency and autoimmunity in the development of AIDS. Optimal treatments favor therapeutics targeting on the regulation of metabolism to restore immune homeostasis.

  20. Autoimmune diseases and myelodysplastic syndromes.

    PubMed

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

    2016-05-01

    Immune dysregulation and altered T-cell hemostasis play important roles in the pathogenesis of myelodysplastic syndromes (MDS). Recent studies suggest an increased risk of MDS among patients with autoimmune diseases. Here, we investigated the prevalence of autoimmune diseases among MDS patients, comparing characteristics and outcomes in those with and without autoimmune diseases. From our study group of 1408 MDS patients, 391 (28%) had autoimmune disease, with hypothyroidism being the most common type, accounting for 44% (n = 171) of patients (12% among all MDS patients analyzed). Other autoimmune diseases with ≥5% prevalence included idiopathic thrombocytopenic purpura in 12% (n = 46), rheumatoid arthritis in 10% (n = 41), and psoriasis in 7% (n = 28) of patients. Autoimmune diseases were more common in female MDS patients, those with RA or RCMD WHO subtype, and those who were less dependent on red blood cell transfusion. Median overall survival (OS) was 60 months (95% CI, 50-70) for patients with autoimmune diseases versus 45 months (95% CI, 40-49) for those without (log-rank test, P = 0.006). By multivariate analysis adjusting for revised IPSS and age >60 years, autoimmune diseases were a statistically significant independent factor for OS (HR 0.78; 95% CI, 0.66-0.92; P = 0.004). The rate of acute myeloid leukemia (AML) transformation was 23% (n = 89) in MDS patients with autoimmune disease versus 30% (n = 301) in those without (P = 0.011). Patient groups did not differ in response to azacitidine or lenalidomide treatment. Autoimmune diseases are prevalent among MDS patients. MDS patients with autoimmune diseases have better OS and less AML transformation. PMID:26875020

  1. Autoimmune diseases and myelodysplastic syndromes.

    PubMed

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

    2016-05-01

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

  2. Mast Cell and Autoimmune Diseases

    PubMed Central

    Xu, Yunzhi; Chen, Guangjie

    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. PMID:25944979

  3. Mast cell and autoimmune diseases.

    PubMed

    Xu, Yunzhi; Chen, Guangjie

    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. PMID:25944979

  4. Autoantibodies in autoimmune liver diseases.

    PubMed

    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. Polyglandular autoimmune diseases in a dermatological clinical setting: vitiligo-associated autoimmune diseases.

    PubMed

    Amerio, Paolo; Di Rollo, Daniela; Carbone, Angelo; Auriemma, Matteo; Marra, Maria Elena; De Remigis, Pierluigi; Feliciani, Claudio; Tracanna, Marco; Tulli, Antonio

    2010-01-01

    Vitiligo is an acquired hypomelanotic disorder characterized by depigmented macules resulting from the loss of functional melanocytes. Many different etiological hypotheses have been suggested for vitiligo, the most recent of which involves a combination of interacting environmental and genetic factors. Among the various pieces of evidence in support of an autoimmune origin of vitiligo, there is the epidemiological association with several autoimmune diseases. The most frequently reported association is with autoimmune thyroiditis; however, other diseases such as rheumatoid arthritis, diabetes mellitus, pernicious anemia and chronic urticaria have been described in variable percentages, depending upon the genetics of the population studied. Among the diseases described in association with vitiligo there are the so-called autoimmune polyglandular syndromes (APS). Here we report 31 cases of APS diagnosed in 113 vitiligo patients, according to the newest classification. Autoimmune association was more present in generalized non segmental vitiligo and was more frequent in females. The most frequent association was with thyroid autoimmune disease, followed by autoimmune gastritis and alopecia areata. ANA positivity was similar to that reported previously in the general population. We stress the importance of an assessment for autoimmune diseases in vitiligo patients. PMID:20395193

  6. Progesterone and Autoimmune Disease

    PubMed Central

    Hughes, Grant C.

    2011-01-01

    Sexual dimorphism in human immune systems is most apparent in the female predominance of certain autoimmune diseases (ADs) like systemic lupus erythematosus (SLE). Epidemiologic, observational and experimental evidence strongly suggest sex steroids are important modulators of genetic risk in human AD. In this regard, the roles of progesterone (Pg), an immunomodulatory female sex steroid, are poorly understood. Several lines of investigation indicate Pg and synthetic progestins impact risk of AD and immune-mediated injury in different ways depending on their concentrations and their engagement of various Pg receptors expressed in immune organs, immune cells or tissues targeted by immune attack. At low physiologic levels, Pg may enhance interferon-alpha (IFN-α) pathways important in SLE pathogenesis. Commonly used synthetic progestins may have the opposite effect. At pregnancy levels, Pg may suppress disease activity in rheumatoid arthritis (RA) and multiple sclerosis (MS) via inhibition of T helper type 1 (Th1) and Th17 pathways and induction of anti-inflammatory molecules. Importantly, Pg’s immunomodulatory effects differ from those of estrogens and androgens. An additional layer of complexity arises from apparent interdependence of sex hormone signaling pathways. Identifying mechanisms by which Pg and other sex steroids modulate risk of AD and immune-mediated injury will require clarification of their cellular and molecular targets in vivo. These future studies should be informed by recent genetic discoveries in human AD, particularly those revealing their sex-specific genetic associations. PMID:22193289

  7. Sex differences in autoimmune diseases

    PubMed Central

    2011-01-01

    Women are more susceptible to a variety of autoimmune diseases including systemic lupus erythematosus (SLE), multiple sclerosis (MS), primary biliary cirrhosis, rheumatoid arthritis and Hashimoto's thyroiditis. This increased susceptibility in females compared to males is also present in animal models of autoimmune diseases such as spontaneous SLE in (NZBxNZW)F1 and NZM.2328 mice, experimental autoimmune encephalomyelitis (EAE) in SJL mice, thyroiditis, Sjogren's syndrome in MRL/Mp-lpr/lpr mice and diabetes in non-obese diabetic mice. Indeed, being female confers a greater risk of developing these diseases than any single genetic or environmental risk factor discovered to date. Understanding how the state of being female so profoundly affects autoimmune disease susceptibility would accomplish two major goals. First, it would lead to an insight into the major pathways of disease pathogenesis and, secondly, it would likely lead to novel treatments which would disrupt such pathways. PMID:21208397

  8. Estrogens and autoimmune diseases.

    PubMed

    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

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

    PubMed

    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.

  10. Cardiovascular disease biomarkers across autoimmune diseases.

    PubMed

    Ahearn, Joseph; Shields, Kelly J; Liu, Chau-Ching; Manzi, Susan

    2015-11-01

    Cardiovascular disease is increasingly recognized as a major cause of premature mortality among those with autoimmune disorders. There is an urgent need to identify those patients with autoimmune disease who are at risk for CVD so as to optimize therapeutic intervention and ultimately prevention. Accurate identification, monitoring and stratification of such patients will depend upon a panel of biomarkers of cardiovascular disease. This review will discuss some of the most recent biomarkers of cardiovascular diseases in autoimmune disease, including lipid oxidation, imaging biomarkers to characterize coronary calcium, plaque, and intima media thickness, biomarkers of inflammation and activated complement, genetic markers, endothelial biomarkers, and antiphospholipid antibodies. Clinical implementation of these biomarkers will not only enhance patient care but also likely accelerate the pharmaceutical pipeline for targeted intervention to reduce or eliminate cardiovascular disease in the setting of autoimmunity.

  11. A Report of Three Cases With Acquired Generalized Lipodystrophy With Distinct Autoimmune Conditions Treated With Metreleptin

    PubMed Central

    Lebastchi, Jasmin; Ajluni, Nevin; Neidert, Adam

    2015-01-01

    Context: Acquired generalized lipodystrophy (AGL) is associated with leptin deficiency as a result of adipose tissue loss and hypertriglyceridemia, insulin resistance, and hepatic steatosis. It may coexist with other autoimmune diseases such as Hashimoto's thyroiditis, rheumatoid arthritis, hemolytic anemia, and chronic active hepatitis. Metreleptin therapy has been shown to improve metabolic abnormalities in lipodystrophy, but the effect on AGL patients with active autoimmune disease is unknown. Case Description: We report 3 cases of pediatric patients with AGL and distinct active autoimmune diseases who were treated with metreleptin over a period of 4–6 years. Case 1 is a 9-year-old girl with active juvenile dermatomyositis, who was successfully treated with leptin with no worsening of her dermatomoysitis. Case 2 is a 16-year-old female with Graves' disease, who could discontinue all her antidiabetic medication completely with improved triglyceride levels. Case 3 is an 11-year-old boy with active autoimmune hepatitis and chronic urticaria, whose hyperphagia has resolved and his liver enzymes and hepatosplenomegaly have improved. Conclusion: Metreleptin therapy is of considerable clinical benefit to reduce insulin resistance and hypertriglyceridemia and did not appear to alter the clinical course of autoimmune disease nor clinical efficacy of immunosuppressive treatments. Our observations suggest that risk or presence of autoimmune disease should not lead to withholding of metreleptin treatment from patients with AGL, but should prompt close clinical follow up in light of cautionary preclinical data. PMID:26390101

  12. Autoimmune diseases and reproductive aging

    PubMed Central

    Bove, Riley

    2013-01-01

    As the population ages, more individuals with autoimmune diseases are experiencing reproductive senescence. Understanding the impact of menopause and age-related androgen decline on disease onset and course, as well as the potential for hormonal interventions, is critically important. In men, lupus erythematosis (SLE), rheumatoid arthritis (RA), and multiple sclerosis (MS) are associated with lower androgen levels. However, the impact of age-related declines in testosterone, as well as of testosterone replacement, on disease course remains underexplored. In women, the course of all three diseases with onset after the age of menopause differs from that with onset before menopause. Early age at menopause is associated with increased disease risk, and after menopause, disease course changes in SLE and RA. Less is known about MS. This article summarizes what is known about the relationship between reproductive aging and autoimmune diseases in men and women, and highlights areas for further investigation. PMID:23522436

  13. Therapeutic apheresis in autoimmune diseases

    PubMed Central

    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.

  14. Cell therapy for autoimmune diseases

    PubMed Central

    Dazzi, Francesco; van Laar, Jacob M; Cope, Andrew; Tyndall, Alan

    2007-01-01

    Cell therapy, pioneered for the treatment of malignancies in the form of bone marrow transplantation, has subsequently been tested and successfully employed in autoimmune diseases. Autologous haemopoietic stem cell transplantation (HSCT) has become a curative option for conditions with very poor prognosis such as severe forms of scleroderma, multiple sclerosis, and lupus, in which targeted therapies have little or no effect. The refinement of the conditioning regimens has virtually eliminated transplant-related mortality, thus making HSCT a relatively safe choice. Although HSCT remains a nonspecific approach, the knowledge gained in this field has led to the identification of new avenues. In fact, it has become evident that the therapeutic efficacy of HSCT cannot merely be the consequence of a high-dose immuno-suppression, but rather the result of a resetting of the abnormal immune regulation underlying autoimmune conditions. The identification of professional and nonprofessional immunosuppressive cells and their biological properties is generating a huge interest for their clinical exploitation. Regulatory T cells, found abnormal in several autoimmune diseases, have been proposed as central to achieve long-term remissions. Mesenchymal stem cells of bone marrow origin have more recently been shown not only to be able to differentiate into multiple tissues, but also to exert a potent antiproliferative effect that results in the inhibition of immune responses and prolonged survival of haemopoietic stem cells. All of these potential resources clearly need to be investigated at the preclinical level but support a great deal of enthusiasm for cell therapy of autoimmune diseases. PMID:17367542

  15. Diet, microbiota and autoimmune diseases.

    PubMed

    Vieira, S M; Pagovich, O E; Kriegel, M A

    2014-05-01

    There is growing evidence that the commensal bacteria in the gastrointestinal tract (the gut microbiota) influence the development of autoimmunity in rodent models. Since humans have co-evolved with commensals for millennia, it is likely that people, who are genetically predisposed to autoimmunity, harbor gut microbial communities that similarly influence the onset and/or severity of disease. Beyond the current efforts to identify such disease-promoting or -preventing commensals ("pathobionts" or "symbionts"), it will be important to determine what factors modulate them. Dietary changes are known to affect both the composition and function of the gut microbial communities, which in turn can alter the innate and adaptive immune system. In this review, we focus on the relationships between diet, microbiota, and autoimmune diseases. We hypothesize that the beneficial and life-prolonging effects of caloric restriction on a variety of autoimmune models including lupus might partly be mediated by its effects on the gut microbiome and associated virome, the collection of all viruses in the gut. We give recent examples of the immunomodulatory potential of select gut commensals and their products or diet-derived metabolites in murine models of arthritis, multiple sclerosis, and type 1 diabetes. Lastly, we summarize the published phenotypes of germ-free mouse models of lupus and speculate on any role of the diet-sensitive microbiome and virome in systemic lupus and the related antiphospholipid syndrome.

  16. Associated Autoimmune Diseases

    MedlinePlus

    ... only. Other helpful information is available at www.GLUTEN.net. Advances in celiac disease are fast-paced. ... should not be used to diagnose or treat gluten-related disorders or other medical conditions. For questions ...

  17. [Biermer's disease and autoimmune hemolytic anemia].

    PubMed

    Nafil, Hatim; Tazi, Illias; Mahmal, Lahoucine

    2012-01-01

    Biermer's disease is an autoimmune atrophic gastritis of the fundus predominantly responsible for a malabsorption of vitamin B12. Despite its association with several autoimmune disorders, few observations have reported an association with autoimmune hemolytic anemia (AIHA). We report a case of Biermer's disease associated with AIHA in a patient of 66 years old. PMID:22796620

  18. [Biermer's disease and autoimmune hemolytic anemia].

    PubMed

    Nafil, Hatim; Tazi, Illias; Mahmal, Lahoucine

    2012-01-01

    Biermer's disease is an autoimmune atrophic gastritis of the fundus predominantly responsible for a malabsorption of vitamin B12. Despite its association with several autoimmune disorders, few observations have reported an association with autoimmune hemolytic anemia (AIHA). We report a case of Biermer's disease associated with AIHA in a patient of 66 years old.

  19. Evaluation of autoimmune thyroid disease in melasma.

    PubMed

    Rostami Mogaddam, Majid; Iranparvar Alamdari, Manouchehr; Maleki, Nasrollah; Safavi Ardabili, Nastaran; Abedkouhi, Selma

    2015-06-01

    Melasma is one of the most frequently acquired hyperpigmentation disorders clinically characterized by symmetrical brown patches on sun-exposed areas. To date, few studies have been conducted about the relationship between thyroid autoimmun-ity and melasma. To evaluate the thyroid dysfunction and autoimmunity in nonpregnant women with melasma. A total of 70 women with melasma and 70 age-matched healthy women with no history of melasma were enrolled in the study. We studied the thyroid hormone profile in both groups. The statistical analysis was performed using SPSS software. Patients with melasma had 18.5% frequency of thyroid disorders, and 15.7% had positive anti-TPO, while subjects from the control group had a 4.3% frequency of thyroid abnormalities, and only 5.7% had positive anti-TPO. There was a significantly higher prevalence of thyroid dysfunction in women with melasma compared with control group (P = 0.008). This study suggests that there is a relationship between thyroid autoimmunity and melasma. However, to make recommendations on screening for thyroid disease in patients with melasma, future research of good methodological quality is needed.

  20. [Autoimmune Diseases of Digestive System].

    PubMed

    Ivashkinl, V T; Sheptulina, A F; Raĭkhelson, K L; Losik, E A; Ivashkin, K V; Okhlobystin, A V; Baranskaia, E K; Polouvektova, E A; Shifrin, O S

    2015-01-01

    Autoimmune diseases of digestive system refer to pathological conditions, caused by autoimmune mechanisms, and their etiology remains unknown. This is a group of relatively rare diseases, however, during the last years a marked tendency towards the raise in incidence andprevalence is observed, which led to an increase in number of clinical investigations on etiology, pathogenesis, and, accordingly, development of new diagnostic methods and therapies. Results of such trials shown, for example, that the pathogenesis of chronic cholestatic liver diseases is associated with nuclear receptors function, while the main etiological and pathogenic factor of inflammatory bowel diseases represents gut microbiota. Despite new achievements in autoinmune diseases of digestive system research, therapies are low effective and are accompanied by a huge number of adverse events. The fact that these diseases may lead to malignant tumors is also worth noting. For example, patients with primary sclerosing cholangitis have a 160 times higher risk of cholangiocellular carcinoma, while 10-14% ofpatients with celiac disease may develop malignancies of esophagus, small and large intestine. Thus, these diseases require further investigation with a purpose of more accurate diagnostic methods for the detection of disease at early stages and new effective and safe therapies development.

  1. Propylthiouracil-induced autoimmune disease.

    PubMed

    Paiaulla, Santosh; Venkategowda, Pradeep Marur; Rao, S Manimala; Balaraju, Banda

    2015-08-01

    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. PMID:26321810

  2. Shaking Out Clues to Autoimmune Disease

    MedlinePlus

    ... of Autoimmunity-Causing T Cells Landmark Analysis Probes Nature vs. Nurture in Multiple Sclerosis Understanding Autoimmune Diseases Immune Cells Reference: Nature. 2013 Mar 6. doi: 10.1038/nature11981. [Epub ...

  3. Questions and Answers on Autoimmunity and Autoimmune Diseases

    MedlinePlus

    ... for Updates Join Our Email List For Email Marketing you can trust. Contact AARDA National Office 22100 ... Grassroots Fundraising Workplace Giving Special Events AARDA on Facebook Copyright © 2004 - 2016. American Autoimmune Related Diseases Association, ...

  4. Secondary autoimmune diseases occurring after HSCT for an autoimmune disease: a retrospective study of the EBMT Autoimmune Disease Working Party.

    PubMed

    Daikeler, Thomas; Labopin, Myriam; Di Gioia, Massimo; Abinun, Mario; Alexander, Tobias; Miniati, Irene; Gualandi, Francesca; Fassas, Athanasios; Martin, Thierry; Schwarze, Carl Philipp; Wulffraat, Nico; Buch, Maya; Sampol, Antonia; Carreras, Enric; Dubois, Benedicte; Gruhn, Bernd; Güngör, Tayfun; Pohlreich, David; Schuerwegh, Annemie; Snarski, Emilian; Snowden, John; Veys, Paul; Fasth, Anders; Lenhoff, Stig; Messina, Chiara; Voswinkel, Jan; Badoglio, Manuela; Henes, Jörg; Launay, David; Tyndall, Alan; Gluckman, Eliane; Farge, Dominique

    2011-08-11

    To specify the incidence and risk factors for secondary autoimmune diseases (ADs) after HSCT for a primary AD, we retrospectively analyzed AD patients treated by HSCT reported to EBMT from 1995 to 2009 with at least 1 secondary AD (cases) and those without (controls). After autologous HSCT, 29 of 347 patients developed at least 1 secondary AD within 21.9 (0.6-49) months and after allogeneic HSCT, 3 of 16 patients. The observed secondary ADs included: autoimmune hemolytic anemia (n = 3), acquired hemophilia (n = 3), autoimmune thrombocytopenia (n = 3), antiphospholipid syndrome (n = 2), thyroiditis (n = 12), blocking thyroid-stimulating hormone receptor antibody (n = 1), Graves disease (n = 2), myasthenia gravis (n = 1), rheumatoid arthritis (n = 2), sarcoidosis (n = 2), vasculitis (n = 1), psoriasis (n = 1), and psoriatic arthritis (n = 1). After autologous HSCT for primary AD, the cumulative incidence of secondary AD was 9.8% ± 2% at 5 years. Lupus erythematosus as primary AD, and antithymocyte globulin use plus CD34(+) graft selection were important risk factors for secondary AD by multivariate analysis. With a median follow-up of 6.2 (0.54-11) years after autologous HSCT, 26 of 29 patients with secondary AD were alive, 2 died during their secondary AD (antiphospholipid syndrome, hemophilia), and 1 death was HSCT-related. This European multicenter study underlines the need for careful management and follow-up for secondary AD after HSCT.

  5. [Autoimmune thyroid disease and associated diseases].

    PubMed

    Lapcević, Mirjana

    2005-10-01

    Autoimmune thyroid disease (ATD) is a multifactorial, genetic disease. It is the sequelae of the impaired immunoregulation, tolerance and poor recognition of one's own proteins, oligopolysaccharides and polypeptides, due to development of somatic lymphocyte mutations. It is manifested by different clinical and morphological entities, inter-related by etiopathogenetic association, i.e., all of them are caused by disorder of immune system regulation. Chronic autoimmune thyroidism (Thyreoiditis lymphocytaria Hashimoto, HT), as well as immunogenic hyperthyroidism (Morbus Graves Basedow, MGB) are frequently associated with autoimmune diseases of other organs, such as: chronic insufficiency of salivary glands (Sy Sjögren), autoimmune hemolytic anemia, megalocytic pernicious anemia, thrombocytopenia, Rheumatoid arthritis, Diabetes mellitus (more often type 2, but also type 1), Morbus Addison, Coeliakia, and other autoimmune diseases such as systemic diseases of connecting tissue (Lupus erythematosus-SLE, Sclerodermia, Vasculitis superficialis). The incidence of autoimmune diseases has been at increase in all age groups of our population. The prevalence of organ-specific and organ-nonspecific antibodies increases with the age. Antigenicity of thyroid epithelial cell may be triggered by different chemical and biological agents (repeated viral infections), repeated stress, and in individuals with genetic propensity. Unrecognized ATD progressively leads to hypothyroidism with hyperlipidemia, blood vessel changes, osteoporosis, deformities, invalidity which substantially reduces the quality of life of patient and requires medical attention and expensive treatment on what account it is medically and socio-economically significant. Multiple diagnostic procedures contribute to faster recognition of this condition. The goal of the primary health care physician (given that preclinical phase of ATD and other associated diseases have different duration) and other specialists is to

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

    PubMed Central

    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

  7. Immunomodulatory vaccines against autoimmune diseases.

    PubMed

    Sela, Michael

    2006-01-01

    Vaccines are for healthy people, to prevent them from becoming ill. Such prophylactic vaccines have been a great success. Therapeutic vaccines become more and more important, especially as life expectancy increases. Efforts to develop vaccines against such diseases as cancer, AIDS, hepatitis, tuberculosis, Alzheimer disease, and mad cow disease have not yet reached the stage where they can be successfully used on a daily basis. However, significant progress has been made in the realm of autoimmune diseases, resulting (at least in one case) in an immunomodulatory vaccine against multiple sclerosis that was developed in the author's laboratory, and that is in daily use by about 100,000 patients. The drug or therapeutic vaccine against the exacerbating-remitting type of multiple sclerosis is a copolymer of four amino acid residues, denoted Copaxone, which are related to myelin basic protein. This paper discusses Copaxone as well as a candidate immunomodulatory vaccine against myasthenia gravis, a peptide derived from the nicotinic acetylcholine receptor. Copolymer 1 (Cop 1, glatiramer acetate, Copaxone) is a synthetic amino acid random copolymer that is immunologically cross-reactive with myelin basic protein and suppresses experimental allergic encephalomyelitis in several animal species. Cop 1 slows the progression of disability and reduces the relapse rate in exacerbating-remitting multiple sclerosis patients. Cop 1 is a potent inducer of T helper 2 (Th2) regulatory cells in mice and humans; and Th2 cells are found in both the brains and spinal cords of Cop 1-treated mice and humans. MG and experimental autoimmune MG are T cell-regulated, antibody-mediated autoimmune diseases. Two peptides, representing sequences of the human AChR-alpha-subunit, p195-212 and p259-271, are immunodominant T-cell epitopes in MG patients and two strains of mice. Altered peptide ligand, composed of the randomly arranged two single amino acid analogs inhibits in vitro and in vivo MG

  8. Cardiovascular Involvement in Autoimmune Diseases

    PubMed Central

    Amaya-Amaya, Jenny

    2014-01-01

    Autoimmune diseases (AD) represent a broad spectrum of chronic conditions that may afflict specific target organs or multiple systems with a significant burden on quality of life. These conditions have common mechanisms including genetic and epigenetics factors, gender disparity, environmental triggers, pathophysiological abnormalities, and certain subphenotypes. Atherosclerosis (AT) was once considered to be a degenerative disease that was an inevitable consequence of aging. However, research in the last three decades has shown that AT is not degenerative or inevitable. It is an autoimmune-inflammatory disease associated with infectious and inflammatory factors characterized by lipoprotein metabolism alteration that leads to immune system activation with the consequent proliferation of smooth muscle cells, narrowing arteries, and atheroma formation. Both humoral and cellular immune mechanisms have been proposed to participate in the onset and progression of AT. Several risk factors, known as classic risk factors, have been described. Interestingly, the excessive cardiovascular events observed in patients with ADs are not fully explained by these factors. Several novel risk factors contribute to the development of premature vascular damage. In this review, we discuss our current understanding of how traditional and nontraditional risk factors contribute to pathogenesis of CVD in AD. PMID:25177690

  9. Rett syndrome: An autoimmune disease?

    PubMed

    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

  10. Autoimmune mechanisms in pernicious anaemia & thyroid disease.

    PubMed

    Osborne, David; Sobczyńska-Malefora, Agata

    2015-09-01

    Pernicious anaemia (PA) and some types of thyroid disease result from autoimmune processes. The autoimmune mechanisms in these conditions have not been fully elucidated. This review discusses the autoimmune mechanisms involved in PA and how these affect diagnosis and disease progression. In addition to gastric antibodies, antibodies to the vitamin B12 binding protein transcobalamin which can result in high serum B12 levels are also addressed with regard to how they affect clinical practice. The role of autoimmune susceptibility is investigated by comparing PA to one of its most common comorbidities, autoimmune thyroid disease (AITD). Thyroid disease (although not exclusively AITD) and B12 deficiency are both also implicated in the pathology of hyperhomocysteinemia, an elevated homocysteine in plasma. Since hyperhomocysteinemia is a risk factor for cardiovascular occlusive disease, this review also addresses how thyroid disease in particular leads to changes in homocysteine levels. PMID:25936607

  11. Parkinson's disease: Autoimmunity and neuroinflammation.

    PubMed

    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

  12. Helicobacter pylori and skin autoimmune diseases

    PubMed Central

    Magen, Eli; Delgado, Jorge-Shmuel

    2014-01-01

    Autoimmune skin diseases are characterized by dysregulation of the immune system resulting in a loss of tolerance to skin self-antigen(s). The prolonged interaction between the bacterium and host immune mechanisms makes Helicobacter pylori (H. pylori) a plausible infectious agent for triggering autoimmunity. Epidemiological and experimental data now point to a strong relation of H. pylori infection on the development of many extragastric diseases, including several allergic and autoimmune diseases. H. pylori antigens activate cross-reactive T cells and induce autoantibodies production. Microbial heat shock proteins (HSP) play an important role of in the pathogenesis of autoimmune diseases because of the high level of sequence homology with human HSP. Eradication of H. pylori infection has been shown to be effective in some patients with chronic autoimmune urticaria, psoriasis, alopecia areata and Schoenlein-Henoch purpura. There is conflicting and controversial data regarding the association of H. pylori infection with Behçet’s disease, scleroderma and autoimmune bullous diseases. No data are available evaluating the association of H. pylori infection with other skin autoimmune diseases, such as vitiligo, cutaneous lupus erythematosus and dermatomyositis. The epidemiological and experimental evidence for a possible role of H. pylori infection in skin autoimmune diseases are the subject of this review. PMID:24587626

  13. Autoimmune diseases associated with neurofibromatosis type 1.

    PubMed

    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.

  14. Monogenic autoimmune diseases of the endocrine system.

    PubMed

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

    2016-10-01

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

  15. Monogenic autoimmune diseases of the endocrine system.

    PubMed

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

    2016-10-01

    The most common endocrine diseases, type 1 diabetes, hyperthyroidism, and hypothyroidism, are the result of autoimmunity. Clustering of autoimmune endocrinopathies can result from polygenic predisposition, or more rarely, may present as part of a wider syndrome due to a mutation within one of seven genes. These monogenic autoimmune diseases show highly variable phenotypes both within and between families with the same mutations. The average age of onset of the monogenic forms of autoimmune endocrine disease is younger than that of the common polygenic forms, and this feature combined with the manifestation of other autoimmune diseases, specific hallmark features, or both, can inform clinicians as to the relevance of genetic testing. A genetic diagnosis can guide medical management, give an insight into prognosis, inform families of recurrence risk, and facilitate prenatal diagnoses. PMID:27474216

  16. Criteria for environmentally associated autoimmune diseases.

    PubMed

    Miller, Frederick W; Pollard, K Michael; Parks, Christine G; Germolec, Dori R; Leung, Patrick S C; Selmi, Carlo; Humble, Michael C; Rose, Noel R

    2012-12-01

    Increasing evidence supports a role for the environment in the development of autoimmune diseases, as reviewed in the accompanying three papers from the National Institute of Environmental Health Sciences Expert Panel Workshop. An important unresolved issue, however, is the development of criteria for identifying autoimmune disease phenotypes for which the environment plays a causative role, herein referred to as environmentally associated autoimmune diseases. There are several different areas in which such criteria need to be developed, including: 1) identifying the necessary and sufficient data to define environmental risk factors for autoimmune diseases meeting current classification criteria; 2) establishing the existence of and criteria for new environmentally associated autoimmune disorders that do not meet current disease classification criteria; and 3) identifying in clinical practice specific environmental agents that induce autoimmune disease in individual patients. Here we discuss approaches that could be useful for developing criteria in these three areas, as well as factors that should be considered in evaluating the evidence for criteria that can distinguish individuals with such disorders from individuals without such disorders with high sensitivity and specificity. Current studies suggest that multiple lines of complementary evidence will be important and that in many cases there will be clinical, serologic, genetic, epigenetic, and/or other laboratory features that could be incorporated as criteria for environmentally associated autoimmune diseases to improve diagnosis and treatment and possibly allow for preventative strategies in the future.

  17. Acquired cystic kidney disease.

    PubMed

    Levine, E

    1996-09-01

    ACKD is characterized by the development of many fluid-filled renal cysts and sometimes neoplasms in the kidneys of individuals with chronic renal failure but without a history of hereditary cystic disease. The condition is seen mainly in dialysis patients, but often begins in patients with ESRD before dialysis is started. Most patients with ACKD are asymptomatic, but the disorder may be associated with such serious complications as retroperitoneal hemorrhage and metastatic renal cell carcinoma. The diagnosis of ACKD and its complications is best achieved by CT scanning, although US and MR imaging may be useful in evaluation, particularly in patients not treated with dialysis. Cyst hemorrhage is common in ACKD and may cause flank pain and hematuria. Hemorrhagic cysts may be recognized by their CT scan, sonographic, or MR imaging features. Hemorrhagic cysts may rupture into the perinephric space causing large perinephric hematomas. These can usually be treated-conservatively. Patients with ACKD, particularly those treated with dialysis, have an increased risk of renal cell carcinoma. Renal cell carcinoma may also develop in the native kidneys of renal transplant recipients with good graft function many years after transplantation. Annual imaging of the native kidneys of all dialysis patients or of transplant recipients for the development of carcinoma is not justified, however, because it has not been shown to have a significant effect on patient outcome. Screening may, however, be useful in selected dialysis patients with good general medical condition and who have known risk factors for renal cell carcinoma including prolonged dialysis, large kidneys, ACKD, and male gender. Screening of the native kidneys of transplant recipients may be performed when they are referred for US evaluation of the renal allograft.

  18. Human autoimmune diseases: a comprehensive update.

    PubMed

    Wang, Lifeng; Wang, Fu-Sheng; Gershwin, M Eric

    2015-10-01

    There have been significant advances in our understanding of human autoimmunity that have led to improvements in classification and diagnosis and, most importantly, research advances in new therapies. The importance of autoimmunity and the mechanisms that lead to clinical disease were first recognized about 50 years ago following the pioneering studies of Macfarlane Burnett and his Nobel Prize-winning hypothesis of the 'forbidden clone'. Such pioneering efforts led to a better understanding not only of autoimmunity, but also of lymphoid cell development, thymic education, apoptosis and deletion of autoreactive cells. Contemporary theories suggest that the development of an autoimmune disease requires a genetic predisposition and environmental factors that trigger the immune pathways that lead, ultimately, to tissue destruction. Despite extensive research, there are no genetic tools that can be used clinically to predict the risk of autoimmune disease. Indeed, the concordance of autoimmune disease in identical twins is 12-67%, highlighting not only a role for environmental factors, but also the potential importance of stochastic or epigenetic phenomena. On the other hand, the identification of cytokines and chemokines, and their cognate receptors, has led to novel therapies that block pathological inflammatory responses within the target organ and have greatly improved the therapeutic effect in patients with autoimmune disease, particularly rheumatoid arthritis. Further advances involving the use of multiplex platforms for diagnosis and identification of new therapeutic agents should lead to major breakthroughs within the next decade. PMID:26212387

  19. Coherent Somatic Mutation in Autoimmune Disease

    PubMed Central

    Ross, Kenneth Andrew

    2014-01-01

    Background Many aspects of autoimmune disease are not well understood, including the specificities of autoimmune targets, and patterns of co-morbidity and cross-heritability across diseases. Prior work has provided evidence that somatic mutation caused by gene conversion and deletion at segmentally duplicated loci is relevant to several diseases. Simple tandem repeat (STR) sequence is highly mutable, both somatically and in the germ-line, and somatic STR mutations are observed under inflammation. Results Protein-coding genes spanning STRs having markers of mutability, including germ-line variability, high total length, repeat count and/or repeat similarity, are evaluated in the context of autoimmunity. For the initiation of autoimmune disease, antigens whose autoantibodies are the first observed in a disease, termed primary autoantigens, are informative. Three primary autoantigens, thyroid peroxidase (TPO), phogrin (PTPRN2) and filaggrin (FLG), include STRs that are among the eleven longest STRs spanned by protein-coding genes. This association of primary autoantigens with long STR sequence is highly significant (). Long STRs occur within twenty genes that are associated with sixteen common autoimmune diseases and atherosclerosis. The repeat within the TTC34 gene is an outlier in terms of length and a link with systemic lupus erythematosus is proposed. Conclusions The results support the hypothesis that many autoimmune diseases are triggered by immune responses to proteins whose DNA sequence mutates somatically in a coherent, consistent fashion. Other autoimmune diseases may be caused by coherent somatic mutations in immune cells. The coherent somatic mutation hypothesis has the potential to be a comprehensive explanation for the initiation of many autoimmune diseases. PMID:24988487

  20. Environmental Exposures and Autoimmune Thyroid Disease

    PubMed Central

    2010-01-01

    Background Environmental exposures, ranging from perchlorate in rocket fuel to polychlorinated biphenols, have been shown to influence thyroid function. Although most of these agents are associated with reduced thyroid hormone levels or impaired thyroid hormone action, a number of environmental exposures confer an increased risk of autoimmune thyroid disease. Summary Factors that increase autoimmune thyroid disease risk include radiation exposure, both from nuclear fallout and medical radiation, increased iodine intake, as well as several contaminants in the environment that influence the thyroid. Although ∼70% of the risk for developing autoimmune thyroid disease is attributable to genetic background, environmental triggers are thought to play a role in the development of autoimmune thyroid disease in susceptible individuals. Conclusions Understanding the association of environmental agents with thyroid dysfunction can be utilized to reduce the risk to populations. Knowledge of the specific factors that trigger autoimmune thyroid disease and their mode of action, however, may also inform risk reduction in the individual patient. These factors are especially relevant for those at increased risk of autoimmune thyroid disease based on family history. PMID:20578899

  1. Allergic Disease and Autoimmune Effectors Pathways

    PubMed Central

    Rottem, Menachem; Gershwin, M. Eric; Shoenfeld, Yehuda

    2002-01-01

    Allergy and autoimmunity result from dysregulation of the immune system. Until recently, it was generally accepted that the mechanisms that govern these disease processes are quite disparate; however, new discoveries suggest possible common pathogenetic effector pathways. This review illustrates the concomitant presentation of these conditions and the potential relationship or common mechanism in some cases, by looking at the key elements that regulate the immune response in both allergic and autoimmunite conditions: mast cells, antibodies, T cells, cytokines, and genetic determinants. The parallel appearance of allergic and autoimmune conditions in the some patients may reveal that such aberrations of the immune system have a common pathophysiologic mechanism. Mast cells, which play a key role in allergic reactions, and the wealth of inflammatory mediators they express, make it likely that they have profound effects on many autoimmune processes. Activation of protein kinases by inflammatory cytokines and environmental stresses may contribute to both allergic and autoimmune diseases. The presence of autoantibodies in some allergic conditions suggests an autoimmune basis for these conditions. Because of the central role T cells play in immune reactivity, the T-cell receptor (TCR) loci have long been considered important candidates for common disease susceptibility within the immune system such as asthma, atopy, and autoimmunity. Immunomodulation is the key to a successful treatment of allergic and autoimmune conditions. PMID:12885156

  2. How pregnancy can affect autoimmune diseases progression?

    PubMed

    Piccinni, Marie-Pierre; Lombardelli, Letizia; Logiodice, Federica; Kullolli, Ornela; Parronchi, Paola; Romagnani, Sergio

    2016-01-01

    Autoimmune disorders are characterized by tissue damage, caused by self-reactivity of different effectors mechanisms of the immune system, namely antibodies and T cells. Their occurrence may be associated with genetic and/or environmental predisposition and to some extent, have implications for fertility and obstetrics. The relationship between autoimmunity and reproduction is bidirectional. This review only addresses the impact of pregnancy on autoimmune diseases and not the influence of autoimmunity on pregnancy development. Th17/Th1-type cells are aggressive and pathogenic in many autoimmune disorders and inflammatory diseases. The immunology of pregnancy underlies the role of Th2-type cytokines to maintain the tolerance of the mother towards the fetal semi-allograft. Non-specific factors, including hormonal changes, favor a switch to Th2-type cytokine profile. In pregnancy Th2, Th17/Th2 and Treg cells accumulate in the decidua but may also be present in the mother's circulation and can regulate autoimmune responses influencing the progression of autoimmune diseases. PMID:27651750

  3. Pregnancy and autoimmune connective tissue diseases.

    PubMed

    Marder, Wendy; Littlejohn, Emily A; Somers, Emily C

    2016-02-01

    Autoimmune connective tissue diseases predominantly affect women and often occur during the reproductive years. Thus, specialized issues in pregnancy planning and management are commonly encountered in this patient population. This chapter provides a current overview of pregnancy as a risk factor for onset of autoimmune disease, considerations related to the course of pregnancy in several autoimmune connective tissue diseases, and disease management and medication issues before pregnancy, during pregnancy, and in the postpartum period. A major theme that has emerged across these inflammatory diseases is that active maternal disease during pregnancy is associated with adverse pregnancy outcomes, and that maternal and fetal health can be optimized when conception is planned during times of inactive disease and through maintaining treatment regimens compatible with pregnancy.

  4. Pregnancy and autoimmune connective tissue diseases.

    PubMed

    Marder, Wendy; Littlejohn, Emily A; Somers, Emily C

    2016-02-01

    Autoimmune connective tissue diseases predominantly affect women and often occur during the reproductive years. Thus, specialized issues in pregnancy planning and management are commonly encountered in this patient population. This chapter provides a current overview of pregnancy as a risk factor for onset of autoimmune disease, considerations related to the course of pregnancy in several autoimmune connective tissue diseases, and disease management and medication issues before pregnancy, during pregnancy, and in the postpartum period. A major theme that has emerged across these inflammatory diseases is that active maternal disease during pregnancy is associated with adverse pregnancy outcomes, and that maternal and fetal health can be optimized when conception is planned during times of inactive disease and through maintaining treatment regimens compatible with pregnancy. PMID:27421217

  5. [Autoimmune connective tissue diseases and vaccination].

    PubMed

    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.

  6. Low-dose exposure to inorganic mercury accelerates disease and mortality in acquired murine lupus.

    PubMed

    Via, Charles S; Nguyen, Phuong; Niculescu, Florin; Papadimitriou, John; Hoover, Dennis; Silbergeld, Ellen K

    2003-08-01

    Inorganic mercury (iHg) is known to induce autoimmune disease in susceptible rodent strains. Additionally, in inbred strains of mice prone to autoimmune disease, iHg can accelerate and exacerbate disease manifestations. Despite these well-known links between iHg and autoimmunity in animal models, no association between iHg alone and autoimmune disease in humans has been documented. However, it is possible that low-level iHg exposure can interact with disease triggers to enhance disease expression or susceptibility. To address whether exposure to iHg can alter the course of subsequent acquired autoimmune disease, we used a murine model of acquired autoimmunity, lupus-like chronic graft-versus-host disease (GVHD), in which autoimmunity is induced using normal, nonautoimmune prone donor and F1 recipient mice resistant to Hg-induced autoimmunity. Our results indicate that a 2-week exposure to low-dose iHg (20 or 200 micro g/kg every other day) to donor and host mice ending 1 week before GVHD induction can significantly worsen parameters of disease severity, resulting in premature mortality. iHg pretreatment clearly worsened chronic lupus-like disease, rather than GVHD worsening iHg immunotoxicity. These results are consistent with the hypothesis that low-level, nontoxic iHg preexposure may interact with other risk factors, genetic or acquired, to promote subsequent autoimmune disease development.

  7. Autism and Autoimmune Disease: A Family Study

    ERIC Educational Resources Information Center

    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)

  8. [Glycosylation of autoantibodies in autoimmunes diseases].

    PubMed

    Goulabchand, R; Batteux, F; Guilpain, P

    2013-12-01

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

  9. Recent Advances in Autoimmune Thyroid Diseases

    PubMed Central

    Yoo, Won Sang

    2016-01-01

    Autoimmune thyroid disease (AITD) includes hyperthyroid Graves disease, hypothyroid autoimmune thyroiditis, and subtle subclinical thyroid dysfunctions. AITD is caused by interactions between genetic and environmental predisposing factors and results in autoimmune deterioration. Data on polymorphisms in the AITD susceptibility genes, related environmental factors, and dysregulation of autoimmune processes have accumulated over time. Over the last decade, there has been progress in the clinical field of AITD with respect to the available diagnostic and therapeutic methods as well as clinical consensus. The updated clinical guidelines allow practitioners to identify the most reasonable and current approaches for proper management. In this review, we focus on recent advances in understanding the genetic and environmental pathogenic mechanisms underlying AITD and introduce the updated set of clinical guidelines for AITD management. We also discuss other aspects of the disease such as management of subclinical thyroid dysfunction, use of levothyroxine plus levotriiodothyronine in the treatment of autoimmune hypothyroidism, risk assessment of long-standing antithyroid drug therapy in recurrent Graves' hyperthyroidism, and future research needs. PMID:27586448

  10. Autoimmune thyroid disease and chronic urticaria.

    PubMed

    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.

  11. Hepatitis B virus (HBV) and autoimmune disease.

    PubMed

    Maya, Ram; Gershwin, M Eric; Shoenfeld, Yehuda

    2008-02-01

    The etiology and pathogenesis of autoimmune diseases have long been an enigmatic subject that have involved genetic and environmental factors. Recent intriguing data has contributed to the mechanisms involved, including the relationship of infectious agents and loss of tolerance. This loss of tolerance is illustrated by the data on the immune response to Hepatitis B virus such as the molecular mimicry between HBV antigens and self proteins, the generation of immune complexes between HBV antigens and antibodies, and apoptosis/tissue damage resulting in the exposure of intracellular antigens to the immune system. In this paper, we review the current database related to HBV infection and a variety of autoimmune conditions, including autoimmune hepatitis, systemic lupus erythematosus, aplastic anemia, antiphospholipid syndrome, polyarteritis nodosa, rheumatoid arthritis, type 1 diabetes, multiple sclerosis, thyroid disease and uveitis. PMID:18270862

  12. Fibrosis in Autoimmune and Cholestatic Liver Disease

    PubMed Central

    Penz-Österreicher, Melitta; Österreicher, Christoph H.; Trauner, Michael

    2011-01-01

    Autoimmune and cholestatic liver disease account for a significant part of end-stage liver disease and are leading indications for liver transplantation. Especially cholestatic liver diseases (primary biliary cirrhosis and primary sclerosing cholangitis) appear to be different from other chronic liver diseases with regards to pathogenesis. Portal fibroblasts located in the connective tissue surrounding bile ducts appear to be different from hepatic stellate cells with regards to expression of marker proteins and response the profibrogenic and mitogenic stimuli. In addition there is increasing evidence for a cross talk between activated cholangiocytes and portal myofibroblasts. Several animal models have improved our understanding of the mechanisms underlying these chronic liver diseases. In the present review, we discuss the current concepts and ideas with regards to myofibroblastic cell populations, mechanisms of fibrosis, summarize characteristic histological findings and currently employed animal models of autoimmune and cholestatic liver disease. PMID:21497742

  13. Scurfy mice: A model for autoimmune disease

    SciTech Connect

    Godfrey, V.L.

    1993-01-01

    Autoimmune disease-the condition in which the body attacks its own tissue-has been an object of public concern recently. Former President George Bush and his wife Barbara both are afflicted with Graves' disease in which the body's own immune system attakcs the thyroid gland. The safety of breast implants was called into question because of evidence that some recipients had developed autoimmune disorders such a rheumatoid arthritis, systemic lupus erythematosus, and scleroderma. Women, the media pointed out, have a higher-than-average incidence of many autoimmune disorders. These events suggest the need to know more about what makes the immune system work so well and what makes it go awry. At ORNL's Biology Division, progress is being in understanding the underlying causes of immune disease by studying mice having a disease that causes them to be underdeveloped; to have scaly skin, small ears, and large spleens; to open their eyes late; and to die early. These [open quotes]scurfy[close quotes]mice are helping us better understand the role of the thymus gland in autoimmune disease.

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

    PubMed

    Lundin, Knut E A; Wijmenga, Cisca

    2015-09-01

    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 have been gained. However, genetic screening is not sensitive and specific enough to accurately predict disease development. The current method to diagnose individuals with coeliac disease is serological testing for the presence of autoantibodies whilst the patient is on a regular, gluten-containing diet, followed by gastroduodenoscopy with duodenal biopsy. Serological test results can also predict the probability of coeliac disease development, even if asymptomatic. In patients with autoimmune diseases known to occur alongside coeliac disease (particularly type 1 diabetes mellitus or thyroid disorders), disease screening-and subsequent treatment if coeliac disease is detected-could have beneficial effects on progression or potential complications of both diseases, owing to the effectiveness of gluten-free dietary interventions in coeliac disease. However, whether diagnosis of coeliac disease and subsequent dietary treatment can prevent autoimmune diseases is debated. In this Review, the genetic and immunological features of coeliac disease, overlap with other autoimmune diseases and implications for current screening strategies will be discussed.

  15. Is hypertension an autoimmune disease?

    PubMed Central

    Pober, Jordan S.

    2014-01-01

    T cells are required for significant blood pressure elevation in mouse models of hypertension. Recent evidence suggests that the treatments that raise blood pressure in these animal models also cause oxidation within DCs, resulting in formation of isoketal adducts of self-proteins, which activate antigen-presenting functions of these cells and serve as a source of modified self-antigens. T cells specific for these modified self-antigens then produce cytokines that promote blood pressure elevation, consistent with the idea that hypertension is an autoimmune response to altered self. Here, I will review the new evidence for this idea put forth by Kirabo and colleagues in this issue of the JCI, identify a number of as yet unanswered questions, and discuss some of the therapeutic implications. PMID:25244091

  16. Autologous hematopoietic stem cell transplantation in autoimmune diseases.

    PubMed

    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

  17. Anti-cytokine autoantibodies in autoimmune diseases

    PubMed Central

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

    2012-01-01

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

  18. Autoimmune Pathogenesis of Chagas Heart Disease

    PubMed Central

    Bonney, Kevin M.; Engman, David M.

    2016-01-01

    Chagas heart disease is an inflammatory cardiomyopathy that develops in approximately one-third of individuals infected with the protozoan parasite Trypanosoma cruzi. Since the discovery of T. cruzi by Carlos Chagas >100 years ago, much has been learned about Chagas disease pathogenesis; however, the outcome of T. cruzi infection is highly variable and difficult to predict. Many mechanisms have been proposed to promote tissue inflammation, but the determinants and the relative importance of each have yet to be fully elucidated. The notion that some factor other than the parasite significantly contributes to the development of myocarditis was hypothesized by the first physician-scientists who noted the conspicuous absence of parasites in the hearts of those who succumbed to Chagas disease. One of these factors—autoimmunity—has been extensively studied for more than half a century. Although questions regarding the functional role of autoimmunity in the pathogenesis of Chagas disease remain unanswered, the development of autoimmune responses during infection clearly occurs in some individuals, and the implications that this autoimmunity may be pathogenic are significant. In this review, we summarize what is known about the pathogenesis of Chagas heart disease and conclude with a view of the future of Chagas disease diagnosis, pathogenesis, therapy, and prevention, emphasizing recent advances in these areas that aid in the management of Chagas disease. PMID:25857229

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

    PubMed

    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. Imaging combined autoimmune and infectious disease microarrays

    NASA Astrophysics Data System (ADS)

    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

  1. Complicating autoimmune diseases in myasthenia gravis: a review.

    PubMed

    Nacu, Aliona; Andersen, Jintana Bunpan; Lisnic, Vitalie; Owe, Jone Furlund; Gilhus, Nils Erik

    2015-01-01

    Myasthenia gravis (MG) is a rare autoimmune disease of skeletal muscle endplates. MG subgroup is relevant for comorbidity, but usually not accounted for. MG patients have an increased risk for complicating autoimmune diseases, most commonly autoimmune thyroid disease, systemic lupus erythematosus and rheumatoid arthritis. In this review, we present concomitant autoimmune disorders associated with the different MG subgroups, and show how this influences treatment and prognosis. Concomitant MG should always be considered in patients with an autoimmune disorder and developing new neuromuscular weakness, fatigue or respiratory failure. When a second autoimmune disorder is suspected, MG should be included as a differential diagnosis.

  2. Complicating autoimmune diseases in myasthenia gravis: a review

    PubMed Central

    Nacu, Aliona; Andersen, Jintana Bunpan; Lisnic, Vitalie; Owe, Jone Furlund; Gilhus, Nils Erik

    2015-01-01

    Abstract Myasthenia gravis (MG) is a rare autoimmune disease of skeletal muscle endplates. MG subgroup is relevant for comorbidity, but usually not accounted for. MG patients have an increased risk for complicating autoimmune diseases, most commonly autoimmune thyroid disease, systemic lupus erythematosus and rheumatoid arthritis. In this review, we present concomitant autoimmune disorders associated with the different MG subgroups, and show how this influences treatment and prognosis. Concomitant MG should always be considered in patients with an autoimmune disorder and developing new neuromuscular weakness, fatigue or respiratory failure. When a second autoimmune disorder is suspected, MG should be included as a differential diagnosis. PMID:25915571

  3. Prenatal immunotoxicant exposure and postnatal autoimmune disease.

    PubMed Central

    Holladay, S D

    1999-01-01

    Reports in humans and rodents indicate that immune development may be altered following perinatal exposure to immunotoxic compounds, including chemotherapeutics, corticosteroids, polycyclic hydrocarbons, and polyhalogenated hydrocarbons. Effects from such exposure may be more dramatic or persistent than following exposure during adult life. For example, prenatal exposure to the insecticide chlordane or to the polycyclic aromatic hydrocarbon benzo[(italic)a(/italic)]pyrene produces what appears to be lifelong immunosuppression in mice. Whether prenatal immunotoxicant exposure may predispose the organism to postnatal autoimmune disease remains largely unknown. In this regard, the therapeutic immunosuppressant cyclosporin A (CsA) crosses the placenta poorly. However, lethally irradiated rodents exposed to CsA postsyngeneic bone marrow transplant (i.e., during re-establishment of the immune system) develop T-cell-mediated autoimmune disease, suggesting this drug may produce a fundamental disruption in development of self-tolerance by T cells. The environmental contaminant 2,3,7, 8-tetrachlorodibenzo-(italic)p(/italic)-dioxin (TCDD) crosses the placenta and produces fetal thymic effects (italic)in vivo(/italic) similar to effects of CsA in fetal thymic organ culture, including inhibited thymocyte maturation and reduced expression of thymic major histocompatability complex class II molecules. These observations led to the suggestion that gestational exposure to TCDD may interfere with normal development of self-tolerance. Possibly supporting this hypothesis, when mice predisposed to development of autoimmune disease were treated with TCDD during gestation, postnatal autoimmunity was exacerbated. Similar results have been reported for mice exposed to diethylstilbestrol during development. These reports suggest that prenatal exposure to certain immunotoxicants may play a role in postnatal expression of autoimmunity. PMID:10502532

  4. Roles of A20 in autoimmune diseases.

    PubMed

    Zhang, Min; Peng, Ling-Long; Wang, Ying; Wang, Jian-Shu; Liu, Jiao; Liu, Meng-Meng; Hu, Jia; Song, Bin; Yang, Hai-Bing

    2016-04-01

    A20 (TNFAIP3), known to inhibit NF-κB function by deubiquitinating-specific NF-κB signaling molecules, has been found in many cell types of the immune system. Recent findings suggest that A20 is essential for the development and functional performance of dendritic cell, B cell, T cell and macrophage. A number of studies further demonstrate that these cells are crucial in the pathogenesis of autoimmune diseases, such as type 1 diabetes, systemic lupus erythematosus, inflammatory bowel disease, ankylosing arthritis, Sjögren's syndrome and rheumatoid arthritis. In this article, we focus on the recent advances on the roles of A20 in autoimmune diseases and discuss the therapeutic significance of these new findings. PMID:26135958

  5. Avian models with spontaneous autoimmune diseases

    PubMed Central

    Wick, Georg; Andersson, Leif; Hala, Karel; Gershwin, M. Eric; Selmi, Carlo F.; Erf, Gisela F.; Lamont, Susan J.; Sgonc, Roswitha

    2012-01-01

    Autoimmune diseases in human patients only become clinically manifest when the disease process has developed to a stage where functional compensation by the afflicted organ or system is not possible any more. In order to understand the initial etiologic and pathogenic events that are generally not yet accessible in humans, appropriate animal models are required. In this respect, spontaneously developing models - albeit rare – reflect the situation in humans much more closely than experimentally induced models, including knockout and transgenic mice. The present review describes three spontaneous chicken models for human autoimmune diseases, the Obese strain (OS) with a Hashimoto-like autoimmune thyroiditis, the University of California at Davis lines 200 and 206 (UCD-200 and 206) with a scleroderma-like disease and the amelanotic Smyth line with a vitiligo-like syndrome (SLV). Special emphasis is given to the new opportunities to unravel the genetic basis of these diseases in view of the recently completed sequencing of the chicken genome. PMID:17145302

  6. Achalasia and thyroid disease: possible autoimmune connection?

    PubMed

    Quidute, Ana Rosa P; Freitas, Eduardo Vasconcelos de; Lima, Tadeu Gonçalves de; Feitosa, Ana Márcia Lima; Santos, Joyce Paiva dos; Correia, José Walter

    2012-12-01

    Many cases have been published showing a co-existence of autoimmune thyroid diseases (AITDs) and other autoimmune diseases. About a quarter of patients with achalasia have a concurrent thyroid disease, most commonly associated with hypothyroidism. Although relatively rare, the association of achalasia and hyperthyroidism requires attention. The physiopathology of Grave's Disease (GD) involves B- and T-mediator lymphocytes, which have an affinity for known thyroid antigens: thyroglobulin, thyroid-peroxidase, and thyrotrophin receptor. Currently, however, the real physiopathogenesis of achalasia continues to be unknown. Some important findings are suggestive of an autoimmune mechanism: significant infiltration of the myoenteric plexus by monocytes, presence of the class II-Human Histocompatibility Complex DQwl antigen and antibodies to myoenteric neurons. The present case reports a patient who, despite testing negative for Chagas' disease, had achalasia, progressed to developing significant wasting and worsening of his quality of life, was later diagnosed with hyperthyroidism. After endoscopic esophageal dilatation and radioiodine ablation of the thyroid gland, there was great improvement in the patient clinical condition. PMID:23329193

  7. Autoimmune Inner Ear Disease (AIED)

    MedlinePlus

    ... Other Topics Military Resources Infographics & Presentations Videos Paid Advertisement Meniere's Disease SPC-Flakes have been clinically shown ... Mention “VEDA” to receive a 15% discount. Paid Advertisement Disclaimer Information on this website is not intended ...

  8. Oral Tolerance: Therapeutic Implications for Autoimmune Diseases

    PubMed Central

    Faria, Ana M. C.; Weiner, Howard L.

    2006-01-01

    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. PMID:17162357

  9. Cirrhosis and autoimmune liver disease: Current understanding

    PubMed Central

    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

  10. [Regulatory B cells in human autoimmune diseases].

    PubMed

    Miyagaki, Tomomitsu

    2015-01-01

    B cells have been generally considered to be positive regulators of immune responses because of their ability to produce antigen-specific antibodies and to activate T cells through antigen presentation. Impairment of B cell development and function may cause autoimmune diseases. Recently, specific B cell subsets that can negatively regulate immune responses have been described in mouse models of a wide variety of autoimmune diseases. The concept of those B cells, termed regulatory B cells, is now recognized as important in the murine immune system. Among several regulatory B cell subsets, IL-10-producing regulatory B cells are the most widely investigated. On the basis of discoveries from studies of such mice, human regulatory B cells that produce IL-10 in most cases are becoming an active area of research. There have been emerging data suggesting the importance of human regulatory B cells in various diseases. Revealing the immune regulation mechanisms of human regulatory B cells in human autoimmune diseases could lead to the development of novel B cell targeted therapies. This review highlights the current knowledge on regulatory B cells, mainly IL-10-producing regulatory B cells, in clinical research using human samples. PMID:26725860

  11. [Vaccinations in patients with autoimmune diseases].

    PubMed

    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. Autoimmune disease and epigenome regulation.

    PubMed

    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

  13. [Relation between autoimmune thyroid diseases and connective tissue diseases].

    PubMed

    Barragán-Garfias, Jorge Alberto; Zárate, Arturo

    2013-01-01

    The main physiological function of the immune system consists in the defense against infectious micro-organisms. Sometimes there is a loss of immunological tolerance with the consequence of ignorance of self-antibodies. Some thyroid diseases are related to autoimmune diseases associated with the most common exocrine glands between them. There are also the autoimmune thyroid organ specific diseases, such as Graves-Basedow and the Hashimoto thyroiditis. It has been shown that there is a higher prevalence of autoimmune thyroid diseases in patients with connective tissue diseases (systemic autoimmune) such as Sjögren syndrome, rheumatoid arthritis, systemic lupus erithmatosis and systemic myopathic diseases. In the same way a higher prevalence of antinuclear antibodies against antigens extracted from the nucleus in patients with a thyroid autoimmune disease has been identified. There is a high percentage of patients with subclinical thyroid diseases, and it is recommended for patients with connective tissue diseases with hypo- or hyperthyroidism to have thyroid globulin and peroxide antibodies measured.

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

    PubMed

    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%; 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. PMID:27427767

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

    PubMed Central

    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%; 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. PMID:27427767

  16. The complement system in systemic autoimmune disease.

    PubMed

    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.

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

    PubMed

    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

  18. Large leg ulcers due to autoimmune diseases

    PubMed Central

    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 (CYC), cyclosporine (CyA) 100mg/day, IVIG 125G, ciprofloxacin+IV Iloprost+enoxaparin+aspirin (AAVAA), hyperbaric oxygen therapy (HO), maggot debridement and autologous skin transplantation were performed and the LLU healed. Case 2. A 45-year old women with MCTD developed multiple LLU’s with non-specific inflammation by biopsy. MethP, PR, hydroxychloroquine (HCQ), azathioprine (AZA), CYC, IVIG, AAVAA failed. Treatment for underlying the LLU tibial osteomyelitis and addition of CyA was followed by the LLU healing. Case 3. A 20-year-old man with history of polyarteritis nodosa (PAN) developed painful LLU’s due to small vessel vasculitis (biopsy). MethP, PR 1 mg/kg, CYC, CyA 100 mg/d, AAVAA failed. MRSA sepsis and relapse of systemic PAN developed. IV vancomycin, followed by ciprofloxacin, monthly IVIG (150 g/for 5 days) and infliximab (5 mg/kg) were instituted and the LLU’s healed. Conclusions LLU are extremely resistant to therapy. Combined use of multiple medications and services are needed for healing of LLU due to autoimmune diseases. PMID:21169912

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

    PubMed

    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

  20. Treating prolactinoma can prevent autoimmune diseases.

    PubMed

    Watad, Abdulla; Versini, Mathilde; Jeandel, Pierre-Yves; Amital, Howard; Shoenfeld, Yehuda

    2015-04-01

    Prolactin (PRL) is a pleiotropic hormone; in addition to a wide variety of endocrine effects, PRL also exhibits immunostimulating effects. Therefore, there is increasing evidence linking PRL with a large number of systemic and organ specific autoimmune diseases. Herein, we report the case of an adolescent girl diagnosed with multiple sclerosis (MS) occurring in the context of untreated prolactinoma evolving since childhood. This raises the exciting question of the involvement of PRL in the pathogenesis of MS. It is likely that early treatment of hyperprolactinemia in this case would have significantly reduced the risk of developing MS or even prevented its occurrence.

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

    PubMed Central

    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

  2. Autoimmune diseases in the TH17 era.

    PubMed

    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

  3. Immune-Neuroendocrine Interactions and Autoimmune Diseases

    PubMed Central

    Jara, Luis J.; Navarro, Carmen; Medina, Gabriela; Vera-Lastra, Olga; Blanco, Francisco

    2006-01-01

    The relationship between immune-neuroendocrine system is firmly established. The messengers of this connection are hormones, neuropeptides, neurotransmitters and cytokines. The immune-neuroendocrine system have the capacity to synthesize and release these molecules, which, in turn, can stimulate or suppress the activity of immune or neuroendocrine cells by binding to receptors. In fact, hormones, neuropeptides and neurotransmitters participate in innate and adaptive immune response.Autoimmune rheumatic diseases (ARD) are characterized by aberrant production of pro-inflammatory cytokines, which are a potent activator of the HPA axis. In consequence, high levels of pro-inflammatory hormones such as estrogens and prolactin, and low levels of glucocorticoids, an anti-inflammatory hormone, have been described in the active phase of ARD. In addition, high levels of pro-inflammatory hormones and cytokines have also been frequently detected in organ involvement of patients with ARD, suggesting an abnormal local neuroendocrine immune interaction. There is evidence that hormonal changes may appear before the symptomatic phase of the disease. Therefore, it is possible that a pro-inflammatory hormone favors the rupture of tolerance, which is a key feature of autoimmune diseases. The interactions between the immune-neuroendocrine system have a major impact on our understanding of the pathogenic mechanisms, diagnosis and therapy of ARD. PMID:17162354

  4. The MicroRNA-21 in Autoimmune Diseases

    PubMed Central

    Wang, Shaowen; Wan, Xiaochun; Ruan, Qingguo

    2016-01-01

    MicroRNA-21 (miR-21) is an oncomiR and significantly upregulated in a wide range of cancers. It is strongly involved in apoptosis and oncogenesis, since most of its reported targets are tumor suppressors. Recently, miR-21 was found to be correlated with the pathogenesis of autoimmune diseases and may play an essential role in regulating autoimmune responses. In particular, miR-21 promotes Th17 cell differentiation, which mediates the development of multiple autoimmune diseases. In this article, we review the current research on the mechanisms that regulate miR-21 expression, the potential of miR-21 as a diagnostic biomarker for autoimmune disease and the mechanisms by which miR-21 promotes the development of autoimmune disease. We also discussed the therapeutic potential of targeting miR-21 in treating patients with autoimmune disease. PMID:27271606

  5. The MicroRNA-21 in Autoimmune Diseases.

    PubMed

    Wang, Shaowen; Wan, Xiaochun; Ruan, Qingguo

    2016-06-03

    MicroRNA-21 (miR-21) is an oncomiR and significantly upregulated in a wide range of cancers. It is strongly involved in apoptosis and oncogenesis, since most of its reported targets are tumor suppressors. Recently, miR-21 was found to be correlated with the pathogenesis of autoimmune diseases and may play an essential role in regulating autoimmune responses. In particular, miR-21 promotes Th17 cell differentiation, which mediates the development of multiple autoimmune diseases. In this article, we review the current research on the mechanisms that regulate miR-21 expression, the potential of miR-21 as a diagnostic biomarker for autoimmune disease and the mechanisms by which miR-21 promotes the development of autoimmune disease. We also discussed the therapeutic potential of targeting miR-21 in treating patients with autoimmune disease.

  6. A Genomic Approach to Human Autoimmune Diseases

    PubMed Central

    Pascual, Virginia; Chaussabel, Damien; Banchereau, Jacques

    2010-01-01

    The past decade has seen an explosion in the use of DNA-based microarrays. These techniques permit to assess RNA abundance on a genome-wide scale. Medical applications emerged in the field of cancer, with studies of both solid tumors and hematological malignancies leading to the development of tests that are now used to personalize therapeutic options. Microarrays have also been used to analyze the blood transcriptome in a wide range of diseases. In human autoimmune diseases, these studies are showing potential for identifying therapeutic targets as well as biomarkers for diagnosis, assessment of disease activity and response to treatment. More quantitative and sensitive high throughput RNA profiling methods are starting to be available and will be necessary for transcriptome analyses to become routine tests in the clinical setting. We expect this to crystallize within the coming decade, as they become part of the personalized medicine armamentarium. PMID:20192809

  7. Psoriasis is not an autoimmune disease?

    PubMed

    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.

  8. Spondyloarthropathies in Autoimmune Diseases and Vice Versa

    PubMed Central

    Pérez-Fernández, Oscar M.; Mantilla, Rubén D.; Cruz-Tapias, Paola; Rodriguez-Rodriguez, Alberto; Rojas-Villarraga, Adriana; Anaya, Juan-Manuel

    2012-01-01

    Polyautoimmunity is one of the major clinical characteristics of autoimmune diseases (ADs). The aim of this study was to investigate the prevalence of ADs in spondyloarthropathies (SpAs) and vice versa. This was a two-phase cross-sectional study. First, we examined the presence of ADs in a cohort of patients with SpAs (N = 148). Second, we searched for the presence of SpAs in a well-defined group of patients with ADs (N = 1077) including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and Sjögren's syndrome (SS). Among patients with SpAs, ankylosing spondylitis was observed in the majority of them (55.6%). There were two patients presenting with SS in the SpA group (1.4%) and 5 patients with autoimmune thyroiditis (3.5%). The global prevalence of ADs in SpAs was 4.86%. In the ADs group, there were 5 patients with SpAs (0.46%). Our results suggest a lack of association between SpAs and ADs. Accordingly, SpAs might correspond more to autoinflammatory diseases rather than to ADs. PMID:22400103

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

    PubMed Central

    Anaya, Juan-Manuel; Gómez, LuisMiguel; Castiblanco, John

    2006-01-01

    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. PMID:17162361

  10. Ovarian autoimmune disease: clinical concepts and animal models

    PubMed Central

    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 association with other autoimmune diseases, particularly autoimmune adrenal disease, and takes a toll on both society and individual health. Studies in mice have revealed at least two mechanisms that protect the ovary from autoimmune attack. These mechanisms include control of autoreactive T cells by thymus-derived regulatory T cells, as well as a role for the autoimmune regulator (AIRE), a transcriptional regulator that induces expression of tissue-restricted antigens in medullary thymic epithelial cells during development of T cells. Although the latter mechanism is incompletely defined, it is well established that failure of either results in autoimmune-mediated targeting and depletion of ovarian follicles. In this review, we will address the clinical features and consequences of autoimmune-mediated ovarian infertility in women, as well as the possible mechanisms of disease as revealed by animal models. PMID:25327908

  11. Treatment of autoimmune liver disease: current and future therapeutic options

    PubMed Central

    Trivedi, Palak J.

    2013-01-01

    Autoimmune liver disease spans three predominant processes, from the interface hepatitis of autoimmune hepatitis to the lymphocytic cholangitis of primary biliary cirrhosis, and finally the obstructive fibrosing sclerotic cholangiopathy of primary sclerosing cholangitis. Although all autoimmune in origin, they differ in their epidemiology, presentation and response to immunosuppressive therapy and bile acid based treatments. With an ongoing better appreciation of disease aetiology and pathogenesis, treatment is set ultimately to become more rational. We provide an overview of current and future therapies for patients with autoimmune liver disease, with an emphasis placed on some of the evidence that drives current practice. PMID:23634279

  12. Infections as a cause of autoimmune rheumatic diseases.

    PubMed

    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

  13. An Overview of Organ-Specific Autoimmune Diseases Including Immunotherapy.

    PubMed

    Mastrandrea, Lucy D

    2015-01-01

    A significant number of individuals are affected by autoimmune diseases, which are caused by aberrant recognition of self by the immune system. A wide variety of cells and organ systems are targets of pathologic activation of the immune mediators. Effective and safe therapies aimed at managing the chronic inflammatory aspect of many autoimmune diseases remain elusive. This review will focus on the available interventions and discuss the future of the field to prevent organ destruction by the autoimmune process. PMID:26575465

  14. Pharmacometabolomics-aided Pharmacogenomics in Autoimmune Disease.

    PubMed

    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.

  15. Introducing Polyautoimmunity: Secondary Autoimmune Diseases No Longer Exist

    PubMed Central

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

    2012-01-01

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

  16. Non-MHC genes linked to autoimmune disease.

    PubMed

    Deitiker, Philip; Atassi, M Zouhair

    2012-01-01

    The genetic traits that result in autoimmune diseases represent complicating factors in explicating the molecular and cellular elements of autoimmune responses and how these responses can be overcome or manipulated. This article focuses on the major non-major histocompatibility complex genes that have been found to be linked to autoimmune diseases. A given gene may associate with a number of autoimmune diseases and, conversely, a given disease may link to a number of common autoimmune disease (AD) genes. Collaboration and interaction among genes and the number of diseases that develop and the extensive risk factors shared among ADs further complicate the outcome. This article describes the various relationships between gene regions associated with multiple ADs and the complexity of those relationships.

  17. Autoimmune thrombocytopenia (AITP) and thyroid autoimmune disease (TAD): overlapping syndromes?

    PubMed Central

    Cordiano, I; Betterle, C; Spadaccino, C A; Soini, B; Girolami, A; Fabris, F

    1998-01-01

    The pathogenesis of thrombocytopenia associated with TAD and the occurrence of overlapping traits between TAD and AITP are still a matter of debate. For this reason, we investigated for the presence and specificity of platelet and thyroid autoantibodies in 18 TAD patients with thrombocytopenia, 19 TAD patients without thrombocytopenia and in 22 patients with primary AITP without clinical signs of TAD. Platelet-associated IgG and/or specific circulating platelet autoantibodies were detected in 83% of patients with TAD and thrombocytopenia, in 10% of patients with TAD without thrombocytopenia and in 86% of patients with primary AITP. The reactivity of serum autoantibodies, assayed by MoAb immobilization of platelet antigens (MAIPA), was directed against platelet glycoproteins Ib and/or IIb/IIIa in 50% of the patients with TAD and thrombocytopenia, as in 46% of the patients with primary AITP. Thyroid autoantibodies were found in 89% of patients with TAD and thrombocytopenia, in 95% of patients with TAD without thrombocytopenia, and in 18% of patients with primary AITP. Thyrotropin (TSH) levels determined in three of four AITP patients with thyroid autoantibodies revealed a subclinical hyperthyroidism in one patient. The present study supports the autoimmune aetiology of thrombocytopenia associated with TAD, since the prevalence and specificity of platelet autoantibodies are similar in TAD and primary AITP. The results indicate also that there exists an overlap between thyroid and platelet autoimmunity with or without clinical manifestations. PMID:9737665

  18. Celiac Disease and Autoimmune-Associated Conditions

    PubMed Central

    Lauret, Eugenia; Rodrigo, Luis

    2013-01-01

    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. PMID:23984314

  19. HLA and autoimmune endocrine disease 1985.

    PubMed

    Farid, N R; Thompson, C

    1986-02-01

    We typed patient groups with type I diabetes (n = 78), Graves' disease (n = 81), goitrous autoimmune (n = 52), "silent" (n = 18) and postpartum thyroiditis (n = 15) for human leucocyte antigens (HLA) A, B, C, DR and DQ. The results were compared to those obtained from 256 healthy controls typed for HLA-A, -B, -C and 140 typed for -DR. All these 140 controls were genotyped. Previously described associations of DR3 (OR (odds ratio) = 2.68, p less than 0.005) and DR4 (OR = 3.26, p less than 0.0001) in type I diabetes is confirmed. In this series, however, HLA-DR3/DR4 heterozygotes were apparently at no greater risk for type I diabetes than DR3 or DR4 homozygotes. The relative risk conferred by DR3/DR4 heterozygotes (6.48) was less than that for DR3 homozygosity (2.8), suggesting a recessive major histocompatibility complex-related susceptibility to type I diabetes. Graves' disease was associated with DR3 (OR = 3.02, p less than 0.0005); the increased frequency of DR3 homozygotes in this series is consistent with recessive HLA-linked susceptibility to Graves' disease proposed on the basis of family data. Hashimoto's thyroiditis, on the other hand, was associated with HLA-DR4 (OR = 3.08, p less than 0.0001), the latter finding confirming our earlier report on 21 patients. The increase of HLA-DR4 in both post-partum and silent thyroiditis suggests that these conditions are immunogenetically related, and may well represent variants of chronic autoimmune thyroiditis.

  20. Subsequent leukaemia in autoimmune disease patients.

    PubMed

    Hemminki, Kari; Liu, Xiangdong; Försti, Asta; Ji, Jianguang; Sundquist, Jan; Sundquist, Kristina

    2013-06-01

    Previous studies have shown that patients diagnosed with some autoimmune (AI) diseases are at an increased risk of leukaemia but limited data are available on survival. We systematically analysed the risks (standardized incidence ratio, SIR) and survival (hazard ratio, HR) in nine types of leukaemia among 402 462 patients hospitalized for any of 33 AI diseases and compared to persons not hospitalized for AI diseases. Risk for all leukaemia was increased after 13 AI diseases and survival was decreased after six AI diseases. SIRs were increased after all AI diseases for seven types of leukaemia, including SIR 1·69 (95% confidence interval (CI): 1·29-2·19) for acute lymphoblastic leukaemia (ALL), 1·85 (95% CI: 1·65-2·07) for acute myeloid leukaemia, 1·68 (95% CI: 1·37-2·04) for chronic myeloid leukaemia, 2·20 (95% CI: 1·69-2·81) for 'other myeloid leukaemia', 2·45 (95% 1·99-2·98) for 'other and unspecified leukaemia', 1·81 (95% CI: 1·11-2·81) for monocytic leukaemia, and 1·36 (95% CI: 1·08-1·69) for myelofibrosis. The HRs were increased for four types of leukaemia, most for myelofibrosis (1·74, 95% CI: 1·33-2·29) and ALL (1·42, 95% CI: 1·03-1·95). Some AI diseases, including rheumatoid arthritis, were associated with increased SIRs and HRs in many types of leukaemia. The present data showed increases in risk and decreases in survival for many types of leukaemia after various AI diseases. Leukaemia is a rare complication in AI disease but findings about this comorbidity at the time of leukaemia diagnosis may help to optimize the treatment and improve survival.

  1. Recurrence of autoimmune liver diseases after liver transplantation

    PubMed Central

    Faisal, Nabiha; Renner, Eberhard L

    2015-01-01

    Liver transplantation (LT) is the most effective treatment modality for end stage liver disease caused by many etiologies including autoimmune processes. That said, the need for transplantation for autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC), but not for primary sclerosing cholangitis (PSC), has decreased over the years due to the availability of effective medical treatment. Autoimmune liver diseases have superior transplant outcomes than those of other etiologies. While AIH and PBC can recur after LT, recurrence is of limited clinical significance in most, but not all cases. Recurrent PSC, however, often progresses over years to a stage requiring re-transplantation. The exact incidence and the predisposing factors of disease recurrence remain debated. Better understanding of the pathogenesis and the risk factors of recurrent autoimmune liver diseases is required to develop preventive measures. In this review, we discuss the current knowledge of incidence, diagnosis, risk factors, clinical course, and treatment of recurrent autoimmune liver disease (AIH, PBC, PSC) following LT. PMID:26689244

  2. Emerging role of long noncoding RNAs in autoimmune diseases.

    PubMed

    Wu, Guo-Cui; Pan, Hai-Feng; Leng, Rui-Xue; Wang, De-Guang; Li, Xiang-Pei; Li, Xiao-Mei; Ye, Dong-Qing

    2015-09-01

    Long noncoding RNA (lncRNA), with size larger than 200 nucleotides, is a new class of noncoding RNA. Emerging evidence has revealed that lncRNAs play a key role in the regulation of immunological functions and autoimmunity. Herein, we review the recent findings of lncRNA regulation in immune functions and in the development of autoimmunity and autoimmune disease. In addition, we focus on the involvement of lncRNA regulation in innate and adaptive immune responses, immune cell development, and differential expression of lncRNAs in autoimmune diseases, including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), type 1 diabetes mellitus (T1DM), multiple sclerosis (MS), autoimmune thyroid disease (AITD), psoriasis, polymyositis/dermatomyositis (PM/DM) and Crohn's disease (CD). PMID:25989481

  3. Ocular Involvement in Systemic Autoimmune Diseases.

    PubMed

    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.

  4. Involvement of dendritic cells in autoimmune diseases in children

    PubMed Central

    López de Padilla, Consuelo M; Reed, Ann M

    2007-01-01

    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. PMID:17625003

  5. The mechanisms and applications of T cell vaccination for autoimmune diseases: a comprehensive review.

    PubMed

    Huang, Xin; Wu, Haijing; Lu, Qianjin

    2014-10-01

    Autoimmune diseases (ADs) are a spectrum of diseases originating from loss of immunologic self-tolerance and T cell abnormal autoreactivity, causing organ damage and death. However, the pathogenic mechanism of ADs remains unclear. The current treatments of ADs include nonsteroidal anti-inflammatory drugs (NSAIDS), antimalarials, corticosteroids, immunosuppressive drugs, and biological therapies. With the need to prevent side effects resulting from current treatments and acquire better clinical remission, developing a novel pharmaceutical treatment is extremely urgent. The concept of T cell vaccination (TCV) has been raised as the finding that immunization with attenuated autoreactive T cells is capable of inducing T cell-dependent inhibition of autoimmune responses. TCV may act as an approach to control unwanted adaptive immune response through eliminating the autoreactive T cells. Over the past decades, the effect of TCV has been justified in several animal models of autoimmune diseases including experimental autoimmune encephalomyelitis (EAE), murine autoimmune diabetes in nonobese diabetic (NOD) mice, collagen-induced arthritis (CIA), and so on. Meanwhile, clinical trials of TCV have confirmed the safety and efficacy in corresponding autoimmune diseases ranging from multiple sclerosis (MS) to systemic lupus erythematosus (SLE). This review aims to summarize the ongoing experimental and clinical trials and elucidate possible molecule mechanisms of TCV.

  6. Juvenile autoimmune hepatitis: Spectrum of the disease

    PubMed Central

    Maggiore, Giuseppe; Nastasio, Silvia; Sciveres, Marco

    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 and organ-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 autoantibody 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. PMID:25067998

  7. Autoimmune thyroid disease in systemic lupus erythematosus

    PubMed Central

    Pyne, D; Isenberg, D

    2002-01-01

    Objective: To report the prevalence of autoimmune thyroid disease and thyroid antibodies in 300 patients with SLE, followed up at our centre between 1978 and 2000, by a retrospective analysis of case notes. Results: The prevalence (5.7%) of hypothyroidism in our cohort was higher than in the normal population (1%), while that of hyperthyroidism (1.7%) was not significantly different. Overall 42/300 (14%) of our cohort had thyroid antibodies, rising to 15/22 (68%) in the subgroup who also had thyroid disease (p<0.001). Both antimicrosomal and antithyroglobulin antibodies were detected. The antibodies were found in equally high frequency in the hyperthyroid subgroup (80% patients), whereas in the hypothyroid subgroup antimicrosomal antibodies were more frequent than antithyroglobulin antibodies (64% v 41%). There was no significant difference in the frequency with which antimicrosomal or antithyroglobulin antibodies were detected between the hyperthyroid and hypothyroid subgroups (p>0.2). Conclusion: Our patients with SLE had a prevalence of hypothyroidism, but not hyperthyroidism, greater than that of the normal population. The presence of either condition was associated with a higher frequency of both antimicrosomal and antithyroglobulin antibodies. PMID:11779764

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

    PubMed Central

    Adams Waldorf, Kristina M.; Nelson, J. Lee

    2009-01-01

    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 cells in the mother and of maternal cells in her offspring for decades after birth. The long-term persistence of a small number of cells (or DNA) from a genetically disparate individual is referred to as microchimerism. While microchimerism is common in healthy individuals and is likely to have health benefits, microchimerism has been implicated in some autoimmune diseases such as systemic sclerosis. In this paper, we will first discuss short-term effects of pregnancy on women with autoimmune disease. Pregnancy-associated changes will be reviewed for selected autoimmune diseases including rheumatoid arthritis, systemic lupus erythematosus and autoimmune thyroid disease. The pregnancy-induced amelioration of rheumatoid arthritis presents a window of opportunity for insights into both immunological mechanisms of fetal-maternal tolerance and pathogenic mechanisms in autoimmunity. A mechanistic hypothesis for the pregnancy-induced amelioration of rheumatoid arthritis will be described. We will then discuss the legacy of maternal-fetal cell transfer from the perspective of autoimmune diseases. Fetal and maternal microchimerism will be reviewed with a focus on systemic sclerosis (scleroderma), autoimmune thyroid disease, neonatal lupus and type I diabetes mellitus. PMID:18716941

  9. Antigen-based immunotherapy for autoimmune disease: current status

    PubMed Central

    Hirsch, Darren Lowell; Ponda, Punita

    2015-01-01

    Autoimmune diseases are common chronic disorders that not only have a major impact on the quality of life but are also potentially life-threatening. Treatment modalities that are currently favored have conferred significant clinical benefits, but they may have considerable side effects. An optimal treatment strategy for autoimmune disease would specifically target disease-associated antigens and limit systemic side effects. Similar to allergen-specific immunotherapy for allergic rhinitis, antigen-specific immunotherapy for autoimmune disease aims to induce immune deviation and promote tolerance to specific antigens. In this review, we present the current status of studies and clinical trials in both human and animal hosts that use antigen-based immunotherapy for autoimmune disease. PMID:27471707

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

    PubMed

    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

  11. DNA methylation perspectives in the pathogenesis of autoimmune diseases.

    PubMed

    Sun, Bao; Hu, Lei; Luo, Zhi-Ying; Chen, Xiao-Ping; Zhou, Hong-Hao; Zhang, Wei

    2016-03-01

    DNA methylation is now widely recognized as being critical to maintain the function of immune cells. Recent studies suggest that aberrant DNA methylation levels not only can result in immune cells autoreactivity in vitro, but also are related to autoimmunity in vivo. Environmental factors and genetic polymorphisms cause abnormal methylation, which affects the expression of certain immune-related genes, being becoming hot spot of explaining the mechanism of autoimmune diseases. This paper reviews the importance of abnormal methylation during the development of common autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis and type 1 diabetes, aiming at a better understanding of the pathogenesis of autoimmune diseases and providing new ideas for the treatment of these diseases. PMID:26821302

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

    MedlinePlus

    ... that are suspected to be autoimmune-related. The diseases themselves can affect almost any part of the body, including the kidneys, skin, heart, liver, lymph nodes, thyroid and the central nervous system. ...

  13. The relationship between autoimmunity and specific immunotherapy for allergic diseases

    PubMed Central

    Bozek, Andrzej; Kołodziejczyk, Krzysztof; Bednarski, Piotr

    2015-01-01

    The aim of this study was to perform a 20-year post-specific immunotherapy (SIT) observational evaluation for an assessment of any manifestations of autoimmune disease or the appearance of autoantibodies in serum. In total, 1,888 patients (902 women and 986 men) were observed. The mean age of the patients was 34.1±12.4 y at the start of the prospective observation after finishing SIT. New incidences of autoimmune disease and/or the presence of autoantibodies in serum were monitored. The SIT group was compared with control groups consisting of allergic patients who had very received SIT and with non-allergic subjects. There were no significant differences in the autoimmune disease prevalence between the allergic patients with or without SIT. However, significantly higher prevalence of 4 different autoimmune diseases (AID) were observed in the non-allergic patients during the same period. Additionally, the incidence of 8 different autoantibodies was significantly higher in non-allergic patients than in control subjects. Hashimoto disease was the most common autoimmune disease observed. The results of this long-term observational study indicated a lack of a significant prevalence of new instances of autoimmune disease during 20 y of observation post-SIT and at a rate lower than that of non-allergic control subjects, suggesting that SIT is safe in this regard in the long term. PMID:26431066

  14. Vitamin D in systemic and organ-specific autoimmune diseases.

    PubMed

    Agmon-Levin, Nancy; Theodor, Emanuel; Segal, Ramit Maoz; Shoenfeld, Yehuda

    2013-10-01

    Lately, vitamin D has been linked with metabolic and immunological processes, which established its role as an essential component of human health preservation. Vitamin D has been defined as natural immune modulators, and upon activation of its receptors (VDRs), it regulates calcium metabolism, cellular growth, proliferation and apoptosis, and other immunological functions. Epidemiological data underline a strong correlation between poor vitamin D status and higher risk for chronic inflammatory illnesses of various etiologies, including autoimmune diseases. Epidemiological, genetic, and basic studies indicated a potential role of vitamin D in the pathogenesis of certain systemic and organ-specific autoimmune diseases. These studies demonstrate correlation between low vitamin D and prevalence of diseases. In addition, VDRs' polymorphisms observed in some of these autoimmune diseases may further support a plausible pathogenic link. Notably, for some autoimmune disease, no correlation with vitamin D levels could be confirmed. Thus, in the current review we present the body of evidence regarding the plausible roles of vitamin D and VDR's polymorphism in the pathogenesis of autoimmunity. We summarize the data regarding systemic (i.e., systemic lupus erythematosus, rheumatoid arthritis, etc.) and organ-specific (i.e., multiple sclerosis, diabetes mellitus, primary biliary cirrhosis, etc.) autoimmune diseases, in which low level of vitamin D was found comparing to healthy subjects. In addition, we discuss the correlations between vitamin D levels and clinical manifestations and/or activity of diseases. In this context, we address the rational for vitamin D supplementation in patients suffering from autoimmune diseases. Further studies addressing the mechanisms by which vitamin D affects autoimmunity and the proper supplementation required are needed. PMID:23238772

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

    PubMed

    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.

  16. Occupational exposure to crystalline silica and autoimmune disease.

    PubMed

    Parks, C G; Conrad, K; Cooper, G S

    1999-10-01

    Occupational exposure to silica dust has been examined as a possible risk factor with respect to several systemic autoimmune diseases, including scleroderma, rheumatoid arthritis, systemic lupus erythematosus, and some of the small vessel vasculitidies with renal involvement (e.g., Wegener granulomatosis). Crystalline silica, or quartz, is an abundant mineral found in sand, rock, and soil. High-level exposure to respirable silica dust can cause chronic inflammation and fibrosis in the lung and other organs. Studies of specific occupational groups with high-level silica exposure (e.g., miners) have shown increased rates of autoimmune diseases compared to the expected rates in the general population. However, some clinic- and population-based studies have not demonstrated an association between silica exposure and risk of autoimmune diseases. This lack of effect may be due to the limited statistical power of these studies to examine this association or because the lower- or moderate-level exposures that may be more common in the general population were not considered. Experimental studies demonstrate that silica can act as an adjuvant to nonspecifically enhance the immune response. This is one mechanism by which silica might be involved in the development of autoimmune diseases. Given that several different autoimmune diseases may be associated with silica dust exposure, silica dust may act to promote or accelerate disease development, requiring some other factor to break immune tolerance or initiate autoimmunity. The specific manifestation of this effect may depend on underlying differences in genetic susceptibility or other environmental exposures.

  17. Occupational exposure to crystalline silica and autoimmune disease.

    PubMed Central

    Parks, C G; Conrad, K; Cooper, G S

    1999-01-01

    Occupational exposure to silica dust has been examined as a possible risk factor with respect to several systemic autoimmune diseases, including scleroderma, rheumatoid arthritis, systemic lupus erythematosus, and some of the small vessel vasculitidies with renal involvement (e.g., Wegener granulomatosis). Crystalline silica, or quartz, is an abundant mineral found in sand, rock, and soil. High-level exposure to respirable silica dust can cause chronic inflammation and fibrosis in the lung and other organs. Studies of specific occupational groups with high-level silica exposure (e.g., miners) have shown increased rates of autoimmune diseases compared to the expected rates in the general population. However, some clinic- and population-based studies have not demonstrated an association between silica exposure and risk of autoimmune diseases. This lack of effect may be due to the limited statistical power of these studies to examine this association or because the lower- or moderate-level exposures that may be more common in the general population were not considered. Experimental studies demonstrate that silica can act as an adjuvant to nonspecifically enhance the immune response. This is one mechanism by which silica might be involved in the development of autoimmune diseases. Given that several different autoimmune diseases may be associated with silica dust exposure, silica dust may act to promote or accelerate disease development, requiring some other factor to break immune tolerance or initiate autoimmunity. The specific manifestation of this effect may depend on underlying differences in genetic susceptibility or other environmental exposures. PMID:10970168

  18. Perspectives of the relationship between IL-7 and autoimmune diseases.

    PubMed

    Wang, Xiao-Song; Li, Bao-Zhu; Hu, Lin-Feng; Wen, Peng-Fei; Zhang, Min; Pan, Hai-Feng; Ye, Dong-Qing

    2013-12-01

    Interleukin (IL)-7 is one of the IL-2 family cytokines comprised of IL-2, IL-4, IL-7, IL-9, IL-15, as well as IL-21. IL-7 is mainly secreted by stroma cells in primary lymphoid tissues, playing an essential role in the program of T cell development. Recently, studies have revealed that physiological function exerted by immunocytes can be influenced by aberrant IL-7 signaling, which is common in abnormal autoimmunity regulation. There is also increasing evidence that IL-7 is involved in several autoimmune diseases, such as rheumatoid arthritis, type I diabetes, multiple sclerosis and systemic lupus erythematosus, etc. Targeting components in IL-7 signaling pathways may have potential significance for treating numerous autoimmune diseases. In this review, we therefore summarize our current understandings regarding the relationship between IL-7 and autoimmune diseases so as to render more valuable information on this kind of research. PMID:23934388

  19. Novel insights into Tim-4 function in autoimmune diseases.

    PubMed

    Fang, Xin-Yu; Xu, Wang-Dong; Pan, Hai-Feng; Leng, Rui-Xue; Ye, Dong-Qing

    2015-06-01

    T-cell immunoglobulin domain and mucin domain-4 (Tim-4) was first recognized as a costimulatory molecule regulating T-cell activation. Dysregulation of Tim-4 has been found in some autoimmune conditions, particularly in the immune cells. Recently, Tim-4 was found to be critical for regulating T cells, with the ability of inhibiting naïve CD4(+) T cells and Th17 cells, increasing Th2 cell development. Tim-4 can also enhance T cell expansion via linker for activation of T cells, extracellular signal-regulated kinase (ERK) and Protein kinase B (PKB, also known as Akt) signaling pathways. Moreover, the Tim-4 signaling pathway may affect multiple molecular processes in autoimmune diseases. A number of previous studies have demonstrated that Tim-4 influences chronic autoimmune diseases, such as rheumatoid arthritis (RA) and systemic lupus erythematosus. In addition, an association between Tim-4 polymorphisms and susceptibility to several autoimmune diseases have been identified, such as RA. Taken together, recent works have indicated that Tim-4 may represent a novel target for the treatment of autoimmune diseases. In this article, we will discuss the Tim-4 function and the therapeutic potential of modulating the Tim-4 in autoimmune diseases.

  20. Anti-CD38 autoimmunity in patients with chronic autoimmune thyroiditis or Graves' disease

    PubMed Central

    Antonelli, A; Fallahi, P; Nesti, C; Pupilli, C; Marchetti, P; Takasawa, S; Okamoto, H; Ferrannini, E

    2001-01-01

    Autoantibodies directed against human CD38 (an enzyme catalysing the interconversion of NAD+ and cyclic ADP-ribose) have been demonstrated recently in patients with type 2 diabetes. We tested 220 consecutive Caucasian patients with autoimmune chronic thyroiditis, 104 patients with Graves' disease, 220 subjects from the general population (control I) and 78 healthy control subjects not affected by thyroid autoimmune disorders (control II) for the presence of anti-CD38 autoimmunity. Using Western blot analysis and optical densitometry, a specific band corresponding to human recombinant CD38 was identified in the serum of several subjects. By defining anti-CD38 positivity as a standardized optical reading >3 s.d. higher than the mean value of control I, 10·4% of patients with thyroiditis and 7·7% of Graves' patients were anti-CD38 positive (P = 0·0009 versus 1·8% of control I). Similarly, 13·1% of patients with thyroiditis and 10·5% of Graves' patients had a standardized optical reading >3 s.d. higher than the mean value of the subjects not affected by thyroid autoimmune disorders (P = 0·002 versus 1·2% of control II). Anti-CD38 autoimmunity did not differ between euthyroid, hyperthyroid or hypothyroid patients or between patients with or without thyroid hypoechogenicity. Anti-CD38 autoantibodies were associated with higher levels of circulating antithyroid-peroxidase antibodies (P = 0·03) and they were more frequent in Graves' patients with ophthalmopathy (P < 0·05). Anti-CD38 autoantibodies are a new autoimmune marker in chronic autoimmune thyroiditis and Graves' disease. The specific role of CD38 and its autoantibodies in the modulation of thyroid cell function or growth remains to be investigated. PMID:11737057

  1. Pathogenesis of endometriosis: natural immunity dysfunction or autoimmune disease?

    PubMed

    Matarese, Giuseppe; De Placido, Giuseppe; Nikas, Yorgos; Alviggi, Carlo

    2003-05-01

    Endometriosis is a chronic inflammatory disease, characterized by implantation and growth of endometrial tissue outside the uterine cavity. This disabling condition is considered one of the most frequent diseases in gynecology, affecting 15-20% of women in their reproductive life. Pelvic endometriosis, the most common form of the disease, is associated with increased secretion of pro-inflammatory cytokines, neo-angiogenesis, intrinsic anomalies of the refluxed endometrium and impaired function of cell-mediated natural immunity. Recently, endometriosis has also been considered to be an autoimmune disease, owing to the presence of autoantibodies, the association with other autoimmune diseases and recurrent immune-mediated abortion. These findings are in apparent contradiction with the reduced cell-mediated natural immunity observed during the disease. In this review, we focus on the multiple processes underlying the complex pathogenesis of endometriosis, with particular emphasis on the role played by the immune system with the induction of autoimmunity. PMID:12763528

  2. Recent Advances in the Genetics of Autoimmune Disease

    PubMed Central

    Gregersen, Peter K.; Olsson, Lina M.

    2010-01-01

    Extraordinary technical advances in the field of human genetics over the past few years have catalyzed an explosion of new information about the genetics of human autoimmunity. In particular, the ability to scan the entire genome for common polymorphisms that associate with disease has led to the identification of numerous new risk genes involved in autoimmune phenotypes. Several themes are emerging. Autoimmune disorders have a complex genetic basis; multiple genes contribute to disease risk, each with generally modest effects independently. In addition, it is now clear that common genes underlie multiple autoimmune disorders. There is also heterogeneity among subphenotypes within a disease and across major racial groups. The current crop of genetic associations are only the start of a complete catalog of genetic factors for autoimmunity, and it remains unclear to what extent common variation versus multiple rare variants contribute to disease susceptibility. The current review focuses on recent discoveries within functionally related groups of genes that provide clues to novel pathways of pathogenesis for human autoimmunity. PMID:19302045

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

    PubMed

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

    2015-06-16

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

  4. Environmental triggers and epigenetic deregulation in autoimmune disease.

    PubMed

    Javierre, Biola M; Hernando, Henar; Ballestar, Esteban

    2011-12-01

    The study of epigenetic mechanisms in the pathogenesis of autoimmune diseases is receiving unprecedented attention from clinicians and researchers in the field. Autoimmune disorders comprise a wide range of genetically complex diseases, including systemic lupus erythematosus, rheumatoid arthritis, type 1 diabetes, and multiple sclerosis. Together they affect a significant proportion of the population and have a great economic impact on public health systems. Epigenetic mechanisms control gene expression and are influenced by external stimuli, linking environment and gene function. A variety of environmental agents, such as viral infection, hormones, certain drugs, and pollutants, have been found to influence the development of autoimmune diseases. On the other hand, there is considerable evidence of epigenetic changes, particularly DNA methylation alterations, in diseases like systemic lupus erythematosus, rheumatoid arthritis, or multiple sclerosis. However, the gap in our understanding between the specific effects of external agents and the influence on epigenetic profiles has not yet been filled. Here we review a number of studies describing epigenetic alterations in autoimmune diseases and a range of environmental factors that influence the development of autoimmune diseases. We also discuss potential mechanisms linking environment and epigenetics, consider the prospects for future epigenetic studies addressing the relationship between environment and epigenetics, and comment on the use of drugs with an epigenetic-reversing effect in the clinical management of these diseases. PMID:22204770

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

    PubMed

    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

  6. The human microbiome in rheumatic autoimmune diseases: A comprehensive review.

    PubMed

    Coit, Patrick; Sawalha, Amr H

    2016-09-01

    The human microbiome consists of the total diversity of microbiota and their genes. High-throughput sequencing has allowed for inexpensive and rapid evaluation of taxonomic representation and functional capability of the microbiomes of human body sites. Autoimmune and inflammatory rheumatic diseases are characterized by dysbiosis of the microbiome. Microbiome dysbiosis can be influenced by host genetics and environmental factors. Dysbiosis is also associated with shifts in certain functional pathways. The goal of this article is to provide a current and comprehensive review of the unique characteristics of the microbiome of patients with autoimmune and inflammatory rheumatic diseases, measured using high-throughput sequencing. We also highlight the need for broader studies utilizing a longitudinal approach to better understand how the human microbiome contributes to disease susceptibility, and to characterize the role of the interaction between host genetics and microbial diversity in the pathogenesis of autoimmune diseases, disease manifestations, and progression. PMID:27493014

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

    PubMed Central

    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

  8. Coagulation and Autoimmunity in Scleroderma Interstitial Lung Disease

    PubMed Central

    Ludwicka-Bradley, Anna; Silver, Richard M.; Bogatkevich, Galina S.

    2010-01-01

    Objectives Interstitial lung disease in systemic sclerosis (SSc-ILD) is often an irreversible and progressive fibrosing process that now is the leading cause of scleroderma-related deaths. In this review we present our current understanding of the role played by coagulation and particularly by thrombin in autoimmune-mediated tissue injury and fibrosis, mainly as it relates to SSc-ILD. Methods We used PubMed to search for articles published up to October 2010 for keywords referring to autoimmunity, coagulation, pulmonary fibrosis, and scleroderma. Results SSc-ILD is an autoimmune disease associated with lymphocyte activation and release of various cytokines and growth factors. The production of autoantibodies is a central feature in SSc. Activation of the coagulation cascade with release of thrombin is 1 of the earliest events following tissue injury. Thrombin contributes to autoimmune responses by activating of pathogenic Th2 lymphocyte profile in SSc. Thrombin also modulates tissue repair responses, stimulates transformation of epithelial cells, endothelial cells, and fibroblasts into myofibroblast phenotype, and induces secretion of several pro-immune and profibrotic factors, which serve as antigens for pathogenic autoantibodies production in SSc-ILD. Conclusions The identification of links between autoimmunity and coagulation would provide new insights into the pathogenesis of pulmonary fibrosis associated with autoimmune diseases and further acknowledge the importance of thrombin in the development of SSc-ILD. PMID:21168185

  9. Current Status of Therapy in Autoimmune Liver Disease

    PubMed Central

    Al-Harthi, Nadya; Heathcote, E. Jenny

    2009-01-01

    Therapeutic strategies for autoimmune liver diseases are increasingly established. Although proportionately uncommon, specialist centers have with time refined the best approaches for each disease, based on an improved understanding of the spectrum of presentation. The major treatment aims are to prevent end-stage liver disease and its associated complications. As a result of drugs such as ursodeoxycholic acid, predniso(lo)ne and azathioprine, both primary biliary cirrhosis and autoimmune hepatitis are now less commonly indications for liver transplantation. Unfortunately, the same inroads in treatment efficacy have as yet not been made for primary sclerosing cholangitis, although the recognition that a subset of patients may have a treatable secondary sclerosing cholangitis (IgG4 related) is helping a proportion. With better biological understanding, more specific interventions are expected that will benefit all those with autoimmune liver diseases. PMID:21180531

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

    PubMed

    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.

  11. Is Tourette's syndrome an autoimmune disease?

    PubMed

    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.

  12. The role of AIRE in human autoimmune disease.

    PubMed

    Akirav, Eitan M; Ruddle, Nancy H; Herold, Kevan C

    2011-01-01

    The autoimmune regulator (AIRE) gene encodes a transcription factor involved in the presentation of tissue-restricted antigens during T-cell development in the thymus. Mutations of this gene lead to type 1 autoimmune polyglandular syndrome (APS-1), also termed autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) syndrome, which is characterized by the clinical presentation of at least two of a triad of underlying disorders: Addison disease, hypoparathyroidism and chronic mucocutaneous candidiasis. This Review describes the process of positive and negative selection of developing T cells in the thymus and the role of AIRE as a regulator of peripheral antigen presentation. Furthermore, it addresses how mutations of this gene lead to the failure to eliminate autoreactive T cells, which can lead to clinical autoimmune syndromes. PMID:21102544

  13. Pink Light on Mitochondria in Autoimmunity and Parkinson Disease.

    PubMed

    Mantegazza, Adriana R; Marks, Michael S

    2016-07-12

    Mitochondrial dysfunction and T cell autoimmunity have been independently implicated in Parkinson disease pathogenesis. In a recent publication in Cell, Matheoud et al. (2016) link them by describing a new mechanism, activated in familial forms of Parkinson disease, in which mitochondrial proteins are processed for recognition by CD8+ T cells. PMID:27411006

  14. Peripheral blood T-lymphocyte subsets in autoimmune thyroid disease.

    PubMed

    Covas, M I; Esquerda, A; García-Rico, A; Mahy, N

    1992-01-01

    Interest in T-lymphocyte subsets has arisen because of their involvement in the autoimmune process. Contradictory results have been published in the literature about the number of peripheral blood lymphocyte subsets in autoimmune diseases. In order to investigate the number and distribution of peripheral blood lymphocyte subsets in autoimmune thyroid disease, the levels of total T-lymphocytes (CD3), T-helper (CD4) and T-suppressor/cytotoxic (CD8) lymphocytes were determined in 44 patients with Graves' disease (1), multinodular goiter (2) and Hashimoto's thyroiditis (3). All patients had high levels of antithyroglobulin and thyroid antiperoxidase (antimicrosomal) antibodies. The T subset levels were related to the functional thyroid status, measured as serum free thyroxine (FT4) and thyrotropin (TSH). Our data show the existence of a strong influence of functional status on CD3, CD4 and CD8 levels, as reflected in the significant correlations obtained with FT4 (negative) and TSH (positive). A significant decrease in all populations was observed in Graves' disease hyperthyroid patients. A decrease in the CD4/CD8 ratio in Hashimoto's thyroiditis hypothyroid patients was observed, in contrast to an increase in the ratio in autoimmune hyperthyroid patients. This points to the CD4/CD8 ratio as a differential characteristic between the two autoimmune (hypothyroid and hyperthyroid) entities, independent of free thyroxine levels. No significant correlation was found between antithyroid antibody levels and peripheral blood T-lymphocyte subsets or serum levels of FT4 and TSH.

  15. Emerging role of Interleukin-22 in autoimmune diseases

    PubMed Central

    Pan, Hai-Feng; Li, Xiang-Pei; Zheng, Song Guo; Ye, Dong-Qing

    2014-01-01

    Interleukin-22 (IL-22) is an IL-10 family cytokine member that was recently discovered to be mainly produced by Th17 cells. Previous studies have indicated the importance of IL-22 in host defense against Gram-negative bacterial organisms (in gut and lung). Recently, there is emerging evidence that IL-22 is involved in the development and pathogenesis of several autoimmune diseases, such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), multiple sclerosis (MS), Sjögren’s syndrome (SS) and psoriasis. Therapeutics targeting IL-22 therefore may have promise for treating various autoimmune diseases. In this review, we discuss the recent progression of the involvement of IL-22 in the development and pathogenesis of autoimmune diseases, as well as its clinical implications and therapeutic potential. PMID:22906768

  16. Autoimmune pathogenesis of Chagas heart disease: looking back, looking ahead.

    PubMed

    Bonney, Kevin M; Engman, David M

    2015-06-01

    Chagas heart disease is an inflammatory cardiomyopathy that develops in approximately one-third of individuals infected with the protozoan parasite Trypanosoma cruzi. Since the discovery of T. cruzi by Carlos Chagas >100 years ago, much has been learned about Chagas disease pathogenesis; however, the outcome of T. cruzi infection is highly variable and difficult to predict. Many mechanisms have been proposed to promote tissue inflammation, but the determinants and the relative importance of each have yet to be fully elucidated. The notion that some factor other than the parasite significantly contributes to the development of myocarditis was hypothesized by the first physician-scientists who noted the conspicuous absence of parasites in the hearts of those who succumbed to Chagas disease. One of these factors-autoimmunity-has been extensively studied for more than half a century. Although questions regarding the functional role of autoimmunity in the pathogenesis of Chagas disease remain unanswered, the development of autoimmune responses during infection clearly occurs in some individuals, and the implications that this autoimmunity may be pathogenic are significant. In this review, we summarize what is known about the pathogenesis of Chagas heart disease and conclude with a view of the future of Chagas disease diagnosis, pathogenesis, therapy, and prevention, emphasizing recent advances in these areas that aid in the management of Chagas disease.

  17. [Acquired and congenital heart diseases during pregancy].

    PubMed

    De Feo, Stefania; Iacovoni, Attilio; Faggiano, Pompilio

    2012-05-01

    Heart diseases are the leading cause of maternal morbidity and mortality. The number of patients with congenital heart diseases reaching childbearing age, as well as the proportion of women with acquired conditions, such as ischemic heart disease, becoming pregnant is constantly increasing. All women with known heart disease should have pre-pregnancy counseling, to assess maternal and fetal risk. Women at moderate or high risk should be under the care of a specialist prenatal team with experience in managing women with heart disease during pregnancy. Conditions that are considered at particularly high risk (mortality >10%) include Marfan syndrome with dilated aortic root, severe left ventricular dysfunction, severe left heart obstructive lesions, and pulmonary hypertension. Peripartum cardiomyopathy is a rare and potentially fatal disease related to pregnancy and the postnatal period that presents with symptoms of congestion and/or hypoperfusion and may rapidly progress to acute and life-threatening heart failure. However, the majority of women with heart disease can tolerate pregnancy; therefore an adequate multidisciplinary approach with the gynecologist, anesthesiologist and cardiologist should be advocated in order to reduce maternal and fetal risks associated with pregnancy.

  18. Dendritic cells in autoimmune thyroid disease.

    PubMed

    Kabel, P J; Voorbij, H A; van der Gaag, R D; Wiersinga, W M; de Haan, M; Drexhage, H A

    1987-01-01

    Dendritic cells form a morphologically distinct class of cells characterized by shape, reniform nucleus, absent to weak acid-phosphatase activity and strong Class II MHC determinant positivity. Functionally they are the most efficient cells in antigen presentation to T-lymphocytes which indicates their role in the initiation of an immune response. Using immunehistochemical techniques we studied the presence of dendritic cells in normal Wistar rat and human thyroids, in thyroids of BBW rats developing thyroid autoimmunity and in Graves' goitres. Dendritic cells could be identified in all thyroids studied and were positioned underneath the thyrocytes in between the follicles. Skin dendritic cells travel via lymphatics to draining lymph nodes, thus forming an antigen presenting cell system. It is likely that a similar cell system exists on the level of the thyroid for dendritic cells have also been detected in thyroid draining lymph nodes. In normal thyroid tissue of both human and rat dendritic cells were relatively scarce. During the initial phases of the thyroid autoimmune response in the BBW rat (before the appearance of Tg-antibodies in the circulation) numbers of thyroid dendritic cells increased. Intrathyroidal T-helper cells, B-cells or plasma cells could not be found. The thyroid draining lymph node contained large numbers of plasma cells. During the later stages of the thyroid autoimmune response in the BB/W rat (after the appearance of Tg-antibodies in the circulation) and in Graves' goitres dendritic cells were not only present in high number, but 20-30% were seen in contact with now-present intrathyroidal T-helper lymphocytes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3475920

  19. Dendritic cells in autoimmune thyroid disease.

    PubMed

    Kabel, P J; Voorbij, H A; van der Gaag, R D; Wiersinga, W M; de Haan, M; Drexhage, H A

    1987-01-01

    Dendritic cells form a morphologically distinct class of cells characterized by shape, reniform nucleus, absent to weak acid-phosphatase activity and strong Class II MHC determinant positivity. Functionally they are the most efficient cells in antigen presentation to T-lymphocytes which indicates their role in the initiation of an immune response. Using immunehistochemical techniques we studied the presence of dendritic cells in normal Wistar rat and human thyroids, in thyroids of BBW rats developing thyroid autoimmunity and in Graves' goitres. Dendritic cells could be identified in all thyroids studied and were positioned underneath the thyrocytes in between the follicles. Skin dendritic cells travel via lymphatics to draining lymph nodes, thus forming an antigen presenting cell system. It is likely that a similar cell system exists on the level of the thyroid for dendritic cells have also been detected in thyroid draining lymph nodes. In normal thyroid tissue of both human and rat dendritic cells were relatively scarce. During the initial phases of the thyroid autoimmune response in the BBW rat (before the appearance of Tg-antibodies in the circulation) numbers of thyroid dendritic cells increased. Intrathyroidal T-helper cells, B-cells or plasma cells could not be found. The thyroid draining lymph node contained large numbers of plasma cells. During the later stages of the thyroid autoimmune response in the BB/W rat (after the appearance of Tg-antibodies in the circulation) and in Graves' goitres dendritic cells were not only present in high number, but 20-30% were seen in contact with now-present intrathyroidal T-helper lymphocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

  20. Age impact on autoimmune thyroid disease in females

    NASA Astrophysics Data System (ADS)

    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.

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

    PubMed

    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.

  2. [Acquired cystic renal disease. Association with hypernephroma].

    PubMed

    Comesaña, E; Pesqueira, D; Tardáguila, F; De la Fuente, A; Antón, I; Vidal, L; Zungri, E

    1992-02-01

    Emergence of multiple bilateral renal cysts observed in patients undergoing periodic haemodialysis is 40%. The pathology, known as Acquired Cystic Renal Disease (A.C.R.D.) presents a high association to renal cancer. Two cases of A.C.R.D. and their association with hypernephroma, one resulting in secondary retroperitoneal haemorrhage and the other in intracystic haemorrhage, are presented. Forms and diagnosis are analyzed, insisting upon the need of monitoring the patients in haemodialysis from the point of view of tumour emergence.

  3. The use of hematopoietic stem cells in autoimmune diseases.

    PubMed

    Ben Nasr, Moufida; Bassi, Roberto; Usuelli, Vera; Valderrama-Vasquez, Alessandro; Tezza, Sara; D'Addio, Francesca; Fiorina, Paolo

    2016-06-01

    Hematopoietic stem cells (HSCs) have been shown recently to hold much promise in curing autoimmune diseases. Newly diagnosed Type 1 diabetes individuals have been successfully reverted to normoglycemia by administration of autologous HSCs in association with a nonmyeloablative regimen (antithymocyte globulin + cyclophasmide). Furthermore, recent trials reported positive results by using HSCs in treatment of systemic sclerosis, multiple sclerosis and rheumatoid arthritis as well. Early data suggested that HSCs possess immunological properties that may be harnessed to alleviate the symptoms of individuals with autoimmune disorders and possibly induce remission of autoimmune diseases. Mechanistically, HSCs may facilitate the generation of regulatory T cells, may inhibit the function of autoreactive T-cell function and may reshape the immune system. PMID:27165670

  4. Modulation by Melatonin of the Pathogenesis of Inflammatory Autoimmune Diseases

    PubMed Central

    Lin, Gu-Jiun; Huang, Shing-Hwa; Chen, Shyi-Jou; Wang, Chih-Hung; Chang, Deh-Ming; Sytwu, Huey-Kang

    2013-01-01

    Melatonin is the major secretory product of the pineal gland during the night and has multiple activities including the regulation of circadian and seasonal rhythms, and antioxidant and anti-inflammatory effects. It also possesses the ability to modulate immune responses by regulation of the T helper 1/2 balance and cytokine production. Autoimmune diseases, which result from the activation of immune cells by autoantigens released from normal tissues, affect around 5% of the population. Activation of autoantigen-specific immune cells leads to subsequent damage of target tissues by these activated cells. Melatonin therapy has been investigated in several animal models of autoimmune disease, where it has a beneficial effect in a number of models excepting rheumatoid arthritis, and has been evaluated in clinical autoimmune diseases including rheumatoid arthritis and ulcerative colitis. This review summarizes and highlights the role and the modulatory effects of melatonin in several inflammatory autoimmune diseases including multiple sclerosis, systemic lupus erythematosus, rheumatoid arthritis, type 1 diabetes mellitus, and inflammatory bowel disease. PMID:23727938

  5. Subclasses of immunoglobulins and autoantibodies in autoimmune diseases.

    PubMed

    Outschoorn, I; Rowley, M J; Cook, A D; Mackay, I R

    1993-01-01

    The differing capacity of subclasses of IgG to bind to protein A and protein G was used in a sequential affinity purification procedure to examine immunoglobulin isotypes and subclasses in autoimmune disease. The utility of the procedure is that affinity-purified fractions containing particular isotypes and subclasses of immunoglobulin can be analyzed for their content of autoantibodies using standard techniques. For each of four autoimmune diseases studied, chronic active hepatitis, Sjogren's syndrome, primary biliary cirrhosis, and rheumatoid arthritis, there were characteristic protein elution profiles and the various disease-specific autoantibodies showed preferential distributions among the isotypes and subclasses. Moreover there was not an absolute correlation between an increased level of a particular subclass and the occurrence of antibodies of that subclass. The occurrence of highly disease-specific immunoglobulin subclass profiles suggests that the hypergammaglobulinemia associated with autoimmunity cannot be attributed entirely to polyclonal B-cell activation. Rather, there are disease-specific alterations in isotype subclass switching which may reflect different cytokine-dependent influences on autoimmune B cells and their products.

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

    PubMed Central

    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

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

    PubMed

    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

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

    SciTech Connect

    Aaltonen, J.; Bjoerses, P.; Peltonen, L.

    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.

  9. Cannabinoids and autoimmune diseases: A systematic review.

    PubMed

    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

  10. Autologous hematopoietic stem cell transplantation for autoimmune diseases.

    PubMed

    Gratwohl, A; Passweg, J; Bocelli-Tyndall, C; Fassas, A; van Laar, J M; Farge, D; Andolina, M; Arnold, R; Carreras, E; Finke, J; Kötter, I; Kozak, T; Lisukov, I; Löwenberg, B; Marmont, A; Moore, J; Saccardi, R; Snowden, J A; van den Hoogen, F; Wulffraat, N M; Zhao, X W; Tyndall, A

    2005-05-01

    Experimental data and early phase I/II studies suggest that high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (HSCT) can arrest progression of severe autoimmune diseases. We have evaluated the toxicity and disease response in 473 patients with severe autoimmune disease treated with autologous HSCT between 1995 and 2003, from 110 centers participating in the European Group for Blood and Marrow Transplantation (EBMT) autoimmune disease working party database. Survival, transplant-related mortality, treatment response and disease progression were assessed. In all, 420 patients (89%; 86+/-4% at 3 years, median follow-up 20 months) were alive, 53 (11%) had died from transplant-related mortality (N=31; 7+/-3% at 3 years) or disease progression (N=22; 9+/-4% at 3 years). Of 370 patients, 299 evaluable for response (81%) showed a treatment response, which was sustained in 213 (71% of responders). Response was associated with disease (P<0.001), was better in patients who received cyclophosphamide during mobilization (relative risk (RR)3.28 (1.57-6.83)) and was worse with increasing age (>40 years, RR0.29 (0.11-0.82)). Disease progression was associated with disease (P<0.001) and conditioning intensity (high intensity, RR1; intermediate intensity, RR1.81 (0.96-3.42)); low intensity, RR2.34 (1.074-5.11)). These data from the collective EBMT experience support the hypothesis that autologous HSCT can alter disease progression in severe autoimmune disease.

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

    NASA Astrophysics Data System (ADS)

    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.

  12. Why are women predisposed to autoimmune rheumatic diseases?

    PubMed Central

    2009-01-01

    The majority of autoimmune diseases predominate in females. In searching for an explanation for this female excess, most attention has focused on hormonal changes - both exogenous changes (for example, oral contraceptive pill) and fluctuations in endogenous hormone levels particularly related to menstruation and pregnancy history. Other reasons include genetic differences, both direct (influence of genes on sex chromosomes) and indirect (such as microchimerism), as well as gender differences in lifestyle factors. These will all be reviewed, focusing on the major autoimmune connective tissue disorders: rheumatoid arthritis, systemic lupus erythematosus and scleroderma. PMID:19863777

  13. [Metabolic disorders and nutritional status in autoimmune thyroid diseases].

    PubMed

    Kawicka, Anna; Regulska-Ilow, Bożena; Regulska-Ilow, Bożena

    2015-01-02

    In recent years, the authors of epidemiological studies have documented that autoimmune diseases are a major problem of modern society and are classified as diseases of civilization. Autoimmune thyroid diseases (ATDs) are caused by an abnormal immune response to autoantigens present in the thyroid gland - they often coexist with other autoimmune diseases. The most common dysfunctions of the thyroid gland are hypothyroidism, Graves-Basedow disease and Hashimoto's disease. Hashimoto's thyroiditis can be the main cause of primary hypothyroidism of the thyroid gland. Anthropometric, biochemical and physicochemical parameters are used to assess the nutritional status during the diagnosis and treatment of thyroid diseases. Patients with hypothyroidism are often obese, whereas patients with hyperthyroidism are often afflicted with rapid weight loss. The consequence of obesity is a change of the thyroid hormones' activity; however, weight reduction leads to their normalization. The activity and metabolic rate of thyroid hormones are modifiable. ATDs are associated with abnormalities of glucose metabolism and thus increased risk of developing diabetes mellitus type 1 and type 2. Celiac disease (CD) also increases the risk of developing other autoimmune diseases. Malnutrition or the presence of numerous nutritional deficiencies in a patient's body can be the cause of thyroid disorders. Coexisting deficiencies of such elements as iodine, iron, selenium and zinc may impair the function of the thyroid gland. Other nutrient deficiencies usually observed in patients suffering from ATD are: protein deficiencies, vitamin deficiencies (A, C, B6, B5, B1) and mineral deficiencies (phosphorus, magnesium, potassium, sodium, chromium). Proper diet helps to reduce the symptoms of the disease, maintains a healthy weight and prevents the occurrence of malnutrition. This article presents an overview of selected documented studies and scientific reports on the relationship of metabolic

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

    ClinicalTrials.gov

    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

  15. Molecular Mimicry as a Mechanism of Autoimmune Disease

    PubMed Central

    Cusick, Matthew F.; Libbey, Jane E.; Fujinami, Robert S.

    2012-01-01

    A variety of mechanisms have been suggested as the means by which infections can initiate and/or exacerbate autoimmune diseases. One mechanism is molecular mimicry, where a foreign antigen shares sequence or structural similarities with self-antigens. Molecular mimicry has typically been characterized on an antibody or T cell level. However, structural relatedness between pathogen and self does not account for T cell activation in a number of autoimmune diseases. A proposed mechanism that could have been misinterpreted for molecular mimicry is the expression of dual T cell receptors (TCR) on a single T cell. These T cells have dual reactivity to both foreign and self-antigens leaving the host vulnerable to foreign insults capable of triggering an autoimmune response. In this review, we briefly discuss what is known about molecular mimicry followed by a discussion of the current understanding of dual TCRs. Finally, we discuss three mechanisms, including molecular mimicry, dual TCRs and chimeric TCRs, by which dual reactivity of the T cell may play a role in autoimmune diseases. PMID:22095454

  16. Prevalence of Sjögren's syndrome in autoimmune diseases.

    PubMed Central

    Coll, J; Rives, A; Griñó, M C; Setoain, J; Vivancos, J; Balcells, A

    1987-01-01

    Investigations were carried out in 122 patients in order to identify features of Sjögren's syndrome (keratoconjunctivitis sicca and xerostomia). There were 78 patients with autoimmune diseases (rheumatoid arthritis 21, scleroderma 16, sicca syndrome 16, primary biliary cirrhosis 14, and other autoimmune disorders 11), 11 patients with chronic liver disease other than primary biliary cirrhosis, and 33 patients with a variety of non-autoimmune conditions or no obvious disease. Keratoconjunctivitis sicca was diagnosed by Schirmer's test and rose bengal staining. The oral component was diagnosed by labial biopsy and salivary scintigraphy. Forty nine patients had a definite Sjögren's syndrome, and 77 patients had the syndrome definitely or probably. Definite Sjögren's syndrome occurred in 62% of patients with rheumatoid arthritis, in 69% of patients with scleroderma, and in 71% of patients with primary biliary cirrhosis. Sjögren's syndrome was not present in any of the patients with non-autoimmune conditions. These results show that in an unselected group of patients with Sjögren's syndrome the prevalence of rheumatoid arthritis (26%), scleroderma (22%), sicca syndrome (22%), and primary biliary cirrhosis (20%) is similar. Also the occurrence of Sjögren's syndrome in primary biliary cirrhosis is even higher than that in rheumatoid arthritis. PMID:3592784

  17. Oral tolerance: mechanisms and therapy of autoimmune diseases.

    PubMed

    Koh, D R

    1998-01-01

    Oral tolerance is a state of immune hyporesponsiveness induced by the oral or mucosal exposure to antigens. This state is dependent on the dose of the oral antigen administered, with a low dose stimulating regulatory T cell development leading to an active immune suppression that is transferable via T cells. The active mechanism appears to be a cytokine mediated immune deviation with a predominant Th2 and Th3 response (TGF-beta). In contrast, high dose oral antigens lead to clonal deletion and anergy. The active suppression of low dose oral tolerance can also suppress an unrelated immune response (bystander suppression) paving the way for therapy of autoimmune diseases like rheumatoid arthritis. Oral tolerance has been effective in the treatment of autoimmune diseases like experimental autoimmune encephalomyelitis (EAE), collagen-induced arthritis (CIA) and insulin-dependent diabetes in animals. However, recent studies in human autoimmune diseases have not been as effective but the results are encouraging and more work is required to understand the mechanisms involved and other factors that may modulate the response. PMID:9588275

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

    PubMed

    Ponsonby, Anne-Louise; McMichael, Anthony; van der Mei, Ingrid

    2002-12-27

    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. PMID:12505287

  19. Future therapeutics for the induction of peripheral immune tolerance in autoimmune disease and organ transplantation.

    PubMed

    Cobbold, Stephen P

    2009-05-01

    Rodent models of transplantation and autoimmune disease have demonstrated that it is possible to induce lifelong and specific immunological tolerance to both self and graft antigens in the absence of any continued immunosuppression. If this situation could be achieved clinically, it would avoid many of the longer-term complications of immunosuppression, such as the increased risk of infection, cancer and other side effects, such as nephrotoxicity. In this review, we shall consider the interplay between regulatory T cells, dendritic cells and the tissue itself, and the resulting local protective mechanisms that are coordinated to maintain the tolerant state and an acquired local immune privilege. The current status of attempts to apply tolerogenic approaches to the clinical treatment of autoimmune diseases and to induce either tolerance to organ grafts or sufficient immune regulation so that conventional immunosuppression can be minimized will also be considered. PMID:20635961

  20. [Immunomodulatory properties of stem mesenchymal cells in autoimmune diseases].

    PubMed

    Sánchez-Berná, Isabel; Santiago-Díaz, Carlos; Jiménez-Alonso, Juan

    2015-01-20

    Autoimmune diseases are a cluster of disorders characterized by a failure of the immune tolerance and a hyperactivation of the immune system that leads to a chronic inflammation state and the damage of several organs. The medications currently used to treat these diseases usually consist of immunosuppressive drugs that have significant systemic toxic effects and are associated with an increased risk of opportunistic infections. Recently, several studies have demonstrated that mesenchymal stem cells have immunomodulatory properties, a feature that make them candidates to be used in the treatment of autoimmune diseases. In the present study, we reviewed the role of this therapy in the treatment of systemic lupus erythematosus, Sjögren's syndrome, systemic sclerosis, Crohn's disease and multiple sclerosis, as well as the potential risks associated with its use. PMID:24636281

  1. [Immunomodulatory properties of stem mesenchymal cells in autoimmune diseases].

    PubMed

    Sánchez-Berná, Isabel; Santiago-Díaz, Carlos; Jiménez-Alonso, Juan

    2015-01-20

    Autoimmune diseases are a cluster of disorders characterized by a failure of the immune tolerance and a hyperactivation of the immune system that leads to a chronic inflammation state and the damage of several organs. The medications currently used to treat these diseases usually consist of immunosuppressive drugs that have significant systemic toxic effects and are associated with an increased risk of opportunistic infections. Recently, several studies have demonstrated that mesenchymal stem cells have immunomodulatory properties, a feature that make them candidates to be used in the treatment of autoimmune diseases. In the present study, we reviewed the role of this therapy in the treatment of systemic lupus erythematosus, Sjögren's syndrome, systemic sclerosis, Crohn's disease and multiple sclerosis, as well as the potential risks associated with its use.

  2. Autoantibodies with Enzymatic Properties in Human Autoimmune Diseases

    PubMed Central

    Wootla, Bharath; Lacroix-Desmazes, Sébastien; Warrington, Arthur E.; Bieber, Allan J.; Kaveri, Srini V.; Rodriguez, Moses

    2011-01-01

    Immunoglobulins (Ig) or antibodies are heavy plasma proteins, with sugar chains added to amino acid residues by N-linked glycosylation and occasionally by O-linked glycosylation. The versatility of antibodies is demonstrated by the various functions that they mediate such as neutralization, agglutination, fixation with activation of complement and activation of effector cells. In addition to this plethora of functions, some antibodies express enzymatic activity. Antibodies endowed with enzymatic properties have been described in human autoimmune manifestations for more than a decade in a variety of disorders such as autoimmune thyroiditis, systemic erythematosus (SLE), scleroderma, rheumatoid arthritis (RA), multiple sclerosis (MS) and acquired hemophilia (AH). Antibodies isolated from these conditions were able to specifically hydrolyze thyroglobulin, DNA, RNA, myelin basic protein (MBP), and factor VIII (FVIII) or factor IX (FIX), respectively. The therapeutic relevance of these findings is discussed. PMID:21624820

  3. Obesity in autoimmune diseases: not a passive bystander.

    PubMed

    Versini, Mathilde; Jeandel, Pierre-Yves; Rosenthal, Eric; Shoenfeld, Yehuda

    2014-09-01

    In the last decades, autoimmune diseases have experienced a dramatic increase in Western countries. The involvement of environmental factors is strongly suspected to explain this rise. Particularly, over the same period, obesity has followed the same outbreak. Since the exciting discovery of the secretory properties of adipose tissue, the relationship between obesity and autoimmunity and the understanding of the underlying mechanisms have become of major interest. Indeed, the fat tissue has been found to produce a wide variety of "adipokines", involved in the regulation of numerous physiological functions, including the immune response. By conducting a systematic literature review, we extracted 329 articles regarding clinical, experimental and pathophysiological data on the relationship between obesity, adipokines - namely leptin, adiponectin, resistin, visfatin - and various immune-mediated conditions, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), inflammatory bowel disease (IBD), multiple sclerosis (MS), type-1 diabetes (T1D), psoriasis and psoriatic arthritis (PsA), and thyroid autoimmunity (TAI), especially Hashimoto thyroiditis (HT). The strongest levels of evidence support an increased risk of RA (OR=1.2-3.4), MS (OR=2), psoriasis and PsA (OR=1.48-6.46) in obese subjects. A higher risk of IBD, T1D and TAI is also suggested. Moreover, obesity worsens the course of RA, SLE, IBD, psoriasis and PsA, and impairs the treatment response of RA, IBD, psoriasis and PsA. Extensive clinical data and experimental models demonstrate the involvement of adipokines in the pathogenesis of these autoimmune diseases. Obesity appears to be a major environmental factor contributing to the onset and progression of autoimmune diseases. PMID:25092612

  4. Is pregnancy a risk factor for rheumatic autoimmune diseases?

    PubMed Central

    Marder, Wendy; Somers, Emily C

    2014-01-01

    Purpose of review To review the association of pregnancy with the risk of subsequent development of rheumatic autoimmune diseases in women, including rheumatoid arthritis, systemic lupus erythematosus, and scleroderma. Recent findings There is a small but growing literature related to the risk of autoimmune rheumatic disease in association with pregnancy history. However, results conflict both in terms of the direction and magnitude of risk of disease in relationship to prior pregnancy history. Although anecdotal evidence tends to favor the premise that pregnancy is protective against certain diseases, such as rheumatoid arthritis, the heterogeneity of results precludes the ability to confirm an association in either direction. There is indication that time elapsed since pregnancy may influence risk, with the postpartum year being of particular relevance. Summary To date, a clear pattern has not emerged regarding pregnancy and the future risk of autoimmune rheumatic diseases. This topic requires greater study, and given the strong female preponderance of these diseases, future research efforts should seek to resolve this important issue. PMID:24646947

  5. Plasticity of Th17 Cells in Autoimmune Kidney Diseases.

    PubMed

    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.

  6. Pathogenesis of thyroid autoimmune disease: the role of cellular mechanisms.

    PubMed

    Ramos-Leví, Ana Maria; Marazuela, Mónica

    2016-10-01

    Hashimoto's thyroiditis (HT) and Graves' disease (GD) are two very common organ-specific autoimmune diseases which are characterized by circulating antibodies and lymphocyte infiltration. Although humoral and cellular mechanisms have been classically considered separately in the pathogenesis of autoimmune thyroid diseases (AITD), recent research suggests a close reciprocal relationship between these two immune pathways. Several B- and T-cell activation pathways through antigen-presenting cells (APCs) and cytokine production lead to specific differentiation of T helper (Th) and T regulatory (Treg) cells. This review will focus on the cellular mechanisms involved in the pathogenesis of AITD. Specifically, it will provide reasons for discarding the traditional simplistic dichotomous view of the T helper type 1 and 2 pathways (Th1/Th2) and will focus on the role of the recently characterized T cells, Treg and Th17 lymphocytes, as well as B lymphocytes and APCs, especially dendritic cells (DCs).

  7. Siglec-1 and -2 as potential biomarkers in autoimmune disease.

    PubMed

    Eakin, Amanda J; Bustard, Michael J; McGeough, Cathy M; Ahmed, Tahanver; Bjourson, Anthony J; Gibson, David S

    2016-06-01

    Autoimmune diseases (ADs) are currently treated with anti-inflammatory and immunosuppressive drugs, aimed at reducing symptoms of disease in order to improve quality of life for patients. However, for a significant number of patients these therapies are ineffective, leading to an increased risk of irreversible damage and eventual disability in certain cases. Growing evidence has implicated glycosylated proteins and their cognate receptors in modulation of the autoimmune response. This review will summarize these findings with particular focus on sialic acid-binding immunoglobulin-like lectin (Siglec)-1 and Siglec-2 involvement in AD. Fluctuations in these glycosylation-dependent pathways could act as sentinels of disease activity or drug responses. If validated, protein modification and cellular response markers could help clinicians achieve remission earlier. PMID:26752092

  8. Siglec-1 and -2 as potential biomarkers in autoimmune disease.

    PubMed

    Eakin, Amanda J; Bustard, Michael J; McGeough, Cathy M; Ahmed, Tahanver; Bjourson, Anthony J; Gibson, David S

    2016-06-01

    Autoimmune diseases (ADs) are currently treated with anti-inflammatory and immunosuppressive drugs, aimed at reducing symptoms of disease in order to improve quality of life for patients. However, for a significant number of patients these therapies are ineffective, leading to an increased risk of irreversible damage and eventual disability in certain cases. Growing evidence has implicated glycosylated proteins and their cognate receptors in modulation of the autoimmune response. This review will summarize these findings with particular focus on sialic acid-binding immunoglobulin-like lectin (Siglec)-1 and Siglec-2 involvement in AD. Fluctuations in these glycosylation-dependent pathways could act as sentinels of disease activity or drug responses. If validated, protein modification and cellular response markers could help clinicians achieve remission earlier.

  9. The pleiotropic role of HDL in autoimmune diseases.

    PubMed

    Parra, Sandra; Castro, Antoni; Masana, Luis

    2015-01-01

    As is widely known, the classic function of HDL is reverse cholesterol transport (RCT), thus removing cholesterol from peripheral tissues. Early epidemiological studies, such as Framingham's, stated that increased HDL levels were associated with a significant decrease in relative risk for cardiovascular disease (CVD) mortality. However, those with heightened expectations in recent years for the development of therapeutic targets to increase HDL levels have been disappointed, because efforts have demonstrated the opposite effect on cardiovascular and global mortality. However, in contrast, studies have highlighted the complexity and the intriguing role of HDL in different pathological conditions, such as infections, neoplasms, and autoimmune diseases. In this review an attempt is made to summarize some biological pathways that link HDL function with the immune system, and its possible clinical repercussions in autoimmune diseases.

  10. Mycobacterial disease, immunosuppression, and acquired immunodeficiency syndrome.

    PubMed Central

    Collins, F M

    1989-01-01

    The mycobacteria are an important group of acid-fast pathogens ranging from obligate intracellular parasites such as Mycobacterium leprae to environmental species such as M. gordonae and M. fortuitum. The latter may behave as opportunistic human pathogens if the host defenses have been depleted in some manner. The number and severity of such infections have increased markedly with the emergence of the acquired immunodeficiency syndrome (AIDS) epidemic. These nontuberculous mycobacteria tend to be less virulent for humans than M. tuberculosis, usually giving rise to self-limiting infections involving the cervical and mesenteric lymph nodes of young children. However, the more virulent serovars of M. avium complex can colonize the bronchial and intestinal mucosal surfaces of healthy individuals, becoming virtual members of the commensal gut microflora and thus giving rise to low levels of skin hypersensitivity to tuberculins prepared from M. avium and M. intracellulare. Systemic disease develops when the normal T-cell-mediated defenses become depleted as a result of old age, cancer chemotherapy, or infection with human immunodeficiency virus. As many as 50% of human immunodeficiency virus antibody-positive individuals develop mycobacterial infections at some time during their disease. Most isolates of M. avium complex from AIDS patients fall into serotypes 4 and 8. The presence of these drug-resistant mycobacteria in the lungs of the AIDS patient makes their effective clinical treatment virtually impossible. More effective chemotherapeutic, prophylactic, and immunotherapeutic reagents are urgently needed to treat this rapidly increasing patient population. PMID:2680057

  11. How do autoimmune diseases cluster in families? A systematic review and meta-analysis

    PubMed Central

    2013-01-01

    Background A primary characteristic of complex genetic diseases is that affected individuals tend to cluster in families (that is, familial aggregation). Aggregation of the same autoimmune condition, also referred to as familial autoimmune disease, has been extensively evaluated. However, aggregation of diverse autoimmune diseases, also known as familial autoimmunity, has been overlooked. Therefore, a systematic review and meta-analysis were performed aimed at gathering evidence about this topic. Methods Familial autoimmunity was investigated in five major autoimmune diseases, namely, rheumatoid arthritis, systemic lupus erythematosus, autoimmune thyroid disease, multiple sclerosis and type 1 diabetes mellitus. Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines were followed. Articles were searched in Pubmed and Embase databases. Results Out of a total of 61 articles, 44 were selected for final analysis. Familial autoimmunity was found in all the autoimmune diseases investigated. Aggregation of autoimmune thyroid disease, followed by systemic lupus erythematosus and rheumatoid arthritis, was the most encountered. Conclusions Familial autoimmunity is a frequently seen condition. Further study of familial autoimmunity will help to decipher the common mechanisms of autoimmunity. PMID:23497011

  12. [Pregnancy in systemic autoimmune diseases: Myths, certainties and doubts].

    PubMed

    Danza, Álvaro; Ruiz-Irastorza, Guillermo; Khamashta, Munther

    2016-10-01

    Systemic autoimmune diseases especially affect young women during childbearing age. The aim of this review is to update systemic lupus erythematosus, antiphospholipid syndrome and systemic sclerosis management during pregnancy. These diseases present variable maternal and fetal risks. Studies show that an appropriate disease control and a reasonable remission period prior to pregnancy are associated with satisfactory obstetric outcomes. Antiphospholipid autoantibodies profile, anti-Ro/anti-La antibodies, pulmonary pressure and activity evaluation are crucial to assess the pregnancy risk. Monitoring requires a multidisciplinary team, serial analytic controls and Doppler ultrasound of maternal and fetal circulation. Evaluation of the activity of the disease is essential. PMID:27143525

  13. [Pregnancy in systemic autoimmune diseases: Myths, certainties and doubts].

    PubMed

    Danza, Álvaro; Ruiz-Irastorza, Guillermo; Khamashta, Munther

    2016-10-01

    Systemic autoimmune diseases especially affect young women during childbearing age. The aim of this review is to update systemic lupus erythematosus, antiphospholipid syndrome and systemic sclerosis management during pregnancy. These diseases present variable maternal and fetal risks. Studies show that an appropriate disease control and a reasonable remission period prior to pregnancy are associated with satisfactory obstetric outcomes. Antiphospholipid autoantibodies profile, anti-Ro/anti-La antibodies, pulmonary pressure and activity evaluation are crucial to assess the pregnancy risk. Monitoring requires a multidisciplinary team, serial analytic controls and Doppler ultrasound of maternal and fetal circulation. Evaluation of the activity of the disease is essential.

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

    PubMed

    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.

  15. [Endogenous retroviruses are associated with autoimmune diseases].

    PubMed

    Nexø, Bjørn A; Jensen, Sara B; Hansen, Bettina; Laska, Magdalena J

    2016-06-13

    Retroviruses can be transmitted in two fundamentally different ways: 1) They can be horizontally transmitted as infectious virus, or 2) they can integrate in the germ line and be transmitted to offspring and the offsprings' offspring as DNA. The latter is called endogenous viruses. The mode of transmission is called vertical. Viral variants of importance for development of disease must be more frequent among diseased persons than among healthy individuals. Multiple sclerosis, diabetes and rheumatoid arthritis are all associated with sets of endogenouos retroviruses but not the same sets. If a virus grows and this contributes to disease, one should be able to alleviate disease with antiretroviral drugs. We call for clinical trials to elucidate this issue. PMID:27292833

  16. IL-10 Modulates Th17 Pathogenicity during Autoimmune Diseases

    PubMed Central

    Guo, Beichu

    2016-01-01

    The immune system is essential for host defense against pathogen infections; however dysregulated immune response may lead to inflammatory or autoimmune diseases. Elevated activation of both innate immune cells and T cells such as Th17 cells are linked to many autoimmune diseases, including Multiple Sclerosis (MS), arthritis and inflammatory bowel disease (IBD). To keep immune homeostasis, the immune system develops a number of negative feedback mechanisms, such as the production of anti-inflammatory cytokine IL-10, to dampen excessive production of inflammatory cytokines and uncontrolled activation of immune cells. Our recent studies uncover a novel immunoregulatory function of interferon (IFN) pathways on the innate and antigen-specific immune response. Our results show that IFNα/β induced IL-10 production from macrophages and Th17 cells, which in turn negatively regulated Th17 function in autoimmune diseases such as Experimental Allergic Encephalomyelitis (EAE), an animal model of human MS. In a chronic colitis model resembling human IBD, we also found that IL-10 inhibited inflammasome/IL-1 pathway, and the pathogenicity of Th17 cells, leading to reduced chronic intestinal inflammation. Results from our and other studies further suggest that IL-10 produced by both macrophages and regulatory T cells may shift Th17 into more regulatory phenotypes, leading to reduced inflammatory response. PMID:27308096

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

    NASA Astrophysics Data System (ADS)

    Sun, Jun; Earl, David J.; Deem, Michael W.

    2005-09-01

    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’s search for antibodies, a balance has evolved between binding affinity and specificity.

  18. Phenomics in Autoimmune and Inflammatory Diseases

    ClinicalTrials.gov

    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

  19. Early Components of the Complement Classical Activation Pathway in Human Systemic Autoimmune Diseases

    PubMed Central

    Lintner, Katherine E.; Wu, Yee Ling; Yang, Yan; Spencer, Charles H.; Hauptmann, Georges; Hebert, Lee A.; Atkinson, John P.; Yu, C. Yung

    2016-01-01

    The complement system consists of effector proteins, regulators, and receptors that participate in host defense against pathogens. Activation of the complement system, via the classical pathway (CP), has long been recognized in immune complex-mediated tissue injury, most notably systemic lupus erythematosus (SLE). Paradoxically, a complete deficiency of an early component of the CP, as evidenced by homozygous genetic deficiencies reported in human, are strongly associated with the risk of developing SLE or a lupus-like disease. Similarly, isotype deficiency attributable to a gene copy-number (GCN) variation and/or the presence of autoantibodies directed against a CP component or a regulatory protein that result in an acquired deficiency are relatively common in SLE patients. Applying accurate assay methodologies with rigorous data validations, low GCNs of total C4, and heterozygous and homozygous deficiencies of C4A have been shown as medium to large effect size risk factors, while high copy numbers of total C4 or C4A as prevalent protective factors, of European and East-Asian SLE. Here, we summarize the current knowledge related to genetic deficiency and insufficiency, and acquired protein deficiencies for C1q, C1r, C1s, C4A/C4B, and C2 in disease pathogenesis and prognosis of SLE, and, briefly, for other systemic autoimmune diseases. As the complement system is increasingly found to be associated with autoimmune diseases and immune-mediated diseases, it has become an attractive therapeutic target. We highlight the recent developments and offer a balanced perspective concerning future investigations and therapeutic applications with a focus on early components of the CP in human systemic autoimmune diseases. PMID:26913032

  20. Acute viral E hepatitis with chronic liver disease (autoimmune hepatitis).

    PubMed

    Desai, H G; Naik, A S

    2005-03-01

    A 36 years old male presented with anorexia, jaundice and ascites. He was suffering from acute viral E hepatitis. In view of ascites, he was investigated for associated asymptomatic chronic liver disease (CLD). The CLD was diagnosed as cirrhosis with autoimmune hepatitis and was treated with steroid with good response. He is maintaining good health with low dose steroid, on follow up for 1 year.

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

    PubMed

    Fatimah, Nafeesah; Ussaid, Ahmad; Rasheed, Aflak

    2016-08-01

    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

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

    PubMed Central

    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

  3. Socioeconomic status. The relationship with health and autoimmune diseases.

    PubMed

    Calixto, Omar-Javier; Anaya, Juan-Manuel

    2014-06-01

    Socioeconomic status (SES) is a hierarchical social classification associated with different outcomes in health and disease. The most important factors influencing SES are income, educational level, occupational class, social class, and ancestry. These factors are closely related to each other as they present certain dependent interactions. Since there is a need to improve the understanding of the concept of SES and the ways it affects health and disease, we review herein the tools currently available to evaluate SES and its relationship with health and autoimmune diseases. PMID:24418307

  4. Socioeconomic status. The relationship with health and autoimmune diseases.

    PubMed

    Calixto, Omar-Javier; Anaya, Juan-Manuel

    2014-06-01

    Socioeconomic status (SES) is a hierarchical social classification associated with different outcomes in health and disease. The most important factors influencing SES are income, educational level, occupational class, social class, and ancestry. These factors are closely related to each other as they present certain dependent interactions. Since there is a need to improve the understanding of the concept of SES and the ways it affects health and disease, we review herein the tools currently available to evaluate SES and its relationship with health and autoimmune diseases.

  5. Biologic therapy for autoimmune diseases: an update.

    PubMed

    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

  6. Novel therapies for memory cells in autoimmune diseases.

    PubMed

    Bhargava, P; Calabresi, P A

    2015-06-01

    Autoimmune diseases are a major cause of morbidity, and their incidence and prevalence continue to rise. Treatments for these diseases are non-specific and result in significant adverse effects. Targeted therapies may help in improving the risk : benefit ratio associated with treatment. Immunological memory is an important feature of the vertebrate immune system that results in the production of cells that are long-lived and able to respond to antigens in a more robust manner. In the setting of autoimmunity this characteristic becomes detrimental due to the ongoing response to a self-antigen(s). These memory cells have been shown to play key roles in various autoimmune diseases such as type 1 diabetes, multiple sclerosis and psoriasis. Memory T cells and B cells can be identified based on various molecules expressed on their surface. Memory T cells can be divided into three main categories - central memory, effector memory and resident memory cells. These subsets have different proliferative potential and cytokine-producing abilities. Utilizing differentially expressed surface molecules or downstream signalling pathway proteins in these cells it is now possible to target memory cells while sparing naive cells. We will discuss the various available options for such a strategy and several potential strategies that may yield successful therapies in the future.

  7. Scavenging nucleic acid debris to combat autoimmunity and infectious disease

    NASA Astrophysics Data System (ADS)

    Holl, Eda K.; Shumansky, Kara L.; Borst, Luke B.; Burnette, Angela D.; Sample, Christopher J.; Ramsburg, Elizabeth A.; Sullenger, Bruce A.

    2016-08-01

    Nucleic acid-containing debris released from dead and dying cells can be recognized as damage-associated molecular patterns (DAMPs) or pattern-associated molecular patterns (PAMPs) by the innate immune system. Inappropriate activation of the innate immune response can engender pathological inflammation and autoimmune disease. To combat such diseases, major efforts have been made to therapeutically target the pattern recognition receptors (PRRs) such as the Toll-like receptors (TLRs) that recognize such DAMPs and PAMPs, or the downstream effector molecules they engender, to limit inflammation. Unfortunately, such strategies can limit the ability of the immune system to combat infection. Previously, we demonstrated that nucleic acid-binding polymers can act as molecular scavengers and limit the ability of artificial nucleic acid ligands to activate PRRs. Herein, we demonstrate that nucleic acid scavengers (NASs) can limit pathological inflammation and nucleic acid-associated autoimmunity in lupus-prone mice. Moreover, we observe that such NASs do not limit an animal’s ability to combat viral infection, but rather their administration improves survival when animals are challenged with lethal doses of influenza. These results indicate that molecules that scavenge extracellular nucleic acid debris represent potentially safer agents to control pathological inflammation associated with a wide range of autoimmune and infectious diseases.

  8. NK Cell Subtypes as Regulators of Autoimmune Liver Disease

    PubMed Central

    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

  9. NK Cell Subtypes as Regulators of Autoimmune Liver Disease.

    PubMed

    Jiao, Guohui; Wang, Bangmao

    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

  10. Cancer among children of parents with autoimmune diseases

    PubMed Central

    Mellemkjær, L; Alexander, F; Olsen, J H

    2000-01-01

    Many different aetiologies for childhood cancer have been suggested, but few are well established. One is that parental autoimmune disease is linked with susceptibility for haematopoietic malignancies in their offspring during childhood. The present study is the first to investigate this hypothesis using a follow-up design. A cohort of 53 811 children of more than 36 000 patients diagnosed with a systemic, organ-specific or suspected autoimmune disease were followed up for cancer incidence in the Danish Cancer Registry during 1968–1993. The parents were identified through the National Registry of Patients, while their children were traced in the Central Population Register. Cancer incidence among the offspring was compared with that in the corresponding childhood population of Denmark. In total, 115 cancers were observed among children aged 0–19 years, yielding a non-significant standardized incidence ratio of 1.07. Lymphomas contributed 21 cases to the overall number of tumours, 60% more than expected (95% confidence interval (CI) 1.0–2.4); leukaemia contributed 37 cases representing an excess of 30% (95% CI 0.9–1.8). Our results give some support to the hypothesis that parental autoimmune disease is associated with childhood lymphoma and leukaemia. © 2000 Cancer Research Campaign PMID:10755414

  11. Scavenging nucleic acid debris to combat autoimmunity and infectious disease.

    PubMed

    Holl, Eda K; Shumansky, Kara L; Borst, Luke B; Burnette, Angela D; Sample, Christopher J; Ramsburg, Elizabeth A; Sullenger, Bruce A

    2016-08-30

    Nucleic acid-containing debris released from dead and dying cells can be recognized as damage-associated molecular patterns (DAMPs) or pattern-associated molecular patterns (PAMPs) by the innate immune system. Inappropriate activation of the innate immune response can engender pathological inflammation and autoimmune disease. To combat such diseases, major efforts have been made to therapeutically target the pattern recognition receptors (PRRs) such as the Toll-like receptors (TLRs) that recognize such DAMPs and PAMPs, or the downstream effector molecules they engender, to limit inflammation. Unfortunately, such strategies can limit the ability of the immune system to combat infection. Previously, we demonstrated that nucleic acid-binding polymers can act as molecular scavengers and limit the ability of artificial nucleic acid ligands to activate PRRs. Herein, we demonstrate that nucleic acid scavengers (NASs) can limit pathological inflammation and nucleic acid-associated autoimmunity in lupus-prone mice. Moreover, we observe that such NASs do not limit an animal's ability to combat viral infection, but rather their administration improves survival when animals are challenged with lethal doses of influenza. These results indicate that molecules that scavenge extracellular nucleic acid debris represent potentially safer agents to control pathological inflammation associated with a wide range of autoimmune and infectious diseases. PMID:27528673

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

    PubMed

    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. PMID:25537044

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

    PubMed

    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.

  14. Subsequent Type 2 Diabetes in Patients with Autoimmune Disease.

    PubMed

    Hemminki, Kari; Liu, Xiangdong; Försti, Asta; Sundquist, Jan; Sundquist, Kristina; Ji, Jianguang

    2015-01-01

    Immunological data show that type 2 diabetes (T2D) manifests autoimmune features. We wanted to test the association epidemiologically by assessing subsequent diagnosis of T2D following diagnosis of autoimmune disease (AId) and subsequent AId after T2D in the same individuals. Patients were identified from three Swedish health databases. A total of 32 different AId were included. Standardized incidence ratios (SIRs) were calculated for T2D diagnosis in patients with previously diagnosed AId and compared to those without a previous AId. Among a total of 757,368 AId patients, 15,103 were diagnosed with T2D, giving an overall SIR for T2D of 1.66. T2D risks were increased after 27 AIds; the highest SIRs were noted for chorea minor (8.00), lupoid hepatitis (5.75), and Addison disease (2.63). T2D was increased after 27 of 32 AIds but we were unable to control for factors such as obesity and smoking. However, the clearly increased risks for T2D in most types of AId patients, and in reverse order increased risks for AId after T2D, do not support an overall confounding by life-style factors. Mechanistic links shared by T2D, AId and life-style factors such as obesity, perhaps through chronic inflammation, may drive autoimmune activation of T2D and many AIds. PMID:26350756

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

    PubMed

    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.

  16. The immunobiology of Campylobacter jejuni: Innate immunity and autoimmune diseases.

    PubMed

    Phongsisay, Vongsavanh

    2016-04-01

    The Gram-negative bacterium Campylobacter jejuni causes gastroenteritis and Guillain-Barré syndrome in humans. Recent advances in the immunobiology of C. jejuni have been made. This review summarizes C. jejuni-binding innate receptors and highlights the role of innate immunity in autoimmune diseases. This human pathogen produces a variety of glycoconjugates, including human ganglioside-like determinants and multiple activators of Toll-like receptors (TLRs). Furthermore, C. jejuni targets MyD88, NLRP3 inflammasome, TIR-domain-containing adapter-inducing interferon-β (TRIF), sialic acid-binding immunoglobulin-like lectins (Siglecs), macrophage galactose-type lectin (MGL), and immunoglobulin-like receptors (TREM2, LMIR5/CD300b). The roles of these innate receptors and signaling molecules have been extensively studied. MyD88-mediated TLR activation or inflammasome-dependent IL-1β secretion is essential for autoimmune induction. TRIF mediates the production of type I interferons that promote humoral immune responses and immunoglobulin class-switching. Siglec-1 and Siglec-7 interact directly with gangliosides. Siglec-1 activation enhances phagocytosis and inflammatory responses. MGL internalizes GalNAc-containing glycoconjugates. TREM2 is well-known for its role in phagocytosis. LMIR5 recognizes C. jejuni components and endogenous sulfoglycolipids. Several lines of evidence from animal models of autoimmune diseases suggest that simultaneous activation of innate immunity in the presence of autoreactive lymphocytes or antigen mimicry may link C. jejuni to immunopathology.

  17. Subsequent Type 2 Diabetes in Patients with Autoimmune Disease

    PubMed Central

    Hemminki, Kari; Liu, Xiangdong; Försti, Asta; Sundquist, Jan; Sundquist, Kristina; Ji, Jianguang

    2015-01-01

    Immunological data show that type 2 diabetes (T2D) manifests autoimmune features. We wanted to test the association epidemiologically by assessing subsequent diagnosis of T2D following diagnosis of autoimmune disease (AId) and subsequent AId after T2D in the same individuals. Patients were identified from three Swedish health databases. A total of 32 different AId were included. Standardized incidence ratios (SIRs) were calculated for T2D diagnosis in patients with previously diagnosed AId and compared to those without a previous AId. Among a total of 757,368 AId patients, 15,103 were diagnosed with T2D, giving an overall SIR for T2D of 1.66. T2D risks were increased after 27 AIds; the highest SIRs were noted for chorea minor (8.00), lupoid hepatitis (5.75), and Addison disease (2.63). T2D was increased after 27 of 32 AIds but we were unable to control for factors such as obesity and smoking. However, the clearly increased risks for T2D in most types of AId patients, and in reverse order increased risks for AId after T2D, do not support an overall confounding by life-style factors. Mechanistic links shared by T2D, AId and life-style factors such as obesity, perhaps through chronic inflammation, may drive autoimmune activation of T2D and many AIds. PMID:26350756

  18. Multisensory body representation in autoimmune diseases.

    PubMed

    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.

  19. Multisensory body representation in autoimmune diseases

    PubMed Central

    Finotti, Gianluca; Costantini, Marcello

    2016-01-01

    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. PMID:26867786

  20. Pathogenesis of Chagas' Disease: Parasite Persistence and Autoimmunity

    PubMed Central

    Teixeira, Antonio R. L.; Hecht, Mariana M.; Guimaro, Maria C.; Sousa, Alessandro O.; Nitz, Nadjar

    2011-01-01

    Summary: Acute Trypanosoma cruzi infections can be asymptomatic, but chronically infected individuals can die of Chagas' disease. The transfer of the parasite mitochondrial kinetoplast DNA (kDNA) minicircle to the genome of chagasic patients can explain the pathogenesis of the disease; in cases of Chagas' disease with evident cardiomyopathy, the kDNA minicircles integrate mainly into retrotransposons at several chromosomes, but the minicircles are also detected in coding regions of genes that regulate cell growth, differentiation, and immune responses. An accurate evaluation of the role played by the genotype alterations in the autoimmune rejection of self-tissues in Chagas' disease is achieved with the cross-kingdom chicken model system, which is refractory to T. cruzi infections. The inoculation of T. cruzi into embryonated eggs prior to incubation generates parasite-free chicks, which retain the kDNA minicircle sequence mainly in the macrochromosome coding genes. Crossbreeding transfers the kDNA mutations to the chicken progeny. The kDNA-mutated chickens develop severe cardiomyopathy in adult life and die of heart failure. The phenotyping of the lesions revealed that cytotoxic CD45, CD8+ γδ, and CD8α+ T lymphocytes carry out the rejection of the chicken heart. These results suggest that the inflammatory cardiomyopathy of Chagas' disease is a genetically driven autoimmune disease. PMID:21734249

  1. Seven newly identified loci for autoimmune thyroid disease.

    PubMed

    Cooper, Jason D; Simmonds, Matthew J; Walker, Neil M; Burren, Oliver; Brand, Oliver J; Guo, Hui; Wallace, Chris; Stevens, Helen; Coleman, Gillian; Franklyn, Jayne A; Todd, John A; Gough, Stephen C L

    2012-12-01

    Autoimmune thyroid disease (AITD), including Graves' disease (GD) and Hashimoto's thyroiditis (HT), is one of the most common of the immune-mediated diseases. To further investigate the genetic determinants of AITD, we conducted an association study using a custom-made single-nucleotide polymorphism (SNP) array, the ImmunoChip. The SNP array contains all known and genotype-able SNPs across 186 distinct susceptibility loci associated with one or more immune-mediated diseases. After stringent quality control, we analysed 103 875 common SNPs (minor allele frequency >0.05) in 2285 GD and 462 HT patients and 9364 controls. We found evidence for seven new AITD risk loci (P < 1.12 × 10(-6); a permutation test derived significance threshold), five at locations previously associated and two at locations awaiting confirmation, with other immune-mediated diseases. PMID:22922229

  2. Seven newly identified loci for autoimmune thyroid disease.

    PubMed

    Cooper, Jason D; Simmonds, Matthew J; Walker, Neil M; Burren, Oliver; Brand, Oliver J; Guo, Hui; Wallace, Chris; Stevens, Helen; Coleman, Gillian; Franklyn, Jayne A; Todd, John A; Gough, Stephen C L

    2012-12-01

    Autoimmune thyroid disease (AITD), including Graves' disease (GD) and Hashimoto's thyroiditis (HT), is one of the most common of the immune-mediated diseases. To further investigate the genetic determinants of AITD, we conducted an association study using a custom-made single-nucleotide polymorphism (SNP) array, the ImmunoChip. The SNP array contains all known and genotype-able SNPs across 186 distinct susceptibility loci associated with one or more immune-mediated diseases. After stringent quality control, we analysed 103 875 common SNPs (minor allele frequency >0.05) in 2285 GD and 462 HT patients and 9364 controls. We found evidence for seven new AITD risk loci (P < 1.12 × 10(-6); a permutation test derived significance threshold), five at locations previously associated and two at locations awaiting confirmation, with other immune-mediated diseases.

  3. Sclerostin serum levels in patients with systemic autoimmune diseases.

    PubMed

    Fernández-Roldán, Concepción; Genre, Fernanda; López-Mejías, Raquel; Ubilla, Begoña; Mijares, Verónica; Cano, Daniel Sánchez; Robles, Concepción López; Callejas-Rubio, José Luis; Fernández, Raquel Ríos; Ruiz, Manuela Expósito; González-Gay, Miguel Á; Ortego Centeno, Norberto

    2016-01-01

    Systemic autoimmune diseases (SADs) are associated with lower bone mass and an increased risk of fractures. Sclerostin has a pivotal role in bone metabolism. Available data on circulating sclerostin levels in healthy subjects are limited, whereas those in SAD patients are absent. Our objective was to determine circulating sclerostin concentrations in systemic lupus erythematosus (SLE), systemic sclerosis (SSc) and Crohn's disease (CD) patients, and to analyze the factors associated with sclerostin concentrations. In this cross-sectional case-control study, serum sclerostin levels were measured in 38 SLE patients, 20 CD patients, 8 SSc patients and 20 healthy controls using a sclerostin ELISA. The mean values of the sclerostin (95% confidence interval) were 35.36 pmol l(-1) (12-101) in patients and 33.92 pmol l(-1) (2.31-100) in control subjects. The mean sclerostin value was 36.4 pmol l(-1) (22.1-48.5) in SLE patients, 26.7 pmol l(-1) (17.3-36.3) in CD patients and 51.8 pmol l(-1) (26.5-77.1) in SSc patients (P=0.001). Serum sclerostin levels were positively correlated with age (P<0.001), body mass index (BMI) (P=0.01) and lumbar spine Z-score (P=0.001) and negatively with creatinine clearance (P=0.001). Glucocorticoid treatment did not affect sclerostin levels. Sclerostin levels seem to have a heterogeneous pattern in different autoimmune diseases. SLE and SSc patients did not differ from healthy controls regarding sclerostin levels. The CD group had significantly lower values compared with SSc patients. Factors associated with sclerostin levels in autoimmune diseases seem to be the same than in the general population. PMID:26909149

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

    PubMed

    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.

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

    PubMed

    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. PMID:27534821

  6. Human leukocyte Antigen-DM polymorphisms in autoimmune diseases

    PubMed Central

    Morrison, Eliot; Wieczorek, Marek; Sticht, Jana; Freund, Christian

    2016-01-01

    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. PMID:27534821

  7. Origin of B-Cell Neoplasms in Autoimmune Disease

    PubMed Central

    Hemminki, Kari; Liu, Xiangdong; Ji, Jianguang; Försti, Asta

    2016-01-01

    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. PMID:27355450

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

    PubMed

    Hemminki, Kari; Liu, Xiangdong; Ji, Jianguang; Försti, Asta

    2016-01-01

    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. PMID:27355450

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

    PubMed

    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.

  10. Clinical Analysis of Pulmonary Nocardiosis in Patients With Autoimmune Disease

    PubMed Central

    Li, Shan; Song, Xin yu; Zhao, Yu yue; Xu, Kai; Bi, Ya lan; Huang, Hui; Xu, Zuo jun

    2015-01-01

    Abstract Nocardiosis is an opportunistic infection that most commonly involves the lung; however, only a few case reports of autoimmune disease complicated by pulmonary nocardiosis exist in the literature. We conducted a retrospective analysis of 24 cases of both autoimmune disease and pulmonary nocardiosis at the Peking Union Medical College Hospital between 1990 and 2012. Fifty-two cases were hospitalized with nocardiosis, 24 of whom had at least 1 autoimmune disease before the diagnosis of pulmonary nocardiosis. The cohort patients consisted of 5 men and 19 women, with a mean age of 44.2 years. All were negative for human immunodeficiency virus. All but 1 patient had received immunosuppressants, including corticosteroids, cyclophosphamide, azathioprine, methotrexate, or hydroxychloroquine. Fever (87.5%), cough (83.3%), and sputum (79.2%) were the most common clinical manifestations. Ten cases were accompanied by subcutaneous nodules and/or cutaneous abscesses, and 4 had brain abscess. Half of them were lymphocytopenic. Thirteen of the 16 cases who underwent lymphocyte subtype analysis had decreased CD4+ T-cell counts. Nineteen cases had decreased serum albumin levels. Nocardia was isolated from sputum (13/24), bronchoalveolar lavage fluid (4/6), lung tissue (5/6), pleural effusions (3/5), skin or cutaneous pus (7/10), and brain tissue (1/1). The most common imaging findings were air-space opacities (83.3%), followed by nodules (62.5%), cavitations (45.8%), and masses (37.5%). Five were administered co-trimoxazole only, and the others were treated with 2 or more antibiotics. All 5 cases with skin abscesses and 2 of the 4 cases with brain abscesses were treated by surgical incision and drainage. None underwent thoracic surgery. Corticosteroid dosages were decreased in all cases, and cytotoxic agents were discontinued in some cases. Twenty-two cases recovered, and 2 died. Pulmonary nocardiosis associated with an underlying autoimmune disease showed a female

  11. Autoimmune thyroid disease and rheumatoid arthritis: relationship and the role of genetics.

    PubMed

    Lazúrová, Ivica; Jochmanová, Ivana; Benhatchi, Karim; Sotak, Stefan

    2014-12-01

    Autoimmune thyroid disease (AITD), known as the most common organ-specific autoimmune disorder, is frequently accompanied by other organ and non-organ-specific autoimmune diseases, including rheumatoid arthritis (RA). Although the exact pathogenic mechanisms of the coexistence of autoimmune disorders are still not completely defined, genetics, immune defects, hormones and environmental factors may play key roles in polyautoimmunity. In this review, the prevalence of AITD and antithyroid autoantibodies in RA patients and rheumatic manifestations in association with thyroid autoimmunity are discussed. Finally, we review the role of genetics in the association of both AITD and RA, especially CTLA-4 and PTPN22 polymorphisms.

  12. CT findings in complications of acquired renal cystic disease.

    PubMed

    Soffer, O; Miller, L R; Lichtman, J B

    1987-01-01

    A 42-year-old man with end-stage renal disease developed acquired renal cystic disease. The left kidney underwent tumorous degeneration necessitating nephrectomy. Eight months later acute hemorrhagic renal cyst rupture culminated in right nephrectomy.

  13. Cell-mediated immunity in idiopathic autoimmune haemolytic disease.

    PubMed Central

    Slavin, S; Aker, M; Plesser, Y M; Rachmilewitz, E A

    1975-01-01

    Membrane antigens from autologous and from allogeneic red blood cells (RBC) induced migration inhibition of splenic leucocytes and transformation of peripheral blood lymphocytes from a patient with idiopathic autoimmune haemolytic disease (AHD). No migration inhibition occurred following stimulation of splenic leucocytes obtained during splenectomy from a patient with beta-thalassaemia major. Lymphocyte transformation did not occur when normal lymphocytes were stimulated by similar RBC membrane preparations. These findings indicate that autosensitization in AHD may be a function of both humoral and cellular immune mechanisms. PMID:1204245

  14. Dementia associated with toxic causes and autoimmune disease.

    PubMed

    Schofield, Peter

    2005-01-01

    Toxic causes of dementia include exposure to heavy metals such as lead, mercury and aluminum as well as to carbon monoxide and solvents. Autoimmune conditions include such entities as multiple sclerosis, systemic lupus erythematosus, Behçet's disease and Sjögren's syndrome. These conditions share broadly similar cognitive effects giving rise to impairments with subcortical features. Individuals are often affected at a relatively young age. Optimal preventative strategies include avoidance of toxic substances. Comprehensive neuropsychological assessment is valuable not only diagnostically and for monitoring but also to identify the patients' strengths and weaknesses, so that compensatory strategies can be recommended.

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

    PubMed Central

    Cárdenas Roldán, Jorge; Amaya-Amaya, Jenny; Castellanos-de la Hoz, Juan; Giraldo-Villamil, Juliana; Montoya-Ortiz, Gladys; Cruz-Tapias, Paola; Rojas-Villarraga, Adriana; Mantilla, Rubén D.; Anaya, Juan-Manuel

    2012-01-01

    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. PMID:23209899

  16. Single Nucleotide Polymorphism Clustering in Systemic Autoimmune Diseases

    PubMed Central

    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

  17. CD226 Gly307Ser association with multiple autoimmune diseases.

    PubMed

    Hafler, J P; Maier, L M; Cooper, J D; Plagnol, V; Hinks, A; Simmonds, M J; Stevens, H E; Walker, N M; Healy, B; Howson, J M M; Maisuria, M; Duley, S; Coleman, G; Gough, S C L; Worthington, J; Kuchroo, V K; Wicker, L S; Todd, J A

    2009-01-01

    Genome-wide association studies provide insight into multigenic diseases through the identification of susceptibility genes and etiological pathways. In addition, the identification of shared variants among autoimmune disorders provides insight into common disease pathways. We previously reported an association of a nonsynonymous single nucleotide polymorphism (SNP) rs763361/Gly307Ser in the immune response gene CD226 on chromosome 18q22 with type 1 diabetes (T1D) susceptibility. Here, we report efforts toward identifying the causal variant by exonic resequencing and tag SNP mapping of the 18q22 region in both T1D and multiple sclerosis (MS). In addition to the analysis of newly available samples in T1D (2088 cases and 3289 controls) and autoimmune thyroid disease (AITD) (821 cases and 1920 controls), resulting in strong support for the Ser(307) association with T1D (P=3.46 x 10(-9)) and continued potential evidence for AITD (P=0.0345), we provide evidence for association of Gly307Ser with MS (P=4.20 x 10(-4)) and rheumatoid arthritis (RA) (P=0.017). The Ser(307) allele of rs763361 in exon 7 of CD226 predisposes to T1D, MS, and possibly AITD and RA, and based on the tag SNP analysis, could be the causal variant. PMID:18971939

  18. Single Nucleotide Polymorphism Clustering in Systemic Autoimmune Diseases.

    PubMed

    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

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

    PubMed

    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

  20. [Autoimmune thrombocytopenia: diagnosis and treatment].

    PubMed

    Veneri, Dino; Franchini, Massimo

    2005-05-01

    Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disease characterized by an isolated, persistent thrombocytopenia in absence of known causes. In this review, we briefly analyze the most important diagnostic criteria of this autoimmune disorder, with particular consideration to differential diagnosis (false thrombocytopenia, congenital thrombocytopenia, acquired thrombocytopenia, pregnancy-associated thrombocytopenia) and to therapeutic options.

  1. Autoimmune pancreatitis: an underdiagnosed autoimmune disease with clinical, imaging and serological features.

    PubMed

    Sánchez-Castañón, María; de las Heras-Castaño, Gonzalo; López-Hoyos, Marcos

    2010-02-01

    Since Sarles et al. [Sarles H, Sarles JC, Muratore R, Guien C. Chronic inflammatory sclerosis of the pancreas-an autonomous pancreatic disease? Am J Dig Dis 1961; 6: 688-698.] reported a case of pancreatitis associated with hypergammaglobulinemia, many cases have been described, which led to the current concept of "autoimmune pancreatitis (AIP)". Lymphoplasmacytic infiltration and fibrosis on histology together with elevated IgG levels or the presence of autoantibodies on laboratory examinations supported the concept of AIP. In recent years, based on histological and immunohistochemical examination of various organs of patients with AIP, a novel clinicopathological entity, IgG4-related slerosing disease, has been proposed. AIP is a systemic disease that is characterized by dense infiltration of IgG4-positive plasma cells and T lymphocytes in various organs. Clinical manifestations are related with pancreas dysfunction but other organs may be affected such as bile duct, gallbladder, salivary gland, retroperitoneum, kidney, lung and prostate. Increased serum IgG4 levels, the presence of several autoantibodies such as anti-carbonic anhydrase II antibodies (ACA-II), immunostaining IgG4 positive in pancreas tissue and a very good response to steroid therapy are useful for the diagnosis of AIP that can mimic pancreatic cancer.

  2. Autoimmune pancreatitis and IgG4-related systemic diseases

    PubMed Central

    Zhang, Lizhi; Smyrk, Thomas C

    2010-01-01

    Autoimmune pancreatitis (AIP) is a rare form of chronic pancreatitis that is characterized by lymphoplasmacytic infiltrate, storiform fibrosis, obliterative phlebitis, and increased IgG4+ plasma cells. Serum IgG4 levels usually are elevated. Patients with AIP frequently have disease affecting other organs or sites; these tissues show similar histologic changes, including increased IgG4+ plasma cell infiltrate and response to corticosteroid therapy. A new clinicopathologic concept of IgG4-related systemic disease (ISD) has been proposed. These diseases often are not limited to the pancreas, and the pancreas may not be involved at all. In this article, we review the literature and our own experience to detail the clinicopathologic features of AIP and extrapancreatic lesions in ISD. PMID:20606730

  3. Porous silicon biosensor for the detection of autoimmune diseases

    NASA Astrophysics Data System (ADS)

    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.

  4. The ‘hygiene hypothesis’ for autoimmune and allergic diseases: an update

    PubMed Central

    Okada, H; Kuhn, C; Feillet, H; Bach, J-F

    2010-01-01

    According to the ‘hygiene hypothesis’, the decreasing incidence of infections in western countries and more recently in developing countries is at the origin of the increasing incidence of both autoimmune and allergic diseases. The hygiene hypothesis is based upon epidemiological data, particularly migration studies, showing that subjects migrating from a low-incidence to a high-incidence country acquire the immune disorders with a high incidence at the first generation. However, these data and others showing a correlation between high disease incidence and high socio-economic level do not prove a causal link between infections and immune disorders. Proof of principle of the hygiene hypothesis is brought by animal models and to a lesser degree by intervention trials in humans. Underlying mechanisms are multiple and complex. They include decreased consumption of homeostatic factors and immunoregulation, involving various regulatory T cell subsets and Toll-like receptor stimulation. These mechanisms could originate, to some extent, from changes in microbiota caused by changes in lifestyle, particularly in inflammatory bowel diseases. Taken together, these data open new therapeutic perspectives in the prevention of autoimmune and allergic diseases. PMID:20415844

  5. [Ulcerative colitis associated with autoimmune hepatitis: a differential form of inflammatory bowel disease?].

    PubMed

    Giraldo Escobar, L M; Crespo Madrid, N; Vila Miravet, V; Pujol Muncunill, G; Varea Calderón, V; Martín de Carpi, J

    2015-01-01

    Inflammatory bowel Disease (IBD) is a group of chronic inflammatory diseases that can be associated with different autoimmune diseases, including autoimmune hepatitis (AIH). Some specific and differential characteristics in children with IBD associated to AIH have been described. Our aim is to describe the clinical pattern of this association observed in our patients, confirming its differential characteristics as compared to classical IBD in children.

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

    PubMed Central

    Correia, Inês; Marques, Inês B.; Ferreira, Rogério; Sousa, Lívia

    2016-01-01

    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. PMID:27127515

  7. New Platform Technology for Comprehensive Serological Diagnostics of Autoimmune Diseases

    PubMed Central

    Willitzki, Annika; Hiemann, Rico; Peters, Vanessa; Sack, Ulrich; Schierack, Peter; Rödiger, Stefan; Anderer, Ursula; Conrad, Karsten; Bogdanos, Dimitrios P.; Reinhold, Dirk; Roggenbuck, Dirk

    2012-01-01

    Antibody assessment is an essential part in the serological diagnosis of autoimmune diseases. However, different diagnostic strategies have been proposed for the work up of sera in particular from patients with systemic autoimmune rheumatic disease (SARD). In general, screening for SARD-associated antibodies by indirect immunofluorescence (IIF) is followed by confirmatory testing covering different assay techniques. Due to lacking automation, standardization, modern data management, and human bias in IIF screening, this two-stage approach has recently been challenged by multiplex techniques particularly in laboratories with high workload. However, detection of antinuclear antibodies by IIF is still recommended to be the gold standard method for antibody screening in sera from patients with suspected SARD. To address the limitations of IIF and to meet the demand for cost-efficient autoantibody screening, automated IIF methods employing novel pattern recognition algorithms for image analysis have been introduced recently. In this respect, the AKLIDES technology has been the first commercially available platform for automated interpretation of cell-based IIF testing and provides multiplexing by addressable microbead immunoassays for confirmatory testing. This paper gives an overview of recently published studies demonstrating the advantages of this new technology for SARD serology. PMID:23316252

  8. Neutrophilic Skin Lesions in Autoimmune Connective Tissue Diseases

    PubMed Central

    Hau, Estelle; Vignon Pennamen, Marie-Dominique; Battistella, Maxime; Saussine, Anne; Bergis, Maud; Cavelier-Balloy, Benedicte; Janier, Michel; Cordoliani, Florence; Bagot, Martine; Rybojad, Michel; Bouaziz, Jean-David

    2014-01-01

    Abstract The pathophysiology of neutrophilic dermatoses (NDs) and autoimmune connective tissue diseases (AICTDs) is incompletely understood. The association between NDs and AICTDs is rare; recently, however, a distinctive subset of cutaneous lupus erythematosus (LE, the prototypical AICTD) with neutrophilic histological features has been proposed to be included in the spectrum of lupus. The aim of our study was to test the validity of such a classification. We conducted a monocentric retrospective study of 7028 AICTDs patients. Among these 7028 patients, a skin biopsy was performed in 932 cases with mainly neutrophilic infiltrate on histology in 9 cases. Combining our 9 cases and an exhaustive literature review, pyoderma gangrenosum, Sweet syndrome (n = 49), Sweet-like ND (n = 13), neutrophilic urticarial dermatosis (n = 6), palisaded neutrophilic granulomatous dermatitis (n = 12), and histiocytoid neutrophilic dermatitis (n = 2) were likely to occur both in AICTDs and autoinflammatory diseases. Other NDs were specifically encountered in AICTDs: bullous LE (n = 71), amicrobial pustulosis of the folds (n = 28), autoimmunity-related ND (n = 24), ND resembling erythema gyratum repens (n = 1), and neutrophilic annular erythema (n = 1). The improvement of AICTDS neutrophilic lesions under neutrophil targeting therapy suggests possible common physiopathological pathways between NDs and AICTDs. PMID:25546688

  9. Targeting of type I interferon in systemic autoimmune diseases.

    PubMed

    Crow, Mary K; Olferiev, Mikhail; Kirou, Kyriakos A

    2015-02-01

    Increased blood levels of type I interferon (IFN-I) and expression of a broad signature of gene transcripts that reflect induction by IFN-I are observed in many patients with systemic autoimmune diseases, and that pattern is most striking in systemic lupus erythematosus (SLE). Persistent production of IFN-α, the most abundant subtype measured in these patients, is an important feature of the immunopathogenesis of lupus and has stimulated current efforts to develop and test therapeutics that either block IFN-I or its receptor directly or target components of the IFN-I pathway involved in induction of or response to IFN-I. In this review data from animal models of chronic viral infection, examples of lupus-like syndromes associated with single-gene mutations that impact the IFN-I pathway, and longitudinal studies of patients with lupus are described and support the rationale for therapeutic targeting of the IFN-I pathway. However, the complexity of IFN-I regulation and the diversity of its effects on immune system function suggest that the definitive demonstration of that pathway as a valid and productive therapeutic target will only come from clinical trials of agents tested in patients with systemic autoimmune disease, with patients with lupus likely to be the most informative.

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

    PubMed Central

    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 systemic lupus erythematosus (SLE), multiple sclerosis (MS), and ankylosing spondylitis (AS). In general, females are more susceptible to SLE and MS but less susceptible to AS, where the expression of FOXP3 and its protein complex are perturbed by multiple factors, including hormonal fluctuations, inflammatory cytokines, and danger signals. Therefore, it is critical to explore the potential molecular mechanisms involved and these differences linked to gender. Here, we review recent findings on the regulation of FOXP3 activity in Treg cells and also discuss gender difference in the determination of Treg cell function in autoimmune diseases. PMID:26441996

  11. JAKpot! New small molecules in autoimmune and inflammatory diseases

    PubMed Central

    Ghoreschi, Kamran; Gadina, Massimo

    2013-01-01

    Cytokines are key mediators of the development and homeostasis of hematopoietic cells, critical for host defense, but also for the development of autoimmune and inflammatory diseases like psoriasis or rheumatoid arthritis (RA). Blocking cytokines activity by interfering with the ligand-receptor association has been successfully employed to treat several immune disorders. A subgroup of cytokines signals through receptors requiring the association with a family of cytoplasmic protein tyrosine kinases known as Janus kinases (Jaks). Jaks have recently gained significant attention as therapeutic targets in inflammation and autoimmunity and several Jak inhibitory small molecules have been developed. The first two Jak inhibitors, tofacitinib and ruxolitinib, have been approved for the treatment of RA and primary myelofibrosis, respectively. Efficacy and safety data suggest that some of these oral Jak inhibitors as well as their topical formulations may soon enter the daily clinical practice for treating patients with psoriasis, lupus erythematosus or other inflammatory skin diseases. While biologics typically target one single cytokine, these new immunomodulators can inhibit signals from multiple cytokines intracellularly and therefore could be useful when other therapies are ineffective. Thus, Jak inhibitors may replace some traditional immunosuppressive agents and help patients not responding to previous therapies. PMID:24131352

  12. The skin in autoimmune diseases-Unmet needs.

    PubMed

    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. PMID:27481041

  13. The skin in autoimmune diseases-Unmet needs.

    PubMed

    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.

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

    PubMed

    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.

  15. Comparative genomics for the investigation of autoimmune diseases.

    PubMed

    Möller, Steffen; Zettl, Uwe K; Serrano-Fernández, Pablo; Goertsches, Robert

    2006-01-01

    The complete DNA sequence of the human genome and of several related mammals are now available, due to the investments of enormous resources and advances in sequencing technology. Novel technologies have been developed to compare multiple genomes with each other, thus specifying regions of sequence similarity among mammals and with their pathogens. Larger blocks of sequence similarity (syntenic regions) have been determined and made publicly available. In many ways, novel insights can be gained by such data when combining external genetic or clinical information for these syntenic loci. These novel tools have proven to be successful in inferring functional equivalence between loci of multiple genomes. This review reports on the role of comparative genomics in research on autoimmune diseases, a field with strong dependencies on animal models of human diseases and the problem of an adequate information transfer between multiple organisms and research areas. PMID:17073670

  16. Genetic homogeneity of autoimmune polyglandular disease type I

    SciTech Connect

    Bjoerses, P.; Aaltonen, J.; Vikman, A.

    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.

  17. [Of worms and men--Administration of helminth products as an innovative approach to treatment of autoimmune diseases].

    PubMed

    Sega, Yahel; Versini, Mathilde; Shoenfeld, Yehuda

    2015-07-01

    In areas where helminth infections are common, there is a low prevalence of autoimmune diseases. This observation gave rise to the hygiene hypothesis, claiming that certain organisms which were abundant in the human microenvironment hold an immunoregulatory and immunosuppressive effect, therefore, their eradication led to an increase in immune mediated diseases. This hypothesis laid the foundation for several directions of research which demonstrated an immunosuppressive and immunoregulatory effect of helminths on both the acquired and the innate immune systems. These studies led to the examination of the therapeutic potential of helminths and their components in treating different autoimmune diseases such as inflammatory bowel disease, rheumatoid arthritis, multiple sclerosis, and systemic lupus erythematosus. The administration of helminth products in murine models of these diseases exhibited a positive effect on disease expression, morbidity and mortality, as well as the ability to prevent the onset of disease to some extent (when given in a preventive protocol). Recently, a synthetic molecule composed of phosphorylcholine (a product of the nematode a. vitae) combined with the protein tuftsin, which is produced by human splenocytes, was shown to exert the aforementioned positive effects on a murine model of systemic lupus erythematosus (SLE). These discoveries point to a new direction in research for developing helminth-based therapies for autoimmune diseases.

  18. Role of the MHC2TA gene in autoimmune diseases

    PubMed Central

    Martínez, Alfonso; Sánchez‐Lopez, Marta; Varadé, Jezabel; Mas, Ana; Martín, M Carmen; de las Heras, Virginia; Arroyo, Rafael; Mendoza, Juan Luis; Díaz‐Rubio, Manuel; Fernández‐Gutiérrez, Benjamín; de la Concha, Emilio G; Urcelay, Elena

    2007-01-01

    Objectives Expression of major histocompatibility complex (MHC) class II genes is almost exclusively regulated by the class II transactivator. A promoter polymorphism (−168A/G, rs3087456) in the MHC2TA gene was associated with increased susceptibility to rheumatoid arthritis, multiple sclerosis and myocardial infarction in a northern European population. However, no evidence of association of this MHC2TA variant with the two autoimmune diseases could be subsequently detected in independent cohorts. Aim To test the aforementioned single nucleotide polymorphism and another G→C change (nt1614 from coding sequence, rs4774) to analyse the haplotype pattern in this MHC2TA gene. Methods A case–control study was performed with 350 patients with rheumatoid arthritis, 396 patients with multiple sclerosis, 663 patients with inflammatory bowel disease (IBD) and 519 healthy controls from Madrid. Genotyping was ascertained by using TaqMan assays‐on‐demand on a 7900HT analyser, following the manufacturer's suggestions (Applied Biosystems, Foster City, California, USA). Haplotypes were inferred with the expectation–maximisation algorithm implemented by the Arlequin software. Results No independent association with these autoimmune diseases was found for either polymorphism in the Spanish cohorts tested. However, when haplotypes were compared between patients with rheumatoid arthritis and controls, a significant difference in their overall frequency distribution was observed, evidencing a protective haplotype (−168A/1614C, p = 0.006; odds ratio (OR) 0.7) and a risk haplotype (−168G/1614C, p = 0.019; OR 1.6). Patients with multiple sclerosis mirrored these results, but no effect on IBD was identified. Conclusions The MHC2TA gene influences predisposition to rheumatoid arthritis and multiple sclerosis, but not to IBD. The −168G allele is not an aetiological variant in itself, but a genetic marker of susceptibility/protection haplotypes. PMID:17012290

  19. Effects of Latent Toxoplasmosis on Autoimmune Thyroid Diseases in Pregnancy

    PubMed Central

    Kaňková, Šárka; Procházková, Lucie; Flegr, Jaroslav; Calda, Pavel; Springer, Drahomíra; Potluková, Eliška

    2014-01-01

    Background Toxoplasmosis, one of the most common zoonotic diseases worldwide, can induce various hormonal and behavioural alterations in infected hosts, and its most common form, latent toxoplasmosis, influences the course of pregnancy. Autoimmune thyroid diseases (AITD) belong to the well-defined risk factors for adverse pregnancy outcomes. The aim of this study was to investigate whether there is a link between latent toxoplasmosis and maternal AITD in pregnancy. Methods Cross-sectional study in 1248 consecutive pregnant women in the 9–12th gestational weeks. Serum thyroid-stimulating hormone (TSH), thyroperoxidase antibodies (TPOAb), and free thyroxine (FT4) were assessed by chemiluminescence; the Toxoplasma status was detected by the complement fixation test (CFT) and anti-Toxoplasma IgG enzyme-linked immunosorbent assay (ELISA). Results Overall, 22.5% of the women were positive for latent toxoplasmosis and 14.7% were screened positive for AITD. Women with latent toxoplasmosis had more often highly elevated TPOAb than the Toxoplasma-negative ones (p = 0.004), and latent toxoplasmosis was associated with decrease in serum TSH levels (p = 0.049). Moreover, we found a positive correlation between FT4 and the index of positivity for anti-Toxoplasma IgG antibodies (p = 0.033), which was even stronger in the TPOAb-positive Toxoplasma-positive women, (p = 0.014), as well as a positive correlation between FT4 and log2 CFT (p = 0.009). Conclusions Latent toxoplasmosis was associated with a mild increase in thyroid hormone production in pregnancy. The observed Toxoplasma-associated changes in the parameters of AITD are mild and do not seem to be clinically relevant; however, they could provide new clues to the complex pathogenesis of autoimmune thyroid diseases. PMID:25350671

  20. Autoimmune disease and vaccination: impact on infectious disease prevention and a look at future applications.

    PubMed

    McKinnon, John E; Maksimowicz-McKinnon, Kathleen

    2016-01-01

    Vaccines hold promise both for the prevention of infections and as potential immunologic therapy for patients with autoimmune disease (AD). These patients are at high risk for both common and opportunistic infections, but this risk can be significantly reduced and even obviated with the use of recommended available vaccines. Unfortunately, patients with ADs are not routinely offered or provided indicated vaccinations and have higher rates of complications from vaccine-preventable illnesses than patients without ADs. In addition, vaccine therapy is currently under study for the treatment of autoimmune disorders, with early studies demonstrating immunomodulatory effects that may counter undesired immune activation and alleviate disease activity.

  1. Alzheimer's disease: An acquired neurodegenerative laminopathy

    PubMed Central

    Frost, Bess

    2016-01-01

    ABSTRACT The nucleus is typically depicted as a sphere encircled by a smooth surface of nuclear envelope. For most cell types, this depiction is accurate. In other cell types and in some pathological conditions, however, the smooth nuclear exterior is interrupted by tubular invaginations of the nuclear envelope, often referred to as a “nucleoplasmic reticulum,” into the deep nuclear interior. We have recently reported a significant expansion of the nucleoplasmic reticulum in postmortem human Alzheimer's disease brain tissue. We found that dysfunction of the nucleoskeleton, a lamin-rich meshwork that coats the inner nuclear membrane and associated invaginations, is causal for Alzheimer's disease-related neurodegeneration in vivo. Additionally, we demonstrated that proper function of the nucleoskeleton is required for survival of adult neurons and maintaining genomic architecture. Here, we elaborate on the significance of these findings in regard to pathological states and physiological aging, and discuss cellular causes and consequences of nuclear envelope invagination. PMID:27167528

  2. Alzheimer's disease: An acquired neurodegenerative laminopathy.

    PubMed

    Frost, Bess

    2016-05-01

    The nucleus is typically depicted as a sphere encircled by a smooth surface of nuclear envelope. For most cell types, this depiction is accurate. In other cell types and in some pathological conditions, however, the smooth nuclear exterior is interrupted by tubular invaginations of the nuclear envelope, often referred to as a "nucleoplasmic reticulum," into the deep nuclear interior. We have recently reported a significant expansion of the nucleoplasmic reticulum in postmortem human Alzheimer's disease brain tissue. We found that dysfunction of the nucleoskeleton, a lamin-rich meshwork that coats the inner nuclear membrane and associated invaginations, is causal for Alzheimer's disease-related neurodegeneration in vivo. Additionally, we demonstrated that proper function of the nucleoskeleton is required for survival of adult neurons and maintaining genomic architecture. Here, we elaborate on the significance of these findings in regard to pathological states and physiological aging, and discuss cellular causes and consequences of nuclear envelope invagination.

  3. Alzheimer's disease: An acquired neurodegenerative laminopathy.

    PubMed

    Frost, Bess

    2016-05-01

    The nucleus is typically depicted as a sphere encircled by a smooth surface of nuclear envelope. For most cell types, this depiction is accurate. In other cell types and in some pathological conditions, however, the smooth nuclear exterior is interrupted by tubular invaginations of the nuclear envelope, often referred to as a "nucleoplasmic reticulum," into the deep nuclear interior. We have recently reported a significant expansion of the nucleoplasmic reticulum in postmortem human Alzheimer's disease brain tissue. We found that dysfunction of the nucleoskeleton, a lamin-rich meshwork that coats the inner nuclear membrane and associated invaginations, is causal for Alzheimer's disease-related neurodegeneration in vivo. Additionally, we demonstrated that proper function of the nucleoskeleton is required for survival of adult neurons and maintaining genomic architecture. Here, we elaborate on the significance of these findings in regard to pathological states and physiological aging, and discuss cellular causes and consequences of nuclear envelope invagination. PMID:27167528

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

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

    PubMed

    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.

  6. Cancer Risk in Patients With Inflammatory Systemic Autoimmune Rheumatic Diseases

    PubMed Central

    Yu, Kuang-Hui; Kuo, Chang-Fu; Huang, Lu Hsiang; Huang, Wen-Kuan; See, Lai-Chu

    2016-01-01

    Abstract The aim of this study was to determine whether inflammation is related to cancer development, and whether the incidence of cancer is increased and occurs in a site-specific manner in patients with systemic autoimmune rheumatic diseases (SARDs). This study included a nationwide dynamic cohort of patients with various newly diagnosed SARDs from 1997 to 2010 with follow-up until 2012. This study included 75,123 patients with SARDs. During 562,870 person-years of follow-up, 2844 patients developed cancer. Between 1997 and 2010, the highest number of newly diagnosed SARDs cases were rheumatoid arthritis (n = 35,182), followed by systemic lupus erythematosus (SLE, n = 15,623), Sjögren syndrome (n = 11,998), Kawasaki disease (n = 3469), inflammatory bowel disease (n = 2853), scleroderma (n = 1814), Behçet disease (n = 1620), dermatomyositis (n = 1119), polymyositis (n = 811), and vasculitis other than Kawasaki disease (n = 644). A significant standardized incidence ratio (SIR) of overall cancer was observed for patients with SLE (1.41; 95% confidence interval [CI], 1.28–1.56), Sjögren syndrome (1.19; 95% CI, 1.08–1.30), scleroderma (1.27; 95% CI, 1.02–1.59), dermatomyositis (4.79; 95% CI, 4.01–5.73), polymyositis (1.47; 95% CI, 1.05–2.06), vasculitis excluding Kawasaki disease (1.75; 95% CI, 1.20–2.55), and Kawasaki disease (2.88; 95% CI, 1.60–5.20). Overall, patients with most SARDs had a significantly higher risk of inflammation-associated site-specific cancers and hematologic malignancies. This study confirms that autoimmunity is associated with site-specific and hematological malignancies and provides clinical evidence of an association between inflammation and subsequent site-specific cancer development. These findings support the importance of inflammation in site-specific organ system carcinogenesis. PMID:27149461

  7. Pros and cons of stem cell transplantation for autoimmune disease.

    PubMed

    Thomas, E D

    1997-05-01

    The data and discussion at this symposium have provided a most useful analysis of the autoimmune diseases and their potential for therapy by stem cell transplantation. These diseases are characterized by threat to life and particularly by chronic, painful and debilitating courses that warrant aggressive therapy. Selection of patients will be difficult because of the variable disease course and the necessity to choose patients who still have reversible disease. The safety of both autologous and allogeneic stem cell grafting has progressed to the point where, in many cases, the risks of the disease far outweigh those of transplantation. In my opinion the data presented at this symposium show that we should proceed cautiously with both autologous and allogeneic stem cell grafts. Purified stem cells, which have the advantage of being free of lymphocytes, should be used for the first series of autologous studies. These studies are attractive because of the low risk of transplant related complications but are less likely to be curative. Allogeneic grafts from perfectly matched donors have the advantage of providing a completely new immunological environment. For this reason, I believe that curative results are most probable after allogeneic stem cell engraftment. Emphasis should be on the identification of patients with HLA matched siblings. Initially, these studies will be carried out in patients with advanced disease, as was the case in the early days of transplantation for leukemia. In considering more aggressive treatment for autoimmune diseases it appears there are 3 possible approaches. First, and most conservative, is to store peripheral blood stem cells for possible future marrow rescue and then to give higher doses of immunosuppressive agents, especially in combination, to see whether there is an improvement over conventional doses. Second, for those who prefer a conservative approach to stem cell transplantation, is to give myeloablative and lymphoablative

  8. Behcet's disease in acquired immune deficiency syndrome.

    PubMed

    Siddiqui, Beenish; Fernandes, Denise; Chaucer, Benjamin; Chevenon, Marie; Nandi, Minesh; Saverimuttu, Jessie; Nfonoyim, Jay

    2016-01-01

    HIV/AIDS patients often present with orogenital ulcers. In the immunocompromised patient diagnosis of these ulcers pose a challenge, as there is a myriad of etiologies. We present a case of an HIV/AIDS patient with recurrent orogenital aphthosis that was confirmed to have concomitant diagnosis of Behcet's disease. Proper awareness of the causes of these ulcers is essential for prompt and effective treatment. While rare causes may be at the bottom of a differential list in an immunocompetent host, when HIV/AIDS is involved these rare causes often percolate to the top. PMID:26793479

  9. Immune Tolerance for Autoimmune Disease and Cell Transplantation

    PubMed Central

    Luo, Xunrong; Miller, Stephen D.; Shea, Lonnie D.

    2016-01-01

    The undesired destruction of healthy cells, either endogenous or transplanted, by the immune system results in the loss of tissue function or limits strategies to restore tissue function. Current therapies typically involve non-specific immunosuppression that may prevent the appropriate response to an antigen, thereby decreasing humoral immunity and increasing the risks of patient susceptibility to opportunistic infections, viral reactivation, and neoplasia. The induction of antigen-specific immunological tolerance to block undesired immune responses to self- or allogeneic antigens, while maintaining the integrity of the remaining immune system, has the potential to transform the current treatment of autoimmune disease and serve as a key enabling technology for therapies based on cell transplantation. PMID:26928211

  10. Aptamer Oligonucleotides: Novel Potential Therapeutic Agents in Autoimmune Disease.

    PubMed

    Li, Weibin; Lan, Xiaopeng

    2015-08-01

    Aptamers are single-stranded deoxyribonucleic acid or ribonucleic acid oligonucleotides generated in vitro based on affinity for certain target molecules by a process known as Systematic Evolution of Ligands by Exponential Enrichment. Aptamers can bind their target molecules with high specificity and selectivity by means of structure compatibility, stacking of aromatic rings, electrostatic and van der Waals interactions, and hydrogen bonding. With several advantages over monoclonal antibodies and other conventional small-molecule therapeutics, such as high specificity and affinity, negligible batch to batch variation, flexible modification and stability, lack of toxicity and low immunogenicity, aptamers are becoming promising novel diagnostic and therapeutic agents. This review focuses on the development of aptamers as potential therapeutics for autoimmune diseases, including diabetes mellitus, multiple sclerosis, rheumatoid arthritis, myasthenia gravis, and systemic lupus erythematosus. PMID:25993618

  11. Pathologically confirmed autoimmune encephalitis in suspected Creutzfeldt-Jakob disease

    PubMed Central

    Maat, Peter; de Beukelaar, Janet W.; Jansen, Casper; Schuur, Maaike; van Duijn, Cornelia M.; van Coevorden, Marleen H.; de Graaff, Esther; Titulaer, Maarten; Rozemuller, Annemieke J.

    2015-01-01

    Objective: To determine the clinical features and presence in CSF of antineuronal antibodies in patients with pathologically proven autoimmune encephalitis derived from a cohort of patients with suspected Creutzfeldt-Jakob disease (CJD). Methods: The Dutch Surveillance Centre for Prion Diseases performed 384 autopsies on patients with suspected CJD over a 14-year period (1998–2011). Clinical information was collected from treating physicians. Antineuronal antibodies were tested in CSF obtained postmortem by immunohistochemistry on fresh frozen rat brain sections, by Luminex assay for the presence of well-characterized onconeural antibodies, and by cell-based assays for antibodies against NMDAR, GABABR1/2, GABAAR GLUR1/2, LGI1, Caspr2, and DPPX. Results: In 203 patients, a diagnosis of definite CJD was made, while in 181 a variety of other conditions were diagnosed, mainly neurodegenerative. In 22 of these 181, the neuropathologist diagnosed autoimmune encephalitis. One patient was excluded because of lack of clinical information. Inflammatory infiltrates were predominantly perivascular and consisted mainly of T cells. The predominant locations were basal ganglia and thalamus (90%) and temporal lobes and hippocampus (81%). In 6 patients (29%), antineuronal antibodies were detected in postmortem CSF, directed against Hu, NMDAR, GABABR1/2, Caspr2, and an unidentified synaptic antigen in 2. The most frequent symptoms were dementia (90%), gait disturbance (86%), cerebellar signs (67%), and neuropsychiatric symptoms (67%). Immunopathologic and clinical findings did not differ between autoantibody-negative patients and patients with antineuronal antibodies. Conclusions: It is important to consider immune-mediated disorders in the differential diagnosis of rapidly progressive neurologic deficits. PMID:26601117

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

    PubMed

    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.

  13. Cardiac autoimmunity in HIV related heart muscle disease

    PubMed Central

    Currie, P; Goldman, J; Caforio, A; Jacob, A; Baig, M; Brettle, R; Haven, A; Boon, N; McKenna, W

    1998-01-01

    Objective—To assess the frequency of circulating cardiac specific autoantibodies in HIV positive patients with and without echocardiographic evidence of left ventricular dysfunction.
Subjects—74 HIV positive patients including 28 with echocardiographic evidence of heart muscle disease, 52 HIV negative people at low risk of HIV infection, and 14 HIV negative drug users who had all undergone non-invasive cardiac assessment were studied along with a group of 200 healthy blood donors.
Results—Cardiac autoantibodies detected by indirect immunofluorescence (serum dilution 1/10) were more common in the HIV positive patients (15%), particularly the HIV heart muscle disease group (21%), than in HIV negative controls (3.5%) (both p < 0.001). By ELISA (dilution 1/320), abnormal anti-α myosin autoantibody concentrations were found more often in HIV patients with heart muscle disease (43%) than in HIV positive patients with normal hearts (19%) or in HIV negative controls (3%) (p < 0.05 and p < 0.001, respectively). Anti-α myosin autoantibody concentrations were greater in HIV positive patients than in HIV negative controls, regardless of cardiac status ((mean SD) 0.253 (0.155) v 0.170 (0.076); p = 0.003). In particular the mean antibody concentration was higher in the HIV heart muscle disease patients (0.291 (0.160) v 0.170 (0.076); p = 0.001) than in HIV negative controls. On follow up, six subjects with normal echocardiograms but raised autoantibody concentrations had died after a median of 298 days, three with left ventricular abnormalities at necropsy. This compared with a median survival of 536 days for 21 HIV positive patients with normal cardiological and immunological results.
Conclusions—There is an increased frequency of circulating cardiac specific autoantibodies in HIV positive individuals, particularly those with heart muscle disease. The data support a role for cardiac autoimmunity in the pathogenesis of HIV related heart

  14. Risk of cancer of unknown primary after hospitalization for autoimmune diseases.

    PubMed

    Hemminki, Kari; Sundquist, Kristina; Sundquist, Jan; Ji, Jianguang

    2015-12-15

    Cancer of unknown primary (CUP) is a heterogeneous syndrome diagnosed at metastatic sites. The etiology is unknown but immune dysfunction may be a contributing factor. Patients with autoimmune diseases were identified from the Swedish Hospital Discharge Register and linked to the Swedish Cancer Registry. Standardized incidence ratios (SIRs) were calculated for subsequent CUP and compared with subjects without autoimmune diseases. A total of 789,681 patients were hospitalized for any of 32 autoimmune diseases during years 1964-2012; 2,658 developed subsequent CUP, giving an overall SIR of 1.27. A total of 16 autoimmune diseases were associated with an increased risk for CUP; polymyositis/dermatomyositis showed the highest SIR of 3.51, followed by primary biliary cirrhosis (1.81) and Addison's disease (1.77). CUP risk is known to be reduced in long-time users of pain-relieving nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin. For patients with ankylosing spondylitis and with some other autoimmune diseases, with assumed chronic medication by NSAIDSs, CUP risks decreased in long-term follow-up. The overall risk of CUP was increased among patients diagnosed with autoimmune diseases, which call for clinical attention and suggest a possible role of immune dysfunction in CUP. The associations with many autoimmune diseases were weak which may imply that autoimmunity may not synergize with CUP-related immune dysfunction. However, long-term NSAID medication probably helped to curtail risks in some autoimmune diseases and CUP risks were generally higher in autoimmune diseases for which NSAIDs are not used and for these CUP appears to be a serious side effect.

  15. Risk of cancer of unknown primary after hospitalization for autoimmune diseases.

    PubMed

    Hemminki, Kari; Sundquist, Kristina; Sundquist, Jan; Ji, Jianguang

    2015-12-15

    Cancer of unknown primary (CUP) is a heterogeneous syndrome diagnosed at metastatic sites. The etiology is unknown but immune dysfunction may be a contributing factor. Patients with autoimmune diseases were identified from the Swedish Hospital Discharge Register and linked to the Swedish Cancer Registry. Standardized incidence ratios (SIRs) were calculated for subsequent CUP and compared with subjects without autoimmune diseases. A total of 789,681 patients were hospitalized for any of 32 autoimmune diseases during years 1964-2012; 2,658 developed subsequent CUP, giving an overall SIR of 1.27. A total of 16 autoimmune diseases were associated with an increased risk for CUP; polymyositis/dermatomyositis showed the highest SIR of 3.51, followed by primary biliary cirrhosis (1.81) and Addison's disease (1.77). CUP risk is known to be reduced in long-time users of pain-relieving nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin. For patients with ankylosing spondylitis and with some other autoimmune diseases, with assumed chronic medication by NSAIDSs, CUP risks decreased in long-term follow-up. The overall risk of CUP was increased among patients diagnosed with autoimmune diseases, which call for clinical attention and suggest a possible role of immune dysfunction in CUP. The associations with many autoimmune diseases were weak which may imply that autoimmunity may not synergize with CUP-related immune dysfunction. However, long-term NSAID medication probably helped to curtail risks in some autoimmune diseases and CUP risks were generally higher in autoimmune diseases for which NSAIDs are not used and for these CUP appears to be a serious side effect. PMID:26103152

  16. Are human endogenous retroviruses triggers of autoimmune diseases? Unveiling associations of three diseases and viral loci.

    PubMed

    Nexø, Bjørn A; Villesen, Palle; Nissen, Kari K; Lindegaard, Hanne M; Rossing, Peter; Petersen, Thor; Tarnow, Lise; Hansen, Bettina; Lorenzen, Tove; Hørslev-Petersen, Kim; Jensen, Sara B; Bahrami, Shervin; Lajer, Maria; Schmidt, Kathrine L M; Parving, Hans-Henrik; Junker, Peter; Laska, Magdalena J

    2016-02-01

    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 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 was associated with each of the three diseases. Although there was a significant overlap, most loci only occurred in one of the studied disease. Remarkably, within each disease, there was a statistical interaction (synergy) between two loci. Additional synergy between retroviral loci and human lymphocyte antigens is reported for multiple sclerosis. We speculate the possibility that recombinants or mixed viral particles are formed and that the resulting viruses stimulate the innate immune system, thereby initiating the autoimmune response. PMID:26091722

  17. In healthy primates, circulating autoreactive T cells mediate autoimmune disease.

    PubMed Central

    Genain, C P; Lee-Parritz, D; Nguyen, M H; Massacesi, L; Joshi, N; Ferrante, R; Hoffman, K; Moseley, M; Letvin, N L; Hauser, S L

    1994-01-01

    A T cell response against myelin basic protein (MBP) is thought to contribute to the central nervous system (CNS) inflammation that occurs in the human demyelinating disease multiple sclerosis. To test whether MBP-reactive T cells that are normally retrieved from the circulation are capable of inducing CNS disease, MBP-reactive T cell clones were isolated from the peripheral blood of healthy, unimmunized Callithrix jacchus (C. jacchus) marmosets. This primate species is characterized by a natural chimerism of bone marrow elements between siblings that should make possible adoptive transfer of MBP-reactive T cells. We report that MBP-reactive T cell clones efficiently and reproducibly transfer CNS inflammatory disease between members of C. jacchus chimeric sets. The demyelination that is characteristic of experimental allergic encephalomyelitis induced in C. jacchus by immunization against human white matter did not occur after adoptive transfer of the MBP-reactive clones. It was noteworthy that encephalitogenic T cell clones were diverse in terms of their recognition of different epitopes of MBP, distinguishing the response in C. jacchus from that in some inbred rodents in which restricted recognition of MBP occurs. These findings are the first direct evidence that natural populations of circulating T cells directed against a CNS antigen can mediate an inflammatory autoimmune disease. Images PMID:7521889

  18. Stem cell transplantation and mesenchymal cells to treat autoimmune diseases.

    PubMed

    Tyndall, Alan; van Laar, Jacob M

    2016-06-01

    Since the start of the international stem cell transplantation project in 1997, over 2000 patients have received a haematopoietic stem cell transplant (HSCT), mostly autologous, as treatment for a severe autoimmune disease, the majority being multiple sclerosis (MS), systemic sclerosis (SSc) and Crohn's disease. There was an overall 85% 5-year survival and 43% progression-free survival. Around 30% of patients in all disease subgroups had a complete response, often durable despite full immune reconstitution. In many cases, e.g. systemic sclerosis, morphological improvement such as reduction of skin collagen and normalization of microvasculature was documented, beyond any predicted known effects of intense immunosuppression alone. It is hoped that the results of the three running large prospective randomized controlled trials will allow modification of the protocols to reduce the high transplant-related mortality which relates to regimen intensity, age of patient, and comorbidity. Mesenchymal stromal cells (MSC), often incorrectly called stem cells, have been the intense focus of in vitro studies and animal models of rheumatic and other diseases over more than a decade. Despite multiple plausible mechanisms of action and a plethora of positive in vivo animal studies, few randomised controlled clinical trials have demonstrated meaningful clinical benefit in any condition so far. This could be due to confusion in cell product terminology, complexity of clinical study design and execution or agreement on meaningful outcome measures. Within the rheumatic diseases, SLE and rheumatoid arthritis (RA) have received most attention. Uncontrolled multiple trial data from over 300 SLE patients have been published from one centre suggesting a positive outcome; one single centre comparative study in 172 RA was positive. In addition, small numbers of patients with Crohn's disease, multiple sclerosis, primary Sjögren's disease, polymyositis/dermatomyositis and type II diabetes

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

    Cancer.gov

    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

  20. Immune thrombocytopenia and autoimmune thyroid disease: a controversial overlap

    PubMed Central

    de Campos, Fernando Peixoto Ferraz

    2015-01-01

    Immune thrombocytopenia (ITP) is an entity characterized by a platelet count of less than 100 × 109/L in the absence of other causes of thrombocytopenia, such as viral infections, rheumatic diseases, or drugs. Grave’s disease is also an autoimmune condition in which thrombocytopenia is often observed. Moreover, in the literature, many reports show a marked interference of the thyroid dysfunction (mainly hyperthyroidism) in the control of thrombocytopenia. Although this issue still remains debatable, the authors report the case of a young woman with a previous diagnosis of ITP with a brilliant initial response to corticotherapy. Some years after this diagnosis, the patient presented thyrotoxicosis due to Grave’s disease and the thrombocytopenia relapsed, but this time there was no response to the glucocorticoids. Only after the radioiodine I-131 thyroid ablation the control of thrombocytopenia was achieved. The authors call attention to this overlap and for testing thyroid function in every patient with an unexpected negative response to corticotherapy. PMID:26484334

  1. Thyroid peroxidase and the induction of autoimmune thyroid disease.

    PubMed Central

    McLachlan, S M; Atherton, M C; Nakajima, Y; Napier, J; Jordan, R K; Clark, F; Rees Smith, B

    1990-01-01

    Animal models of autoimmune thyroid disease are associated with thyroglobulin (Tg) as autoantigen whereas in man the autoimmune response to microsomal antigen/thyroid peroxidase (TPO) appears to play a major role in thyroiditis. Consequently, we have compared the ability of TPO and Tg to induce thyroid autoantibodies and thyroid damage in mice known to be susceptible (CBA/J) or resistant (BALB/c) to thyroiditis induced using murine Tg. Groups of three to five mice were immunized twice using Freund's complete adjuvant with 80-100 micrograms highly purified porcine (p) TPO, pTg, rat (r) Tg, human Tg, bovine serum albumin (BSA) or BSA + 0.2 micrograms pTg (the level of Tg contamination of TPO). Four weeks after immunization with TPO, plasma from CBA/J (but not BALB/c) mice contained IgG class antibodies which bound to TPO-coated tubes in the presence or absence of excess Tg (and could therefore be clearly distinguished from Tg antibodies) but there was no evidence of thyroiditis in either strain of mice. In contrast, in CBA/J mice immunized with rTg and, to a lesser extent in mice that had received pTg, thyroid tissue was infiltrated with lymphoid cells and/or neutrophils and antibodies to pTg (but not pTPO) were present. Our observations demonstrate that induction of TPO antibody alone is insufficient to lead to thyroiditis in CBA/J mice. Further, these studies emphasize the complex interactions between MHC and different thyroid antigens in the processes leading to thyroid destruction. PMID:2311297

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

    PubMed

    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

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

    PubMed

    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.

  4. Imaging of acquired coronary diseases: From children to adults.

    PubMed

    Dehaene, A; Jacquier, A; Falque, C; Gorincour, G; Gaubert, J Y

    2016-05-01

    Acquired coronary diseases include aneurysms, fistulae, dissections, and stenosis. Aneurysms may occur secondarily to Kawasaki disease, a childhood vasculitis, the prognosis of which depends on the coronary involvement, or they may be degenerative, infectious, inflammatory, or traumatic in origin. Fistulae develop between the coronary arterial system and a pulmonary or bronchial artery, or cardiac cavity. Dissections may occur spontaneously or may be post-traumatic. These coronary abnormalities may be found incidentally or may present as complications, infarction or rupture. The goals of this article are to understand acquired childhood and adult coronary diseases and their usual means of presentation, the ways of investigating them, and the principles of their treatment. PMID:27130480

  5. Autoimmune pancreatitis: a systemic immune complex mediated disease.

    PubMed

    Deshpande, Vikram; Chicano, Sonia; Chiocca, Sonia; Finkelberg, Dmitry; Selig, Martin K; Mino-Kenudson, Mari; Brugge, William R; Colvin, Robert B; Lauwers, Gregory Y

    2006-12-01

    Autoimmune pancreatitis (AIP) is a mass forming inflammatory pancreatobiliary-centric disease. Recent reports of multiorgan inflammatory mass forming lesions with increased numbers of IgG4 positive plasma cells suggest that AIP may have a systemic component. In this study, we explore the systemic nature of AIP, investigate the relevance of subtyping AIP, perform a systematic study of tissue IgG4 immunoperoxidase, and ultrastructurally evaluate the presence of immune complexes. Our study group consisted of 36 patients with AIP, 21 of whom underwent a Whipple procedure. On the basis of the pattern of inflammation, pancreatic involvement was subtyped as ductocentric (AIP-D) or lobulocentric (AIP-L). Extrapancreatic lesions included bile duct (n=3), salivary glands (n=3), lung (n=2), gallbladder (n=11), and kidney (n=4). Clinical and radiologic data was recorded. Immunohistochemistry for IgG4 was performed on both pancreatic and extrapancreatic tissues and the numbers of IgG4 positive plasma cells were semiquantitatively scored. A control cohort composed of pancreatic adenocarcinoma (n=19) and chronic pancreatitis-not otherwise specified (NOS) (n=14) was also evaluated. Eleven pancreatic specimens, including 2 cases of chronic pancreatitis-NOS and 4 kidneys were evaluated ultrastructurally. The pancreas, bile duct, gall bladder, salivary gland, kidney, and lung lesions were characterized by dense lymphoplasmacytic infiltrates with reactive fibroblasts and venulitis. IgG4 positive plasma cells were identified in all pancreatic and extrapancreatic lesions. The AIP cases showed significantly more pancreatic IgG4 positive plasma cells than chronic pancreatitis-NOS or adenocarcinoma (P=0.001). However, IgG4 positive cells were identified in 57.1% of chronic pancreatitis-NOS and 47.4% of ductal adenocarcinoma. Fifteen of 21 resected cases were classified as AIP-D, and 6 as AIP-L, the latter notably showing significantly more IgG4 positive plasma cells than the former (P=0

  6. Emerging Role and Therapeutic Implication of Wnt Signaling Pathways in Autoimmune Diseases

    PubMed Central

    Shi, Juan; Chi, Shuhong; Xue, Jing; Yang, Jiali; Li, Feng; Liu, Xiaoming

    2016-01-01

    The Wnt signaling pathway plays a key role in many biological aspects, such as cellular proliferation, tissue regeneration, embryonic development, and other systemic effects. Under a physiological condition, it is tightly controlled at different layers and arrays, and a dysregulated activation of this signaling has been implicated into the pathogenesis of various human disorders, including autoimmune diseases. Despite the fact that therapeutic interventions are available for ameliorating disease manifestations, there is no curative therapy currently available for autoimmune disorders. Increasing lines of evidence have suggested a crucial role of Wnt signaling during the pathogenesis of many autoimmune diseases; in addition, some of microRNAs (miRNAs), a class of small, noncoding RNA molecules capable of transcriptionally regulating gene expression, have also recently been demonstrated to possess both physiological and pathological roles in autoimmune diseases by regulating the Wnt signaling pathway. This review summarizes currently our understanding of the pathogenic roles of Wnt signaling in several major autoimmune disorders and miRNAs, those targeting Wnt signaling in autoimmune diseases, with a focus on the implication of the Wnt signaling as potential biomarkers and therapeutic targets in immune diseases, as well as miRNA-mediated regulation of Wnt signaling activation in the development of autoimmune diseases. PMID:27110577

  7. The role of genetic factors in autoimmune disease: implications for environmental research.

    PubMed Central

    Cooper, G S; Miller, F W; Pandey, J P

    1999-01-01

    Studies in both humans and in animal models of specific disorders suggest that polymorphisms of multiple genes are involved in conferring either a predisposition to or protection from autoimmune diseases. Genes encoding polymorphic proteins that regulate immune responses or the rates and extent of metabolism of certain chemical structures have been the focus of much of the research regarding genetic susceptibility. We examine the type and strength of evidence concerning genetic factors and disease etiology, drawing examples from a number of autoimmune diseases. Twin studies of rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), type I diabetes, and multiple sclerosis (MS) indicate that disease concordance in monozygotic twins is 4 or more times higher than in dizygotic twins. Strong familial associations (odds ratio ranging from 5-10) are seen in studies of MS, type I diabetes, Graves disease, discoid lupus, and SLE. Familial association studies have also reported an increased risk of several systemic autoimmune diseases among relatives of patients with a systemic autoimmune disease. This association may reflect a common etiologic pathway with shared genetic or environmental influences among these diseases. Recent genomewide searches in RA, SLE, and MS provide evidence for multiple susceptibility genes involving major histocompatibility complex (MHC) and non-MHC loci; there is also evidence that many autoimmune diseases share a common set of susceptibility genes. The multifactorial nature of the genetic risk factors and the low penetrance of disease underscore the potential influence of environmental factors and gene-environment interactions on the etiology of autoimmune diseases. PMID:10502533

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

    ClinicalTrials.gov

    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

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

    PubMed

    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.

  10. Mesenchymal Stem Cell Therapy for Autoimmune Disease: Risks and Rewards.

    PubMed

    Munir, Hafsa; McGettrick, Helen M

    2015-09-15

    Mesenchymal stem cells (MSC) possess a range of immunomodulatory properties which they exert through soluble mediators and through direct cell-cell contact. Due to these immune regulatory properties, the safety and clinical efficacy of MSC treatment has been tested in a number of autoimmune disorders. In this review we analyze the current data from early phase trials into Crohn's disease, systemic lupus erythematosus, and rheumatoid arthritis. In general, no adverse side effects were observed in patients treated with MSC; however, their clinical efficacy is difficult to interpret. Systemic or site-specific administration of MSC has been reported to exert potent immunomodulatory effects in 7 of the 11 trials discussed. Nonetheless, the mechanism(s) by which MSC exert their regulatory effects in vivo remain largely unknown. We discuss potential limitations or safety concerns associated with MSC therapy, including the heterogeneity of MSC and their potential contribution to disease pathogenesis, which need to be considered when designing future clinical trials, along with the need to standardize trial design. Although we are bridging the translational gap between scientific observations on MSC function and clinical applications for therapy, our understanding of basic MSC biology is still limited. Despite these issues, large, double-blinded, multicenter clinical trials are already underway. Further research into the endogenous function of MSC is required to elucidate the mechanism by which therapeutic MSC are acting.

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

    PubMed

    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.

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

    PubMed

    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.

  13. Genetics of autoimmune diseases: insights from population genetics

    PubMed Central

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

    2015-01-01

    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. PMID:26223182

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

    PubMed Central

    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.

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

    PubMed Central

    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

  16. Assessing the risk of laboratory-acquired meningococcal disease.

    PubMed

    Sejvar, James J; Johnson, David; Popovic, Tanja; Miller, J Michael; Downes, Frances; Somsel, Patricia; Weyant, Robbin; Stephens, David S; Perkins, Bradley A; Rosenstein, Nancy E

    2005-09-01

    Neisseria meningitidis is infrequently reported as a laboratory-acquired infection. Prompted by two cases in the United States in 2000, we assessed this risk among laboratorians. We identified cases of meningococcal disease that were possibly acquired or suspected of being acquired in a laboratory by placing an information request on e-mail discussion groups of infectious disease, microbiology, and infection control professional organizations. A probable case of laboratory-acquired meningococcal disease was defined as illness meeting the case definition for meningococcal disease in a laboratorian who had occupational exposure to an N. meningitidis isolate of the same serogroup within 14 days of illness onset. Sixteen cases of probable laboratory-acquired meningococcal disease occurring worldwide between 1985 and 2001 were identified, including six U.S. cases between 1996 and 2000. Nine cases (56%) were serogroup B; seven (44%) were serogroup C. Eight cases (50%) were fatal. All cases occurred among clinical microbiologists. In 15 cases (94%), isolate manipulation was performed without respiratory protection. We estimated that an average of three microbiologists are exposed to the 3,000 meningococcal isolates seen in U.S. laboratories yearly and calculated an attack rate of 13/100,000 microbiologists between 1996 and 2001, compared to 0.2/100,000 among U.S. adults in general. The rate and case/fatality ratio of meningococcal disease among microbiologists are higher than those in the general U.S. population. Specific risk factors for laboratory-acquired infection are likely associated with exposure to droplets or aerosols containing N. meningitidis. Prevention should focus on the implementation of class II biological safety cabinets or additional respiratory protection during manipulation of suspected meningococcal isolates.

  17. Cytokine Gene Polymorphisms and Human Autoimmune Disease in the Era of Genome-Wide Association Studies

    PubMed Central

    2012-01-01

    Cytokine (receptor) genes have traditionally attracted great interest as plausible genetic risk factors for autoimmune disease. Since 2007, the implementation of genome-wide association studies has facilitated the robust identification of allelic variants in more than 35 cytokine loci as susceptibility factors for a wide variety of over 15 autoimmune disorders. In this review, we catalog the gene loci of interleukin, chemokine, and tumor necrosis factor receptor superfamily and ligands that have emerged as autoimmune risk factors. We examine recent progress made in the clarification of the functional mechanisms by which polymorphisms in the genes coding for interleukin-2 receptor alpha (IL2RA), IL7R, and IL23R may alter risk for autoimmune disease, and discuss opposite autoimmune risk alleles found, among others, at the IL10 locus. PMID:22191464

  18. Hypergammaglobulinemia in the pediatric population as a marker for underlying autoimmune disease: a retrospective cohort study

    PubMed Central

    2013-01-01

    Background The significance of hypergammaglobulinemia as a marker of immune activation is unknown, as a differential diagnosis for hypergammaglobulinemia in children has not been adequately established. The goal of this study was to identify conditions associated with hypergammaglobulinemia in children, with the hypothesis that elevated immunoglobulin levels may precede or predict the development of autoimmune conditions. Methods We reviewed the medical records for all children with IgG level ≥2000 mg/dL treated at a tertiary care children’s hospital from January 1, 2000 through December 31, 2009. We compared clinical and laboratory features of these patients, and developed an algorithm to predict the likelihood of underlying autoimmunity based on these characteristics. Results After excluding children who had received IVIG, a total of 442 patients with hypergammaglobulinemia were identified. Of these, nearly half had autoimmune conditions, most frequently systemic lupus erythematosus and lupus-related disorders. Autoimmune gastrointestinal disorders such as inflammatory bowel disease were also common. Infectious diseases were the next largest category of diseases, followed with much less frequency by malignant, drug-related, and other conditions. In comparison with non-autoimmune conditions, patients with autoimmune disease had higher IgG levels, lower white blood cell counts, lower hemoglobin values, and lower C-reactive protein (CRP) levels. Multivariable logistic regression confirmed that CRP (P = 0.002), white blood cell count (P < 0.001), hemoglobin (P = 0.015), and female gender (P < 0.001) are independent risk factors for autoimmune disease in patients with high IgG levels. Conclusions In a cohort of pediatric patients at a tertiary care children’s hospital, hypergammaglobulinemia was most commonly associated with autoimmune diseases. In female patients with hypergammaglobulinemia, the presence of leukopenia, anemia, and normal CRP

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

    PubMed

    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

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

    PubMed

    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.

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

    PubMed

    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

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

    PubMed Central

    Ivarsson, Anneli; 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 screening-detected, were identified. Per case, 4 referents were matched. Blood samples were analyzed for autoantibodies against thyroid peroxidase (TPOAb). The cut-off value for TPO positivity was set to 100 U/mL. Results. Altogether, 335 celiac disease cases were found. In the entire celiac disease group, 7.2% (24/335) had elevated titers of TPOAb compared to 2.8% (48/1695) of the referents. Among the previously diagnosed celiac disease cases, 7.5% (7/93, OR 2.8, 95% CI 1.2–6.4) was TPOAb positive and among screening-detected cases, 7.0% (17/242, OR 2.6, 95% CI 1.5–4.6) was TPOAb positive. Conclusion. Children with celiac disease showed a higher prevalence of thyroid autoimmunity. We could not confirm the hypothesis that untreated celiac disease is associated with increased risk of developing thyroid autoimmunity. Early initiation of celiac disease treatment might not lower the risk for other autoimmune diseases. PMID:24592326

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

    PubMed

    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

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

    PubMed

    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.

  5. A case of autoimmune hepatitis combined with Graves' disease.

    PubMed

    Jhee, Jong Hyun; Kim, Hyun Ju; Kang, Wonseok; Kim, Sewha; Kim, Do Young

    2015-01-01

    A 25-year-old woman presented with jaundice, palpitation, and weight loss of 5 kg during a period of 2 weeks. Laboratory tests showed elevated levels of liver enzymes (AST 1,282 IU/L, ALT 1,119 IU/L) and total bilirubin (6.4 mg/dL); negative for hepatitis virus infection; elevated serum levels of triiodothyronine (T3, 3.60 ng/dL), free thyroxine (fT4, 3.82 ng/dL), and lowered serum level of thyroid stimulating hormone (TSH, <0.025 μIU/mL); and positive for thyroid stimulating antibody and anti-mitochondrial antibody (AMA). The liver biopsy findings were consistent with autoimmune hepatitis (AIH). Accordingly, oral steroid therapy was started with 60 mg of prednisolone under the impression of AIH associated with Graves' disease. After a week of steroid therapy, the clinical manifestation showed significant improvement, with normalization of both liver and thyroid functions. Diagnosis of the liver condition of patients who present with hyperthyroidism and liver dysfunction is important, so that appropriate therapy can be promptly initiated. PMID:25603854

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

    PubMed

    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.

  7. THE ETIOLOGY OF AUTOIMMUNE THYROID DISEASE: A STORY OF GENES AND ENVIRONMENT

    PubMed Central

    Tomer, Yaron; Huber, Amanda

    2013-01-01

    Autoimmune thyroid diseases (AITD), including Graves’ disease (GD) and Hashimoto’s thyroiditis (HT) are prevalent autoimmune diseases, affecting up to 5% of the general population. Autoimmune thyroid diseases arise due to complex interactions between environmental and genetic factors. Significant progress has been made in our understanding of the genetic and environmental triggers contributing to AITD. However, the interactions between genes and environment are yet to be defined. Among the major AITD susceptibility genes that have been identified and characterized is the HLADR gene locus, as well as non-MHC genes including the CTLA-4, CD40, PTPN22, thyroglobulin, and TSH receptor genes. The major environmental triggers of AITD include iodine, medications, infection, smoking, and possibly stress. Recent data on the genetic predisposition to AITD lead to novel putative mechanisms by which the genetic-environmental interactions may lead to the development of thyroid autoimmunity. PMID:19307103

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

    PubMed

    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

  9. AIRE genetic variants and predisposition to polygenic autoimmune disease: The case of Graves' disease and a systematic literature review.

    PubMed

    Colobran, Roger; Giménez-Barcons, Mireia; Marín-Sánchez, Ana; Porta-Pardo, Eduard; Pujol-Borrell, Ricardo

    2016-08-01

    Autoimmune Regulator (AIRE) is a transcriptional regulator that is crucial for establishing central tolerance as illustrated by the Mendelian Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy (APECED) syndrome associated with AIRE-inactivating recessive or dominant mutations. Polymorphisms in AIRE have been proposed to be implicated in genetic susceptibility to non-Mendelian organ specific autoimmune diseases. Because there is evidence that in predisposition to Graves' disease (GD) central tolerance is crucial, we investigated whether AIRE polymorphisms could modulate risk of GD. A case-control association study using 29 variants and conducted in 150 GD patients and 200 controls did not detect any significant association. This result is not exceptional: a systematic review of the literature, including GWAS, on the association of AIRE variants with organ specific autoimmune diseases did not show clear associations; similarly heterozygous recessive mutations are not associated to non-Mendelian autoimmunity. Dominant negative mutations of AIRE are associated to autoimmunity but as mild forms of APECED rather than to non-Mendelian organ specific autoimmunity. The lack of association of common AIRE polymorphisms with polygenic autoimmune diseases is counterintuitive as many other genes less relevant for immunological tolerance have been found to be associated. These findings give rise to the intriguing possibility that evolution has excluded functionally modifying polymorphisms in AIRE.

  10. Rheumatologic Manifestations in Iranian Patients with Autoimmune Thyroid Diseases

    PubMed Central

    Hezarkhani, Sharabeh; Aghaei, Mehrdad; Shamekhi, Maryam; Nomali, Mahin

    2014-01-01

    Background: Autoimmune thyroid diseases (ATDs) are the most common endocrine diseases which result in rheumatologic manifestations. Some studies have shown association between rheumatologic disorders and ATDs. Thus, the aim of this study was to assess the frequency of rheumatologic manifestations in patients with ATDs. Materials and Methods: In this cross-sectional descriptive study during 2010 to 2011, 65 patients with ATDs referred to the Rheumatology clinic of 5 Azar Hospital in Gorgan (North of Iran) were studied via systematic random sampling and patients with positive antithyroid peroxides (anti-TPO) were included in the study. These patients were examined by a rheumatologist for diagnosis of rheumatologic manifestations and tested for serum levels of TSH, Free T3 and T4, Anti-Nuclear Antibodies (ANAs) and Rheumatoid Factor (RF). SPSS software (version 16) and descriptive statistics were used for data analysis. Results: Nine males (14.8%) and 56 females (86.2%) with mean age of 38.81±1.44 years were studied. Overall, Rheumatologic manifestations were seen in 86.2 % (n=56). In this study, the most frequent rheumatologic manifestations were Carpal Tunnel Syndrome (36.1%) and Osteoarthritis (23%). Reynaud’s phenomenon (RP) (10.7%), Discopathy (8.9%), Fibromyalgia (5.3%), Myopathy (3.6%), Rheumatoid arthritis (3.6%) and trigger finger (3.6%) were other manifestations, respectively. Conclusion: In this region, there is a high frequency of rheumatologic manifestations in patients with ATDs. Thus, initial evaluation and regular checkings are recommended. PMID:25478383

  11. The nexus between atopic disease and autoimmunity: a review of the epidemiological and mechanistic literature.

    PubMed

    Rabin, R L; Levinson, A I

    2008-07-01

    There has been considerable interest in defining the relationship between the expression of allergic and autoimmune diseases in populations of patients. Are patients with autoimmune disease 'protected' from developing allergic (immunoglobulin E-mediated) diseases? Does the establishment of an atopic phenotype reduce the risk of the subsequent development of autoimmune diseases? Although there are clinical studies addressing this question, methodological problems, particularly in identification of atopic subjects, limits their usefulness. Moreover, an immune-based explanation of the observed epidemiological findings has relied on a paradigm that is currently undergoing increased scrutiny and modification to include newly defined effector cell subsets and the interaction between genetic and environmental factors, such as early endotoxin or mycobacterial exposure. To address this question, we reviewed a series of clinical reports that addressed coincidence or co-prevalence of atopy with four autoimmune diseases: psoriasis, rheumatoid arthritis, multiple sclerosis and type I diabetes mellitus. We present a model whereby active T helper type 1 (Th1) inflammation may suppress the development of atopy, and atopy may suppress the severity but not necessarily the onset of autoimmunity, and then discuss our model in the context of mechanisms of adaptive immunity with particular reference to the Th1/Th2 paradigms. Because the ultimate goal is to ameliorate or cure these diseases, our discussion may help to predict or interpret unexpected consequences of novel therapeutic agents used to target autoimmune or atopic diseases. PMID:18505431

  12. Obesity as a Risk and Severity Factor in Rheumatic Diseases (Autoimmune Chronic Inflammatory Diseases)

    PubMed Central

    Gremese, Elisa; Tolusso, Barbara; Gigante, Maria Rita; Ferraccioli, Gianfranco

    2014-01-01

    The growing body of evidence recognizing the adipose tissue (AT) 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 AT 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. PMID:25426122

  13. Clonal Evolution in Two Patients with Autoimmune Disease and Lymphoreticular Neoplasia

    PubMed Central

    Adam, M.; Thorburn, Marigold J.; Gibbs, W. N.; Brooks, S. E. H.; Hanchard, B.

    1970-01-01

    Two cases are described, one with proven lymphosarcoma and doubtful autoimmune disease, and the second with the reverse situation, in which circulating abnormal mononuclear cells showed PHA responsiveness and an abnormal chromosomal constitution (clonal evolution). These findings are discussed in the light of previous cytogenetic studies of lymphoreticular neoplasia and autoimmune disease and the relationship between these two conditions. ImagesFigs. 2-3Fig. 9Fig. 4Figs. 6-7Figs. 1,5Fig. 8 PMID:4393772

  14. Problems in veterinary ultrasonographic analysis of acquired heart disease.

    PubMed

    Bond, B R

    1991-12-01

    Echocardiography in veterinary medicine has both enhanced our ability to diagnose and treat cardiac diseases in small animals and added confusion to what we already know. Because we can actually see the heart beating and visualize blood flows within the cardiac chambers as well as measure velocities of blood flows, we have a tool that increases our non-invasive diagnostic abilities. On the other hand, the lines between different heart diseases are not always clear-cut, and the more we learn about heart disease the more we see the shades of distinction between different diseases become blurred. This chapter will look at the main abnormalities we see in veterinary medicine (mitral regurgitation, pericardial disease, and the different feline and canine cardiomyopathies) and will attempt to help the veterinary echocardiographer avoid common problems encountered in acquired heart disease as well as use echocardiographic information to gain a better understanding of the disease process occurring in animals. PMID:1839366

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

    PubMed Central

    Khan, Deena; Ansar Ahmed, S.

    2015-01-01

    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. PMID:26236331

  16. M. paratuberculosis Heat Shock Protein 65 and Human Diseases: Bridging Infection and Autoimmunity

    PubMed Central

    Dow, Coad Thomas

    2012-01-01

    Mycobacterium avium subspecies paratuberculosis (MAP) is the known infectious cause of Johne's disease, an enteric inflammatory disease mostly studied in ruminant animals. MAP has also been implicated in the very similar Crohn's disease of humans as well as sarcoidosis. Recently, MAP has been associated with juvenile sarcoidosis (Blau syndrome), autoimmune diabetes, autoimmune thyroiditis, and multiple sclerosis. While it is intuitive to implicate MAP in granulomatous diseases where the microbe participates in the granuloma, it is more difficult to assign a role for MAP in diseases where autoantibodies are a primary feature. MAP may trigger autoimmune antibodies via its heat shock proteins. Mycobacterial heat shock protein 65 (HSP65) is an immunodominant protein that shares sequential and conformational elements with several human host proteins. This molecular mimicry is the proposed etiopathology by which MAP stimulates autoantibodies associated with autoimmune (type 1) diabetes, autoimmune (Hashimoto's) thyroiditis, and multiple sclerosis. This paper proposes that MAP is a source of mycobacterial HSP65 and acts as a trigger of autoimmune disease. PMID:23056923

  17. Therapeutic Potential of IL-17-Mediated Signaling Pathway in Autoimmune Liver Diseases

    PubMed Central

    Zhang, Haiyan; Bernuzzi, Francesca; Lleo, Ana; Ma, Xiong; Invernizzi, Pietro

    2015-01-01

    Emerging evidence reveals that various cytokines and tissue microenvironments contribute to liver inflammation and autoimmunity, and IL-17 family is one of highlights acknowledged. Although the implication of IL-17 family in most common autoimmune diseases (such as psoriasis, inflammatory bowel disease, and rheumatoid arthritis) has been extensively characterized, the role of this critical family in pathophysiology of autoimmune liver diseases (AILD) still needs to be clarified. In the review, we look into the intriguing biology of IL-17 family and further dissect on the intricate role of IL-17-mediated pathway in AILD. Considering encouraging data from preclinical and clinical trials, IL-17 targeted therapy has shown promises in several certain autoimmune conditions. However, blocking IL-17-mediated pathway is just beginning, and more fully investigation and reflection are required. Taking together, targeting IL-17-mediated responses may open up new areas of potential clinical treatment for AILD. PMID:26146463

  18. Molecular mimicry: its evolution from concept to mechanism as a cause of autoimmune diseases.

    PubMed

    Oldstone, Michael B A

    2014-06-01

    On a clonal level, certain antibodies and T cells can interact with dissimilar antigens found in microbes and in host cells. More than 5% of over 800 monoclonal antibodies derived from multiple RNA and DNA viruses, as well as from a large number of T cell clones, engage in such interactions. Several of these cross-reactions, which we termed molecular mimicry, are against unique host proteins involved in autoimmune responses and diseases. Thus, molecular mimicry initiated as a host response to a virus or a microbial infection, but alternatively cross-reacting with an appropriate host-antigen, can be a mechanism for instigating an autoimmune disease. Molecular mimicry provides an explanation for the genetic observation that identical twins rarely manifest the same autoimmune disease and the documented epidemiologic evidence that microbial and/or viral infections often precede autoimmune disorders. PMID:24694269

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

    PubMed

    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

  20. Exome Analysis of Patients with Concurrent Pediatric Inflammatory Bowel Disease and Autoimmune Disease

    PubMed Central

    Andreoletti, Gaia; Ashton, James J.; Coelho, Tracy; Willis, Claire; Haggarty, Rachel; Gibson, Jane; Holloway, John; Batra, Akshay; Afzal, Nadeem A.; Beattie, Robert Mark

    2015-01-01

    Background: Pediatric Inflammatory Bowel Disease (PIBD) is a chronic condition seen in genetically predisposed individuals. Genome-wide association studies have implicated >160 genomic loci in IBD with many genes coding for proteins in key immune pathways. This study looks at autoimmune disease burden in patients diagnosed with PIBD and interrogates exome data of a subset of patients. Methods: Patients were recruited from the Southampton Genetics of PIBD cohort. Clinical diagnosis of autoimmune disease in these individuals was ascertained from medical records. For a subset of patients with PIBD and concurrent asthma, exome data was interrogated to ascertain the burden of pathogenic variants within genes implicated in asthma. Association testing was conducted between cases and population controls using the SKAT-O test. Results: Forty-nine (28.3%) PIBD children (18.49% CD, 8.6% UC, and 21.15% IBDU patients) had a concurrent clinical diagnosis of at least one other autoimmune disorder; asthma was the most prevalent, affecting 16.2% of the PIBD cohort. Rare and common variant association testing revealed 6 significant genes (P < 0.05) before Bonferroni adjustment. Three of these genes were previously implicated in both asthma and IBD (ZPBP2 IL1R1, and IL18R1) and 3 in asthma only (PYHIN1, IL2RB, and GSTP1). Conclusions: One-third of our cohort had a concurrent autoimmune condition. We observed higher incidence of asthma compared with the overall pediatric prevalence. Despite a small sample size, SKAT-O evaluated a significant burden of rare and common mutations in 6 genes. Variant burden suggests that a systemic immune dysregulation rather than organ-specific could underpin immune dysfunction for a subset of patients. PMID:25895113

  1. Genetic variations in ZFP36 and their possible relationship to autoimmune diseases.

    PubMed

    Carrick, Danielle Mercatante; Chulada, Patricia; Donn, Rachelle; Fabris, Martina; McNicholl, Janet; Whitworth, William; Blackshear, Perry J

    2006-05-01

    The ZFP36 gene codes for TTP, a regulator of TNF alpha. In mice, TTP deficiency results in a systemic autoimmune inflammatory syndrome with severe arthritis. We hypothesized that genetic variations in ZFP36 are associated with autoimmune disease in humans. The primary objective of this study was to identify human ZFP36 genetic variants in autoimmune disease cases and controls, determine their frequencies in a general clinic population, and construct haplotypes. We resequenced ZFP36 in 316 individuals with autoimmune diseases and identified 28 polymorphisms and determined the frequency of all the known ZFP36 polymorphisms in 484 participants of the Environmental Polymorphism Registry, a regional registry being conducted by the NIEHS. Based on the sequence-verified ZFP36 genotypes, 34 haplotypes were constructed. As a secondary objective, we examined autoimmune disease cases and controls for potential ZFP36 genetic associations. One novel polymorphism, ZFP36*8, a C to T transition in the protein coding domain, was significantly associated with rheumatoid arthritis (RA) in African-Americans (RR=1.23, 95% CI: 1.11-1.36). The data presented here suggest a tentative association between ZFP36 and RA. This finding, as well as the ZFP36 polymorphisms and haplotypes identified here, should form the basis for future association studies in autoimmune diseases.

  2. Autoimmune hepatitis.

    PubMed

    Roberts, E A

    1995-01-01

    Autoimmune hepatitis can present as either acute or chronic disease in children. Clinical and laboratory features, including association with extrahepatic autoimmune syndromes and prompt response to immunosuppressive treatment, circulating autoantibodies and hypergammaglobulinemia, suggest an immune etiology. However, the disease mechanism remains uncertain. Different types of autoimmune hepatitis are defined on the basis of which autoantibodies are present: anti-smooth muscle (type 1), anti-liver/kidney microsomal (type 2), or anti-soluble liver antigen (type 3). Diseases which may be clinically similar to autoimmune hepatitis must be excluded before the diagnosis of autoimmune hepatitis is established: Wilson's disease, primary sclerosing cholangitis, chronic hepatitis B or C, and drug-induced liver disease are among the most important entities. Corticosteroids alone or with azathioprine constitute the usual treatment for autoimmune hepatitis. Although some children achieve a complete remission, or even recovery, and can stop immunosuppressive treatment, others required low-dose prednisone treatment indefinitely.

  3. Microbiomic and Posttranslational Modifications as Preludes to Autoimmune Diseases.

    PubMed

    Opdenakker, Ghislain; Proost, Paul; Van Damme, Jo

    2016-09-01

    Diagnosis and treatment of autoimmunity has mainly relied on adaptive immunity. Infection and inflammation induce cytokines and chemokines and activate myeloid cells to release enzymes. Proteases cleave host proteins into a molar excess of remnant peptides. Additional enzymes modify these peptides into putative autoantigens prior to T and B cell activation. We propose that post-translational modifications may be a means of generating auto-reactive peptides. Microbes also provide proteases and modifying enzymes to the host, and we posit that this may result in autoantigen generation. This could help explain, at least in part, the recently discovered connections between microbiota and autoimmunity. Better explorations of the innate prelude phase of autoimmunity in conjunction with environmental factors might provide novel, broadly applicable therapies. PMID:27491925

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

    PubMed Central

    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

  5. 76 FR 13111 - Compassionate Allowances for Autoimmune Disease, Office of the Commissioner; Hearing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-10

    ... ADMINISTRATION 20 CFR Parts 404, 405, and 416 Compassionate Allowances for Autoimmune Disease, Office of the... diseases and other serious medical conditions that we should consider under the Compassionate Allowance process. These hearings concerned rare diseases, cancers, traumatic brain injury and stroke,...

  6. Mucosal-associated invariant T cells in autoimmunity, immune-mediated diseases and airways disease.

    PubMed

    Hinks, Timothy S C

    2016-05-01

    Mucosal-associated invariant T (MAIT) cells are a novel class of innate-like T cells, expressing a semi-invariant T-cell receptor (TCR) and able to recognize small molecules presented on the non-polymorphic MHC-related protein 1. Their intrinsic effector-memory phenotype, enabling secretion of pro-inflammatory cytokines, and their relative abundance in humans imply a significant potential to contribute to autoimmune processes. However, as MAIT cells were unknown until recently and specific immunological tools were unavailable, little is known of their roles in disease. Here I review observations from clinical studies and animal models of autoimmune and immune-mediated diseases including the roles of MAIT cells in systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease and airways diseases. MAIT cell deficiencies are frequently observed in peripheral blood, and at sites of disease such as the airways in asthma. However, MAIT cells have a specific sensitivity to suppression by therapeutic corticosteroids that may confound many of these observations, as may the tendency of the surface marker CD161 to activation-induced down-regulation. Nonetheless, the dependence on bacteria for the development of MAIT cells suggests a potentially important protective role linking the influences of early life microbial exposures and subsequent development of autoimmunity. Conversely, MAIT cells could contribute to chronic inflammation either through TCR-independent activation, or potentially by TCR recognition of as yet undiscovered ligands. Future research will be greatly facilitated by the immunological tools that are now available, including murine genetic models and human and murine specific tetramers.

  7. Mucosal-associated invariant T cells in autoimmunity, immune-mediated diseases and airways disease.

    PubMed

    Hinks, Timothy S C

    2016-05-01

    Mucosal-associated invariant T (MAIT) cells are a novel class of innate-like T cells, expressing a semi-invariant T-cell receptor (TCR) and able to recognize small molecules presented on the non-polymorphic MHC-related protein 1. Their intrinsic effector-memory phenotype, enabling secretion of pro-inflammatory cytokines, and their relative abundance in humans imply a significant potential to contribute to autoimmune processes. However, as MAIT cells were unknown until recently and specific immunological tools were unavailable, little is known of their roles in disease. Here I review observations from clinical studies and animal models of autoimmune and immune-mediated diseases including the roles of MAIT cells in systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease and airways diseases. MAIT cell deficiencies are frequently observed in peripheral blood, and at sites of disease such as the airways in asthma. However, MAIT cells have a specific sensitivity to suppression by therapeutic corticosteroids that may confound many of these observations, as may the tendency of the surface marker CD161 to activation-induced down-regulation. Nonetheless, the dependence on bacteria for the development of MAIT cells suggests a potentially important protective role linking the influences of early life microbial exposures and subsequent development of autoimmunity. Conversely, MAIT cells could contribute to chronic inflammation either through TCR-independent activation, or potentially by TCR recognition of as yet undiscovered ligands. Future research will be greatly facilitated by the immunological tools that are now available, including murine genetic models and human and murine specific tetramers. PMID:26778581

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

    PubMed

    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.

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

    PubMed Central

    Root-Bernstein, Robert; Fairweather, DeLisa

    2014-01-01

    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. PMID:25484004

  10. Behçet's disease diagnosed after acute HIV infection: viral replication activating underlying autoimmunity?

    PubMed

    Roscoe, Clay; Kinney, Rebecca; Gilles, Ryan; Blue, Sky

    2015-05-01

    Behçet's disease is an autoimmune systemic vasculitis that can occur after exposure to infectious agents. Behçet's disease also has been associated with HIV infection, including de novo development of this condition during chronic HIV infection and resolution of Behçet's disease symptoms following initiation of antiretroviral therapy. We describe a patient who presented with systemic vasculitis with skin and mucous membrane ulcerations in the setting of acute HIV infection, who was eventually diagnosed with Behçet's disease, demonstrating a possible link between acute HIV infection, immune activation and development of autoimmunity.

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

    PubMed

    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

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

    PubMed

    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

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

    ERIC Educational Resources Information Center

    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…

  14. Antigen Presentation, Autoantigens, and Immune Regulation in Multiple Sclerosis and Other Autoimmune Diseases

    PubMed Central

    Riedhammer, Christine; Weissert, Robert

    2015-01-01

    Antigen presentation is in the center of the immune system, both in host defense against pathogens, but also when the system is unbalanced and autoimmune diseases like multiple sclerosis (MS) develop. It is not just by chance that a major histocompatibility complex gene is the major genetic susceptibility locus in MS; a feature that MS shares with other autoimmune diseases. The exact etiology of the disease, however, has not been fully understood yet. T cells are regarded as the major players in the disease, but most probably a complex interplay of altered central and peripheral tolerance mechanisms, T-cell and B-cell functions, characteristics of putative autoantigens, and a possible interference of environmental factors like microorganisms are at work. In this review, new data on all these different aspects of antigen presentation and their role in MS will be discussed, probable autoantigens will be summarized, and comparisons to other autoimmune diseases will be drawn. PMID:26136751

  15. New Murine Model of Early Onset Autoimmune Thyroid Disease/Hypothyroidism and Autoimmune Exocrinopathy of the Salivary Gland.

    PubMed

    Kayes, Timothy Daniel; Weisman, Gary A; Camden, Jean M; Woods, Lucas T; Bredehoeft, Cole; Downey, Edward F; Cole, James; Braley-Mullen, Helen

    2016-09-15

    Sixty to seventy percent of IFN-γ(-/-) NOD.H-2h4 mice given sodium iodide (NaI)-supplemented water develop a slow onset autoimmune thyroid disease, characterized by thyrocyte epithelial cell (TEC) hyperplasia and proliferation (H/P). TEC H/P develops much earlier in CD28(-/-) mice and nearly 100% (both sexes) have severe TEC H/P at 4 mo of age. Without NaI supplementation, 50% of 5- to 6-mo-old CD28(-/-)IFN-γ(-/-) mice develop severe TEC H/P, and 2-3 wk of NaI is sufficient for optimal development of severe TEC H/P. Mice with severe TEC H/P are hypothyroid, and normalization of serum thyroxine levels does not reduce TEC H/P. Activated CD4(+) T cells are sufficient to transfer TEC H/P to SCID recipients. Thyroids of mice with TEC H/P have infiltrating T cells and expanded numbers of proliferating thyrocytes that highly express CD40. CD40 facilitates, but is not required for, development of severe TEC H/P, as CD40(-/-)IFN-γ(-/-)CD28(-/-) mice develop severe TEC H/P. Accelerated development of TEC H/P in IFN-γ(-/-)CD28(-/-) mice is a result of reduced regulatory T cell (Treg) numbers, as CD28(-/-) mice have significantly fewer Tregs, and transfer of CD28(+) Tregs inhibits TEC H/P. Essentially all female IFN-γ(-/-)CD28(-/-) NOD.H-2h4 mice have substantial lymphocytic infiltration of salivary glands and reduced salivary flow by 6 mo of age, thereby providing an excellent new model of autoimmune exocrinopathy of the salivary gland. This is one of very few models where autoimmune thyroid disease and hypothyroidism develop in most mice by 4 mo of age. This model will be useful for studying the effects of hypothyroidism on multiple organ systems. PMID:27521344

  16. New Murine Model of Early Onset Autoimmune Thyroid Disease/Hypothyroidism and Autoimmune Exocrinopathy of the Salivary Gland.

    PubMed

    Kayes, Timothy Daniel; Weisman, Gary A; Camden, Jean M; Woods, Lucas T; Bredehoeft, Cole; Downey, Edward F; Cole, James; Braley-Mullen, Helen

    2016-09-15

    Sixty to seventy percent of IFN-γ(-/-) NOD.H-2h4 mice given sodium iodide (NaI)-supplemented water develop a slow onset autoimmune thyroid disease, characterized by thyrocyte epithelial cell (TEC) hyperplasia and proliferation (H/P). TEC H/P develops much earlier in CD28(-/-) mice and nearly 100% (both sexes) have severe TEC H/P at 4 mo of age. Without NaI supplementation, 50% of 5- to 6-mo-old CD28(-/-)IFN-γ(-/-) mice develop severe TEC H/P, and 2-3 wk of NaI is sufficient for optimal development of severe TEC H/P. Mice with severe TEC H/P are hypothyroid, and normalization of serum thyroxine levels does not reduce TEC H/P. Activated CD4(+) T cells are sufficient to transfer TEC H/P to SCID recipients. Thyroids of mice with TEC H/P have infiltrating T cells and expanded numbers of proliferating thyrocytes that highly express CD40. CD40 facilitates, but is not required for, development of severe TEC H/P, as CD40(-/-)IFN-γ(-/-)CD28(-/-) mice develop severe TEC H/P. Accelerated development of TEC H/P in IFN-γ(-/-)CD28(-/-) mice is a result of reduced regulatory T cell (Treg) numbers, as CD28(-/-) mice have significantly fewer Tregs, and transfer of CD28(+) Tregs inhibits TEC H/P. Essentially all female IFN-γ(-/-)CD28(-/-) NOD.H-2h4 mice have substantial lymphocytic infiltration of salivary glands and reduced salivary flow by 6 mo of age, thereby providing an excellent new model of autoimmune exocrinopathy of the salivary gland. This is one of very few models where autoimmune thyroid disease and hypothyroidism develop in most mice by 4 mo of age. This model will be useful for studying the effects of hypothyroidism on multiple organ systems.

  17. B cells in autoimmune diseases: Insights from analyses of immunoglobulin variable (Ig V) gene usage

    PubMed Central

    Foreman, Angela Lee; Van de Water, Judy; Gougeon, Marie-Lise; Gershwin, M. Eric

    2007-01-01

    The role of B cells in autoimmune diseases has not been fully elucidated. It is also unclear whether breaking of B cell tolerance in patients with autoimmune diseases is due to underlying defects in the molecular mechanisms involved in the arrangement of antibody genes or deficiencies in the subsequent selective influences that shape the antibody repertoire. Analysis of immunoglobulin (Ig) variable (V) gene usage is beginning to provide answers to some of these questions. Such analyses have identified some differences in the basic Ig V gene repertoire of patients with autoimmune diseases compared to healthy controls, even though none of these differences can be considered major. Defects in positive and negative selection, mutational targeting and, in some cases, receptor editing have also been detected. In addition, analysis of Ig V gene usage in target organs and tissues of patients with autoimmune diseases have clearly demonstrated that there is a highly compartmentalized clonal expansion of B cells driven by a limited number of antigens in these tissues. Great progress has been made in the structural and functional characterization of disease-associated antibodies, largely because of the development of the combinatorial library technique. Use of antibodies generated by this technique offers great promise in identifying B cell epitopes on known target antigens and in gaining greater insights into the pathogenic role of B cells in both B- and T-cell-mediated autoimmune diseases. PMID:17537385

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

    PubMed

    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

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

    PubMed

    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.

  20. Exercise as a therapeutic tool to counteract inflammation and clinical symptoms in autoimmune rheumatic diseases.

    PubMed

    Perandini, Luiz Augusto; de Sá-Pinto, Ana Lúcia; Roschel, Hamilton; Benatti, Fabiana Braga; Lima, Fernanda Rodrigues; Bonfá, Eloisa; Gualano, Bruno

    2012-12-01

    Chronic inflammation is a common feature shared by several autoimmune rheumatic diseases, such as rheumatoid arthritis, systemic lupus erythematosus, idiopathic inflammatory myopathies, systemic sclerosis, and ankylosing spondylitis. Therefore, blocking or reducing inflammation is one of the major treatment strategies in these diseases. In this context, exercise training has emerged as a potential therapeutic tool in counteracting systemic inflammation, thereby leading to better clinical outcomes. The aims of this review are i) to provide a summary of the clinical effects of exercise training in selected autoimmune rheumatic diseases; and ii) to discuss the potential anti-inflammatory role of exercise training in autoimmune rheumatic diseases, stressing the gaps in literature and the clinical and scientific perspectives in the field.

  1. Little peptide, big effects: the role of LL-37 in inflammation and autoimmune disease.

    PubMed

    Kahlenberg, J Michelle; Kaplan, Mariana J

    2013-11-15

    The innate immune system utilizes many approaches for defense against invading microorganisms, including complement-mediated lysis, engulfment, formation of neutrophil extracellular traps, and release of antimicrobial peptides. Although classically thought to be driven by adaptive immunity, the development of autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus is increasingly associated with dysregulated innate immune pathways. An emerging theme within this literature is the contribution of antimicrobial peptides to the development of autoimmune disorders. This is best exemplified in atopic dermatitis and psoriasis where the defensins and the single human cathelicidin, LL-37, may contribute to disease. Furthermore, in the past few years, a role for LL-37 has emerged in the pathogenesis of systemic lupus erythematosus, rheumatoid arthritis, atherosclerosis, and possibly other diseases. In this review, we discuss the role of LL-37 and its murine ortholog, mCRAMP, in the modulation of immune and inflammatory pathways and their effects on autoimmune and inflammatory diseases.

  2. The Postnatal Maternal Environment Affects Autoimmune Disease Susceptibility in A/J mice

    PubMed Central

    Case, Laure K.; Rio, Roxana del; Bonney, Elizabeth A.; Zachary, James F.; Blankenhorn, Elizabeth P.; Tung, Kenneth S. K.; Teuscher, Cory

    2009-01-01

    The postnatal maternal environment is known to increase susceptibility to a number of autoimmune diseases. Here we asked whether the postnatal maternal environment could influence autoimmune disease development to day 3 thymectomy (d3tx)-induced autoimmune ovarian disease (AOD) and experimental allergic encephalomyelitis (EAE) in cross-fostered A/J and B6 mice. A/J pups foster-nursed by B6 mothers exhibit an increase in autoimmune disease development while cross-fostering B6 pups on A/J mothers did not alter their susceptibility. The increase in AOD incidence seen in foster-nursed d3tx A/J mice correlated with a decrease in the total number of CD4+ T cells in the lymph nodes of these animals. Analysis of the cellular composition in the milk revealed that B6 mice shed significantly more maternally derived lymphocytes into their milk compared to A/J mothers. These data suggest that there are maternally derived postnatal factors that influence the development of autoimmune disease in A/J mice. PMID:19914609

  3. Human adjuvant disease: remission of silicone induced autoimmune disease after explanation of breast augmentation.

    PubMed Central

    kaiser, W; Biesenbach, G; Stuby, U; Grafinger, P; Zazgornik, J

    1990-01-01

    Autoimmune diseases following silicone or paraffin implantation are rarely encountered complications of plastic surgery. A 42 year old woman is presented who developed clinical and immunological features of systemic lupus erythematosus 11 years after silicone augmentation. After explanation antinuclear antibody titres decreased from 1/1280 to 1/160, C4 complement fraction and the previously raised angiotensin converting enzyme normalised in step with clinical improvement. It is important that plastic surgeons and rheumatologists should be aware of this possible association. PMID:2256743

  4. Prevalence of coeliac disease among adult patients with autoimmune hypothyroidism in Jordan.

    PubMed

    Farahid, O H; Khawaja, N; Shennak, M M; Batieha, A; El-Khateeb, M; Ajlouni, K

    2014-02-11

    The prevalence of coeliac disease among patients with autoimmune hypothyroidism has not been studied before in Jordan and other Arab countries. A cross-sectional record-based review was made of all adult autoimmune hypothyroidism patients who attended a referral centre in Jordan, during an 8-month period. Coeliac disease in these patients was diagnosed by the attending physician based on positive serological tests for anti-endomysial antibodies IgA and IgG followed by duodenal biopsy to confirm the diagnosis of coeliac disease. Of 914 patients recruited, 117 (12.8%) were seropositive for coeliac disease. Of 87 seropositive patients who underwent duodenal biopsy, 39 had positive histological findings of coeliac disease (44.8%). Extrapolating from these findings the overall rate of coeliac disease among autoimmune hypothyroidism patients was estimated to be 5.7%. In multivariate logistic regression coeliac disease was significantly associated with older age (> 40 years), presence of other autoimmune diseases, vitamin B12 deficiency and anaemia.

  5. The role of natural killer cells in pathogenesis of autoimmune diseases

    PubMed Central

    Górska, Elżbieta

    2016-01-01

    There is growing evidence that NK cell-mediated immunoregulation plays an important role in the control of autoimmunity. NK cells are a subset of lymphocytes that generally contribute to innate immunity but have also a great impact on the function of T and B lymphocytes. The major role of NK cells is cytotoxic reaction against neoplastic, infected and autoreactive cells, but they regulatory function seems to play more important role in the pathogenesis of autoimmune diseases. Numerous studies suggested the involvement of NK cells in pathogenesis of such a common autoimmune diseases as juvenile rheumatoid arthritis, type I diabetes and autoimmune thyroid diseases. The defects of NK cells regulatory function as well as cytotoxic abilities are common in patients with autoimmune diseases with serious consequences including HLH hemophagocytic lymphocytosis (HLH) and macrophage activation syndrome (MAS). The early diagnosis of NK cells defect responsible for the loss of the protective abilities is crucial for the prevention of life-threatening complications and implementation of necessary treatment. PMID:26862312

  6. SEX-SPECIFIC ENVIRONMENTAL INFLUENCES ON THE DEVELOPMENT OF AUTOIMMUNE DISEASES

    PubMed Central

    Tiniakou, Eleni; Costenbader, Karen H.; Kriegel, Martin A.

    2013-01-01

    Sex differences in autoimmune diseases are evolutionarily tied to the fact that the female immune system is confronted with intense alterations during menstrual cycles, pregnancy and childbirth. These events may be associated with breaches in the mucosal epithelial layers that are shielding us from environmental factors. Associations between environmental agents and autoimmune diseases have been described extensively in prior studies. Little evidence, however, exists for sex-specific environmental effects on autoimmune diseases. In this review, we summarize studies involving this often-neglected aspect. We give examples of environmental factors that may influence the sex bias in autoimmunity. We conclude that most studies do not give insight into sex-specific environmental effects due to the influence of gender-selective social, occupational or other exposures. Prospective studies are needed in order to determine true sex-biased environmental influences. Finally, humanized murine models might aid in better understanding the mechanisms involved in sex-specific environmental effects on autoimmune diseases. PMID:23507400

  7. The role of natural killer cells in pathogenesis of autoimmune diseases.

    PubMed

    Popko, Katarzyna; Górska, Elżbieta

    2015-01-01

    There is growing evidence that NK cell-mediated immunoregulation plays an important role in the control of autoimmunity. NK cells are a subset of lymphocytes that generally contribute to innate immunity but have also a great impact on the function of T and B lymphocytes. The major role of NK cells is cytotoxic reaction against neoplastic, infected and autoreactive cells, but they regulatory function seems to play more important role in the pathogenesis of autoimmune diseases. Numerous studies suggested the involvement of NK cells in pathogenesis of such a common autoimmune diseases as juvenile rheumatoid arthritis, type I diabetes and autoimmune thyroid diseases. The defects of NK cells regulatory function as well as cytotoxic abilities are common in patients with autoimmune diseases with serious consequences including HLH hemophagocytic lymphocytosis (HLH) and macrophage activation syndrome (MAS). The early diagnosis of NK cells defect responsible for the loss of the protective abilities is crucial for the prevention of life-threatening complications and implementation of necessary treatment. PMID:26862312

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

    PubMed

    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.

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

    PubMed

    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

  10. Sleep Disorders and Increased Risk of Autoimmune Diseases in Individuals without Sleep Apnea

    PubMed Central

    Hsiao, Yi-Han; Chen, Yung-Tai; Tseng, Ching-Min; Wu, Li-An; Lin, Wei-Chen; Su, Vincent Yi-Fong; Perng, Diahn-Warng; Chang, Shi-Chuan; Chen, Yuh-Min; Chen, Tzeng-Ji; Lee, Yu-Chin; Chou, Kun-Ta

    2015-01-01

    Study Objectives: To explore the association between the non-apnea sleep disorder (NSD) and autoimmune diseases. Design: Cohort study. Setting: Nationwide database research. Participants: 84,996 adult patients with NSD diagnoses recorded in the Taiwan National Health Insurance Research Database between 2000 and 2003, after excluding those with antecedent autoimmune diseases. A comparison cohort of 84,996 participants was formed by age-, gender-, income-, and urbanization-matched controls. Interventions: None. Measurements and Results: The two cohorts were followed up for occurrence of autoimmune diseases, including rheumatoid arthritis (RA), ankylosing spondylitis (AS), systemic lupus erythematosus (SLE), Sjögren's syndrome (SS), and systemic sclerosis (SSc). A Cox proportional hazards regression model was used for muti-variate adjustment. In patients with NSD, the overall risk for incident autoimmune diseases was significantly higher than in controls (adjusted hazard ratio [HR] = 1.47, 95% confidence interval [CI] = 1.41–1.53). With regard to individual diseases, the risks for SLE, RA, AS and SS among NSD patients were also significantly higher than in controls (HR [95% CI] for SLE, RA, AS, and SS were 1.81 [1.50–2.18], 1.45 [1.36–1.54], 1.53 [1.38–1.70], and 1.51 [1.43–1.60], respectively), whereas the increased risk for SSc did not reach statistical significance (HR: 1.36 [0.82–2.26]). Conclusion: Patients with non-apnea sleep disorder were associated with a higher risk for developing autoimmune diseases. Citation: Hsiao YH, Chen YT, Tseng CM, Wu LA, Lin WC, Su VY, Perng DW, Chang SC, Chen YM, Chen TJ, Lee YC, Chou KT. Sleep disorders and increased risk of autoimmune diseases in individuals without sleep apnea. SLEEP 2015;38(4):581–586. PMID:25669189

  11. Toxins Targeting the Kv1.3 Channel: Potential Immunomodulators for Autoimmune Diseases.

    PubMed

    Zhao, Yipeng; Huang, Jie; Yuan, Xiaolu; Peng, Biwen; Liu, Wanhong; Han, Song; He, Xiaohua

    2015-05-19

    Autoimmune diseases are usually accompanied by tissue injury caused by autoantigen-specific T-cells. KV1.3 channels participate in modulating calcium signaling to induce T-cell proliferation, immune activation and cytokine production. Effector memory T (TEM)-cells, which play major roles in many autoimmune diseases, are controlled by blocking KV1.3 channels on the membrane. Toxins derived from animal venoms have been found to selectively target a variety of ion channels, including KV1.3. By blocking the KV1.3 channel, these toxins are able to suppress the activation and proliferation of TEM cells and may improve TEM cell-mediated autoimmune diseases, such as multiple sclerosis and type I diabetes mellitus.

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

    PubMed

    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.

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

    PubMed

    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. PMID:27215114

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

    PubMed Central

    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

  15. Vitamin D Actions on CD4(+) T Cells in Autoimmune Disease.

    PubMed

    Hayes, Colleen Elizabeth; Hubler, Shane L; Moore, Jerott R; Barta, Lauren E; Praska, Corinne E; Nashold, Faye E

    2015-01-01

    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 are summarized 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(+) T-regulatory cell and CD4(+) T-regulatory cell type 1 (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, unanswered questions and potentially informative future research directions are highlighted to speed delivery of etiology-based strategies to reduce autoimmune disease.

  16. Vitamin D Actions on CD4+ T Cells in Autoimmune Disease

    PubMed Central

    Hayes, Colleen Elizabeth; Hubler, Shane L.; Moore, Jerott R.; Barta, Lauren E.; Praska, Corinne E.; Nashold, Faye E.

    2015-01-01

    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 are summarized 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+ T-regulatory cell and CD4+ T-regulatory cell type 1 (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, unanswered questions and potentially informative future research directions are highlighted to speed delivery of etiology-based strategies to reduce autoimmune disease. PMID:25852682

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

    PubMed

    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.

  18. Proliferating brain cells are a target of neurotoxic CSF in systemic autoimmune disease

    PubMed Central

    Sakic, Boris; Kirkham, David L.; Ballok, David A.; Mwanjewe, James; Fearon, Ian M.; Macri, Joseph; Yu, Guanhua; Sidor, Michelle M.; Denburg, Judah A.; Szechtman, Henry; Lau, Jonathan; Ball, Alexander K.; Doering, Laurie C.

    2006-01-01

    Brain atrophy, neurologic and psychiatric (NP) manifestations are common complications in the systemic autoimmune disease, lupus erythematosus (SLE). Here we show that the cerebrospinal fluid (CSF) from autoimmune MRL-lpr mice and a deceased NP-SLE patient reduce the viability of brain cells which proliferate in vitro. This detrimental effect was accompanied by periventricular neurodegeneration in the brains of autoimmune mice and profound in vivo neurotoxicity when their CSF was administered to the CNS of a rat. Multiple ionic responses with microfluorometry and protein peaks on electropherograms suggest more than one mechanism of cellular demise. Similar to the CSF from diseased MRL-lpr mice, the CSF from a deceased SLE patient with a history of psychosis, memory impairment, and seizures, reduced viability of the C17.2 neural stem cell line. Proposed mechanisms of cytotoxicity involve binding of intrathecally synthesized IgG autoantibodies to target(s) common to different mammalian species and neuronal populations. More importantly, these results indicate that the viability of proliferative neural cells can be compromised in systemic autoimmune disease. Antibody-mediated lesions of germinal layers may impair the regenerative capacity of the brain in NP-SLE and possibly, brain development and function in some forms of CNS disorders in which autoimmune phenomena have been documented. PMID:16198428

  19. Mammalian target of rapamycin activation underlies HSC defects in autoimmune disease and inflammation in mice.

    PubMed

    Chen, Chong; Liu, Yu; Liu, Yang; Zheng, Pan

    2010-11-01

    The mammalian target of rapamycin (mTOR) is a signaling molecule that senses environmental cues, such as nutrient status and oxygen supply, to regulate cell growth, proliferation, and other functions. Unchecked, sustained mTOR activity results in defects in HSC function. Inflammatory conditions, such as autoimmune disease, are often associated with defective hematopoiesis. Here, we investigated whether hyperactivation of mTOR in HSCs contributes to hematopoietic defects in autoimmunity and inflammation. We found that in mice deficient in Foxp3 (scurfy mice), a model of autoimmunity, the development of autoimmune disease correlated with progressive bone marrow loss and impaired regenerative capacity of HSCs in competitive bone marrow transplantation. Similarly, LPS-mediated inflammation in C57BL/6 mice led to massive bone marrow cell death and impaired HSC function. Importantly, treatment with rapamycin in both models corrected bone marrow hypocellularity and partially restored hematopoietic activity. In cultured mouse bone marrow cells, treatment with either of the inflammatory cytokines IL-6 or TNF-α was sufficient to activate mTOR, while preventing mTOR activation in vivo required simultaneous inhibition of CCL2, IL-6, and TNF-α. These data strongly suggest that mTOR activation in HSCs by inflammatory cytokines underlies defective hematopoiesis in autoimmune disease and inflammation.

  20. Human ITCH E3 ubiquitin ligase deficiency causes syndromic multisystem autoimmune disease.

    PubMed

    Lohr, Naomi J; Molleston, Jean P; Strauss, Kevin A; Torres-Martinez, Wilfredo; Sherman, Eric A; Squires, Robert H; Rider, Nicholas L; Chikwava, Kudakwashe R; Cummings, Oscar W; Morton, D Holmes; Puffenberger, Erik G

    2010-03-12

    Ubiquitin ligases play an important role in the regulation of the immune system. Absence of Itch E3 ubiquitin ligase in mice has been shown to cause severe autoimmune disease. Using autozygosity mapping in a large Amish kindred, we identified a linkage region on chromosome 20 and selected candidate genes for screening. We describe, in ten patients, identification of a mutation resulting in truncation of ITCH. These patients represent the first reported human phenotype associated with ITCH deficiency. These patients not only have multisystem autoimmune disease but also display morphologic and developmental abnormalities. This disorder underscores the importance of ITCH ubiquitin ligase in many cellular processes. PMID:20170897

  1. Human ITCH E3 Ubiquitin Ligase Deficiency Causes Syndromic Multisystem Autoimmune Disease

    PubMed Central

    Lohr, Naomi J.; Molleston, Jean P.; Strauss, Kevin A.; Torres-Martinez, Wilfredo; Sherman, Eric A.; Squires, Robert H.; Rider, Nicholas L.; Chikwava, Kudakwashe R.; Cummings, Oscar W.; Morton, D. Holmes; Puffenberger, Erik G.

    2010-01-01

    Ubiquitin ligases play an important role in the regulation of the immune system. Absence of Itch E3 ubiquitin ligase in mice has been shown to cause severe autoimmune disease. Using autozygosity mapping in a large Amish kindred, we identified a linkage region on chromosome 20 and selected candidate genes for screening. We describe, in ten patients, identification of a mutation resulting in truncation of ITCH. These patients represent the first reported human phenotype associated with ITCH deficiency. These patients not only have multisystem autoimmune disease but also display morphologic and developmental abnormalities. This disorder underscores the importance of ITCH ubiquitin ligase in many cellular processes. PMID:20170897

  2. Autoimmune Neutropenia as a Cause of Periodontal Disease in Preschool Children.

    PubMed

    Hajishengallis, Evlambia; Rashewsky, Stephanie; Kulkarni, Cyelee; Stathopoulou, Panagiota

    2016-01-01

    In autoimmune neutropenia, autoantibodies attack neutrophils resulting in their destruction or alteration of their function. Since neutrophils have important immunologic functions, aberrations in their homeostasis lead to increased susceptibility to diseases, such as periodontitis. Periodontitis as a manifestation of neutropenia can affect adults and children. In this paper, we describe the treatment of periodontal disease in a 2-year-old female with autoimmune neutropenia. The importance of an interdisciplinary approach, frequent recalls, and meticulous mechanical therapy in stabilizing her periodontal condition, despite ongoing systemic infections is emphasized.

  3. Autoimmune Neutropenia as a Cause of Periodontal Disease in Preschool Children.

    PubMed

    Hajishengallis, Evlambia; Rashewsky, Stephanie; Kulkarni, Cyelee; Stathopoulou, Panagiota

    2016-01-01

    In autoimmune neutropenia, autoantibodies attack neutrophils resulting in their destruction or alteration of their function. Since neutrophils have important immunologic functions, aberrations in their homeostasis lead to increased susceptibility to diseases, such as periodontitis. Periodontitis as a manifestation of neutropenia can affect adults and children. In this paper, we describe the treatment of periodontal disease in a 2-year-old female with autoimmune neutropenia. The importance of an interdisciplinary approach, frequent recalls, and meticulous mechanical therapy in stabilizing her periodontal condition, despite ongoing systemic infections is emphasized. PMID:26696110

  4. Autoimmune hepatitis

    MedlinePlus

    Lupoid hepatitis; Chronic acute liver disease ... This form of hepatitis is an autoimmune disease . The body's immune system cannot tell the difference between healthy body tissue and harmful, outside ...

  5. Evasion and Interactions of the Humoral Innate Immune Response in Pathogen Invasion, Autoimmune Disease, and Cancer

    PubMed Central

    Rettig, Trisha A.; Harbin, Julie N.; Harrington, Adelaide; Dohmen, Leonie; Fleming, Sherry D.

    2015-01-01

    The humoral innate immune system is composed of three major branches, complement, coagulation, and natural antibodies. To persist in the host, pathogens, such as bacteria, viruses, and cancers must evade parts of the innate humoral immune system. Disruptions in the humoral innate immune system also play a role in the development of autoimmune diseases. This review will examine how gram positive bacteria, viruses, cancer, and the autoimmune conditions Systemic Lupus Erythematosus and Anti-phospholipid syndrome, interact with these immune system components. Through examining evasion techniques it becomes clear that interplay between these three systems exists. By exploring the interplay and the evasion/disruption of the humoral innate immune system, we can develop a better understanding of pathogenic infections, cancer, and autoimmune disease development. PMID:26145788

  6. BAFF and rheumatic autoimmune disorders: implications for disease management and therapy.

    PubMed

    Bosello, S; Pers, J-O; Rochas, C; Devauchelle, V; De Santis, M; Daridon, C; Saraux, A; Ferraccioli, G F; Youinou, P

    2007-01-01

    Interest in B-cells has been revived due to the description of new functions. Supporting a role for B-cells in the genesis of autoimmune diseases is the fact that the B-cell activating factor of the TNF ligand family (BAFF) is essential in their physiology. However, in each disease, this is restricted to a subgroup of patients. Based on experiments in mice, and validated in humans, this new cytokine has been highlighted. Excessive production of BAFF alters immune tolerance by rescuing self-binding B-cells. Overexpression in mice leads to autoimmune manifestation, and BAFF levels are elevated in the serum of autoimmune patients. Similar abnormalities occur in chronic lymphocytic leukemia. Recent works suggest that antagonizing the protein (or competing for its receptors) is relevant to the treatment. Advances in our understanding of the BAFF system offers the opportunity to improve our therapeutic approach.

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

    PubMed Central

    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

  8. Acquired Cell-Mediated Immunodepression in Acute Chagas' Disease

    PubMed Central

    Teixeira, Antonio R. L.; Teixeira, Glória; Macêdo, Vanize; Prata, Aluizio

    1978-01-01

    In this study two groups of patients with acute Chagas' disease were identified. Group one consisted of five patients with apparent acute Chagas' disease. These patients showed symptoms and signals of an acute illness, such as high fever and enlarged spleen. One of these patients developed severe myocarditis and heart failure. Group two consisted of seven patients with inapparent acute Chagas' disease. This was a nonclinical entity, not perceived by the patient who did not seek medical care. The diagnosis was made by the shift of a serologic test which indicates the presence of immunoglobulin M antibodies to Trypanosoma cruzi. The patients with apparent acute Chagas' disease showed positive delayed-type skin response to T. cruzi antigen. Also, their leukocytes showed significant inhibition of migration in the presence of this antigen. By contrast, the patients with the inapparent acute Chagas' disease did not show positive delayed-type skin response to T. cruzi antigen and no significant inhibition was observed when their cells migrated in the presence of this antigen. Of interest, none of these patients was capable of developing contact sensitivity to 2,4-dinitrochlorobenzene. However, three out of five patients with the apparent acute disease and all the normal control subjects showed positive contact reaction after sensitization to this drug. The results of these experiments would suggest that the thymus-derived (T)-lymphocyte function is depressed in patients with the clinically inapparent acute Chagas' disease. This immunodepression seems to be acquired in the course of the T. cruzi infection because all patients showed positive delayed-type skin response to at least one ubiquitous microbial extract, thus indicating previously normal T-cell function. We hypothesize that T. cruzi antigens may directly stimulate T cells with the concomitant release of factors that might become supressive for T-cell responses. Furthermore, the suppressive effect might interfere

  9. [Detecting shared pathways linked to rheumatoid arthritis with other autoimmune diseases in a in silico analysis].

    PubMed

    Zheng, W-Y; Zheng, W-X; Hua, L

    2016-01-01

    Pathway-based analysis approach has exploded in use during the last several years. It is successful in recognizing additional biological insight of disease and finding groupings of risk genes that represent disease developing processes. Therefore, shared pathways, with pleiotropic effects, are important for understanding similar pathogenesis and indicating the common genetic origin of certain diseases. Here, we present a pathway analysis to reveal the potential disease associations between RA and three potential RA-related autoimmune diseases: psoriasis, diabetes mellitus, type 1 (T1D) and systemic lupus erythematosus (SLE). First, a comprehensive knowledge mining of public databases is performed to discover risk genes associated with RA, T1D, SLE and psoriasis; then by enrichment test of these genes, disease-related risk pathways are detected to recognize the pathways common for RA and three other diseases. Finally, the underlying disease associations are evaluated with the association rules mining method. In total, we identify multiple RA risk pathways with significant pleiotropic effects, the most unsurprising of which are the immunology related pathways. Meanwhile for the first time we highlight the involvement of the viral myocarditis pathway related to cardiovascular disease (CVD) in autoimmune diseases such as RA, psoriasis, T1D and SLE. Further Association rule mining results validate the strong association between RA and T1D and RA and SLE. It is clear that pleiotropy is a common property of pathways associated with disease traits. We provide novel pathway associations among RA and three autoimmune diseases. These results ascertain that there are shared genetic risk profiles that predispose individuals to autoimmune diseases. PMID:27414792

  10. Coeliac disease and risk for other autoimmune diseases in patients with Williams-Beuren syndrome

    PubMed Central

    2014-01-01

    Background A higher prevalence of coeliac disease (CD) has been reported in patients with Williams-Beuren syndrome (WBS), though coexistence with other autoimmune diseases has not been evaluated. Objective: The aim of this study was to examine the prevalence of the more frequent autoimmune diseases and organ- and non-organ specific autoantibodies in WBS. Methods We longitudinally analysed 46 WBS patients to evaluate the prevalence and co-occurrence of the major autoantibodies and HLA typing for CD diagnosis. These data were compared with healthy age- and sex-matched controls and Down (DS) and Turner (TS) syndrome patients. Results CD was diagnosed in one (2.2%) WBS patient; this differed significantly from DS and TS (respectively, 10.5% and 9.4%; P < 0.005) but not from healthy controls (0.6%; P = NS). However, no patients with WBS showed anti-thyroid antibodies or other organ- and non-organ specific autoantibodies, which differed significantly from DS (respectively, 10.5% and 7.0%; P < 0.005) and TS (respectively, 9.4% and 9.3%; P < 0.005) patients but not from healthy controls (1.1% and 2.3%). The frequencies of CD-specific HLA-DQ heterodimers were not significantly higher than controls, even though the WBS patients more frequently carried the DQA1*0505 allele (57% vs. 39%; P < 0.05). Conclusions CD may not be more frequent in patients with WBS. In fact, no evidence of a significantly higher prevalence of other autoimmune diseases or positivity of the main organ and non-organ specific autoantibodies was found in WBS, such as showed in the healthy controls and unlike by the patients with Turner or Down syndrome. This should prompt us to better understand the occurrence of CD in WBS. Other studies or longer follow-up might be useful to clarify this issue. PMID:24885139

  11. Loss of STAT6 promotes autoimmune disease and atopy on a susceptible genetic background.

    PubMed

    Lau, Maverick; Tsantikos, Evelyn; Maxwell, Mhairi J; Tarlinton, David M; Anderson, Gary P; Hibbs, Margaret L

    2012-12-01

    Atopy and autoimmunity are usually considered opposed immunological manifestations. Lyn(-/-) mice develop lupus-like autoimmune disease yet have coexistent intrinsic allergic traits and are prone to severe, persistent asthma induced exogenously. Recently it has been proposed that the Th2 environment and IgE auto-Abs promotes autoimmune disease in Lyn(-/-) mice. To examine this apparent contradiction, we derived Lyn(-/-) mice with a null mutation in STAT6, a regulator of Th2 immunity that integrates signaling from the IL-4/IL-13 receptor complex. Atopy and spontaneous peritoneal eosinophilia, characteristic of Lyn(-/-) mice, were lost in young Lyn(-/-)STAT6(-/-) mice; however, autoimmune disease was markedly exacerbated. At a time-point where Lyn(-/-) mice showed only mild autoimmune disease, Lyn(-/-)STAT6(-/-) mice had maximal titres of IgG and IgA auto-Abs, impaired renal function, myeloid expansion and a highly activated T cell compartment. Remarkably, low level IgE auto-Abs but not IgG1 auto-Abs were a feature of some aged Lyn(-/-)STAT6(-/-) mice. Furthermore, aged Lyn(-/-)STAT6(-/-) mice showed dramatically increased levels of serum IgE but minimal IgG1, suggesting that class-switching to IgE can occur in the absence of an IgG1 intermediate. The results show that Lyn-deficient mice can overcome the effects of disabling Th2 immunity, highlighting the importance of Lyn in controlling Th2 responses. Our data also indicates that, under certain conditions, STAT6-independent factors can promote IgE class-switching. This work has important clinical implications as many experimental therapies designed for the treatment of asthma or atopy are based on targeting the STAT6 axis, which could potentially reveal life endangering autoimmunity or promote atopy in susceptible individuals.

  12. A systematic review of the incidence and prevalence of autoimmune disease in multiple sclerosis

    PubMed Central

    Reider, Nadia; Cohen, Jeffrey; Stuve, Olaf; Sorensen, Per S; Cutter, Gary; Reingold, Stephen C; Trojano, Maria

    2015-01-01

    Background: As new therapies emerge which increase the risk of autoimmune disease it is increasingly important to understand the incidence of autoimmune disease in multiple sclerosis (MS). Objective: The purpose of this review is to estimate the incidence and prevalence of comorbid autoimmune disease in MS. Methods: The PUBMED, EMBASE, SCOPUS and Web of Knowledge databases, conference proceedings, and reference lists of retrieved articles were searched, and abstracts were independently screened by two reviewers. The data were abstracted by one reviewer using a standardized data collection form, and the findings were verified by a second reviewer. We assessed quality of the included studies using a standardized approach and conducted meta-analyses of population-based studies. Results: Sixty-one articles met the inclusion criteria. We observed substantial heterogeneity with respect to the populations studied, methods of ascertaining comorbidity, and reporting of findings. Based solely on population-based studies, the most prevalent autoimmune comorbidities were psoriasis (7.74%) and thyroid disease (6.44%). Our findings also suggest an increased risk of inflammatory bowel disease, likely uveitis and possibly pemphigoid. Conclusion: Fewer than half of the studies identified were of high quality. Population-based studies that report age, sex and ethnicity-specific estimates of incidence and prevalence are needed in jurisdictions worldwide. PMID:25533299

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

    PubMed

    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.

  14. The Role of TL1A and DR3 in Autoimmune and Inflammatory Diseases

    PubMed Central

    Aiba, Yoshihiro; Nakamura, Minoru

    2013-01-01

    TNF-like ligand 1A (TL1A), which binds its cognate receptor DR3 and the decoy receptor DcR3, is an identified member of the TNF superfamily. TL1A exerts pleiotropic effects on cell proliferation, activation, and differentiation of immune cells, including helper T cells and regulatory T cells. TL1A and its two receptors expression is increased in both serum and inflamed tissues in autoimmune diseases such as inflammatory bowel disease (IBD), rheumatoid arthritis (RA), and ankylosing spondylitis (AS). Polymorphisms of the TNFSF15 gene that encodes TL1A are associated with the pathogenesis of irritable bowel syndrome, leprosy, and autoimmune diseases, including IBD, AS, and primary biliary cirrhosis (PBC). In mice, blocking of TL1A-DR3 interaction by either antagonistic antibodies or deletion of the DR3 gene attenuates the severity of multiple autoimmune diseases, whereas sustained TL1A expression on T cells or dendritic cells induces IL-13-dependent small intestinal inflammation. This suggests that modulation of TL1A-DR3 interaction may be a potential therapeutic target in several autoimmune diseases, including IBD, RA, AS, and PBC. PMID:24453414

  15. Lessons from type 1 diabetes for understanding natural history and prevention of autoimmune disease

    PubMed Central

    Simmons, Kimber; Michels, Aaron W.

    2014-01-01

    Type 1 diabetes (T1D) is a chronic autoimmune disorder resulting from immune mediated destruction of insulin producing beta cells within the pancreatic islets. The natural history of T1D is well defined with distinct stages in disease development. Genetics and environmental factors contribute to disease susceptibility, followed by autoimmune targeting of proteins within beta cells. Preclinical T1D is marked by the presence of islet autoantibodies and normal blood glucose levels. Prediction of T1D is now possible as having two or more islet autoantibodies confers a 100% risk of diabetes development; however the time to disease onset varies amongst individuals. Once enough insulin producing beta cells are destroyed, hyperglycemia results, and treatment with insulin is necessary. With the ability to assess risk and predict disease development, large clinical trials to prevent diabetes onset have been completed and are currently underway. This review focuses on the natural history, prediction, and prevention trials in T1D. We will review the lessons learned from these attempts at preventing a chronic autoimmune disease and apply the paradigm from T1D prevention to other autoimmune disorders including rheumatoid arthritis. PMID:25437293

  16. The therapeutic potential of tumor necrosis factor for autoimmune disease: a mechanistically based hypothesis.

    PubMed

    Kodama, S; Davis, M; Faustman, D L

    2005-08-01

    Excess levels of tumor necrosis factor-alpha (TNF-alpha) have been associated with certain autoimmune diseases. Under the rationale that elevated TNF-alpha levels are deleterious, several anti-TNF-alpha therapies are now available to block the action of TNF-alpha in patients with autoimmune diseases with a chronic inflammatory component to the destructive process. TNF-alpha antagonists have provided clinical benefit to many patients, but their use also is accompanied by new or aggravated forms of autoimmunity. Here we propose a mechanistically based hypothesis for the adverse events observed with TNF-alpha antagonists, and argue for the opposite therapeutic strategy: to boost or restore TNF-alpha activity as a treatment for some forms of autoimmunity. Activation defects in the transcription factor nuclear factor kappaB leave autoreactive T cells sensitive to TNF-alpha-induced apoptosis. Treatment with TNF-alpha, by destroying autoreactive T cells, appears to be a highly targeted strategy to interrupt the pathogenesis of type 1 diabetes, lupus and certain forms of autoimmunity.

  17. Autoimmune epilepsy.

    PubMed

    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.

  18. Autoimmune epilepsy.

    PubMed

    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

  19. Autoimmune hepatitis.

    PubMed

    Heneghan, Michael A; Yeoman, Andrew D; Verma, Sumita; Smith, Alastair D; Longhi, Maria Serena

    2013-10-26

    Autoimmune hepatitis is a disease of the hepatic parenchyma that can present in acute or chronic forms. In common with many autoimmune diseases, autoimmune hepatitis is associated with non-organ-specific antibodies in the context of hepatic autoimmunity. This dichotomy has made definition of a unifying hypothesis in the pathophysiology of the disease difficult, although data from the past 8 years have drawn attention to the role of regulatory T cells. Several triggers have been identified, and the disease arises in genetically susceptible individuals. Clinical and biochemical remission is achievable in up to 85% of cases. For the remaining patients, alternative immunosuppression strategies are an option. Liver transplantation provides an excellent outcome for patients with acute liver failure or complications of end-stage liver disease, including hepatocellular carcinoma. Variant or overlapping syndromes are worthy of consideration when unexpected disease features arise.

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

    ERIC Educational Resources Information Center

    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…

  1. Estrogen-mediated downregulation of AIRE influences sexual dimorphism in autoimmune diseases.

    PubMed

    Dragin, Nadine; Bismuth, Jacky; Cizeron-Clairac, Géraldine; Biferi, Maria Grazia; Berthault, Claire; Serraf, Alain; Nottin, Rémi; Klatzmann, David; Cumano, Ana; Barkats, Martine; Le Panse, Rozen; Berrih-Aknin, Sonia

    2016-04-01

    Autoimmune diseases affect 5% to 8% of the population, and females are more susceptible to these diseases than males. Here, we analyzed human thymic transcriptome and revealed sex-associated differences in the expression of tissue-specific antigens that are controlled by the autoimmune regulator (AIRE), a key factor in central tolerance. We hypothesized that the level of AIRE is linked to sexual dimorphism susceptibility to autoimmune diseases. In human and mouse thymus, females expressed less AIRE (mRNA and protein) than males after puberty. These results were confirmed in purified murine thymic epithelial cells (TECs). We also demonstrated that AIRE expression is related to sexual hormones, as male castration decreased AIRE thymic expression and estrogen receptor α-deficient mice did not show a sex disparity for AIRE expression. Moreover, estrogen treatment resulted in downregulation of AIRE expression in cultured human TECs, human thymic tissue grafted to immunodeficient mice, and murine fetal thymus organ cultures. AIRE levels in human thymus grafted in immunodeficient mice depended upon the sex of the recipient. Estrogen also upregulated the number of methylated CpG sites in the AIRE promoter. Together, our results indicate that in females, estrogen induces epigenetic changes in the AIRE gene, leading to reduced AIRE expression under a threshold that increases female susceptibility to autoimmune diseases. PMID:26999605

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

    PubMed Central

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

    2016-01-01

    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. PMID:27649254

  3. Estrogen-mediated downregulation of AIRE influences sexual dimorphism in autoimmune diseases

    PubMed Central

    Dragin, Nadine; Bismuth, Jacky; Cizeron-Clairac, Géraldine; Biferi, Maria Grazia; Berthault, Claire; Serraf, Alain; Nottin, Rémi; Klatzmann, David; Cumano, Ana; Barkats, Martine; Le Panse, Rozen

    2016-01-01

    Autoimmune diseases affect 5% to 8% of the population, and females are more susceptible to these diseases than males. Here, we analyzed human thymic transcriptome and revealed sex-associated differences in the expression of tissue-specific antigens that are controlled by the autoimmune regulator (AIRE), a key factor in central tolerance. We hypothesized that the level of AIRE is linked to sexual dimorphism susceptibility to autoimmune diseases. In human and mouse thymus, females expressed less AIRE (mRNA and protein) than males after puberty. These results were confirmed in purified murine thymic epithelial cells (TECs). We also demonstrated that AIRE expression is related to sexual hormones, as male castration decreased AIRE thymic expression and estrogen receptor α–deficient mice did not show a sex disparity for AIRE expression. Moreover, estrogen treatment resulted in downregulation of AIRE expression in cultured human TECs, human thymic tissue grafted to immunodeficient mice, and murine fetal thymus organ cultures. AIRE levels in human thymus grafted in immunodeficient mice depended upon the sex of the recipient. Estrogen also upregulated the number of methylated CpG sites in the AIRE promoter. Together, our results indicate that in females, estrogen induces epigenetic changes in the AIRE gene, leading to reduced AIRE expression under a threshold that increases female susceptibility to autoimmune diseases. PMID:26999605

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

    PubMed

    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.

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

    PubMed

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

    2016-01-01

    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. PMID:27649254

  6. Estrogen-mediated downregulation of AIRE influences sexual dimorphism in autoimmune diseases.

    PubMed

    Dragin, Nadine; Bismuth, Jacky; Cizeron-Clairac, Géraldine; Biferi, Maria Grazia; Berthault, Claire; Serraf, Alain; Nottin, Rémi; Klatzmann, David; Cumano, Ana; Barkats, Martine; Le Panse, Rozen; Berrih-Aknin, Sonia

    2016-04-01

    Autoimmune diseases affect 5% to 8% of the population, and females are more susceptible to these diseases than males. Here, we analyzed human thymic transcriptome and revealed sex-associated differences in the expression of tissue-specific antigens that are controlled by the autoimmune regulator (AIRE), a key factor in central tolerance. We hypothesized that the level of AIRE is linked to sexual dimorphism susceptibility to autoimmune diseases. In human and mouse thymus, females expressed less AIRE (mRNA and protein) than males after puberty. These results were confirmed in purified murine thymic epithelial cells (TECs). We also demonstrated that AIRE expression is related to sexual hormones, as male castration decreased AIRE thymic expression and estrogen receptor α-deficient mice did not show a sex disparity for AIRE expression. Moreover, estrogen treatment resulted in downregulation of AIRE expression in cultured human TECs, human thymic tissue grafted to immunodeficient mice, and murine fetal thymus organ cultures. AIRE levels in human thymus grafted in immunodeficient mice depended upon the sex of the recipient. Estrogen also upregulated the number of methylated CpG sites in the AIRE promoter. Together, our results indicate that in females, estrogen induces epigenetic changes in the AIRE gene, leading to reduced AIRE expression under a threshold that increases female susceptibility to autoimmune diseases.

  7. Fulminant community-acquired infectious diseases: diagnostic problems.

    PubMed

    Levin, S; Goodman, L J; Fuhrer, J

    1986-09-01

    The processes presented here do not represent an all-inclusive list of fulminant infectious diseases. Some of the more common acute, overwhelming infections of the central nervous system and lungs are covered elsewhere in this issue. We have selected less common, potentially catastrophic syndromes that might be recognized earlier if certain historical clues, physical findings, or laboratory abnormalities are appreciated. Specific and effective therapy is available for most of the diseases we have chosen. Meningitis due to Naegleria fowleri, a free-living ameba that may invade the central nervous system through the cribriform plate in persons swimming in brackish water, and hemorrhagic mediastinitis due to inhalation of Bacillus anthracis, which is acquired in occupational exposure to goat's hair, wool, or an animal with anthrax, are other examples but are lacking in proven effective therapy. Although most physicians quickly consider exotic and overwhelming infections in the severely compromised patient, fewer recognize this risk in the diabetic, cirrhotic, or healthy person with a unique occupational or travel history. During the present epidemic of AIDS, previous exposure to the HTLV-3 virus must be considered in all severely ill patients. The proper use of new diagnostic tests may permit the physician to intercede effectively if these life-threatening diseases are suspected. PMID:3736273

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

    PubMed Central

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

    2015-01-01

    Autoimmune lymphoproliferative syndrome is frequently caused by mutations in genes involved in the Fas death receptor pathway, but for 20–30% of patients the genetic defect is unknown. We observed that treatment of healthy T cells with interleukin-12 induces upregulation of Fas ligand and Fas ligand-dependent apoptosis. Consistently, interleukin-12 could not induce apoptosis in Fas ligand-deficient T cells from patients with autoimmune lymphoproliferative syndrome. We hypothesized that defects in the interleukin-12 signaling pathway may cause a similar phenotype as that caused by mutations of the Fas ligand gene. To test this, we analyzed 20 patients with autoimmune lymphoproliferative syndrome of unknown cause by whole-exome sequencing. We identified a homozygous nonsense mutation (c.698G>A, p.R212*) in the interleukin-12/interleukin-23 receptor-component IL12RB1 in one of these patients. The mutation led to IL12RB1 protein truncation and loss of cell surface expression. Interleukin-12 and -23 signaling was completely abrogated as demonstrated by deficient STAT4 phosphorylation and interferon γ production. Interleukin-12-mediated expression of membrane-bound and soluble Fas ligand was lacking and basal expression was much lower than in healthy controls. The patient presented with the classical symptoms of autoimmune lymphoproliferative syndrome: chronic non-malignant, non-infectious lymphadenopathy, splenomegaly, hepatomegaly, elevated numbers of double-negative T cells, autoimmune cytopenias, and increased levels of vitamin B12 and interleukin-10. Sanger sequencing and whole-exome sequencing excluded the presence of germline or somatic mutations in genes known to be associated with the autoimmune lymphoproliferative syndrome. Our data suggest that deficient regulation of Fas ligand expression by regulators such as the interleukin-12 signaling pathway may be an alternative cause of autoimmune lymphoproliferative syndrome-like disease. PMID:26113417

  9. Dysbiosis May Trigger Autoimmune Diseases via Inappropriate Post-Translational Modification of Host Proteins

    PubMed Central

    Lerner, Aaron; Aminov, Rustam; Matthias, Torsten

    2016-01-01

    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 post-translational modification of proteins (PTMP) may contribute to the aberrant modification of host proteins thus generating autoimmune responses by the host, resulting in autoimmune diseases. PMID:26903965

  10. Rationale for bone marrow transplantation in the treatment of autoimmune diseases.

    PubMed Central

    Ikehara, S; Good, R A; Nakamura, T; Sekita, K; Inoue, S; Oo, M M; Muso, E; Ogawa, K; Hamashima, Y

    1985-01-01

    Transplantation of normal bone marrow from C3H/HeN nu/nu (H-2k) mice into young MRL/MP-lpr/lpr (MRL/l; H-2k) mice (less than 1.5 mo) prevented the development of autoimmune diseases and characteristic thymic abnormalities in the recipient mice. When female MRL/1 (greater than 2 mo) or male BXSB (H-2b) mice (9 mo) with autoimmune diseases and lymphadenopathy were lethally irradiated and then reconstituted with allogeneic bone marrow cells from young BALB/c nu/nu (H-2d) mice (less than 2 mo), the recipients survived for more than 3 mo after the bone marrow transplantation and showed no graft-versus-host reaction. Histopathological study revealed that lymphadenopathy disappeared and that all evidence of autoimmune disease either was prevented from developing or was completely corrected even after its development in such mice. All abnormal T-cell functions were restored to normal. The newly developed T cells were found to be tolerant of both bone marrow donor-type (BALB/c) and host-type (MRL/1 or BXSB) major histocompatibility complex (MHC) determinants. Therefore, T-cell dysfunction in autoimmune-prone mice can be associated with both the involutionary changes that occur in the thymus of the autoimmune-prone mice and also to abnormalities that reside in the stem cells. However, normal stem cells from BALB/c nu/nu donors can differentiate into normal functional T cells even in mice whose thymus had undergone considerable involution, as in the case of BXSB or MRL/1 mice in the present studies. These findings suggest that marrow transplantation may be a strategy ultimately to be considered as an approach to treatment of life-threatening autoimmune diseases in humans. T-cell dysfunction in autoimmune-prone mice previously attributed to involutionary changes that occur in the thymus of these mice may instead be attributed to abnormalities that basically reside in the stem cells of the autoimmune-prone mice. Images PMID:3887403

  11. Use of MHC II structural features in the design of vaccines for organ-specific autoimmune diseases.

    PubMed

    Moustakas, Antonis K; Papadopoulos, George K

    2009-01-01

    The Major Histocompatibility Complex Class II locus is the primary genetic linkage to autoimmune diseases. Susceptibility to each such disease is linked to different alleles, with a few alleles showing also dominant protection. The design of vaccines for autoimmune diseases is a long sought-after goal. As knowledge about the pathogenesis of these diseases has increased, the tools for such an approach have of necessity been refined. We review below the structural essence of MHC II-linked autoimmune diseases which centers on the binding of antigenic peptides to the disease-linked MHC II proteins, and the consequent activation of cognate TCRs from pathogenic CD4+ T cells. The state of affairs in two organ-specific autoimmune diseases, type 1 diabetes, celiac disease are covered, including attempts to treat these via antigen-specific MHC II-guided measures. We offer a couple of testable suggestions as to how this approach could be improved.

  12. Selectin-mediated leukocyte trafficking during the development of autoimmune disease.

    PubMed

    Angiari, Stefano

    2015-11-01

    Tissue inflammation is a finely regulated process that controls wound healing and allows the clearance of damaged cells, pathogens and irritants. However, excessive or uncontrolled inflammation is detrimental, causing tissue damage and leading to autoimmunity. The recruitment of circulating leukocytes to the target tissue is a key stage in the inflammatory process, and is controlled by a multistep cascade in which adhesive receptors known as selectins mediate initial leukocyte tethering and rolling along vascular surfaces, which is required for their subsequent adhesion and arrest. This review considers the role of selectins and their ligands in the recruitment of circulating leukocytes to peripheral tissues during inflammatory responses that lead to the development of autoimmunity, focusing on data from animal models and clinical trials suggesting that selectins may offer valuable therapeutic targets for the treatment of autoimmune diseases.

  13. A B cell explanation for autoimmune disease: the forbidden clone returns.

    PubMed

    McQueen, Fiona

    2012-04-01

    More than 60 years ago, Burnet first proposed the 'forbidden clone' hypothesis postulating that autoimmune disease arises as a result of persistence of self-reactive clones of lymphocytes that should have been deleted via immune tolerance. These autoreactive clones could effect immune-mediated end-organ damage via peripheral self-antigen recognition. Recent evidence that stretches across the boundaries of many medical specialties supports this proposal, implicating a B cell precursor as the culprit. The success of B cell depleting therapy in rheumatoid arthritis, anti-neutrophil cytoplasmic antibodies (ANCA) associated vasculitis, polymyositis, lupus and autoimmune diseases as diverse as multiple sclerosis and idiopathic thrombocytopenic purpura supports this proposal. Clonality of B cells and plasma cells has been described in a number of autoimmune disorders and the presence of autoantibodies, which may arise years before the onset of clinical disease, supports the notion of autoreactivity within the B cell lineage. T cell activation within the end-organ would be predicted by cognate B-T cell interactions and resultant tissue inflammation and destruction could produce diverse clinical manifestations dictated by the original specificity of the autoimmune B cell.

  14. Meta-analysis of shared genetic architecture across ten pediatric autoimmune diseases.

    PubMed

    Li, Yun R; Li, Jin; Zhao, Sihai D; Bradfield, Jonathan P; Mentch, Frank D; Maggadottir, S Melkorka; Hou, Cuiping; Abrams, Debra J; Chang, Diana; Gao, Feng; Guo, Yiran; Wei, Zhi; Connolly, John J; Cardinale, Christopher J; Bakay, Marina; Glessner, Joseph T; Li, Dong; Kao, Charlly; Thomas, Kelly A; Qiu, Haijun; Chiavacci, Rosetta M; Kim, Cecilia E; Wang, Fengxiang; Snyder, James; Richie, Marylyn D; Flatø, Berit; Førre, Øystein; Denson, Lee A; Thompson, Susan D; Becker, Mara L; Guthery, Stephen L; Latiano, Anna; Perez, Elena; Resnick, Elena; Russell, Richard K; Wilson, David C; Silverberg, Mark S; Annese, Vito; Lie, Benedicte A; Punaro, Marilynn; Dubinsky, Marla C; Monos, Dimitri S; Strisciuglio, Caterina; Staiano, Annamaria; Miele, Erasmo; Kugathasan, Subra; Ellis, Justine A; Munro, Jane E; Sullivan, Kathleen E; Wise, Carol A; Chapel, Helen; Cunningham-Rundles, Charlotte; Grant, Struan F A; Orange, Jordan S; Sleiman, Patrick M A; Behrens, Edward M; Griffiths, Anne M; Satsangi, Jack; Finkel, Terri H; Keinan, Alon; Prak, Eline T Luning; Polychronakos, Constantin; Baldassano, Robert N; Li, Hongzhe; Keating, Brendan J; Hakonarson, Hakon

    2015-09-01

    Genome-wide association studies (GWASs) have identified hundreds of susceptibility genes, including shared associations across clinically distinct autoimmune diseases. We performed an inverse χ(2) meta-analysis across ten pediatric-age-of-onset autoimmune diseases (pAIDs) in a case-control study including more than 6,035 cases and 10,718 shared population-based controls. We identified 27 genome-wide significant loci associated with one or more pAIDs, mapping to in silico-replicated autoimmune-associated genes (including IL2RA) and new candidate loci with established immunoregulatory functions such as ADGRL2, TENM3, ANKRD30A, ADCY7 and CD40LG. The pAID-associated single-nucleotide polymorphisms (SNPs) were functionally enriched for deoxyribonuclease (DNase)-hypersensitivity sites, expression quantitative trait loci (eQTLs), microRNA (miRNA)-binding sites and coding variants. We also identified biologically correlated, pAID-associated candidate gene sets on the basis of immune cell expression profiling and found evidence of genetic sharing. Network and protein-interaction analyses demonstrated converging roles for the signaling pathways of type 1, 2 and 17 helper T cells (TH1, TH2 and TH17), JAK-STAT, interferon and interleukin in multiple autoimmune diseases. PMID:26301688

  15. Meta-analysis of shared genetic architecture across ten pediatric autoimmune diseases

    PubMed Central

    Li, Yun R; Li, Jin; Zhao, Sihai D; Bradfield, Jonathan P; Mentch, Frank D; Maggadottir, S Melkorka; Hou, Cuiping; Abrams, Debra J; Chang, Diana; Gao, Feng; Guo, Yiran; Wei, Zhi; Connolly, John J; Cardinale, Christopher J; Bakay, Marina; Glessner, Joseph T; Li, Dong; Kao, Charlly; Thomas, Kelly A; Qiu, Haijun; Chiavacci, Rosetta M; Kim, Cecilia E; Wang, Fengxiang; Snyder, James; Richie, Marylyn D; Flatø, Berit; Førre, Øystein; Denson, Lee A; Thompson, Susan D; Becker, Mara L; Guthery, Stephen L; Latiano, Anna; Perez, Elena; Resnick, Elena; Russell, Richard K; Wilson, David C; Silverberg, Mark S; Annese, Vito; Lie, Benedicte A; Punaro, Marilynn; Dubinsky, Marla C; Monos, Dimitri S; Strisciuglio, Caterina; Staiano, Annamaria; Miele, Erasmo; Kugathasan, Subra; Ellis, Justine A; Munro, Jane E; Sullivan, Kathleen E; Wise, Carol A; Chapel, Helen; Cunningham-Rundles, Charlotte; Grant, Struan F A; Orange, Jordan S; Sleiman, Patrick M A; Behrens, Edward M; Griffiths, Anne M; Satsangi, Jack; Finkel, Terri H; Keinan, Alon; Prak, Eline T Luning; Polychronakos, Constantin; Baldassano, Robert N; Li, Hongzhe; Keating, Brendan J; Hakonarson, Hakon

    2016-01-01

    Genome-wide association studies (GWASs) have identified hundreds of susceptibility genes, including shared associations across clinically distinct autoimmune diseases. We performed an inverse χ2 meta-analysis across ten pediatric-age-of-onset autoimmune diseases (pAIDs) in a case-control study including more than 6,035 cases and 10,718 shared population-based controls. We identified 27 genome-wide significant loci associated with one or more pAIDs, mapping to in silico–replicated autoimmune-associated genes (including IL2RA) and new candidate loci with established immunoregulatory functions such as ADGRL2, TENM3, ANKRD30A, ADCY7 and CD40LG. The pAID-associated single-nucleotide polymorphisms (SNPs) were functionally enriched for deoxyribonuclease (DNase)-hypersensitivity sites, expression quantitative trait loci (eQTLs), microRNA (miRNA)-binding sites and coding variants. We also identified biologically correlated, pAID-associated candidate gene sets on the basis of immune cell expression profiling and found evidence of genetic sharing. Network and protein-interaction analyses demonstrated converging roles for the signaling pathways of type 1, 2 and 17 helper T cells (TH1, TH2 and TH17), JAK-STAT, interferon and interleukin in multiple autoimmune diseases. PMID:26301688

  16. PTPN22 C1858T polymorphism in Colombian patients with autoimmune diseases.

    PubMed

    Gomez, L M; Anaya, J-M; Gonzalez, C I; Pineda-Tamayo, R; Otero, W; Arango, A; Martín, J

    2005-10-01

    A functional single nucleotide polymorphism (SNP) C1858T in the protein tyrosine phosphatase nonreceptor 22 (PTPN22) gene encoding an intracellular phosphatase with negative regulatory effects on T-cell activation is associated with some autoimmune diseases in Caucasians. Taking into account firstly, that SNP frequencies may vary across populations and, secondly, that replication studies are important to confirm previous associations, we examined the influence of PTPN22 polymorphism in 621 Colombian patients with four autoimmune diseases. Accordingly, 298 patients with rheumatoid arthritis (RA), 143 with systemic lupus erythematosus (SLE), 70 with primary Sjogren's syndrome (pSS) and 110 with Type 1 diabetes (T1D) were studied. The control group consisted of 308 matched healthy individuals. Genotyping of PTPN22 was performed by the real-time polymerase chain reaction technology, using the Taq Man 5'-allele discrimination assay. The 1858 T allele was found to be a risk factor for pSS (odds ratio (OR)=2.42), SLE (OR=2.56), and T1D (OR=1.83). A lower but nonsignificant trend was observed for RA (OR=1.26). These results confirm the influence of PTPN22 in autoimmunity and indicate that autoimmune phenotypes could represent pleiotropic outcomes of nonspecific disease genes that underlie similar immunogenetic mechanisms. PMID:16163373

  17. MicroRNAs in Sjögren’s syndrome as a prototypic autoimmune disease

    PubMed Central

    Alevizos, Ilias; Illei, Gabor G

    2012-01-01

    MicroRNAs are endogenous non-coding RNAs, approximately 22 nucleotides in length. They regulate gene expression and are important in a wide range of physiological and pathological processes. MicroRNA expression is tightly regulated during hematopoiesis and lymphoid cell differentiation and disruption of the entire microRNA network or selected microRNAs may lead to dysregulated immune responses. Abnormalities in microRNA expression related to inflammatory cytokines, Th-17 and regulatory T cells as well as B cells have been described in several autoimmune diseases. Sjögren’s syndrome is characterized by features of systemic autoimmunity and chronic inflammation and dysfunction in exocrine organs. Its clinical characteristics along with the relatively easy access to the target tissue and its product makes Sjögren’s syndrome appealing to study many aspects of microRNAs in a systemic autoimmune disease, such as their potential as diagnostic or prognostic biomarkers and their role in pathogenesis of autoimmunity, inflammation or organ dysfunction. Encouraging preliminary data from pilot studies in Sjögren’s syndrome demonstrate the potential of microRNAs as putative diagnostic and prognostic biomarker candidates which should be tested in larger more definite studies. Combining the comparison of microRNA expression profiles between various clinical subsets of Sjögren’s syndrome with bioinformatic modeling tools may predict formerly unsuspected pathways which may contribute to the disease process and lead to the generation of testable novel hypothesis of pathogenesis. PMID:20457282

  18. The Genomics of Autoimmune Disease in the Era of Genome-Wide Association Studies and Beyond

    PubMed Central

    Lessard, Christopher J; Ice, John A; Adrianto, Indra; Wiley, Graham; Kelly, Jennifer A; Gaffney, Patrick M; Montgomery, Courtney G; Moser, Kathy L

    2012-01-01

    Recent advances in the field of genetics have dramatically changed our understanding of autoimmune disease. Candidate gene and, more recently, genome-wide association (GWA) studies have led to an explosion in the number of loci and pathways known to contribute to autoimmune phenotypes. Since the 1970s, researchers have known that several alleles in the MHC region play a role in the pathogenesis of many autoimmune diseases. More recent work has identified numerous risk loci involving both the innate and adaptive immune responses. However, much remains to be learned about the heritability of autoimmune conditions. Most regions found through GWA scans have yet to isolate the association to the causal allele(s) responsible for conferring disease risk. A role for rare variants (allele frequencies of <1%) has begun to emerge. Future research will use next generation sequencing (NGS) technology to comprehensively evaluate the human genome for risk variants. Whole transcriptome sequencing is now possible, which will provide much more detailed gene expression data. The dramatic drop in the cost and time required to sequence the entire human genome will ultimately make it possible for this technology to be used as a clinical diagnostic tool. PMID:22001415

  19. Haematopoietic stem cell transplantation in autoimmune diseases: From basic science to clinical practice.

    PubMed

    Kelsey, P J; Oliveira, M-C; Badoglio, M; Sharrack, B; Farge, D; Snowden, J A

    2016-01-01

    Based on animal studies and serendipitous clinical cases, haematopoietic stem cell transplantation (HSCT) has been used since 1995 as a specific treatment for patients with severe treatment-resistant autoimmune disease (ADs). Despite other clinical developments for autoimmune diseases, including biological therapies, there has been an ongoing requirement for HSCT in some diseases and several thousand procedures have been registered in databases for a wide variety of diseases, predominantly for treatment with autologous HSCT. Currently, the main indications are multiple sclerosis, systemic sclerosis and Crohn's disease, which are supported by large series and randomised controlled trials (RCTs), whereas retrospective registry analyses support benefit in a range of rarer indications. Research into mechanisms of action has provided insight into how tolerance may be achieved with an intensive one-off treatment. In addition to the profound anti-inflammatory and immunosuppressive effects provided by the cytotoxic regimen, long-term responses in some diseases may be explained by 'resetting' the immune system through thymic reprocessing and generation of increased T-regulatory cell activity. This review aims to summarise the gradual evolution of HSCT in severe autoimmune diseases over the last 20 years, focussing on the recent publication of clinical and scientific studies, as well as evidence-based guidelines and recommendations. PMID:27316390

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

    PubMed Central

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

    2016-01-01

    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

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

    PubMed

    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

  2. [Coexistence of Addison-Biermer's disease with autoimmune thyroiditis - case report].

    PubMed

    Lacka, Katarzyna; Maciejewski, Adam; Florczak-Wyspiańska, Jolanta

    2013-01-01

    Addison-Biermer's anaemia is an autoimmune disease and the most common cause of vitamin B12 deficiency. Hashimoto disease is the most common type of the thyroiditis and also has autoimmunological origin. Frequent coexistence of both mentioned entities has been observed. In the paper we report a case of a woman, who was diagnosed with pernicious anaemia (PA) with predominant neurological symptoms and concomitant autoimmune thyroiditis. Many efforts have been made in order to explain frequent coexistence of mentioned diseases. Both genetic (mainly HLA region genes) and environmental (mostly bacterial infections) factors are considered. The aim of the study (was to emphasize significance of diagnosing thyroid gland diseases among PA patients. It is also important to remember that neurological symptoms are frequent in the course of PA and may precede other complaints. However it should not prevent the right diagnosis. PMID:23488284

  3. The impact of immune dysregulation on the development of autoimmune gastrointestinal and liver disease.

    PubMed

    Levine, Jeremiah

    2014-12-01

    The intestinal epithelium plays an active immunologic role in preventing the uptake of foreign antigens. Additionally, the intestinal mucosa is an active site for immune suppression through the development of oral tolerance. Dysfunction of any aspect of the intestinal barrier, such as impairment of intestinal tight junctions, immunologic dysregulation or decreased oral tolerance will lead to overstimulation of the immune system upon exposure to foreign antigens and subsequent unregulated chronic intestinal inflammation. This persistent inflammatory activity may potentially predispose the patient to the development of intestinal autoimmune disease. An active immune response possibly directed against intestinal flora has been postulated to be the underlying etiology for inflammatory bowel disease. Failure of oral tolerance is thought predispose a patient to celiac disease and possibly eosinophilic esophagitis. Additionally, an active immunologic response to absorbed antigen may be the underlying etiology for the development of autoimmune liver disease.

  4. Evidence for an association between rheumatoid arthritis and autoimmune endocrine disease.

    PubMed

    Thomas, D J; Young, A; Gorsuch, A N; Bottazzo, G F; Cudworth, A G

    1983-06-01

    Evidence is presented for the first time of a significantly increased prevalence of type 1 (insulin-dependent) diabetes in the close relatives of patients with rheumatoid arthritis. Thirty-nine (13%) of 295 patients with classical or definite rheumatoid arthritis had a first or second degree relative with type 1 diabetes and 38 (13%) had a close relative with autoimmune thyroid disease. These findings could be compatible with a possible common genetically determined mechanism of susceptibility to both diseases. PMID:6859961

  5. Overexpression and Secretion of the Soluble CTLA-4 Splice Variant in Various Autoimmune Diseases and in Cases with Overlapping Autoimmunity

    PubMed Central

    2013-01-01

    Aim: To explore the potential genetic association of CTLA-4 Exon1 +49A/G and 3′UTR (AT)n to susceptibility to systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and overlapping (OP) autoimmunity; affected with more than one autoimmune disease. Expression of two major CTLA-4 isoforms; full length (mCTLA-4) and soluble (sCTLA-4) were explored in all subjects. A total of 680-age/gender/ethnically matched Kuwaitis were recruited and polymerase chain reaction (PCR)-fragment analysis was employed for genotyping both markers. mCTLA-4 and sCTLA-4 mRNA expression were analyzed using quantitative real time-PCR. The enzyme-linked immunosorbent assay (ELISA) was used to screen sCTLA-4 in all subjects' sera. Results: Only two CTLA-4 3′UTR (AT)n allelotypes; (AT)15 and (AT)6 were detected. The heterozygous (AT)15/6 genotype confers protectivity rather than susceptibility to SLE (p=0.01, odds ratio=0.43, and confidence interval=0.21–0.86). No significant association was observed between Exon 1 +49A/G and any of the tested diseases. A consistently high serum sCTLA-4 level was observed in RA (6.8 ng/mL, p=0.005), SLE (6.34 ng/mL, p=0.007), and OP (8.75 ng/mL, p=0.012) compared to healthy control. A significant increase in the expression of sCTLA-4 mRNA was observed in OP (p=0.05) and SLE (p=0.047), while a significant increase in the expression of mCTLA-4 (p=0.01) was observed only in OP. Conclusion: The present study is the first to report a statistically significant association between OP and serum sCTLA-4. The novelty of our study is the significance of CTLA-4 in the pathogenesis of OP besides SLE and RA. PMID:23448385

  6. Autoimmunity due to molecular mimicry as a cause of neurological disease

    PubMed Central

    Levin, Michael C.; Lee, Sang Min; Kalume, Franck; Morcos, Yvette; Dohan, F. Curtis; Hasty, Karen A.; Callaway, Joseph C.; Zunt, Joseph; Desiderio, Dominic M.; Stuart, John M.

    2009-01-01

    One hypothesis that couples infection with autoimmune disease is molecular mimicry. Molecular mimicry is characterized by an immune response to an environmental agent that cross-reacts with a host antigen, resulting in disease1,2. This hypothesis has been implicated in the pathogenesis of diabetes, lupus and multiple sclerosis (MS)1–4. There is limited direct evidence linking causative agents with pathogenic immune reactions in these diseases. Our study establishes a clear link between viral infection, autoimmunity and neurological disease in humans. As a model for molecular mimicry, we studied patients with human T-lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP), a disease that can be indistinguishable from MS (refs. 5–7). HAM/TSP patients develop antibodies to neurons8. We hypothesized these antibodies would identify a central nervous system (CNS) autoantigen. Immunoglobulin G isolated from HAM/TSP patients identified heterogeneous nuclear ribonuclear protein-A1 (hnRNP-A1) as the autoantigen. Antibodies to hnRNP-A1 cross-reacted with HTLV-1-tax, the immune response to which is associated with HAM/TSP (refs. 5,9). Immunoglobulin G specifically stained human Betz cells, whose axons are preferentially damaged7. Infusion of autoantibodies in brain sections inhibited neuronal firing, indicative of their pathogenic nature. These data demonstrate the importance of molecular mimicry between an infecting agent and hnRNP-A1 in autoimmune disease of the CNS. PMID:11984596

  7. Type I interferon in organ-targeted autoimmune and inflammatory diseases.

    PubMed

    Crow, Mary K

    2010-01-01

    A significant role for IFNα in the pathogenesis of systemic lupus erythematosus is well supported, and clinical trials of anti-IFNα monoclonal antibodies are in progress in this disease. In other autoimmune diseases characterized by substantial inflammation and tissue destruction, the role of type I interferons is less clear. Gene expression analysis of peripheral blood cells from patients with rheumatoid arthritis and multiple sclerosis demonstrate an interferon signature similar to but less intense than that seen in patients with lupus. In both of those diseases, presence of the interferon signature has been associated with more significant clinical manifestations. At the same time, evidence supports an anti-inflammatory and beneficial role of IFNβ locally in the joints of patients with rheumatoid arthritis and in murine arthritis models, and many patients with multiple sclerosis show a clinical response to recombinant IFNβ. As can also be proposed for type I diabetes mellitus, type I interferon appears to contribute to the development of autoimmunity and disease progression in multiple autoimmune diseases, while maintaining some capacity to control established disease - particularly at local sites of inflammation. Recent studies in both rheumatoid arthritis and multiple sclerosis suggest that quantification of type I interferon activity or target gene expression might be informative in predicting responses to distinct classes of therapeutic agents.

  8. The autoimmune tautology.

    PubMed

    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.

  9. Pharmacological targeting of IDO-mediated tolerance for treating autoimmune disease.

    PubMed

    Penberthy, W Todd

    2007-04-01

    Cells at the maternal-fetal interface express indoleamine 2,3 dioxygenase (IDO) to consume all local tryptophan for the express purpose of starving adjacent maternal T cells of this most limiting and essential amino acid. This stops local T cell proliferation to ultimately result in the most dramatic example of immune tolerance, acceptance of the fetus. By contrast, inhibition of IDO using 1-methyl-tryptophan causes a sudden catastrophic rejection of the mammalian fetus. Immunomodulatory factors including IFNgamma, TNFalpha, IL-1, and LPS use IDO induction in responsive antigen presenting cells (APCs) also to transmit tolerogenic signals to T cells. Thus it makes sense to consider IDO induction towards tolerance for autoimmune diseases in general. Approaches to cell specific therapeutic IDO induction with NAD precursor supplementation to prevent the collateral non-T cell pathogenesis due to chronic TNFalpha-IDO activated tryptophan depletion in autoimmune diseases are reviewed. Tryptophan is an essential amino acid most immediately because it is the only precursor for the endogenous biosynthesis of nicotinamide adenine dinucleotide (NAD). Both autoimmune disease and the NAD deficiency disease pellagra occur in women at greater than twice the frequency of occurrence in men. The importance of IDO dysregulation manifest as autoimmune pellagric dementia is genetically illustrated for Nasu-Hakola Disease (or PLOSL), which is caused by a mutation in the IDO antagonizing genes TYROBP/DAP12 or TREM2. Loss of function leads to psychotic symptoms rapidly progressing to presenile dementia likely due to unchecked increases in microglial IDO expression, which depletes neurons of tryptophan causing neurodegeneration. Administration of NAD precursors rescued entire mental hospitals of dementia patients literally overnight in the 1930's and NAD precursors should help Nasu-Hakola patients as well. NAD depletion mediated by peroxynitrate PARP1 activation is one of the few

  10. Recent Insights in the Epidemiology of Autoimmune Diseases: Improved Prevalence Estimates and Understanding of Clustering of Diseases

    PubMed Central

    Cooper, Glinda S.; Bynum, Milele L.K.; Somers, Emily C.

    2009-01-01

    Previous studies have estimated a prevalence of a broad grouping of autoimmune diseases of 3.2%, based on literature review of studies published between 1965 and 1995, and 5.3%, based on national hospitalization registry data in Denmark. We examine more recent studies pertaining to the prevalence of 29 autoimmune diseases, and use these data to correct for the underascertainment of some diseases in the hospitalization registry data. This analysis results in an estimated prevalence of 7.6–9.4%, depending on the size of the correction factor used. The rates for most diseases for which data are available from many geographic regions span overlapping ranges. We also review studies of the co-occurrence of diseases within individuals and within families, focusing on specific pairs of diseases to better distinguish patterns that may result in insights pertaining to shared etiological pathways. Overall, data support a tendency for autoimmune diseases to co-occur at greater than expected rates within proband patients and their families, but this does not appear to be a uniform phenomenon across all diseases. Multiple sclerosis and rheumatoid arthritis is one disease pair that appears to have a decreased chance of coexistence. PMID:19819109

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

    PubMed

    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.

  12. Does Antigen Masking by Ubiquitin Chains Protect from the Development of Autoimmune Diseases?

    PubMed Central

    Weil, Robert

    2014-01-01

    Autoimmune diseases are characterized by the production of antibodies against self-antigens and generally arise from a failure of central or peripheral tolerance. However, these diseases may develop when newly appearing antigens are not recognized as self by the immune system. The mechanism by which some antigens are “invisible” to the immune system is not completely understood. Apoptotic and complement system defects or autophagy imbalance can generate this antigenic autoreactivity. Under particular circumstances, cellular debris containing autoreactive antigens can be recognized by innate immune receptors or other sensors and can eventually lead to autoimmunity. Ubiquitination may be one of the mechanisms protecting autoreactive antigens from the immune system that, if disrupted, can lead to autoimmunity. Ubiquitination is an essential post-translational modification used by cells to target proteins for degradation or to regulate other intracellular processes. The level of ubiquitination is regulated during T cell tolerance and apoptosis and E3 ligases have emerged as a crucial signaling pathway for the regulation of T cell tolerance toward self-antigens. I propose here that an unrecognized role of ubiquitin and ubiquitin-like proteins could be to render intracellular or foreign antigens (present in cellular debris resulting from apoptosis, complement system, or autophagy defects) invisible to the immune system in order to prevent the development of autoimmunity. PMID:24917867

  13. Hippocampal Damage in Mouse and Human Forms of Systemic Autoimmune Disease

    PubMed Central

    Ballok, David A.; Woulfe, John; Sur, Monalisa; Cyr, Michael; Sakic, Boris

    2006-01-01

    Systemic lupus erythematosus (SLE) is frequently accompanied by neuropsychiatric (NP) and cognitive deficits of unknown etiology. By using autoimmune MRL-lpr mice as an animal model of NP-SLE, we examine the relationship between autoimmunity, hippocampal damage, and behavioral dysfunction. Fluoro Jade B (FJB) staining and anti-ubiquitin (anti-Ub) immunocytochemistry were used to assess neuronal damage in young (asymptomatic) and aged (diseased) mice, while spontaneous alternation behavior (SAB) was used to estimate the severity of hippocampal dysfunction. The causal relationship between autoimmunity and neuropathology was tested by prolonged administration of the immunosuppressive drug cyclophosphamide (CY). In comparison to congenic MRL +/+ controls, SAB acquisition rates and performance in the “reversal” trial were impaired in diseased MRL-lpr mice, suggesting limited use of the spatial learning strategy. FJB-positive neurons and anti-Ub particles were frequent in the CA3 region. Conversely, CY treatment attenuated the SAB deficit and overall FJB staining. Similarly to mouse brain, the hippocampus from a patient who died from NP-SLE showed reduced neuronal density in the CA3 region and dentate gyrus, as well as increased FJB positivity in these regions. Gliosis and neuronal loss were observed in the gray matter, and T lymphocytes and stromal calcifications were common in the choroid plexus. Taken together, these results suggest that systemic autoimmunity induces significant hippocampal damage, which may underlie affective and cognitive deficits in NP-SLE. PMID:15301441

  14. Early onset of autoimmune disease by the retroviral integrase inhibitor raltegravir.

    PubMed

    Beck-Engeser, Gabriele B; Eilat, Dan; Harrer, Thomas; Jäck, Hans-Martin; Wabl, Matthias

    2009-12-01

    Raltegravir is a recently, Food and Drug Administration-approved, small-molecule drug that inhibits retroviral integrase, thereby preventing HIV DNA from inserting itself into the human genome. We report here that the activity profile of raltegravir on the replication of murine leukemia virus is similar to that for HIV, and that the drug specifically affects autoimmune disease in mice, in which endogenous retroelements are suspected to play a role. While NZW and BALB/c mice, which do not succumb to autoimmune disease, are not affected by raltegravir, lupus-prone (NZBxNZW) F(1) mice die of glomerulonephritis more than a month earlier than untreated mice. Raltegravir-treated NZB mice, which share the H-2 haplotype with BALB/c mice, but which are predisposed to autoimmune hemolytic anemia, develop auto-antibodies to their red blood cells >3 months earlier than untreated mice of the same strain. Because nonautoimmune mice are not affected by raltegravir, we consider off-target effects unlikely and attribute the exacerbation of autoimmunity to the inhibition of retroviral integrase. PMID:19923437

  15. Hippocampal damage in mouse and human forms of systemic autoimmune disease.

    PubMed

    Ballok, David A; Woulfe, John; Sur, Monalisa; Cyr, Michael; Sakic, Boris

    2004-01-01

    Systemic lupus erythematosus (SLE) is frequently accompanied by neuropsychiatric (NP) and cognitive deficits of unknown etiology. By using autoimmune MRL-lpr mice as an animal model of NP-SLE, we examine the relationship between autoimmunity, hippocampal damage, and behavioral dysfunction. Fluoro Jade B (FJB) staining and anti-ubiquitin (anti-Ub) immunocytochemistry were used to assess neuronal damage in young (asymptomatic) and aged (diseased) mice, while spontaneous alternation behavior (SAB) was used to estimate the severity of hippocampal dysfunction. The causal relationship between autoimmunity and neuropathology was tested by prolonged administration of the immunosuppressive drug cyclophosphamide (CY). In comparison to congenic MRL +/+ controls, SAB acquisition rates and performance in the "reversal" trial were impaired in diseased MRL-lpr mice, suggesting limited use of the spatial learning strategy. FJB-positive neurons and anti-Ub particles were frequent in the CA3 region. Conversely, CY treatment attenuated the SAB deficit and overall FJB staining. Similarly to mouse brain, the hippocampus from a patient who died from NP-SLE showed reduced neuronal density in the CA3 region and dentate gyrus, as well as increased FJB positivity in these regions. Gliosis and neuronal loss were observed in the gray matter, and T lymphocytes and stromal calcifications were common in the choroid plexus. Taken together, these results suggest that systemic autoimmunity induces significant hippocampal damage, which may underlie affective and cognitive deficits in NP-SLE. PMID:15301441

  16. Functional variants of the interleukin-23 receptor gene in non-gastrointestinal autoimmune diseases.

    PubMed

    Safrany, E; Melegh, B

    2009-01-01

    Variants of the gene of the interleukin-23 receptor (IL23R) were first identified as susceptibility factors in association with inflammatory bowel diseases. Since then it became clear that different variants of the gene play also role in a number of other autoimmune diseases like psoriasis, rheumatoid arthritis, ankylosing spondylitis and multiple sclerosis while in others, like systemic sclerosis, systemic lupus erythematosus or Sjögren syndrome the same effect could not be seen. However, the results are very controversial both in terms of the various polymorphisms and also in population specificity. The aim of the current paper is to overview all available reports on IL23R gene polymorphisms in various autoimmune and inflammatory diseases and to try to give an explanation on the possible effect of the examined variants.

  17. [Vaccinations in patients with autoimmune inflammatory rheumatic diseases--EULAR recommendations for pediatric and adult patients].

    PubMed

    Müller-Ladner, Claudia; Müller-Ladner, Ulf

    2012-10-01

    Since patients with autoimmune inflammatory rheumatic diseases are prone to infectious complications--on one hand due to the rheumatic disease itself, on the other hand due to the immunosuppressive therapy--vaccination is an essential tool to prevent these infectious complications. Although there exist several recommendations for the vaccination of immunocompromised patients, many questions still remain for the distinct clinical situations of patients with autoimmune inflammatory rheumatic diseases. In addition, there are several questions concerning the safety and efficacy of various vaccinations, especially with regard to live-attenuated vaccines. Therefore, EULAR (European League Against Rheumatism) assembled two expert panels to clarify as much of these clinical problems as possible. After extensive literature review and evidence grading, the expert panels published recommendations for the vaccination of adult and pediatric patients, which are outlined in this review article.

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

    PubMed

    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

  19. [Magnetic-resonance tomography in differential diagnosis of brain lesions in demyelinating and systemic autoimmune diseases].

    PubMed

    Totolian, N A

    2005-01-01

    An aim of the study was to establish MRT signs that may be useful for differential diagnosis of multiple sclerosis (MS). Three groups of patients have been examined: 300 patients with MS, 35 with demyelinating diseases (acute disseminated encephalomyelitis, neuromyelitis optica--Devic's syndrome); 90 patients with systemic autoimmune diseases (systemic lupus erythematosus, primary antiphospholipid syndrome, sclerodermatitis, Sjugren's syndrome, autoimmune thyroiditis, vasculitis and vasculopathy). Classification of MRT syndromes in MS and their frequency are presented: syndrome of chronic inflammatory demyelination (79%), syndrome of acute inflammatory demyelination (9%), syndrome of multifocal degenerative leucoencephalopathy (8%), syndrome of combined multifocal diffusive leucoencephalopathy (4%). The similarity and differences in MRT semiotics of the above diseases and MS are described.

  20. Two simultaneous autoimmune processes in a patient presenting with respiratory insufficiency

    PubMed Central

    Troy, Lauren; Hamor, Paul; Bleasel, Jane; Corte, Tamera

    2014-01-01

    The idiopathic inflammatory myopathies, including dermatomyositis, are uncommon acquired autoimmune diseases, sometimes associated with interstitial lung disease. Myasthenia gravis, a separate autoimmune disorder involving the neuromuscular junction, has some overlapping clinical features but has only rarely been reported to occur simultaneously within the same patient. Here we present the first reported case of concomitant dermatomyositis, myasthenia gravis, and interstitial lung disease. PMID:25473554

  1. Celiac disease: Autoimmunity in response to food antigen.

    PubMed

    Stamnaes, J; Sollid, L M

    2015-09-01

    Celiac disease (CD) is an increasingly common disease of the small intestine that occurs in genetically susceptible subjects by ingestion of cereal gluten proteins. Gluten is highly abundant in the modern diet and well tolerated by most individuals. In CD, however, an erroneous but highly specific, adaptive immune response is mounted toward certain parts of the gluten proteome. The resulting intestinal destruction is reversible and resolved upon removal of gluten from the diet. Post-translational modification (deamidation) of gluten peptides by transglutaminase 2 (TG2) is essential for the peptides to act as HLA-DQ-restricted T-cell antigens. Characteristically, deamidated gluten and the self-protein TG2 both become targets of highly disease specific B-cell responses. These antibodies share several peculiar characteristics despite being directed against vastly different antigens, which suggests a common mechanism of development. Importantly, no clear function has been ascribed to the antibodies and their contribution to disease may relate to their function as antigen receptors of the B cells rather than as soluble immunoglobulins. Adaptive immunity against gluten and TG2 appears not to be sufficient for establishment of the disease lesion, and it has been suggested that stress responses in the intestinal epithelium are essential for the development of full-blown disease and tissue damage. In this review we will summarize current concepts of the immune pathology of CD with particular focus on recent advances in our understanding of disease specific B-cell responses.

  2. ACQUIRED PES CAVUS IN CHARCOT-MARIE-TOOTH DISEASE

    PubMed Central

    Carvalho Maranho, Daniel Augusto; Volpon, José Batista

    2015-01-01

    Hereditary motor and sensory neuropathies, especially Charcot-Marie-Tooth disease, are frequently expressed with an acquired cavusvarus foot which is characterized by a fixed increase of the plantar arch and hindfoot inversion. Diagnosis of the underlying condition achieved through careful patient assessment and local evaluations is the keystone for decision-making about the adequate treatment. The cavus may present as an isolated deformity of the forefoot, hindfoot or it may be a combination of both locations. Related deformities, mainly the varus and toe clawing require appropriate evaluation; clinical characteristics such as severity of the deformity, impairment of the muscular power, flexibility and patient's age are important characteristics in the treatment decision. Conservative treatment of the cavusvarus foot with physiotherapy, insoles and shoe modifications are reserved to young patients and mild deformities. However, there is a tendency of the deformity to become more severe over time because of the progressive feature of the underlying neurological condition. So, the surgical treatment by using classical techniques is performed in early stages. Most importantly is the identification of the primary and main components of each deformity to properly correct them, if possible. Muscular transfers are used to treat the dynamic unbalance, retracted structures should be either divided or lengthened and localized osteotomies should be preferred over arthrodeses, which are reserved for stiff and severely deformed feet in adults. PMID:27077056

  3. ACQUIRED PES CAVUS IN CHARCOT-MARIE-TOOTH DISEASE.

    PubMed

    Carvalho Maranho, Daniel Augusto; Volpon, José Batista

    2009-01-01

    Hereditary motor and sensory neuropathies, especially Charcot-Marie-Tooth disease, are frequently expressed with an acquired cavusvarus foot which is characterized by a fixed increase of the plantar arch and hindfoot inversion. Diagnosis of the underlying condition achieved through careful patient assessment and local evaluations is the keystone for decision-making about the adequate treatment. The cavus may present as an isolated deformity of the forefoot, hindfoot or it may be a combination of both locations. Related deformities, mainly the varus and toe clawing require appropriate evaluation; clinical characteristics such as severity of the deformity, impairment of the muscular power, flexibility and patient's age are important characteristics in the treatment decision. Conservative treatment of the cavusvarus foot with physiotherapy, insoles and shoe modifications are reserved to young patients and mild deformities. However, there is a tendency of the deformity to become more severe over time because of the progressive feature of the underlying neurological condition. So, the surgical treatment by using classical techniques is performed in early stages. Most importantly is the identification of the primary and main components of each deformity to properly correct them, if possible. Muscular transfers are used to treat the dynamic unbalance, retracted structures should be either divided or lengthened and localized osteotomies should be preferred over arthrodeses, which are reserved for stiff and severely deformed feet in adults.

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

    PubMed

    Krzewska, Aleksandra; Ben-Skowronek, Iwona

    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

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

    PubMed Central

    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

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

    PubMed

    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

    2015-09-01

    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 non-additive disease contributions of classical HLA alleles in patients and matched controls for five common autoimmune diseases: rheumatoid arthritis (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 of the five diseases, we observed highly significant, non-additive dominance effects (rheumatoid arthritis, P = 2.5 × 10(-12); 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 non-additive dominance effects were explained by interactions between specific classical HLA alleles (rheumatoid arthritis, P = 1.8 × 10(-3); T1D, P = 8.6 × 10(-27); celiac disease, P = 6.0 × 10(-100)). These interactions generally increased disease risk and explained moderate but significant fractions of phenotypic variance (rheumatoid arthritis, 1.4%; T1D, 4.0%; celiac disease, 4.1%) beyond a simple additive model. PMID:26258845

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

    PubMed Central

    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

  8. Effect of IL-17A blockade with secukinumab in autoimmune diseases.

    PubMed

    Patel, Dhavalkumar D; Lee, David M; Kolbinger, Frank; Antoni, Christian

    2013-04-01

    Genetic studies and correlative expression data in diseased tissues have pointed to the role of interleukin (IL)-17 and Th17 cells in the pathogenesis of autoimmune disorders such as psoriasis, inflammatory bowel disease and seronegative spondyloarthropathies. Th17 cells are known to produce the proinflammatory cytokine IL-17A as well as other effector cytokines, including IL-17F and IL-22. Recent research has demonstrated that IL-17A is also expressed by multiple lineages of the innate immune system, including mast cells, neutrophils, dendritic cells, γδ-T cells, macrophages and natural killer cells. It can thus be expected that the inhibition of IL-17A as a therapeutic target in autoimmune disease would exert different physiological effects than the suppression of Th17 cell activity. Early clinical data are now available on secukinumab (AIN457), a recombinant, highly selective, fully human monoclonal anti-IL-17A antibody of the IgG1/κ isotype, enabling a preliminary assessment of the effects of IL-17A inhibition in multiple autoimmune diseases. Rapid and sustained symptom reductions in psoriasis, rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis have been observed in secukinumab-treated patients, with no overt safety signals. In conjunction with studies using the humanised anti-IL-17A monoclonal antibody (mAb) ixekizumab (LY2439821) and the fully human anti-IL-17RA mAb brodalumab (AMG 827), the findings on secukinumab provide evidence for the role of IL-17A in the pathophysiology of autoimmune disease and suggest the potential value of targeting this cytokine.

  9. Familial occurrence of autoimmune liver disease with overlapping features of primary biliary cholangitis and autoimmune hepatitis in a mother and her daughter.

    PubMed

    Omori, Kaoru; Yoshida, Kanako; Yokota, Masaki; Daa, Tsutomu; Kan, Masahiro

    2016-10-01

    We encountered two patients with overlapping features of primary biliary cholangitis and autoimmune hepatitis within the same family. A 68-year-old woman presented at our hospital from a previous medical institution because of the diagnosis of primary biliary cholangitis. Her 49-year-old daughter was admitted with liver dysfunction 4 years later. When compared, these two related patients were found to have overlapping features of primary biliary cholangitis and autoimmune hepatitis. Their human leukocyte antigen haplotype was DRB1*04:05/DRB1*15:02. The clinical and biochemical findings of these two patients immediately improved following treatment with a combination of prednisolone and ursodeoxycholic acid, in accordance with the Japanese guidelines. It is extremely important to identify such pathological conditions as quickly as possible, particularly with the appearance of severe liver dysfunction due to liver cirrhosis, as observed in our case. The Japanese guidelines are considered to be a realistic and useful clinical policy for the swift and efficient treatment of patients with overlapping features of primary biliary cholangitis and autoimmune hepatitis. We suggest that our two patients presented with a genetic predisposition to autoimmune liver disease with overlapping features of primary biliary cholangitis and autoimmune hepatitis within the same family. PMID:27503128

  10. Familial occurrence of autoimmune liver disease with overlapping features of primary biliary cholangitis and autoimmune hepatitis in a mother and her daughter.

    PubMed

    Omori, Kaoru; Yoshida, Kanako; Yokota, Masaki; Daa, Tsutomu; Kan, Masahiro

    2016-10-01

    We encountered two patients with overlapping features of primary biliary cholangitis and autoimmune hepatitis within the same family. A 68-year-old woman presented at our hospital from a previous medical institution because of the diagnosis of primary biliary cholangitis. Her 49-year-old daughter was admitted with liver dysfunction 4 years later. When compared, these two related patients were found to have overlapping features of primary biliary cholangitis and autoimmune hepatitis. Their human leukocyte antigen haplotype was DRB1*04:05/DRB1*15:02. The clinical and biochemical findings of these two patients immediately improved following treatment with a combination of prednisolone and ursodeoxycholic acid, in accordance with the Japanese guidelines. It is extremely important to identify such pathological conditions as quickly as possible, particularly with the appearance of severe liver dysfunction due to liver cirrhosis, as observed in our case. The Japanese guidelines are considered to be a realistic and useful clinical policy for the swift and efficient treatment of patients with overlapping features of primary biliary cholangitis and autoimmune hepatitis. We suggest that our two patients presented with a genetic predisposition to autoimmune liver disease with overlapping features of primary biliary cholangitis and autoimmune hepatitis within the same family.

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

    PubMed Central

    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 polycystic ovary syndrome and Graves’ disease: Is autoimmunity the link between the two diseases

    PubMed Central

    Nisar, Sobia; Shah, Parvez A.; Kuchay, M. Shafi; Bhat, Manzoor A.; Rashid, Aafia; Ahmed, Sanjeed; Ganie, Mohd Ashraf

    2012-01-01

    Introduction: Polycystic ovary syndrome (PCOS) is a common endocrinopathy of women of child-bearing age. Although some studies have suggested an association between PCOS and autoimmune thyroiditis, to our knowledge, only a few cases indicating association between PCOS and Graves’ disease are reported. Objective: We aim to describe this first case series of six women presenting with PCOS and Graves’ disease together. Materials and Methods: Women attending the endocrinology clinic at a tertiary care centre in north India and fulfilling the AE-PCOS criteria for diagnosis of PCOS were studied using a predefined proforma for any clinical, biochemical and imaging features of Graves’ disease. Results: The series consisted of six women with a mean age of 27.5 years and menarche as 12.6 years. All women were lean with mean BMI of 22.73 kg / m2 and three out of six had waist circumference <80 cm. The mean FG score of subjects was 16.66 and average total testosterone was 77.02 ng / dl (25.0-119.64). All the patients had suppressed TSH, the average being 0.052 μIU/ml (0.01-0.15). Thyroid gland was enlarged in all clinically and on ultrasonography and imaging with 99mTc and/or RAIU revealed diffuse increased uptake. Conclusions: The association of a rare disorder like Graves’ disease with a relatively common disorder like PCOS is unlikely to be because of a chance alone and may point to a common aetiopathogenic linkage leaving a scope for molecular characterization. PMID:23226647

  13. Organ-specific disease provoked by systemic autoimmunity.

    PubMed

    Kouskoff, V; Korganow, A S; Duchatelle, V; Degott, C; Benoist, C; Mathis, D

    1996-11-29

    Rheumatoid arthritis (RA) is a chronic joint disease characterized by leukocyte invasion and synoviocyte activation followed by cartilage and bone destruction. Its etiology and pathogenesis are poorly understood. We describe a spontaneous mouse model of this syndrome, generated fortuitously by crossing a T cell receptor (TCR) transgenic line with the NOD strain. All offspring develop a joint disease highly reminiscent of RA in man. The trigger for the murine disorder is chance recognition of a NOD-derived major histocompatibility complex (MHC) class II molecule by the transgenic TCR; progression to arthritis involves CD4+ T, B, and probably myeloid cells. Thus, a joint-specific disease need not arise from response to a joint-specific antigen but can be precipitated by a breakdown in general mechanisms of self-tolerance resulting in systemic self-reactivity. We suggest that human RA develops by an analogous mechanism. PMID:8945509

  14. Adult-Onset Acquired Partial Lipodystrophy Accompanied by Rheumatoid Arthritis

    PubMed Central

    Muto, Yusuke; Fujimura, Taku; Kakizaki, Aya; Tsuchiyama, Kenichiro; Kusakari, Yoshiyuki; Aiba, Setsuya

    2015-01-01

    Lipodystrophy is a group of metabolic disorders, possibly caused by autoimmune disease. In this report, we describe a case of adult-onset acquired partial lipodystrophy accompanied by rheumatoid arthritis without a family history. Interestingly, immunohistochemical staining revealed dense infiltration of IL-27-producing cells as well as MMP-7-and MMP-28-expressing cells, both of which have been reported to facilitate the development of autoimmune disease. Our present case might suggest possible mechanisms for acquired partial lipodystrophy. PMID:26034476

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

    PubMed

    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.

  16. Autoimmune Pancreatitis and IgG4 Related Disease in Three Children

    PubMed Central

    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

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

    PubMed Central

    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

  18. Autoimmune Pancreatitis and IgG4 Related Disease in Three Children

    PubMed Central

    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.

  19. Preclinical efficacy and mechanisms of mesenchymal stem cells in animal models of autoimmune diseases.

    PubMed

    Lee, Hong Kyung; Lim, Sang Hee; Chung, In Sung; Park, Yunsoo; Park, Mi Jeong; Kim, Ju Young; Kim, Yong Guk; Hong, Jin Tae; Kim, Youngsoo; Han, Sang-Bae

    2014-04-01

    Mesenchymal stem cells (MSCs) are present in diverse tissues and organs, including bone marrow, umbilical cord, adipose tissue, and placenta. MSCs can expand easily in vitro and have regenerative stem cell properties and potent immunoregulatory activity. They inhibit the functions of dendritic cells, B cells, and T cells, but enhance those of regulatory T cells by producing immunoregulatory molecules such as transforming growth factor-β, hepatic growth factors, prostaglandin E2, interleukin-10, indolamine 2,3-dioxygenase, nitric oxide, heme oxygenase-1, and human leukocyte antigen-G. These properties make MSCs promising therapeutic candidates for the treatment of autoimmune diseases. Here, we review the preclinical studies of MSCs in animal models for systemic lupus erythematosus, rheumatoid arthritis, Crohn's disease, and experimental autoimmune encephalomyelitis, and summarize the underlying immunoregulatory mechanisms. PMID:24851097

  20. CD20-depleting therapy in autoimmune diseases: from basic research to the clinic.

    PubMed

    Perosa, F; Prete, M; Racanelli, V; Dammacco, F

    2010-03-01

    The B lymphocyte-associated antigen CD20 is becoming an important immunotherapy target for autoimmune diseases, although its biological function has not been defined. Besides rheumatoid arthritis, growing experience with B cell-depleting therapy indicates that it may be effective in Sjögren's syndrome, dermatomyositis-polymyositis, systemic lupus erythematosus and some types of vasculitides. However, controlled clinical trials are still lacking for some of these indications. Infection has not been seen as a major limitation to this therapy, but reports of progressive multifocal leukoencephalopathy in an extremely small number of patients are of concern. Here, we review the therapeutic actions of anti-CD20 antibodies, and the recent and ongoing clinical trials with CD20-depleting therapy in autoimmune diseases.

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

    PubMed

    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

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

    PubMed

    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

  3. Inducing tissue specific tolerance in autoimmune disease with tolerogenic dendritic cells.

    PubMed

    Suwandi, Jessica S; Toes, René E M; Nikolic, Tatjana; Roep, Bart O

    2015-01-01

    Current immunosuppressive therapy acts systemically, causing collateral damage and does not necessarily cope with the cause of rheumatoid arthritis. Tissue specific immune modulation may restore tolerance in patients with autoimmune diseases such as RA, but desires knowledge on relevant target autoantigens. We present the case of type 1 diabetes as prototype autoimmune disease with established autoantigens to set the stage for tissue-specific immune modulation using tolerogenic dendritic cells pulsed with autoantigen in RA. This approach induces autoantigen-specific regulatory T cells that exert their tissue-specific action through a combination of linked suppression and infectious tolerance, introducing a legacy of targeted, localised immune regulation in the proximity of the lesion. Several trials are in progress in RA employing various types of tolerogenic DCs. With knowledge on mode of action and confounding effects of concomitant immunosuppressive therapy, this strategy may provide novel immune intervention that may also prevent RA in high-risk subjects. PMID:26458178

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

    PubMed

    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

  5. Recent concepts of autoimmune pancreatitis and IgG4-related disease.

    PubMed

    Okazaki, Kazuichi; Uchida, Kazushige; Miyoshi, Hideaki; Ikeura, Tsukasa; Takaoka, Makoto; Nishio, Akiyoshi

    2011-10-01

    Recent studies suggested the existence of two subtypes of autoimmune pancreatitis (AIP): type 1 related with IgG4 (lymphoplasmacytic sclerosing pancreatitis; LPSP) and type 2 related with a granulocytic epithelial lesion (idiopathic duct-centric chronic pancreatitis; IDCP). Apart from type 2 AIP, the pathological features of type 1 AIP with increased serum IgG4/IgE levels, abundant infiltration of IgG4+ plasmacytes and lymphocytes, fibrosis, and steroid responsiveness are suggestive of abnormal immunity such as allergy or autoimmunity. Moreover, the patients with type 1 AIP often have extrapancreatic lesions such as sclerosing cholangitis, sclerosing sialadenitis, or retroperitoneal fibrosis showing similar pathological features. Based on these findings, many synonyms have been proposed for these conditions, such as "multifocal idiopathic fibrosclerosis", "IgG4-related autoimmune disease", "IgG4-related sclerosing disease", "IgG4-related plasmacytic disease", and "IgG4-related multiorgan lymphoproliferative syndrome", all of which may refer to the same conditions. Therefore, the Japanese Research Committee for "Systemic IgG4-related Sclerosing Disease" proposed a disease concept and clinical diagnostic criteria based on the concept of multifocal fibrosclerosis in 2009, in which the term "IgG4-related disease" was appointed as a minimal consensus on these conditions. Although the significance of IgG4 in the development of "IgG4-related disease" remains unclear, we have proposed a hypothesis for the development of type 1 AIP, one of the IgG4-related disease. The concept and diagnostic criteria of "IgG4-related disease" will be changed in accordance with future studies. PMID:21170607

  6. Hospital-acquired infections: diseases with increasingly limited therapies.

    PubMed Central

    Swartz, M N

    1994-01-01

    About 5% of patients admitted to acute-care hospitals acquire nosocomial infections. A variety of factors contribute: increasing age of patients; availability, for treatment of formerly untreatable diseases, of extensive surgical and intensive medical therapies; and frequent use of antimicrobial drugs capable of selecting a resistant microbial flora. Nosocomial infections due to resistant organisms have been a problem ever since infections due to penicillinase-producing Staphylococcus aureus were noted within a few years of the introduction of penicillin. By the 1960s aerobic Gram-negative bacilli had assumed increasing importance as nosocomial pathogens, and many strains were resistant to available antimicrobials. During the 1980s the principal organisms causing nosocomial bloodstream infections were coagulase-negative staphylococci, aerobic Gram-negative bacilli, S. aureus, Candida spp., and Enterococcus spp. Coagulase-negative staphylococci and S. aureus are often methicillin-resistant, requiring parenteral use of vancomycin. Prevalence of vancomycin resistance among enterococcal isolates from patients in intensive care units has increased, likely due to increased use of this drug. Plasmid-mediated gentamicin resistance in up to 50% of enterococcal isolates, along with enhanced penicillin resistance in some strains, leaves few therapeutic options. The emergence of Enterobacteriaceae with chromosomal or plasmid-encoded extended spectrum beta-lactamases presents a world-wide problem of resistance to third generation cephalosporins. Control of these infections rests on (i) monitoring infections with such resistant organisms in an ongoing fashion, (ii) prompt institution of barrier precautions when infected or colonized patients are identified, and (iii) appropriate use of antimicrobials through implementation of antibiotic control programs. Images PMID:8146133

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

    PubMed

    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.

  8. Macrophage activation syndrome in a newborn infant born to a mother with autoimmune disease.

    PubMed

    Park, J H; Kim, S H; Kim, H J; Lee, S J; Jeong, D C; Kim, S Y

    2015-02-01

    Macrophage activation syndrome (MAS) is a complication of rheumatic disorders characterized by cytopenia, multiple organ dysfunction and coagulopathy associated with an inappropriate activation of macrophage. In neonatal lupus erythematosus, MAS is rare but fatal, requiring early diagnosis and treatment for optimal outcome. We report a case of MAS in a neonate born to a mother with autoimmune disease, improved by treatment with steroid, intravenous immunoglobulin and cyclosporine.

  9. Sodium Chloride Drives Autoimmune Disease by the Induction of Pathogenic Th17 Cells

    PubMed Central

    Kleinewietfeld, Markus; Manzel, Arndt; Titze, Jens; Kvakan, Heda; Yosef, Nir; Linker, Ralf A.; Muller, Dominik N.; Hafler, David A.

    2013-01-01

    There has been a marked increase in the incidence of autoimmune diseases in the last half-century. While the underlying genetic basis of this class of diseases has recently been elucidated implicating predominantly immune response genes1, changes in environmental factors must ultimately be driving this increase. The newly identified population of interleukin (IL)-17 producing CD4+ helper T cells (Th17 cells) plays a pivotal role in autoimmune diseases2. Pathogenic IL-23 dependent Th17 cells have been shown to be critical for the development of experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis (MS), and genetic risk factors associated with MS are related to the IL23/Th17 pathway1, 2. However, little is known regarding the environmental factors that directly influence Th17 cells. Here we show that increased salt (sodium chloride; NaCl) concentrations found locally under physiological conditions in vivo dramatically boost the induction of murine and human Th17 cells. High-salt conditions activate the p38/MAPK pathway involving the tonicity-responsive enhancer binding protein (TonEBP/NFAT5) and the serum/glucocorticoid-regulated kinase 1 (SGK1) during cytokine-induced Th17 polarization. Gene silencing or chemical inhibition of p38/MAPK, NFAT5 or SGK1 abrogates the high-salt induced Th17 cell development. The Th17 cells generated under high-salt display a highly pathogenic and stable phenotype characterized by the up-regulation of the pro-inflammatory cytokines GM-CSF, TNFα and IL-2. Moreover, mice fed with a high-salt diet develop a more severe form of EAE, in line with augmented central nervous system infiltrating and peripherally induced antigen specific Th17 cells. Thus, increased dietary salt intake might represent an environmental risk factor for the development of autoimmune diseases through the induction of pathogenic Th17 cells. PMID:23467095

  10. Role of RUNX in autoimmune diseases linking rheumatoid arthritis, psoriasis and lupus.

    PubMed

    Alarcón-Riquelme, Marta E

    2004-01-01

    Recent studies investigating the genetic susceptibility of systemic lupus erythematosus, rheumatoid arthritis and psoriasis have revealed a potential role for the RUNX proteins in the development of autoimmune disease. A new pathway of disease pathogenesis opens new avenues of research with thousands of questions that remain to be answered. In this review I attempt to propose how the RUNX proteins might be involved in these diseases and review current knowledge on this very interesting trio of transcription factors that was previously only suspected to be involved in cancer.

  11. A cholesterol and actinide dependent shadow biosphere of archaea and viroids in autoimmune diseases.

    PubMed

    Kurup, Ravikumar; Kurup, Parameswara Achutha

    2012-03-01

    Endogenous digoxin has been related to the pathogenesis of multiple sclerosis and other autoimmune diseases like systemic lupus erythematosis and rheumatoid arthritis. The possibility of endogenous digoxin synthesis by archaea with a mevalonate pathway and cholesterol catabolism was considered. 10 cases each of multiple sclerosis and other autoimmune diseases like systemic lupus erythematosis and rheumatoid arthritis before starting treatment and 10 age and sex matched healthy controls from general population were chosen for the study. Cholesterol substrate was added to the plasma of the patients and the generation of cytochrome F420, free RNA, free DNA, polycyclic aromatic hydrocarbon, hydrogen peroxide, serotonin, pyruvate, ammonia, glutamate, cytochrome C, hexokinase, ATP synthase, HMG CoA reductase, digoxin and bile acids were studied. The changes with the addition of antibiotics and cerium to the patient's plasma were also studied. The statistical analysis was done by ANOVA. The parameters mentioned above were increased the patient's plasma with addition of cholesterol substrate. The addition of antibiotics to the patient's plasma caused a decrease in all the parameters while addition of cerium increased their levels. An actinide dependent shadow biosphere of archaea and viroids is described in multiple sclerosis and other autoimmune diseases like systemic lupus erythematosis and rheumatoid arthritis contributing to their pathogenesis.

  12. The Genetics of Human Autoimmune Disease: A Perspective on Progress in the Field and Future Directions

    PubMed Central

    Seldin, Michael F.

    2015-01-01

    Progress in defining the genetics of autoimmune disease has been dramatically enhanced by large scale genetic studies. Genome-wide approaches examining hundreds or for some diseases thousands of cases and controls have been implemented using high throughput genotyping and appropriate algorithms to provide a wealth of data over the last decade. These studies have identified hundreds of non-HLA loci as well as further defining HLA region variations that predispose to different autoimmune diseases. These studies to identify genetic risk loci are also complemented by progress in gene expression studies including definition of expression quantitative trait loci (eQTL), various alterations in chromatin structure including histone marks, DNase I sensitivity, repressed chromatin regions as well as transcript factor binding sites. Integration of this information can partially explain why particular variations can alter proclivity to autoimmune phenotypes. Despite our incomplete knowledge base with only partial definition of hereditary factors and possible functional connections, this progress has and will continue to facilitate a better understanding of critical pathways and critical changes in immunoregulation. Advances in defining and understanding functional variants potentially can lead to both novel therapeutics and personalized medicine in which therapeutic approaches are chosen based on particular molecular phenotypes and genomic alterations. PMID:26343334

  13. Autoimmune thyroid disease in a cohort of Malaysian SLE patients: frequency, clinical and immunological associations.

    PubMed

    Ong, S G; Choy, C H

    2016-01-01

    Autoimmune thyroid disease (ATD) has been associated with other systemic autoimmune diseases. To date, there is limited data on thyroid disorders and autoimmune thyroid disease in Malaysia. The frequency of ATD among 189 systemic lupus erythematosus (SLE) patients was 6.3%, with 2.6% in the hyperthyroid group and 3.7% in the hypothyroid group. Hypothyroidism developed at a much younger mean age (24.3 years), suggesting that SLE might be a predisposing factor for the development of Hashimoto's thyroiditis. There was a higher rate of thyroid peroxidase antibody (TPO) positivity compared with anti-thyroglobulin antibody (Tg) in the hyperthyroid subgroup. This study also demonstrated a greater proportion of ATD patients who demonstrated high titres (≥ 1:6400) of TPO compared with high titres of Tg. Although there was an association between ATD and the presence of anti-Ro/SSA and/or anti-La/SSB antibodies, the absence of sicca symptoms and negative Schirmer's tests suggest a lack of association with secondary Sjogren's syndrome. A novel association between ATD and antiphospholipid syndrome (APS) was detected in our cohort. Hence we propose that patients affected by APS be routinely screened for ATD.

  14. Iodine Excess as an Environmental Risk Factor for Autoimmune Thyroid Disease

    PubMed Central

    Luo, Yuqian; Kawashima, Akira; Ishido, Yuko; Yoshihara, Aya; Oda, Kenzaburo; Hiroi, Naoki; Ito, Tetsuhide; Ishii, Norihisa; Suzuki, Koichi

    2014-01-01

    The global effort to prevent iodine deficiency disorders through iodine supplementation, such as universal salt iodization, has achieved impressive progress during the last few decades. However, iodine excess, due to extensive environmental iodine exposure in addition to poor monitoring, is currently a more frequent occurrence than iodine deficiency. Iodine excess is a precipitating environmental factor in the development of autoimmune thyroid disease. Excessive amounts of iodide have been linked to the development of autoimmune thyroiditis in humans and animals, while intrathyroidal depletion of iodine prevents disease in animal strains susceptible to severe thyroiditis. Although the mechanisms by which iodide induces thyroiditis are still unclear, several mechanisms have been proposed: (1) excess iodine induces the production of cytokines and chemokines that can recruit immunocompetent cells to the thyroid; (2) processing excess iodine in thyroid epithelial cells may result in elevated levels of oxidative stress, leading to harmful lipid oxidation and thyroid tissue injuries; and (3) iodine incorporation in the protein chain of thyroglobulin may augment the antigenicity of this molecule. This review will summarize the current knowledge regarding excess iodide as an environmental toxicant and relate it to the development of autoimmune thyroid disease. PMID:25050783

  15. The environment, geo-epidemiology, and autoimmune disease: Rheumatoid arthritis.

    PubMed

    Tobón, Gabriel J; Youinou, Pierre; Saraux, Alain

    2010-08-01

    Rheumatoid arthritis (RA) is a chronic inflammatory joint disease characterized by a distinctive pattern of bone and joint destruction. RA patients have an increased risk of death. The incidence and prevalence of RA vary across populations, statistical methods, and disease definitions. In North America and Northern Europe, the incidence of RA is estimated at 20-50 cases per 100,000 population and the prevalence at 0.5-1.1%. Lower incidences and prevalences have been reported in Southern Europe, and few data are available for developing countries. Some studies showed declining incidences and prevalences after the 1960s. RA is a multifactorial disease that results from interactions between genetic and environmental factors. The main genetic factors are HLA-DRB1 and the tyrosine-phosphatase gene PTPN22. Among environmental factors implicated in the development of RA, smoking shows the strongest association with RA susceptibility and is also linked to worse outcomes. The aim of this review is to discuss the available data on the incidence and prevalence of RA, as well as the genetic and environmental risk factors associated with RA.

  16. The environment, geo-epidemiology, and autoimmune disease: Rheumatoid arthritis.

    PubMed

    Tobón, Gabriel J; Youinou, Pierre; Saraux, Alain

    2010-03-01

    Rheumatoid arthritis (RA) is a chronic inflammatory joint disease characterized by a distinctive pattern of bone and joint destruction. RA patients have an increased risk of death. The incidence and prevalence of RA vary across populations, statistical methods, and disease definitions. In North America and Northern Europe, the incidence of RA is estimated at 20 to 50 cases per 100,000 population and the prevalence at 0.5% to 1.1%. Lower incidences and prevalences have been reported in Southern Europe, and few data are available for developing countries. Some studies showed declining incidences and prevalences after the 1960s. RA is a multifactorial disease that results from interactions between genetic and environmental factors. The main genetic factors are HLA-DRB1 and the tyrosine-phosphatase gene PTPN22. Among environmental factors implicated in the development of RA, smoking shows the strongest association with RA susceptibility and is also linked to worse outcomes. The aim of this review is to discuss the available data on the incidence and prevalence of RA, as well as the genetic and environmental risk factors associated with RA.

  17. Clinical holistic medicine: chronic infections and autoimmune diseases.

    PubMed

    Ventegodt, Søren; Merrick, Joav

    2005-02-23

    The consciousness-based (holistic) medical toolbox might be useful in general practice and in cases of recurrent infections and chronic infection or inflammation. From our clinical experiences, there is hope for improvement from a number of diseases caused by disorders affecting the regulation of the immune system when the physician includes the holistic medical approach. Our scientific understanding of the connection between consciousness and cellular order is still limited. Consciousness-based holistic medicine removes (as explained by the holistic process theory of healing) the "blockages" in the tissues of the body and facilitates function and informational exchange of the cells of the body. Many blockages and repressed feelings in an area would imply "noise and disturbances" on the level of intercellular communications, which in turn means major difficulties for the cells of the immune system. For this they are totally dependent on the body information system, which the holistic treatment aims to recover. Processing the blockages increases the coherence of the cells and organism, thus increasing the intercellular flow of information in the area and thus strengthening the immune defense and healing the disease. The area of clinical holistic medicine is going through a rapid development and the toolbox of consciousness-based medicine is available for dealing with many diseases arising from disturbances in the regulation of the immune system. Holistic medicine has yet to be better explained scientifically and our proposed holistic cures have yet to be documented clinically. We invite the medical community to cooperate on this important challenge.

  18. Computational Modelling Approaches on Epigenetic Factors in Neurodegenerative and Autoimmune Diseases and Their Mechanistic Analysis

    PubMed Central

    Khanam Irin, Afroza; Tom Kodamullil, Alpha; Gündel, Michaela; Hofmann-Apitius, Martin

    2015-01-01

    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). PMID:26636108

  19. Atopic dermatitis and association of risk for primary immune thrombocytopenia and autoimmune diseases among children: A nationwide population-based cohort study.

    PubMed

    Wei, Chang-Ching; Lin, Cheng-Li; Shen, Te-Chun; Tsai, Jeng-Dau

    2016-07-01

    Primary immune thrombocytopenia (ITP) is currently defined as an acquired autoimmune disorder with persistent thrombocytopenia. However, the temporal interaction between T helper type 2 cell (Th2)-mediated allergic diseases and T helper type 1 cell (Th1)-mediated ITP remains unknown. Atopic dermatitis (AD) is considered one of the first steps in the atopic march. Herein, we conducted a population-based cohort analysis to investigate the risk of ITP in children with AD in comparison with non-AD controls. We subsequently compared the occurrence of other autoimmune diseases in ITP children in both AD and non-AD cohorts. From 2000 to 2007, 120,704 children with newly diagnosed AD and 241,408 randomly selected non-AD controls were included in the study. By the end of 2008, incidences of ITP in both cohorts and the AD cohort to non-AD cohort hazard ratios (HRs) and confidence intervals (CIs) were measured. Comparison of the occurrence of other autoimmune diseases in ITP between children with and without AD was analyzed. The incidence of ITP during the study period was 1.72-fold greater (95% CI: 1.13-2.62) in the AD cohort than in the non-AD cohort (6.96 vs 4.00 per 100,000 person-years). The risk was greatest among male children, children >2 years, those in densely populated areas, and those with white-collar parents. The HR of ITP in AD children increased significantly with the number of AD-related clinical visits (P < 0.001). The risk of developing ITP in the AD cohort was highest within the first 3 years after the diagnosis of AD (HR: 1.78; CI: 1.14-2.78). The AD cohort with ITP had a higher occurrence rate of other autoimmune diseases than the non-AD cohort with ITP. AD children had a greater risk of developing ITP and other autoimmune diseases. Further research is needed to clarify the role of allergy in the pathogenesis of ITP and autoimmune diseases. PMID:27442647

  20. Autoimmune Manifestations in the 3xTg-AD Model of Alzheimer's Disease

    PubMed Central

    Marchese, Monica; Cowan, David; Head, Elizabeth; Ma, Donglai; Karimi, Khalil; Ashthorpe, Vanessa; Kapadia, Minesh; Zhao, Hui; Davis, Paulina; Sakic, Boris

    2015-01-01

    Background Immune system activation is frequently reported in patients with Alzheimer's disease (AD). However, it remains unknown whether this is a cause, a consequence, or an epiphenomenon of brain degeneration. Objective The present study examines whether immunological abnormalities occur in a well-established murine AD model and if so, how they relate temporally to behavioral deficits and neuropathology. Methods A broad battery of tests was employed to assess behavioral performance and autoimmune/inflammatory markers in 3xTg-AD (AD) mice and wild type controls from 1.5 to 12 months of age. Results Aged AD mice displayed severe manifestations of systemic autoimmune/inflammatory disease, as evidenced by splenomegaly, hepatomegaly, elevated serum levels of anti-nuclear/anti-dsDNA antibodies, low hematocrit, and increased number of double-negative T splenocytes. However, anxiety-related behavior and altered spleen function were evident as early as 2 months of age, thus preceding typical AD-like brain pathology. Moreover, AD mice showed altered olfaction and impaired “cognitive” flexibility in the first 6 months of life, suggesting mild cognitive impairment-like manifestations before general learning/memory impairments emerged at an older age. Interestingly, all of these features were present in 3xTg-AD mice prior to significant amyloid-β or tau pathology. Conclusion The results indicate that behavioral deficits in AD mice develop in parallel with systemic autoimmune/inflammatory disease. These changes antedate AD-like neuropathology, thus supporting a causal link between autoimmunity and aberrant behavior. Consequently, 3xTg-AD mice may be a useful model in elucidating the role of immune system in the etiology of AD. PMID:24150111

  1. Activation of Blood Coagulation in Two Prototypic Autoimmune Skin Diseases: A Possible Link with Thrombotic Risk.

    PubMed

    Cugno, Massimo; Tedeschi, Alberto; Borghi, Alessandro; Bucciarelli, Paolo; Asero, Riccardo; Venegoni, Luigia; Griffini, Samantha; Grovetti, Elena; Berti, Emilio; Marzano, Angelo Valerio

    2015-01-01

    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.

  2. Epigenetic Modulation as a Therapeutic Prospect for Treatment of Autoimmune Rheumatic Diseases.

    PubMed

    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

  3. Epigenetic Modulation as a Therapeutic Prospect for Treatment of Autoimmune Rheumatic Diseases

    PubMed Central

    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.

  4. Epigenetic Modulation as a Therapeutic Prospect for Treatment of Autoimmune Rheumatic Diseases

    PubMed Central

    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

  5. Expert panel workshop consensus statement on the role of the environment in the development of autoimmune disease.

    PubMed

    Parks, Christine G; Miller, Frederick W; Pollard, Kenneth Michael; Selmi, Carlo; Germolec, Dori; Joyce, Kelly; Rose, Noel R; Humble, Michael C

    2014-08-15

    Autoimmune diseases include 80 or more complex disorders characterized by self-reactive, pathologic immune responses in which genetic susceptibility is largely insufficient to determine disease onset. In September 2010, the National Institute of Environmental Health Sciences (NIEHS) organized an expert panel workshop to evaluate the role of environmental factors in autoimmune diseases, and the state of the science regarding relevant mechanisms, animal models, and human studies. The objective of the workshop was to analyze the existing data to identify conclusions that could be drawn regarding environmental exposures and autoimmunity and to identify critical knowledge gaps and areas of uncertainty for future study. This consensus document summarizes key findings from published workshop monographs on areas in which "confident" and "likely" assessments were made, with recommendations for further research. Transcribed notes and slides were reviewed to synthesize an overview on exposure assessment and questions addressed by interdisciplinary panels. Critical advances in the field of autoimmune disease research have been made in the past decade. Collaborative translational and interdisciplinary research is needed to elucidate the role of environmental factors in autoimmune diseases. A focus on exposure assessment methodology is needed to improve the effectiveness of human studies, and more experimental studies are needed to focus on causal mechanisms underlying observed associations of environmental factors with autoimmune disease in humans.

  6. Activation of Helicobacter pylori causes either autoimmune thyroid diseases or carcinogenesis in the digestive tract.

    PubMed

    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.

  7. Caffeic acid phenethyl ester lessens disease symptoms in an experimental autoimmune uveoretinitis mouse model.

    PubMed

    Choi, Jae-Hyeog; Roh, Kug-Hwan; Oh, Hana; Park, Sol-Ji; Ha, Sung-Min; Kang, Mi Seon; Lee, Ji-Hyun; Jung, So Young; Song, Hyunkeun; Yang, Jae Wook; Park, SaeGwang

    2015-05-01

    Experimental autoimmune uveoretinitis (EAU) is an autoimmune disease that models human uveitis. Caffeic acid phenethyl ester (CAPE), a phenolic compound isolated from propolis, possesses anti-inflammatory and immunomodulatory properties. CAPE demonstrates therapeutic potential in several animal disease models through its ability to inhibit NF-κB activity. To evaluate these therapeutic effects in EAU, we administered CAPE in a model of EAU that develops after immunization with interphotoreceptor retinal-binding protein (IRBP) in B10.RIII and C57BL/6 mice. Importantly, we found that CAPE lessened the severity of EAU symptoms in both mouse strains. Notably, treated mice exhibited a decrease in the ocular infiltration of immune cell populations into the retina; reduced TNF-α, IL-6, and IFN-γ serum levels: and inhibited TNF-α mRNA expression in retinal tissues. Although CAPE failed to inhibit IRBP-specific T cell proliferation, it was sufficient to suppress cytokine, chemokine, and IRBP-specific antibody production. In addition, retinal tissues isolated from CAPE-treated EAU mice revealed a decrease in NF-κB p65 and phospho-IκBα. The data identify CAPE as a potential therapeutic agent for autoimmune uveitis that acts by inhibiting cellular infiltration into the retina, reducing the levels of pro-inflammatory cytokines, chemokine, and IRBP-specific antibody and blocking NF-κB pathway activation. PMID:25795054

  8. Autoimmune hepatitis, one disease with many faces: Etiopathogenetic, clinico-laboratory and histological characteristics

    PubMed Central

    Gatselis, Nikolaos K; Zachou, Kalliopi; Koukoulis, George K; Dalekos, George N

    2015-01-01

    Autoimmune hepatitis (AIH) is an unresolving progressive liver disease of unknown etiology characterized by hypergammaglobulinemia, autoantibodies detection and interface hepatitis. Due to the absence of specific diagnostic markers and the large heterogeneity of its clinical, laboratory and histological features, AIH diagnosis may be potentially difficult. Therefore, in this in-depth review we summarize the substantial progress on etiopathogenesis, clinical, serological and histological phenotypes of AIH. AIH has a global distribution affecting any age, both sexes and all ethnic groups. Clinical manifestations vary from asymptomatic to severe or rarely fulminant hepatitis. Hypergammaglobulinemia with selective elevation of IgG is found in most cases. Autoimmune attack is perpetuated, possibly via molecular mimicry, and favored by the impaired control of T-regulatory cells. Histology (interface hepatitis, emperipolesis and hepatic rosette formation) and autoantibodies detection although not pathognomonic, are still the hallmark for a timely diagnosis. AIH remains a major diagnostic challenge. AIH should be considered in every case in the absence of viral, metabolic, genetic and toxic etiology of chronic or acute hepatitis. Laboratory personnel, hepato-pathologists and clinicians need to become more familiar with disease expressions and the interpretation of liver histology and autoimmune serology to derive maximum benefit for the patient. PMID:25574080

  9. Impairment of Regulatory T-Cell Function in Autoimmune Thyroid Disease

    PubMed Central

    Glick, Abigail B.; Wodzinski, Alaina; Fu, Pingfu

    2013-01-01

    Background Autoimmune thyroid disease (AITD) pathogenesis may result from a loss of immune tolerance to thyroid antigens. Regulatory T cells (Tregs) control immune responses, prevent excessive inflammation, and may be dysfunctional in AITD. We investigated the role of Tregs in Hashimoto's thyroiditis (HT) and Graves' disease (GD), complicated by Down syndrome (DS). Our goal was to identify differences in CD4+CD25high Treg function or number in patients with GD and HT, compared to healthy controls (HC). Methods Treg number was assessed by flow cytometric analysis in samples from 20 AITD patients (seven GD, 13 HT), nine HC, and seven individuals with DS, a genetic disorder associated with multiple autoimmune disorders including AITD. Treg function was assessed by the inhibition of proliferation (radioactive thymidine incorporation into DNA) of blood-derived T effector (Teff) cells by Tregs in a coculture. Various methods of stimulation were contrasted. Cytokine levels were determined in conditioned media from the co-cultures. Results No differences were found in the frequency of Tregs as a percentage of CD4+ cells between AITD and HC. AITD Tregs were less capable of inhibiting the proliferation of Teff cells when compared to HC; however, the impairment was dependent on the type of stimulation used. DS patients without AITD exhibited normal Treg function. We observed few differences in cytokine production between HC and AITD patients. Conclusions Tregs from AITD patients are partly dysfunctional, possibly explaining their autoimmunity. Future work will elucidate the diagnostic potential and pathophysiology of Tregs in AITD. PMID:23379353

  10. Novel Phospholipid-Protein Conjugates Allow Improved Detection of Antibodies in Patients with Autoimmune Diseases.

    PubMed

    Samuelsen, Simone V; Maity, Arindam; Nybo, Mads; Macaubas, Claudia; Lønstrup, Lars; Balboni, Imelda M; Mellins, Elizabeth D; Astakhova, Kira

    2016-01-01

    Reliable measurement of clinically relevant autoimmune antibodies toward phospholipid-protein conjugates is highly desirable in research and clinical assays. To date, the development in this field has been limited to the use of natural heterogeneous antigens. However, this approach does not take structural features of biologically active antigens into account and leads to low reliability and poor scientific test value. Here we describe novel phospholipid-protein conjugates for specific detection of human autoimmune antibodies. Our synthetic approach includes mild oxidation of synthetic phospholipid cardiolipin, and as the last step, coupling of the product with azide-containing linker and copper-catalyzed click chemistry with β2-glycoprotein I and prothrombin. To prove utility of the product antigens, we used enzyme-linked immunosorbent assay and three cohorts of samples obtained from patients in Denmark (n = 34) and the USA (n = 27 and n = 14). Afterwards we analyzed correlation of the obtained autoantibody titers with clinical parameters for each patient. Our results prove that using novel antigens clinically relevant autoantibodies can be detected with high repeatability, sensitivity and specificity. Unlike previously used antigens the obtained autoantibody titers strongly correlate with high disease activity and in particular, with arthritis, renal involvement, anti-Smith antibodies and high lymphocyte count. Importantly, chemical composition of antigens has a strong influence on the correlation of detected autoantibodies with disease activity and manifestations. This confirms the crucial importance of antigens' composition on research and diagnostic assays, and opens up exciting perspectives for synthetic antigens in future studies of autoimmunity.

  11. The CREB/CRTC2 Pathway Modulates Autoimmune Disease by Promoting Th17 Differentiation

    PubMed Central

    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

  12. The Role of IL-17 and Th17 Lymphocytes in Autoimmune Diseases.

    PubMed

    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.

  13. Environmental pathways to autoimmune diseases: the cases of primary biliary cirrhosis and multiple sclerosis

    PubMed Central

    Selmi, Carlo; Maria Papini, Anna; Pugliese, Piera; Claudia Alcaro, Maria; Gershwin, M. Eric

    2011-01-01

    The pathways leading to autoimmunity remain enigmatic despite numerous lines of experimental inquiry and epidemiological evidence. The mechanisms leading to the initiation and perpetuation of specific diseases such as primary biliary cirrhosis (PBC) or multiple sclerosis (MS) remain largely enigmatic, although it is established that a combination of genetic predisposition and environmental stimulation is required. The growing number of genome-wide association studies and the largely incomplete concordance for autoimmune diseases in monozygotic twins concur to support the role of the environment (including infectious agents and chemicals) in the breakdown of tolerance leading to autoimmunity through different mechanisms. In the present article we illustrate the current hypotheses related to an environmental impact on the onset of PBC and MS as two representative conditions investigated with complementary approaches. Indeed, while a role of post-translational antigen modifications has been proposed for MS, this field remain unexplored in PBC where, conversely, most evidence is gathered from geoepidemiology and experimental data on xenobiotics or infectious agents. PMID:22295019

  14. Statistical Colocalization of Genetic Risk Variants for Related Autoimmune Diseases in the Context of Common Controls

    PubMed Central

    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

  15. Genetic interrelationship between insulin-dependent diabetes mellitus, the autoimmune thyroid diseases, and rheumatoid arthritis.

    PubMed Central

    Torfs, C P; King, M C; Huey, B; Malmgren, J; Grumet, F C

    1986-01-01

    To investigate the possible coinheritance of autoimmune diseases that are associated with the same HLA antigen, we studied 70 families in which at least two siblings had either type I diabetes mellitus (IDDM), autoimmune thyroid disease (ATD), rheumatoid arthritis (RA), or a combination of these diseases. HLA-A, B, and C typing was performed on all affected sibs in one generation or more. First, we estimated by sib-pair analysis the disease allele frequency (pD) and the mode of inheritance for each disease. According to the method of ascertainment entered into the analysis, the pD for ATD ranged from .120 to .180, for an additive (dominant) mode of inheritance. For RA, the pD ranged from .254 to .341, also for additive inheritance, although recessive inheritance could not be excluded. For IDDM, the pD ranged from .336 to .337 for recessive inheritance; additive inheritance was rejected. Second, we examined the distribution of shared parental haplotypes in pairs of siblings that were discordant for their autoimmune diseases. The results suggested that the same haplotype may predispose to both IDDM and ATD, or IDDM and RA, but not to both RA and ATD. Analysis of pedigrees supported this hypothesis. In 16 families typed for HLA-DR also, the haplotype predisposing to both IDDM and ATD was assigned from pedigree information to DR3 (44%), DR4 (39%), or DR5, DR6, or DR7 (5.5% each). In some families, these haplotypes segregated over several generations with ATD only (either clinical or subclinical), suggesting that in such families, ATD was a marker for a susceptibility to IDDM. In several families, an IDDM haplotype segregated with RA but not with ATD. This suggests that ATD- and RA-associated susceptibilities to IDDM may be biologically different and thus independently increase the risk of IDDM. PMID:3456197

  16. Overlapping genetic susceptibility variants between three autoimmune disorders: rheumatoid arthritis, type 1 diabetes and coeliac disease

    PubMed Central

    2010-01-01

    Introduction Genome wide association studies, replicated by numerous well powered validation studies, have revealed a large number of loci likely to play a role in susceptibility to many multifactorial diseases. It is now well established that some of these loci are shared between diseases with similar aetiology. For example, a number of autoimmune diseases have been associated with variants in the PTPN22, TNFAIP3 and CTLA4 genes. Here we have attempted to define overlapping genetic variants between rheumatoid arthritis (RA), type 1 diabetes (T1D) and coeliac disease (CeD). Methods We selected eight SNPs previously identified as being associated with CeD and six T1D-associated SNPs for validation in a sample of 3,962 RA patients and 3,531 controls. Genotyping was performed using the Sequenom MassArray platform and comparison of genotype and allele frequencies between cases and controls was undertaken. A trend test P-value < 0.004 was regarded as significant. Results We found statistically significant evidence for association of the TAGAP locus with RA (P = 5.0 × 10-4). A marker at one other locus, C1QTNF6, previously associated with T1D, showed nominal association with RA in the current study but did not remain statistically significant at the corrected threshold. Conclusions In exploring the overlap between T1D, CeD and RA, there is strong evidence that variation within the TAGAP gene is associated with all three autoimmune diseases. Interestingly a number of loci appear to be specific to one of the three diseases currently studied suggesting that they may play a role in determining the particular autoimmune phenotype at presentation. PMID:20854658

  17. Follicular Helper T (Tfh) Cells in Autoimmune Diseases and Allograft Rejection

    PubMed Central

    Jeon, Yun-Hui

    2016-01-01

    Production of high affinity antibodies for antigens is a critical component for the immune system to fight off infectious pathogens. However, it could be detrimental to our body when the antigens that B cells recognize are of self-origin. Follicular helper T, or Tfh, cells are required for the generation of germinal center reactions, where high affinity antibody-producing B cells and memory B cells predominantly develop. As such, Tfh cells are considered as targets to prevent B cells from producing high affinity antibodies against self-antigens, when high affinity autoantibodies are responsible for immunopathologies in autoimmune disorders. This review article provides an overview of current understanding of Tfh cells and discusses it in the context of animal models of autoimmune diseases and allograft rejections for generation of novel therapeutic interventions. PMID:27574501

  18. Follicular Helper T (Tfh) Cells in Autoimmune Diseases and Allograft Rejection.

    PubMed

    Jeon, Yun-Hui; Choi, Youn Soo

    2016-08-01

    Production of high affinity antibodies for antigens is a critical component for the immune system to fight off infectious pathogens. However, it could be detrimental to our body when the antigens that B cells recognize are of self-origin. Follicular helper T, or Tfh, cells are required for the generation of germinal center reactions, where high affinity antibody-producing B cells and memory B cells predominantly develop. As such, Tfh cells are considered as targets to prevent B cells from producing high affinity antibodies against self-antigens, when high affinity autoantibodies are responsible for immunopathologies in autoimmune disorders. This review article provides an overview of current understanding of Tfh cells and discusses it in the context of animal models of autoimmune diseases and allograft rejections for generation of novel therapeutic interventions. PMID:27574501

  19. Brazilian society of hepatology recommendations for the diagnosis and management of autoimmune diseases of the liver.

    PubMed

    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.

  20. Fetal microchimeric cells in autoimmune thyroid diseases: harmful, beneficial or innocent for the thyroid gland?

    PubMed

    Lepez, Trees; Vandewoestyne, Mado; Deforce, Dieter

    2013-01-01

    Autoimmune thyroid diseases (AITD) show a female predominance, with an increased incidence in the years following parturition. Fetal microchimerism has been suggested to play a role in the pathogenesis of AITD. However, only the presence of fetal microchimeric cells in blood and in the thyroid gland of these patients has been proven, but not an actual active role in AITD. Is fetal microchimerism harmful for the thyroid gland by initiating a Graft versus Host reaction (GvHR) or being the target of a Host versus Graft reaction (HvGR)? Is fetal microchimerism beneficial for the thyroid gland by being a part of tissue repair or are fetal cells just innocent bystanders in the process of autoimmunity? This review explores every hypothesis concerning the role of fetal microchimerism in AITD.

  1. Brazilian society of hepatology recommendations for the diagnosis and management of autoimmune diseases of the liver.

    PubMed

    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

  2. Risk stratification in autoimmune cholestatic liver diseases: Opportunities for clinicians and trialists.

    PubMed

    Trivedi, Palak J; Corpechot, Christophe; Pares, Albert; Hirschfield, Gideon M

    2016-02-01

    Primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) are infrequent autoimmune cholestatic liver diseases, that disproportionate to their incidence and prevalence, remain very important causes of morbidity and mortality for patients with liver disease. Mechanistic insights spanning genetic risks and biological pathways to liver injury and fibrosis have led to a renewed interest in developing therapies beyond ursodeoxycholic acid that are aimed at both slowing disease course and improving quality of life. International cohort studies have facilitated a much greater understanding of disease heterogeneity, and in so doing highlight the opportunity to provide patients with a more individualized assessment of their risk of progressive liver disease, based on clinical, laboratory, or imaging findings. This has led to a new approach to patient care that focuses on risk stratification (both high and low risk); and furthermore allows such stratification tools to help identify patient subgroups at greatest potential benefit from inclusion in clinical trials. In this article, we review the applicability and validity of risk stratification in autoimmune cholestatic liver disease, highlighting strengths and weaknesses of current and emergent approaches. (Hepatology 2016;63:644-659). PMID:26290473

  3. Cardiovascular Risk in Systemic Autoimmune Diseases: Epigenetic Mechanisms of Immune Regulatory Functions

    PubMed Central

    López-Pedrera, Chary; Pérez-Sánchez, Carlos; Ramos-Casals, Manuel; Santos-Gonzalez, Monica; Rodriguez-Ariza, Antonio; José Cuadrado, Ma

    2012-01-01

    Autoimmune diseases (AIDs) have been associated with accelerated atherosclerosis (AT) leading to increased cardio- and cerebrovascular disease risk. Traditional risk factors, as well as systemic inflammation mediators, including cytokines, chemokines, proteases, autoantibodies, adhesion receptors, and others, have been implicated in the development of these vascular pathologies. Yet, the characteristics of vasculopathies may significantly differ depending on the underlying disease. In recent years, many new genes and signalling pathways involved in autoimmunity with often overlapping patterns between different disease entities have been further detected. Epigenetics, the control of gene packaging and expression independent of alterations in the DNA sequence, is providing new directions linking genetics and environmental factors. Epigenetic regulatory mechanisms comprise DNA methylation, histone modifications, and microRNA activity, all of which act upon gene and protein expression levels. Recent findings have contributed to our understanding of how epigenetic modifications could influence AID development, not only showing differences between AID patients and healthy controls, but also showing how one disease differs from another and even how the expression of key proteins involved in the development of each disease is regulated. PMID:21941583

  4. Risk stratification in autoimmune cholestatic liver diseases: Opportunities for clinicians and trialists

    PubMed Central

    Trivedi, Palak J.; Corpechot, Christophe; Pares, Albert

    2015-01-01

    Primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) are infrequent autoimmune cholestatic liver diseases, that disproportionate to their incidence and prevalence, remain very important causes of morbidity and mortality for patients with liver disease. Mechanistic insights spanning genetic risks and biological pathways to liver injury and fibrosis have led to a renewed interest in developing therapies beyond ursodeoxycholic acid that are aimed at both slowing disease course and improving quality of life. International cohort studies have facilitated a much greater understanding of disease heterogeneity, and in so doing highlight the opportunity to provide patients with a more individualized assessment of their risk of progressive liver disease, based on clinical, laboratory, or imaging findings. This has led to a new approach to patient care that focuses on risk stratification (both high and low risk); and furthermore allows such stratification tools to help identify patient subgroups at greatest potential benefit from inclusion in clinical trials. In this article, we review the applicability and validity of risk stratification in autoimmune cholestatic liver disease, highlighting strengths and weaknesses of current and emergent approaches. (Hepatology 2016;63:644–659) PMID:26290473

  5. Management of Gender-Related Problems in Women with Autoimmune Rheumatic Diseases.

    PubMed

    Rodrigues, Marília; Andreoli, Laura; Tincani, Angela

    2016-01-01

    Autoimmune rheumatic diseases (ARD) affect mainly young women during their reproductive years. Fertility is usually not diminished but the time it takes to conceive is usually longer. Factors related to an ARD or to its treatment are responsible for this effect. In addition, contraception counseling is required to prevent negative fetal outcome and exacerbation of disease symptoms. In recent years, advances in therapies, clarification of risk factors for adverse pregnancy outcomes, and a multidisciplinary approach have vastly improved obstetric management, increasing the possibility of successful pregnancy with a high likelihood of favorable outcome.

  6. Activation of cyclic GMP-AMP synthase by self-DNA causes autoimmune diseases.

    PubMed

    Gao, Daxing; Li, Tuo; Li, Xiao-Dong; Chen, Xiang; Li, Quan-Zhen; Wight-Carter, Mary; Chen, Zhijian J

    2015-10-20

    TREX1 is an exonuclease that digests DNA in the cytoplasm. Loss-of-function mutations of TREX1 are linked to Aicardi-Goutieres Syndrome (AGS) and systemic lupus erythematosus (SLE) in humans. Trex1(-/-) mice exhibit autoimmune and inflammatory phenotypes that are associated with elevated expression of interferon (IFN)-induced genes (ISGs). Cyclic GMP-AMP (cGAMP) synthase (cGAS) is a cytosolic DNA sensor that activates the IFN pathway. Upon binding to DNA, cGAS is activated to catalyze the synthesis of cGAMP, which functions as a second messenger that binds and activates the adaptor protein STING to induce IFNs and other cytokines. Here we show that genetic ablation of cGas in Trex1(-/-) mice eliminated all detectable pathological and molecular phenotypes, including ISG induction, autoantibody production, aberrant T-cell activation, and lethality. Even deletion of just one allele of cGas largely rescued the phenotypes of Trex1(-/-) mice. Similarly, deletion of cGas in mice lacking DNaseII, a lysosomal enzyme that digests DNA, rescued the lethal autoimmune phenotypes of the DNaseII(-/-) mice. Through quantitative mass spectrometry, we found that cGAMP accumulated in mouse tissues deficient in Trex1 or DNaseII and that this accumulation was dependent on cGAS. These results demonstrate that cGAS activation causes the autoimmune diseases in Trex1(-/-) and DNaseII(-/-) mice and suggest that inhibition of cGAS may lead to prevention and treatment of some human autoimmune diseases caused by self-DNA. PMID:26371324

  7. Pharmacological prion protein silencing accelerates central nervous system autoimmune disease via T cell receptor signalling

    PubMed Central

    Hu, Wei; Nessler, Stefan; Hemmer, Bernhard; Eagar, Todd N.; Kane, Lawrence P.; Leliveld, S. Rutger; Müller-Schiffmann, Andreas; Gocke, Anne R.; Lovett-Racke, Amy; Ben, Li-Hong; Hussain, Rehana Z.; Breil, Andreas; Elliott, Jeffrey L.; Puttaparthi, Krishna; Cravens, Petra D.; Singh, Mahendra P.; Petsch, Benjamin; Stitz, Lothar; Racke, Michael K.

    2010-01-01

    The primary biological function of the endogenous cellular prion protein has remained unclear. We investigated its biological function in the generation of cellular immune responses using cellular prion protein gene-specific small interfering ribonucleic acid in vivo and in vitro. Our results were confirmed by blocking cellular prion protein with monovalent antibodies and by using cellular prion protein-deficient and -transgenic mice. In vivo prion protein gene-small interfering ribonucleic acid treatment effects were of limited duration, restricted to secondary lymphoid organs and resulted in a 70% reduction of cellular prion protein expression in leukocytes. Disruption of cellular prion protein signalling augmented antigen-specific activation and proliferation, and enhanced T cell receptor signalling, resulting in zeta-chain-associated protein-70 phosphorylation and nuclear factor of activated T cells/activator protein 1 transcriptional activity. In vivo prion protein gene-small interfering ribonucleic acid treatment promoted T cell differentiation towards pro-inflammatory phenotypes and increased survival of antigen-specific T cells. Cellular prion protein silencing with small interfering ribonucleic acid also resulted in the worsening of actively induced and adoptively transferred experimental autoimmune encephalomyelitis. Finally, treatment of myelin basic protein1–11 T cell receptor transgenic mice with prion protein gene-small interfering ribonucleic acid resulted in spontaneous experimental autoimmune encephalomyelitis. Thus, central nervous system autoimmune disease was modulated at all stages of disease: the generation of the T cell effector response, the elicitation of T effector function and the perpetuation of cellular immune responses. Our findings indicate that cellular prion protein regulates T cell receptor-mediated T cell activation, differentiation and survival. Defects in autoimmunity are restricted to the immune system and not the central

  8. Differential Expression of Glucocorticoid Receptor Noncoding RNA Repressor Gas5 in Autoimmune and Inflammatory Diseases.

    PubMed

    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

  9. 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

    PubMed Central

    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. PMID:27812306

  10. Clinical Relevance of Environmental Factors in the Pathogenesis of Autoimmune Thyroid Disease

    PubMed Central

    2016-01-01

    Genetic factors contribute for about 70% to 80% and environmental factors for about 20% to 30% to the pathogenesis of autoimmune thyroid disease (AITD). Relatives of AITD patients carry a risk to contract AITD themselves. The 5-year risk can be quantified by the so-called Thyroid Events Amsterdam-score, based on serum thyroid-stimulating hormone, thyroid peroxidase (TPO)-antibodies and family history. Subjects at risk may ask what they can do to prevent development of AITD. This review summarizes what is known about modulation of exposure to environmental factors in terms of AITD prevention. To stop smoking decreases the risk on Graves disease but increases the risk on Hashimoto disease. Moderate alcohol intake provides some protection against both Graves and Hashimoto disease. Low selenium intake is associated with a higher prevalence of thyroid autoimmunity, but evidence that selenium supplementation may lower TPO antibodies and prevent subclinical hypothyroidism remains inconclusive. Low serum vitamin D levels are associated with a higher prevalence of TPO antibodies, but intervention studies with extra vitamin D have not been done yet. Stress may provoke Graves hyperthyroidism but not Hashimoto thyroiditis. Estrogen use have been linked to a lower prevalence of Graves disease. The postpartum period is associated with an increased risk of AITD. Taking together, preventive interventions to diminish the risk of AITD are few, not always feasible, and probably of limited efficacy. PMID:27184015

  11. Genetic sharing and heritability of paediatric age of onset autoimmune diseases

    PubMed Central

    Li, Yun R.; Zhao, Sihai D.; Li, Jin; Bradfield, Jonathan P.; Mohebnasab, Maede; Steel, Laura; Kobie, Julie; Abrams, Debra J.; Mentch, Frank D.; Glessner, Joseph T.; Guo, Yiran; Wei, Zhi; Connolly, John J.; Cardinale, Christopher J.; Bakay, Marina; Li, Dong; Maggadottir, S. Melkorka; Thomas, Kelly A.; Qui, Haijun; Chiavacci, Rosetta M.; Kim, Cecilia E.; Wang, Fengxiang; Snyder, James; Flatø, Berit; Førre, Øystein; Denson, Lee A.; Thompson, Susan D.; Becker, Mara L.; Guthery, Stephen L.; Latiano, Anna; Perez, Elena; Resnick, Elena; Strisciuglio, Caterina; Staiano, Annamaria; Miele, Erasmo; Silverberg, Mark S.; Lie, Benedicte A.; Punaro, Marilynn; Russell, Richard K.; Wilson, David C.; Dubinsky, Marla C.; Monos, Dimitri S.; Annese, Vito; Munro, Jane E.; Wise, Carol; Chapel, Helen; Cunningham-Rundles, Charlotte; Orange, Jordan S.; Behrens, Edward M.; Sullivan, Kathleen E.; Kugathasan, Subra; Griffiths, Anne M.; Satsangi, Jack; Grant, Struan F. A.; Sleiman, Patrick M. A.; Finkel, Terri H.; Polychronakos, Constantin; Baldassano, Robert N.; Luning Prak, Eline T.; Ellis, Justine A.; Li, Hongzhe; Keating, Brendan J.; Hakonarson, Hakon

    2015-01-01

    Autoimmune diseases (AIDs) are polygenic diseases affecting 7–10% of the population in the Western Hemisphere with few effective therapies. Here, we quantify the heritability of paediatric AIDs (pAIDs), including JIA, SLE, CEL, T1D, UC, CD, PS, SPA and CVID, attributable to common genomic variations (SNP-h2). SNP-h2 estimates are most significant for T1D (0.863±s.e. 0.07) and JIA (0.727±s.e. 0.037), more modest for UC (0.386±s.e. 0.04) and CD (0.454±0.025), largely consistent with population estimates and are generally greater than that previously reported by adult GWAS. On pairwise analysis, we observed that the diseases UC-CD (0.69±s.e. 0.07) and JIA-CVID (0.343±s.e. 0.13) are the most strongly correlated. Variations across the MHC strongly contribute to SNP-h2 in T1D and JIA, but does not significantly contribute to the pairwise rG. Together, our results partition contributions of shared versus disease-specific genomic variations to pAID heritability, identifying pAIDs with unexpected risk sharing, while recapitulating known associations