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Sample records for autoimmune disease triggered

  1. Pembrolizumab Therapy Triggering an Exacerbation of Preexisting Autoimmune Disease

    PubMed Central

    Phadke, Sneha D.; Ghabour, Ramez; Swick, Brian L.; Swenson, Andrea; Milhem, Mohammed; Zakharia, Yousef

    2016-01-01

    Historically, metastatic melanoma was uniformly and rapidly lethal, and treatment options were limited. In recent years, however, checkpoint inhibitors have emerged as an accepted standard treatment for patients with advanced melanoma. In clinical trials, these agents have been largely well tolerated and have the potential to result in durable responses. Importantly though, one must recognize the unique side effect profile of these therapies, which can trigger or exacerbate underlying autoimmune disease. Whether this autoimmune activation is associated with a clinical response to therapy has been debated, and while not definitive, there is evidence in the literature of a possible association. The 2 cases presented describe this autoimmune phenomenon, along with a review of the existing literature on the relationship between response to immunotherapy and autoimmune side effects. PMID:27826593

  2. 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.

  3. Long interspersed nuclear elements (LINE-1): potential triggers of systemic autoimmune disease.

    PubMed

    Crow, Mary K

    2010-02-01

    Recent advances have identified immune complexes containing nucleic acids as stimuli for toll-like receptors and inducers of type I interferon (IFN). While a similar mechanism may serve to amplify immune system activation and production of inflammatory mediators in vivo in the context of systemic autoimmune diseases, the initial triggers of autoimmunity have not been defined. In this review, we describe a category of potential inducers of autoimmunity, the endogenous retroelements, with a particular focus on long interspersed nuclear elements (LINE-1, L1). Increased expression of L1 transcripts or decreased degradation of L1 DNA or RNA could provide potent stimuli for an innate immune response, priming of the immune system, and induction of autoimmunity and inflammation. Genomic and genetic variations among individuals, sex-related differences in L1 regulation, and environmental triggers are among the potential mechanisms that might account for increased L1 expression. Induction of type I IFN by L1-enriched nucleic acids through TLR-independent pathways could represent a first step in the complex series of events leading to systemic autoimmune disease.

  4. 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.

  5. Autoimmune Diseases

    MedlinePlus

    ... Women - particularly African-American, Hispanic-American, and Native-American women - have a higher risk for some autoimmune diseases. There are more than 80 types of autoimmune diseases, and some have similar symptoms. This makes it hard for your health care provider to know if ...

  6. Toxicology of Autoimmune Diseases

    PubMed Central

    Hultman, Per; Kono, Dwight H.

    2010-01-01

    Susceptibility to most autoimmune diseases is dependent on polygenic inheritance, environmental factors, and poorly defined stochastic events. One of the significant challenges facing autoimmune disease research is in identifying the specific events that trigger loss of tolerance and autoimmunity. Although many intrinsic factors, including age, sex, and genetics, contribute to autoimmunity, extrinsic factors such as drugs, chemicals, microbes, or other environmental factors can also act as important initiators. This review explores how certain extrinsic factors, namely drugs and chemicals, can promote the development of autoimmunity, focusing on a few better characterized agents that, in most instances, have been shown to produce autoimmune manifestations in human populations. Mechanisms of autoimmune disease induction are discussed in terms of research obtained using specific animal models. Although a number of different pathways have been delineated for drug/chemical-induced autoimmunity some similarities do exist and a working model is proposed. PMID:20078109

  7. Two faces of microbiota in inflammatory and autoimmune diseases: triggers and drugs.

    PubMed

    Kverka, Miloslav; Tlaskalova-Hogenova, Helena

    2013-05-01

    The prevalence of chronic autoimmune and inflammatory diseases, such as inflammatory bowel disease, allergies, or rheumatic diseases, is steadily increasing in developed countries. This increase is probably accelerated by environmental factors, such as decrease in infectious burden or changes in food processing. These lifestyle changes then strongly influence the strongest stimulus for the immune system - commensal microbiota. Despite the differences in the affected organ, the immune-mediated diseases have one or more factors in common - microbe either as a trigger or as a protector, mucosal barrier dysfunction, and dysregulation of the immune system. The core questions, which microbes are involved and how these diseases can be cured or even prevented still remain unsolved. Powered by the recent progress in technology, by new insights into the function of immune system, by advances in microbiome research, and extended use of gnotobiological techniques, these mechanisms are now being unravelled and new therapeutic possibilities are emerging. To secure their niche, the microbes devised many ingenious ways, how to dampen the inflammation. Nonpathogenic microorganisms or microbial components isolated from probiotic, commensal or even pathogenic microbes could be, therefore, used to interfere with the pathogenetic mechanisms of immune-mediated diseases.

  8. Autoimmune Diseases

    MedlinePlus

    ... of CAM are herbal products, chiropractic , acupuncture , and hypnosis . If you have an autoimmune disease, you might ... help you to feel your best. Meditation, self-hypnosis, and guided imagery, are simple relaxation techniques that ...

  9. Bone Loss Triggered by the Cytokine Network in Inflammatory Autoimmune Diseases

    PubMed Central

    Amarasekara, Dulshara Sachini; Yu, Jiyeon; Rho, Jaerang

    2015-01-01

    Bone remodeling is a lifelong process in vertebrates that relies on the correct balance between bone resorption by osteoclasts and bone formation by osteoblasts. Bone loss and fracture risk are implicated in inflammatory autoimmune diseases such as rheumatoid arthritis, ankylosing spondylitis, inflammatory bowel disease, and systemic lupus erythematosus. The network of inflammatory cytokines produced during chronic inflammation induces an uncoupling of bone formation and resorption, resulting in significant bone loss in patients with inflammatory autoimmune diseases. Here, we review and discuss the involvement of the inflammatory cytokine network in the pathophysiological aspects and the therapeutic advances in inflammatory autoimmune diseases. PMID:26065006

  10. 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

  11. Interferon triggers experimental synovitis and may potentiate auto-immune disease in humans.

    PubMed

    Rosenbach, T O; Moshonov, S; Zor, U; Yaron, M

    1984-09-01

    From these data it appears that IFN is capable of stimulating prostaglandin E and hyaluronic acid production by human synovial fibroblasts in vitro and of initiating an inflammatory reaction in animal joints. In chronic arthritis its production may result from persisting viral or other antigenic stimulation. IFN may enhance the immune response and mediate the inflammatory process in the joint. Its role in the pathogenesis of rheumatic and various other autoimmune diseases is undergoing further study.

  12. 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.

  13. 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 ...

  14. Rheumatoid Arthritis is an Autoimmune Disease Triggered by Proteus Urinary Tract Infection

    PubMed Central

    Ebringer, Alan; Rashid, Taha

    2006-01-01

    Rheumatoid arthritis (RA) is a chronic and disabling polyarthritic disease, which affects mainly women in middle and old age. Extensive evidence based on the results of various microbial, immunological and molecular studies from different parts of the world, shows that a strong link exists between Proteus mirabilis microbes and RA. We propose that sub-clinical Proteus urinary tract infections are the main triggering factors and that the presence of molecular mimicry and cross-reactivity between these bacteria and RA-targeted tissue antigens assists in the perpetuation of the disease process through production of cytopathic auto-antibodies. Patients with RA especially during the early stages of the disease could benefit from Proteus anti-bacterial measures involving the use of antibiotics, vegetarian diets and high intake of water and fruit juices such as cranberry juice in addition to the currently employed treatments. PMID:16603443

  15. The genetics and epigenetics of autoimmune diseases

    PubMed Central

    Hewagama, Anura; Richardson, Bruce

    2010-01-01

    Self tolerance loss is fundamental to autoimmunity. While understanding of immune regulation is expanding rapidly, the mechanisms causing loss of tolerance in most autoimmune diseases remain elusive. Autoimmunity is believed to develop when genetically predisposed individuals encounter environmental agents that trigger the disease. Recent advances in the genetic and environmental contributions to autoimmunity suggest that interactions between genetic elements and epigenetic changes caused by environmental agents may be responsible for inducing autoimmune disease. Genetic loci predisposing to autoimmunity are being identified through multi-center consortiums, and the number of validated genes is growing rapidly. Recent reports also indicate that the environment can contribute to autoimmunity by modifying gene expression through epigenetic mechanisms. This article will review current understanding of the genetics and epigenetics of lupus, rheumatoid arthritis, multiple sclerosis and type 1 diabetes, using systemic lupus erythematosus as the primary example. Other autoimmune diseases may have a similar foundation. PMID:19349147

  16. The genetics and epigenetics of autoimmune diseases.

    PubMed

    Hewagama, Anura; Richardson, Bruce

    2009-08-01

    Self tolerance loss is fundamental to autoimmunity. While understanding of immune regulation is expanding rapidly, the mechanisms causing loss of tolerance in most autoimmune diseases remain elusive. Autoimmunity is believed to develop when genetically predisposed individuals encounter environmental agents that trigger the disease. Recent advances in the genetic and environmental contributions to autoimmunity suggest that interactions between genetic elements and epigenetic changes caused by environmental agents may be responsible for inducing autoimmune disease. Genetic loci predisposing to autoimmunity are being identified through multi-center consortiums, and the number of validated genes is growing rapidly. Recent reports also indicate that the environment can contribute to autoimmunity by modifying gene expression through epigenetic mechanisms. This article will review current understanding of the genetics and epigenetics of lupus, rheumatoid arthritis, multiple sclerosis and type 1 diabetes, using systemic lupus erythematosus as the primary example. Other autoimmune diseases may have a similar foundation.

  17. Autoimmune Hepatitis

    MedlinePlus

    ... Cholangitis Wilson Disease Liver Disease A-Z Autoimmune Hepatitis What is autoimmune hepatitis? Autoimmune hepatitis is a chronic—or long lasting— ... bacteria, viruses, toxins, and medications. What causes autoimmune hepatitis? A combination of autoimmunity, environmental triggers, and a ...

  18. [Thymoma and autoimmune diseases].

    PubMed

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

    2017-03-29

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

  19. 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 ...

  20. Drugs in autoimmune diseases.

    PubMed

    Herrmann, D B; Bicker, U

    1990-01-01

    Autoimmune diseases arise when autoimmunity or the loss of self tolerance results in tissue damages. Many mechanisms have been proposed for the origin of autoimmunity, including immunologic, viral, hormonal and genetic factors. All known parts of the immunological network are involved in causing immunopathologic symptoms. Therefore, more or less specific immunosuppressants are widely used in the treatment of autoimmune disorders which range from organ-specific, i.e. Hashimoto's thyroiditis, to non-organ-specific or systemic diseases, i.e. systemic lupus erythematosus. Unspecifically acting cytostatics do not only suppress autoimmune reactions but also create severe side-effects due to the impairment of immune responses against foreign antigens, leading, for example, to an increased risk of infections. Moreover, the genotoxic activity of cytostatics might induce malignancies. Corticosteroids are clinically well known and very active agents for the management of acute symptoms but different side-effects limit their use in the treatment of chronic diseases. Cyclosporin A has been an important step forward to a more specific prevention of organ transplant rejections and to the therapy of some autoimmune disorders. Modern approaches to immunosuppression include monoclonal antibodies directed against a variety of different determinants on immunocompetent cells. Ciamexone and Leflunomide which are in early clinical and preclinical development, respectively, might be interesting new drugs. Future immunopharmacologic drug research and development should lead to more specific, low molecular weight, orally active and chemically defined immunosuppressive compounds with good tolerability under long-term treatment of autoimmune diseases.

  1. Auto-immune disease.

    PubMed

    Panayi, G S

    1976-02-01

    Auto-immune disease may result from the interaction of the genetic load of the individual, modification of self-tissue antigens by environmental agents such as virus or drugs and abnormalities of the immunological system itself such as the loss of controlling or suppressor T cells with age. In the majority of people the outcome is tolerance, maintenance of normal tissue architecture and function. In the unfortunate few the outcome is auto-immune disease, that is, failure to recognize "self".

  2. Curcumin and autoimmune disease.

    PubMed

    Bright, John J

    2007-01-01

    The immune system has evolved to protect the host from microbial infection; nevertheless, a breakdown in the immune system often results in infection, cancer, and autoimmune diseases. Multiple sclerosis, rheumatoid arthritis, type 1 diabetes, inflammatory bowel disease, myocarditis, thyroiditis, uveitis, systemic lupus erythromatosis, and myasthenia gravis are organ-specific autoimmune diseases that afflict more than 5% of the population worldwide. Although the etiology is not known and a cure is still wanting, the use of herbal and dietary supplements is on the rise in patients with autoimmune diseases, mainly because they are effective, inexpensive, and relatively safe. Curcumin is a polyphenolic compound isolated from the rhizome of the plant Curcuma longa that has traditionally been used for pain and wound-healing. Recent studies have shown that curcumin ameliorates multiple sclerosis, rheumatoid arthritis, psoriasis, and inflammatory bowel disease in human or animal models. Curcumin inhibits these autoimmune diseases by regulating inflammatory cytokines such as IL-1beta, IL-6, IL-12, TNF-alpha and IFN-gamma and associated JAK-STAT, AP-1, and NF-kappaB signaling pathways in immune cells. Although the beneficial effects of nutraceuticals are traditionally achieved through dietary consumption at low levels for long periods of time, the use of purified active compounds such as curcumin at higher doses for therapeutic purposes needs extreme caution. A precise understanding of effective dose, safe regiment, and mechanism of action is required for the use of curcumin in the treatment of human autoimmune diseases.

  3. Headache in autoimmune diseases.

    PubMed

    John, Seby; Hajj-Ali, Rula A

    2014-03-01

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

  4. Sirolimus for Autoimmune Disease of Blood Cells

    ClinicalTrials.gov

    2017-03-16

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

  5. Prospective Evaluation of Procalcitonin, Soluble Triggering Receptor Expressed on Myeloid Cells-1 and C-Reactive Protein in Febrile Patients with Autoimmune Diseases

    PubMed Central

    Lin, Chou-Han; Hsieh, Song-Chou; Keng, Li-Ta; Lee, Ho-Sheng; Chang, Hou-Tai; Liao, Wei-Yu; Ho, Chao-Chi; Yu, Chong-Jen

    2016-01-01

    Background Both procalcitonin (PCT) and soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) have been investigated separately as indicators of infection in patients with autoimmune diseases. Our study simultaneously evaluated both PCT and sTREM-1 along with C-reactive protein (CRP) in febrile patients with autoimmune diseases. Methods Fifty-nine patients were enrolled in the study. The patients were categorized into the infection group (n = 24) or the disease flare group (n = 35). sTREM-1, PCT and CRP concentrations at fever onset were compared between the two groups of patients. Results sTREM-1 and CRP did not differ between the two groups. PCT [median (range), ng/ml] was higher in the infection group than in the disease flare group [0.53 (0.02–12.85) vs. 0.12 (0.02–19.23), p = 0.001]. The area under the receiver-operating characteristic (ROC) for diagnosis of infection was 0.75 for PCT (p = 0.001), 0.63 for CRP (p = 0.09) and 0.52 for sTREM-1 (p = 0.79). Using 0.2 ng/ml as the cutoff value for PCT, sensitivity was 0.75 and specificity was 0.77. Negative predictive values for PCT were 92%, 87% and 82% for a prevalence of infection of 20%, 30%, and 40%, respectively. Neither immunosuppressants nor biomodulators affected the level of the three biomarkers. However, in patients treated with corticosteroids, the levels of sTREM-1 and CRP were significantly decreased compared with the untreated patients. Conclusions Setting PCT at a lower cutoff value could provide useful information on excluding infection in febrile patients with autoimmune diseases. The possible effect of corticosteroids on the level of sTREM-1 as an infection marker deserves further study. PMID:27096761

  6. Leaky gut and autoimmune diseases.

    PubMed

    Fasano, Alessio

    2012-02-01

    Autoimmune diseases are characterized by tissue damage and loss of function due to an immune response that is directed against specific organs. This review is focused on the role of impaired intestinal barrier function on autoimmune pathogenesis. Together with the gut-associated lymphoid tissue and the neuroendocrine network, the intestinal epithelial barrier, with its intercellular tight junctions, controls the equilibrium between tolerance and immunity to non-self antigens. Zonulin is the only physiologic modulator of intercellular tight junctions described so far that is involved in trafficking of macromolecules and, therefore, in tolerance/immune response balance. When the zonulin pathway is deregulated in genetically susceptible individuals, autoimmune disorders can occur. This new paradigm subverts traditional theories underlying the development of these diseases and suggests that these processes can be arrested if the interplay between genes and environmental triggers is prevented by re-establishing the zonulin-dependent intestinal barrier function. Both animal models and recent clinical evidence support this new paradigm and provide the rationale for innovative approaches to prevent and treat autoimmune diseases.

  7. 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.

  8. 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

  9. Galectin-3 in autoimmunity and autoimmune diseases.

    PubMed

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

    2015-08-01

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

  10. Imaging of autoimmune biliary disease.

    PubMed

    Yeh, Melinda J; Kim, So Yeon; Jhaveri, Kartik S; Behr, Spencer C; Seo, Nieun; Yeh, Benjamin M

    2017-01-01

    Autoimmune biliary diseases are poorly understood but important to recognize. Initially, autoimmune biliary diseases are asymptomatic but may lead to progressive cholestasis with associated ductopenia, portal hypertension, cirrhosis, and eventually liver failure. The three main forms of autoimmune biliary disease are primary biliary cirrhosis, primary sclerosing cholangitis, and IgG4-associated cholangitis. Although some overlap may occur between the three main autoimmune diseases of the bile ducts, each disease typically affects a distinct demographic group and requires a disease-specific diagnostic workup. For all the autoimmune biliary diseases, imaging provides a means to monitor disease progression, assess for complications, and screen for the development of hepatobiliary malignancies that are known to affect patients with these diseases. Imaging is also useful to suggest or corroborate the diagnosis of primary sclerosing cholangitis and IgG4-associated cholangitis. We review the current literature and emphasize radiological findings and considerations for these autoimmune diseases of the bile ducts.

  11. Complement in autoimmune diseases.

    PubMed

    Vignesh, Pandiarajan; Rawat, Amit; Sharma, Madhubala; Singh, Surjit

    2017-02-01

    The complement system is an ancient and evolutionary conserved element of the innate immune mechanism. It comprises of more than 20 serum proteins most of which are synthesized in the liver. These proteins are synthesized as inactive precursor proteins which are activated by appropriate stimuli. The activated forms of these proteins act as proteases and cleave other components successively in amplification pathways leading to exponential generation of final effectors. Three major pathways of complement pathways have been described, namely the classical, alternative and lectin pathways which are activated by different stimuli. However, all the 3 pathways converge on Complement C3. Cleavage of C3 and C5 successively leads to the production of the membrane attack complex which is final common effector. Excessive and uncontrolled activation of the complement has been implicated in the host of autoimmune diseases. But the complement has also been bemusedly described as the proverbial "double edged sword". On one hand, complement is the final effector of tissue injury in autoimmune diseases and on the other, deficiencies of some components of the complement can result in autoimmune diseases. Currently available tools such as enzyme based immunoassays for functional assessment of complement pathways, flow cytometry, next generation sequencing and proteomics-based approaches provide an exciting opportunity to study this ancient yet mysterious element of innate immunity.

  12. Paediatric Autoimmune Liver Disease.

    PubMed

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

    2015-01-01

    In paediatrics, there are 2 liver disorders in which liver damage most likely stems from an autoimmune attack: 'classical' autoimmune hepatitis (AIH) and the AIH/sclerosing cholangitis overlap syndrome (also known as autoimmune sclerosing cholangitis, ASC). The presentation of childhood autoimmune liver disease (AILD) is non-specific and can mimic most other liver disorders. AIH is exquisitely responsive to immunosuppressive treatment, which should be instituted promptly to prevent rapid deterioration and promote remission and long-term survival. Difficult-to-treat or non-responsive patients should be treated with mycophenolate mofetil; if this fails then calcineurin inhibitors can be tried. Persistent failure to respond or lack of adherence to treatment result in end-stage liver disease. These patients, and those with fulminant liver failure at diagnosis, will require liver transplantation. ASC responds to the same immunosuppressive treatment used for AIH when treatment is initiated early. Abnormal liver function tests often resolve within a few months of treatment, although medium- to long-term prognosis is worse than that of AIH because bile duct disease continues to progress despite treatment in approximately 50% of patients. Ursodeoxycholic acid is usually added to conventional treatment regimen in ASC, but whether this actually helps arrest the progression of bile duct disease remains to be established. The pathogenesis of paediatric-onset AILD is not fully understood, although there is mounting evidence that genetic susceptibility, molecular mimicry and impaired immunoregulatory networks contribute to the initiation and perpetuation of the autoimmune attack. Liver damage is thought to be mediated primarily by CD4pos T-cells. While Th1 effector cells are associated with hepatocyte damage in both AIH and ASC, Th17 immune responses predominate in the latter where they correlate with biochemical indices of cholestasis, indicating that IL-17 is involved in the

  13. [THE ENVIRONMENT AND AUTOIMMUNE DISEASES].

    PubMed

    Watad, Abdulla; Amital, Howard; Shoenfeld, Yehuda

    2015-05-01

    The immune system carefully distinguishes between self and non-self-components. Therefore, any small deviation of this balanced function may result in an autoimmune activity and harm against self-antigens (autoantigens). The link between autoimmune diseases and various heredity and environmental factors has been discussed in numerous studies. The infectious factor is still considered to be the most important environmental factor leading to the development of autoimmune disease. Recent studies associated new environmental factors to autoimmunity, such as excessive salt consumption. In this paper, we summarize the relationship between environmental factors and autoimmune diseases covering innovations in this field.

  14. Molecular mimicry and autoimmune thyroid disease.

    PubMed

    Benvenga, Salvatore; Guarneri, Fabrizio

    2016-06-15

    Hypothesized 40 years ago, molecular mimicry has been thereafter demonstrated as an extremely common mechanism by which microbes elude immune response and modulate biosynthetic/metabolic pathways of the host. In genetically predisposed persons and under particular conditions, molecular mimicry between microbial and human antigens can turn a defensive immune response into autoimmunity. Such triggering role and its pathogenetic importance have been investigated and demonstrated for many autoimmune diseases. However, this is not the case for autoimmune thyroid disease, which appears relatively neglected by this field of research. Here we review the available literature on the possible role of molecular mimicry as a trigger of autoimmune thyroid disease. Additionally, we present the results of in silico search for amino acid sequence homologies between some microbial proteins and thyroid autoantigens, and the potential pathogenetic relevance of such homologies. Relevance stems from the overlap with known autoepitopes and the occurrence of specific HLA-DR binding motifs. Bioinformatics data published by our group support and explain the triggering role of Borrelia, Yersinia, Clostridium botulinum, Rickettsia prowazekii and Helicobacter pylori. Our new data suggest the potential pathogenic importance of Toxoplasma gondii, some Bifidobacteria and Lactobacilli, Candida albicans, Treponema pallidum and hepatitis C virus in autoimmune thyroid disease, indicating specific molecular targets for future research. Additionally, the consistency between in silico prediction of cross-reactivity and experimental results shows the reliability and usefulness of bioinformatics tools to precisely identify candidate molecules for in vitro and/or in vivo experiments, or at least narrow down their number.

  15. 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.

  16. Electrosmog and autoimmune disease.

    PubMed

    Marshall, Trevor G; Heil, Trudy J Rumann

    2016-07-13

    Studies in mice have shown that environmental electromagnetic waves tend to suppress the murine immune system with a potency similar to NSAIDs, yet the nature of any Electrosmog effects upon humans remains controversial. Previously, we reported how the human Vitamin-D receptor (VDR) and its ligand, 1,25-dihydroxyvitamin-D (1,25-D), are associated with many chronic inflammatory and autoimmune diseases. We have shown how olmesartan, a drug marketed for mild hypertension, acts as a high-affinity partial agonist for the VDR, and that it seems to reverse disease activity resulting from VDR dysfunction. We here report that structural instability of the activated VDR becomes apparent when observing hydrogen bond behavior with molecular dynamics, revealing that the VDR pathway exhibits a susceptibility to Electrosmog. Further, we note that characteristic modes of instability lie in the microwave frequency range, which is currently populated by cellphone and WiFi communication signals, and that the susceptibility is ligand dependent. A case series of 64 patient-reported outcomes subsequent to use of a silver-threaded cap designed to protect the brain and brain stem from microwave Electrosmog resulted in 90 % reporting "definite" or "strong" changes in their disease symptoms. This is much higher than the 3-5 % rate reported for electromagnetic hypersensitivity in a healthy population and suggests that effective control of environmental Electrosmog immunomodulation may soon become necessary for successful therapy of autoimmune 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.

  18. 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

  19. Mucormycosis in systemic autoimmune diseases.

    PubMed

    Royer, Mathieu; Puéchal, Xavier

    2014-07-01

    Mucormycosis is an emerging infection in systemic autoimmune diseases. All published cases of systemic autoimmune diseases complicated by mucormycosis were reviewed. The clinical features, diagnostic procedures and the main principles of treatment were analyzed. Twenty-four cases of mucormycosis have been reported in systemic auto-immune diseases, of which 83% in systemic lupus erythematosus, all occurring during immunosuppressants. In most cases, the infection was disseminated or rhinocerebral and it had mimicked a flare of the underlying connective tissue disease. A fatal outcome was reported in 58.3% of these patients. In conclusion, mucormycosis often mimics a flare of the underlying systemic disease and is associated with a high mortality rate. Systemic lupus erythematosus is by far the most common associated systemic autoimmune disease. A high degree of awareness is warranted to rapidly rule out infection, of which mucormycosis, in immunocompromised patients with systemic autoimmune disease before a disease flare is conclusively diagnosed.

  20. 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

  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. Gene Therapy for Autoimmune Disease.

    PubMed

    Shu, Shang-An; Wang, Jinjun; Tao, Mi-Hua; Leung, Patrick S C

    2015-10-01

    Advances in understanding the immunological and molecular basis of autoimmune diseases have made gene therapy a promising approach to treat the affected patients. Gene therapy for autoimmune diseases aims to regulate the levels of proinflammatory cytokines or molecules and the infiltration of lymphocytes to the effected sites through successful delivery and expression of therapeutic genes in appropriate cells. The ultimate goal of gene therapy is to restore and maintain the immune tolerance to the relevant autoantigens and improve clinical outcomes for patients. Here, we summarize the recent progress in identifying genes responsible for autoimmune diseases and present examples where gene therapy has been applied as treatments or prevention in autoimmune diseases both in animal models and the clinical trials. Discussion on the advantages and pitfalls of gene therapy strategies employed is provided. The intent of this review is to inspire further studies toward the development of new strategies for successful treatment of autoimmune diseases.

  4. Infections as risk factor for autoimmune diseases - A nationwide study.

    PubMed

    Nielsen, Philip Rising; Kragstrup, Tue Wenzel; Deleuran, Bent Winding; Benros, Michael Eriksen

    2016-11-01

    Viruses, bacteria and other infectious pathogens are the major postulated environmental triggers of autoimmunity. In the present nation-wide study we describe the association between infections and 29 autoimmune diseases. We used the Danish Civil Registration System to identify 4.5 million persons born between 1945 and 2000. Information on infections and autoimmune diseases was obtained from the Danish Hospital Register. The cohort was followed from 1977 to 2012. Incidence rate ratios for developing an autoimmune disease were estimated using poisson regression. We found an association between hospital admission for an infection and 29 autoimmune diseases. This study shows that infections are risk factors for a broad spectrum of autoimmune diseases in a dose-response and temporal manner, in agreement with the hypothesis that infections are an environmental risk factor contributing to the etiology of autoimmune diseases together with genetic factors.

  5. Helicobacter pylori and autoimmune disease: Cause or bystander

    PubMed Central

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

    2014-01-01

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

  6. Viruses as triggers of autoimmunity: facts and fantasies.

    PubMed

    Whitton, J L; Fujinami, R S

    1999-08-01

    Autoimmunity has been proposed as the cause of several human chronic inflammatory diseases, and recent animal studies show that viruses can induce autoimmune disease. These studies demonstrate how viruses might misdirect the immune system, and here we discuss critically the evidence that similar phenomena may lead to human disease.

  7. Epigenetic alterations underlying autoimmune diseases.

    PubMed

    Aslani, Saeed; Mahmoudi, Mahdi; Karami, Jafar; Jamshidi, Ahmad Reza; Malekshahi, Zahra; Nicknam, Mohammad Hossein

    2016-01-01

    Recent breakthroughs in genetic explorations have extended our understanding through discovery of genetic patterns subjected to autoimmune diseases (AID). Genetics, on the contrary, has not answered all the conundrums to describe a comprehensive explanation of causal mechanisms of disease etiopathology with regard to the function of environment, sex, or aging. The other side of the coin, epigenetics which is defined by gene manifestation modification without DNA sequence alteration, reportedly has come in to provide new insights towards disease apprehension through bridging the genetics and environmental factors. New investigations in genetic and environmental contributing factors for autoimmunity provide new explanation whereby the interactions between genetic elements and epigenetic modifications signed by environmental agents may be responsible for autoimmune disease initiation and perpetuation. It is aimed through this article to review recent progress attempting to reveal how epigenetics associates with the pathogenesis of autoimmune diseases.

  8. Is localized autoimmunity the trigger for rheumatoid arthritis? Unravelling new targets for prevention.

    PubMed

    Mankia, Kulveer; Emery, Paul

    2015-09-01

    The systemic autoantibodies that characterize rheumatoid arthritis (RA) are detectable well before patients develop disease and may originate from sites distant to the synovial joints. There is growing evidence that local autoimmune processes occur at mucosal sites in the earliest phases of RA, as well as in predisposed individuals who have not yet progressed to clinical disease. Mucosal autoimmunity has been described at the oral mucosa, lung, and gut in these subjects, and it is conceivable that different sites may provide the primary trigger for systemic autoimmunity in different individuals. At the oral mucosa and lung, risk factors such as periodontal disease and smoking may contribute to autoimmunity by driving the local generation of citrullinated autoantigens. A break in immune tolerance could lead to localized and then systemic autoimmunity, a hypothesis compatible with an etiological model for anti-citrullinated protein antibody (ACPA) positive RA. At the gut mucosa, the composition of the intestinal microbiome is central to local immune regulation. Here, there is evidence from animal models that alteration of the local microbiome can influence the balance of pro- and anti-inflammatory T cells and promote the development of autoimmune disease. In this review, we discuss the evidence for localized mucosal autoimmunity in those with preclinical and early RA. Autoimmunity at the oral mucosa, lung, and gut will be considered as potential initiating sites of RA-related autoimmunity.

  9. Impact of Microbes on Autoimmune Diseases

    PubMed Central

    Danzer, Claudia

    2014-01-01

    Autoimmune and autoinflammatory diseases arise as a consequence of complex interactions of environmental factors with genetic traits. Although specific allelic variations cluster in predisposed individuals and promote the generation and/or expansion of autoreactive T and B lymphocytes, auto-immunity appears in various disease phenotypes and localizes to diverging tissues. Furthermore, the discovery that allelic variations within genes encoding components of the innate immune system drive self-reactive immune responses as well, led to the distinction of immune responses against host tissues into auto-immune and autoinflammatory diseases. In both categories of disorders, different pathogenic mechanisms and/or subsequent orders of tissue assaults may underlie the target cell specificity of the respective autoimmune attack. Furthermore, the transition from the initial tissue assault to the development of full-blown disease is likely driven by several factors. Thus, the development of specific forms of autoimmunity and autoinflammation reflects a multi-factorial process. The delineation of the specific factors involved in the pathogenic process is hampered by the fact that certain symptoms are assembled under the umbrella of a specific disease, although they might originate from diverging pathogenic pathways. These multi-factorial triggers and pathogenic pathways may also explain the inter-individual divergent courses and outcomes of diseases among humans. Here, we will discuss the impact of different environmental factors in general and microbial pathogens in particular on the regulation/ expression of genes encoded within susceptibility alleles, and its consequences on subsequent autoimmune and/or autoinflammatory tissue damage utilizing primarily the chronic cholestatic liver disease primary biliary cirrhosis as model. PMID:23417246

  10. Myocardial Infarction Triggers Chronic Cardiac Autoimmunity in Type 1 Diabetes

    PubMed Central

    Gottumukkala, Raju V.; Lv, HuiJuan; Cornivelli, Lizbeth; Wagers, Amy J.; Kwong, Raymond Y.; Bronson, Roderick; Stewart, Garrick C.; Schulze, P. Christian; Chutkow, William; Wolpert, Howard A.; Lee, Richard T.; Lipes, Myra A.

    2015-01-01

    Patients with type 1 diabetes (T1D) suffer excessive morbidity and mortality following myocardial infarction (MI) that is not fully explained by the metabolic effects of diabetes. Acute MI is known to trigger a profound innate inflammatory response with influx of mononuclear cells and production of proinflammatory cytokines that are crucial for cardiac repair. We hypothesized that these same pathways might exert ‘adjuvant effects’ and induce pathological responses in autoimmune-prone T1D hosts. Here we show that experimental MI in nonobese diabetic (NOD) mice - but not in control C57BL/6 mice - results in a severe post-infarction autoimmune (PIA) syndrome characterized by destructive lymphocytic infiltrates in the myocardium, infarct expansion, sustained cardiac IgG autoantibody production and Th1 effector cell responses against cardiac (α-)myosin. PIA was prevented by inducing tolerance to α-myosin, demonstrating that immune responses to cardiac myosin are required for this disease process. Extending these findings to humans, we developed a panel of immunoassays for cardiac autoantibody detection and found autoantibody positivity in 83% post-MI T1D patients. We further identified shared cardiac myosin autoantibody signatures between post-MI T1D patients and non-diabetic patients with myocarditis – that were absent in post-MI type 2 diabetic patients - and confirmed the presence of myocarditis in T1D by cardiac magnetic resonance imaging techniques. These data provide experimental and clinical evidence for a distinct post-MI autoimmune syndrome in T1D. Our findings suggest that PIA may contribute to worsened post-MI outcomes in T1D, and highlight a role for antigen-specific immunointervention to selectively block this pathway. PMID:22700956

  11. Celiac Disease-Associated Autoimmune Endocrinopathies

    PubMed Central

    Kumar, Vijay; Rajadhyaksha, Manoj; Wortsman, Jacobo

    2001-01-01

    Celiac disease (CD) is an autoimmune disorder induced by gluten intake in genetically susceptible individuals. It is characterized by the presence of serum antibodies to endomysium, reticulin, gliadin, and tissue transglutaminase. The incidence of CD in various autoimmune disorders is increased 10- to 30-fold in comparison to the general population, although in many cases CD is clinically asymptomatic or silent. The identification of such cases with CD is important since it may help in the control of type I diabetes or endocrine functions in general, as well as in the prevention of long-term complications of CD, such as lymphoma. It is believed that CD may predispose an individual to other autoimmune disorders such as type I diabetes, autoimmune thyroid, and other endocrine diseases and that gluten may be a possible trigger. The onset of type I diabetes at an early age in patients with CD, compared to non-CD, and the prevention or delay in onset of diabetes by gluten-free diet in genetically predisposed individuals substantiates this antigen trigger hypothesis. Early identification of CD patients in highly susceptible population may result in the treatment of subclinical CD and improved control of associated disorders. PMID:11427410

  12. Occupational exposures and autoimmune diseases.

    PubMed

    Cooper, Glinda S; Miller, Frederick W; Germolec, Dori R

    2002-02-01

    Autoimmune diseases are pathologic conditions defined by abnormal autoimmune responses and characterized by immune system reactivity in the form of autoantibodies and T cell responses to self-structures. Here we review the limited but growing epidemiologic and experimental literature pertaining to the association between autoimmune diseases and occupational exposure to silica, solvents, pesticides, and ultraviolet radiation. The strongest associations (i.e., relative risks of 3.0 and higher) have been documented in investigations of silica dust and rheumatoid arthritis, lupus, scleroderma and glomerulonephritis. Weaker associations are seen, however, for solvent exposures (in scleroderma, undifferentiated connective tissue disease, and multiple sclerosis) and for farming or pesticide exposures (in rheumatoid arthritis). Experimental studies suggest two different effects of these exposures: an enhanced proinflammatory (TH1) response (e.g., TNF-alpha and IL-1 cytokine production with T cell activation), and increased apoptosis of lymphocytes leading to exposure to or modification of endogenous proteins and subsequent autoantibody formation. The former is a general mechanism that may be relevant across a spectrum of autoimmune diseases, whereas the latter may be a mechanism more specific to particular diseases (e.g., ultraviolet radiation, Ro autoantibodies, and lupus). Occupational exposures are important risk factors for some autoimmune diseases, but improved exposure assessment methods and better coordination between experimental/animal models and epidemiologic studies are needed to define these risks more precisely.

  13. The etiology of autoimmune diseases: the case of myasthenia gravis.

    PubMed

    Bach, Jean-François

    2012-12-01

    Autoimmune diseases comprise a wide variety of disorders, from those that are acute and spontaneously regressive to chronic diseases. Their occurrence is the sign of a loss of tolerance to self-antigens. With few exceptions, the etiology of autoimmune diseases has not been clearly established. In all cases, it is complex, involving genetic, epigenetic, and environmental factors. In this article I will attempt to analyze the various factors that have a triggering or protecting role, with particular reference to myasthenia gravis.

  14. 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.

  15. The Histone Modification Code in the Pathogenesis of Autoimmune Diseases

    PubMed Central

    2017-01-01

    Autoimmune diseases are chronic inflammatory disorders caused by a loss of self-tolerance, which is characterized by the appearance of autoantibodies and/or autoreactive lymphocytes and the impaired suppressive function of regulatory T cells. The pathogenesis of autoimmune diseases is extremely complex and remains largely unknown. Recent advances indicate that environmental factors trigger autoimmune diseases in genetically predisposed individuals. In addition, accumulating results have indicated a potential role of epigenetic mechanisms, such as histone modifications, in the development of autoimmune diseases. Histone modifications regulate the chromatin states and gene transcription without any change in the DNA sequence, possibly resulting in phenotype alteration in several different cell types. In this paper, we discuss the significant roles of histone modifications involved in the pathogenesis of autoimmune diseases, including rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, primary biliary cirrhosis, and type 1 diabetes. PMID:28127155

  16. B cell epitope spreading: mechanisms and contribution to autoimmune diseases.

    PubMed

    Cornaby, Caleb; Gibbons, Lauren; Mayhew, Vera; Sloan, Chad S; Welling, Andrew; Poole, Brian D

    2015-01-01

    While a variety of factors act to trigger or initiate autoimmune diseases, the process of epitope spreading is an important contributor in their development. Epitope spreading is a diversification of the epitopes recognized by the immune system. This process happens to both T and B cells, with this review focusing on B cells. Such spreading can progress among multiple epitopes on a single antigen, or from one antigenic molecule to another. Systemic lupus erythematosus, multiple sclerosis, pemphigus, bullous pemphigoid and other autoimmune diseases, are all influenced by intermolecular and intramolecular B cell epitope spreading. Endocytic processing, antigen presentation, and somatic hypermutation act as molecular mechanisms that assist in driving epitope spreading and broadening the immune response in autoimmune diseases. The purpose of this review is to summarize our current understanding of B cell epitope spreading with regard to autoimmunity, how it contributes during the progression of various autoimmune diseases, and treatment options available.

  17. 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

  18. 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.

  19. [Narcolepsy as an autoimmune disease].

    PubMed

    Sarkanen, Tomi; Vaarala, Outi; Julkunen, Ilkka; Partinen, Markku

    2015-01-01

    Narcolepsy is a sleep disorder of central origin. Hypocretin deficiency is the essential feature of type 1 narcolepsy. The biological background of type 2 narcolepsy (without cataplexy) is less clear. Infections or other external factors are thought to function as triggers of narcolepsy. After the H1N1 vaccination campaign, the incidence of narcolepsy increased clearly in countries where a vaccine boosted with the AS03 adjuvant was used. According to the current view, the increase of narcolepsy in connection with the pandemic vaccine especially in children and adolescents was associated with the virus component of the vaccine, but the adjuvant may also have boosted the development of autoimmune response.

  20. Autoimmune hepatitis: a classic autoimmune liver disease.

    PubMed

    Moy, Libia; Levine, Jeremiah

    2014-12-01

    AIH is characterized by chronic inflammation of the liver, interface hepatitis, hypergammaglobulinemia, and production of autoantibodies. Based on the nature of the serum autoantibodies, two types of AIH are recognized: type 1 (AIH-1), positive for ANA and/or anti-smooth muscle antibody, and type 2 (AIH-2), defined by the positivity for anti-liver kidney microsomal type 1 antibody or for anti-liver cytosol type 1 antibody. AIH demonstrates a female preponderance with the female-to-male ratio of 4:1 in AIH-1 and 10:1 in AIH-2. Several genes confer susceptibility to AIH and influence clinical manifestation, response to treatment, and overall prognosis. Most are located within the human leukocyte antigen (HLA) region, which is involved in the presentation of antigenic peptides to T cells and thus in the initiation of adaptive immune responses. The strongest associations are found within the HLA-DRB1 locus. In patients with increased genetic susceptibility to AIH, immune responses to liver autoantigens could be triggered by molecular mimicry. Because of molecular mimicry, different environmental agents, drugs, and viruses might produce AIH. In AIH, T cells are numerically and functionally impaired, permitting the perpetuation of effector immune responses with ensuing persistent liver destruction. AIH is rare but highly treatable inflammatory condition of the liver. Subclinical and asymptomatic disease is common. AIH therefore needs to be considered in the differential diagnosis of all patients with elevated liver enzymes. Clinical response to immunosuppressive therapy is characteristic and supports the diagnosis.

  1. Rheumatic manifestations of autoimmune thyroid disease: the other autoimmune disease.

    PubMed

    Tagoe, Clement E; Zezon, Anna; Khattri, Saakshi

    2012-06-01

    Autoimmune thyroid disease (AITD) is an inflammatory thyroiditis that in some cases is characterized by lymphocytic infiltration of the thyroid gland, also referred to as chronic lymphocytic thyroiditis or Hashimoto thyroiditis. Hashimoto thyroiditis is one of the commonest causes of hypothyroidism. Hypothyroidism has been associated with osteoarthritis (OA) and inflammatory forms of arthritis and with several well defined connective tissue diseases, which in turn can cause arthritis. The presence of arthritis in patients with AITD with normal thyroid function is now being increasingly recognized. There is also considerable evidence to suggest that AITD is highly associated with fibromyalgia syndrome. We review the current literature on the rheumatologic manifestations of AITD and describe the features in its presentation that set it apart from other forms of autoimmune arthritis.

  2. Autoantibody testing for autoimmune disease.

    PubMed

    Self, Sally E

    2010-09-01

    The proper use and interpretation of serologic testing for diagnosing autoimmune diseases presents a challenge to clinicians for several reasons. Most laboratory tests for autoimmune disease are significantly less than 100% sensitive or specific. In addition, different techniques for the same antibody test may give different results, such as indirect immunofluorescence and multiplex bead assay for antinuclear antibody. Autoantibody testing should only be performed in the context of the clinical workup of patients who have a reasonable likelihood of having the disease for which the testing is relevant. Otherwise, the predictive value of a positive test is too low. Particularly with antinuclear antibody and antineutrophil cytoplasmic antibody testing, clinicians must know the methodology through which the tests are being performed, and should develop a relationship with the laboratory pathologist so that inconsistent or surprising results can be investigated.

  3. [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.

  4. Multiple autoimmune syndrome with celiac disease.

    PubMed

    Harpreet, Singh; Deepak, Jain; Kiran, B

    2016-01-01

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

  5. Multiple autoimmune syndrome with celiac disease

    PubMed Central

    Harpreet, Singh; Kiran, B.

    2016-01-01

    Multiple autoimmune syndrome (MAS) is a condition characterised by three or more autoimmune disorders in a same individual. Familial, immunologic and infectious factors are implicated in the development of MAS. Here we report a case of a 32-year-old woman with co-existence of four auto-immune diseases, namely autoimmune hypothyroidism, Sjögren’s syndrome, systemic lupus erythematosus (SLE) and celiac disease which leads to the final diagnosis of multiple autoimmune syndrome type 3 with celiac disease. Patients with single autoimmune disorder are at 25% risk of developing other autoimmune disorders. The present case emphasises to clinicians that there is a need for continued surveillance for the development of new autoimmune disease in predisposed patients. PMID:28115785

  6. Autoimmune diseases and HIV infection

    PubMed Central

    Virot, Emilie; Duclos, Antoine; Adelaide, Leopold; Miailhes, Patrick; Hot, Arnaud; Ferry, Tristan; Seve, Pascal

    2017-01-01

    Abstract To describe the clinical manifestations, treatments, prognosis, and prevalence of autoimmune diseases (ADs) in human immunodeficiency virus (HIV)-infected patients. All HIV-infected patients managed in the Infectious Diseases Department of the Lyon University Hospitals, France, between January 2003 and December 2013 and presenting an AD were retrospectively included. Thirty-six ADs were found among 5186 HIV-infected patients which represents a prevalence of 0.69% including immune thrombocytopenic purpura (n = 15), inflammatory myositis (IM) (n = 4), sarcoidosis (n = 4), Guillain–Barré syndrome (GBS) (n = 4), myasthenia gravis (n = 2), Graves’ disease (n = 2), and 1 case of each following conditions: systemic lupus erythematosus, rheumatoid arthritis, autoimmune hepatitis, Hashimoto thyroiditis and autoimmune hemolytic anemia. One patient presented 2 ADs. Thirty patients were known to be HIV-infected when they developed an AD. The AD preceded HIV infection in 2 patients. GBS and HIV infection were diagnosed simultaneously in 3 cases. At AD diagnosis, CD4 T lymphocytes count were higher than 350/mm3 in 63% of patients, between 200 and 350/mm3 in 19% and less than 200/mm3 in 19%. Twenty patients benefited from immunosuppressant treatments, with a good tolerance. ADs during HIV infection are uncommon in this large French cohort. Immune thrombocytopenic purpura, sarcoidosis, IM, and GBS appear to be more frequent than in the general population. Immunosuppressant treatments seem to be effective and well tolerated. PMID:28121924

  7. 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 - 2017. American Autoimmune Related Diseases Association, ...

  8. 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

  9. Silica-Triggered Autoimmunity in Lupus-Prone Mice Blocked by Docosahexaenoic Acid Consumption

    PubMed Central

    Bates, Melissa A.; Brandenberger, Christina; Langohr, Ingeborg I.; Kumagai, Kazuyoshi; Lock, Adam L.; Harkema, Jack R.; Holian, Andrij; Pestka, James J.

    2016-01-01

    Occupational exposure to respirable crystalline silica (cSiO2, quartz) is etiologically linked to systemic lupus erythematosus (lupus) and other human autoimmune diseases (ADs). In the female NZBWF1 mouse, a widely used animal model that is genetically prone to lupus, short-term repeated intranasal exposure to cSiO2 triggers premature initiation of autoimmune responses in the lungs and kidneys. In contrast to cSiO2’s triggering action, consumption of the ω-3 polyunsaturated fatty acid docosahexaenoic acid (DHA) prevents spontaneous onset of autoimmunity in this mouse strain. The aim of this study was to test the hypothesis that consumption of DHA will prevent cSiO2-triggered autoimmunity in the female NZBWF1 mouse. Mice (6 wk old) were fed isocaloric AIN-93G diets containing 0.0, 0.4, 1.2 or 2.4% DHA. Two wk after initiating feeding, mice were intranasally instilled with 1 mg cSiO2 once per wk for 4 wk and maintained on experimental diets for an additional 12 wk. Mice were then sacrificed and the lung, blood and kidney assessed for markers of inflammation and autoimmunity. DHA was incorporated into lung, red blood cells and kidney from diet in a concentration-dependent fashion. Dietary DHA dose-dependently suppressed cSiO2-triggered perivascular leukocyte infiltration and ectopic lymphoid tissue neogenesis in the lung. DHA consumption concurrently inhibited cSiO2–driven elevation of proinflammatory cytokines, B-cell proliferation factors, IgG and anti-dsDNA Ig in both bronchoalveolar lavage fluid and plasma. DHA’s prophylactic effects were further mirrored in reduced proteinuria and glomerulonephritis in cSiO2-treated mice. Taken together, these results reveal that DHA consumption suppresses cSiO2 triggering of autoimmunity in female NZBWF1 mice as manifested in the lung, blood and kidney. Our findings provide novel insight into how dietary modulation of the lipidome might be used to prevent or delay triggering of AD by cSiO2. Such knowledge opens the

  10. Vitamin D in autoimmune liver disease.

    PubMed

    Smyk, Daniel S; Orfanidou, Timoklia; Invernizzi, Pietro; Bogdanos, Dimitrios P; Lenzi, Marco

    2013-11-01

    The development of autoimmune disease is based on the interaction of genetic susceptibility and environmental causes. Environmental factors include infectious and non-infectious agents, with some of these factors being implicated in several autoimmune diseases. Vitamin D is now believed to play a role in the development (or prevention) of several autoimmune diseases, based on its immunomodulatory properties. As well, the increasing incidence of autoimmune disease as one moves away from the equator, may be due to the lack of sunlight, which is crucial for the maintenance of normal vitamin D levels. A deficiency in vitamin D levels or vitamin D receptors is commonly indicated in autoimmune diseases, with multiple sclerosis (MS) being one of the best-studied and well-known examples. However, the role of vitamin D in other autoimmune diseases is not well defined, including autoimmune liver diseases such as primary biliary cirrhosis, autoimmune hepatitis, and primary sclerosing cholangitis. This review will examine the role of vitamin D as an immunomodulator, followed by a comparison of vitamin D in MS versus autoimmune liver disease. From this comparison, it will become clear that vitamin D likely plays a role in the development of autoimmune liver disease, but this area requires further investigation.

  11. Viral connection between drug rashes and autoimmune diseases: how autoimmune responses are generated after resolution of drug rashes.

    PubMed

    Aota, Noriko; Shiohara, Tetsuo

    2009-05-01

    Viral infections are most likely triggering factors of autoimmune diseases, although a single vial infection is not sufficient to cause clinically evident autoimmune diseases. Any disease that profoundly alters the immune system may cause perturbed viral infections, thereby rendering otherwise refractory patients susceptible to autoimmune diseases. In this regard, drug-induced hypersensitivity syndrome (DIHS), a drug rash characterized by sequential reactivations of herpesviruses and the subsequent development of autoimmune diseases, offers a unique opportunity to investigate the mechanism of how autoimmunity is elicited after viral infections. Indeed, several autoimmune diseases have been reported to occur at intervals of several months to years after clinical resolution of DIHS. Two representative cases who developed autoimmune diseases three to four years after DIHS are shown. Our recent analyses of the kinetics of a developing disease have shown that fully functional FoxP3(+) regulatory T (Treg) cells are expanded at the acute stage thereby allowing viral reactivations but lose their suppressive function coincident with their contraction upon clinical resolution. The functional defect of Treg cells would be responsible for the subsequent development of autoimmune diseases. Patients with DIHS need close monitoring because of possible progression to autoimmune diseases even after the complete resolution.

  12. Sex-based differences in autoimmune diseases.

    PubMed

    Ortona, Elena; Pierdominici, Marina; Maselli, Angela; Veroni, Caterina; Aloisi, Francesca; Shoenfeld, Yehuda

    2016-01-01

    Autoimmune diseases are characterized by an exaggerated immune response leading to damage and dysfunction of specific or multiple organs and tissues. Most autoimmune diseases are more prevalent in women than in men. Symptom severity, disease course, response to therapy and overall survival may also differ between males and females with autoimmune diseases. Sex hormones have a crucial role in this sex bias, with estrogens being potent stimulators of autoimmunity and androgens playing a protective role. Accumulating evidence indicates that genetic, epigenetic and environmental factors may also contribute to sex-related differences in risk and clinical course of autoimmune diseases. In this review, we discuss possible mechanisms for sex specific differences in autoimmunity with a special focus on three paradigmatic diseases: systemic lupus erythematosus, rheumatoid arthritis, and multiple sclerosis.

  13. Role of leptin in autoimmune diseases.

    PubMed

    Cojocaru, Manole; Cojocaru, Inimioara Mihaela; Siloşi, Isabela; Rogoz, Suzana

    2013-03-01

    Leptin represents a link between metabolism, nutritional status, and immune responses. Leptin is important for optimal functioning of the immune system. Leptin is a cytokine-like hormone with proinflammatory properties linked to autoimmune diseases. Moreover, there has been increasing evidence that leptin is involved in the pathogenesis of various autoimmune diseases. Leptin has been shown to enhance immune reactions in autoimmune diseases that are commonly associated with inflammatory responses. Both high and low levels of leptin might contribute to autoimmune diseases. Leptin has been explored as a potential target for therapeutic development in treating autoimmune diseases. In this review, we review here the most recent advances on the role of leptin in autoimmunity and in immune-rheumatological diseases.

  14. Refractory disease in autoimmune diseases.

    PubMed

    Vasconcelos, Carlos; Kallenberg, Cees; Shoenfeld, Yehuda

    2011-09-01

    Refractory disease (RD) definition has different meanings but it is dynamic, according to knowledge and the availability of new drugs. It should be differentiated from severe disease and damage definitions and it must take into account duration of adequate therapy and compliance of the patient. It can be related to inadequate or inefficacious treatment or to pathogenesis. RD definition has multiple implications to clinical guidelines and to the use of off-label drugs. It should not be regarded as lost cases and prospective studies, registries and clinical trials should be planned.

  15. [Role of hepatitis A and E viruses in the development of autoimmune diseases].

    PubMed

    Iakimchuk, K S; Malinnikova, E Iu; Poleshchuk, V F; Mikhaĭlov, M I

    2011-01-01

    The mechanisms of development of autoimmune diseases may be associated with a complex of genetic, immune, hormonal, and infectious factors. Autoimmune diseases include a wide range of systemic and organ-specific diseases, including autoimmune hepatitis (AIH). It is currently assumed that the pathogenesis of AIH is due to compromised immune regulation in the presence of an exogenous triggering factor. Exogenous factors, such as viruses, may be triggers of AIH. There may be different ways of initiating an autoimmune response by viruses, which includes nonspecific T-lymphocyte activation and molecular mimicry. There is much evidence supporting the initiating role of hepatitis viruses in the development of AIH and other autoimmune diseases. The development of AIH symptoms during hepatitis A and E virus infections has been described elsewhere. The creation of animal models of viral hepatitis is required to confirm the hypothesis that the viruses trigger the development of AIH and other autoimmune manifestations.

  16. Idiopathic Membranous Nephropathy: An Autoimmune Disease

    PubMed Central

    Makker, Sudesh P.; Tramontano, Alfonso

    2011-01-01

    Summary For more than 50 years researchers have debated the evidence for an autoimmune basis of human idiopathic membranous nephritis (MN). Work published in the past 2 years has substantially strengthened the belief that MN is indeed an autoimmune disease of the kidney. Autoantibodies of the IgG4 subclass to at least three podocyte membrane proteins including phospholipase A2-receptor, aldose reductase, and manganese superoxide dismutase have been detected by immunoblotting in sera as well as in acid eluates prepared from renal biopsy tissue of patients with this disease, using either whole tissue or microdissected glomeruli from frozen sections. In each case the podocyte antigen has been shown to co-localize with the subepithelial glomerular immune deposits in renal tissue of the same patients. It is not certain if any of these podocyte proteins is an inciting/primary autoantigen or whether they are secondary antigens recruited by intermolecular epitope-spreading, initiating from a yet-to-be-discovered autoantigen. Although it is clear that autoantibodies to podocyte membrane proteins are elicited in idiopathic MN and contribute to the formation of the subepithelial deposits, many questions remain concerning the triggers for their development and their contribution toward proteinuria and progression of the disease. PMID:21839366

  17. Idiopathic membranous nephropathy: an autoimmune disease.

    PubMed

    Makker, Sudesh P; Tramontano, Alfonso

    2011-07-01

    For more than 50 years researchers have debated the evidence for an autoimmune basis of human idiopathic membranous nephritis (MN). Work published in the past 2 years has substantially strengthened the belief that MN is indeed an autoimmune disease of the kidney. Autoantibodies of the IgG4 subclass to at least three podocyte membrane proteins including phospholipase A(2)-receptor, aldose reductase, and manganese superoxide dismutase have been detected by immunoblotting in sera as well as in acid eluates prepared from renal biopsy tissue of patients with this disease, using either whole tissue or microdissected glomeruli from frozen sections. In each case the podocyte antigen has been shown to co-localize with the subepithelial glomerular immune deposits in renal tissue of the same patients. It is not certain if any of these podocyte proteins is an inciting/primary autoantigen or whether they are secondary antigens recruited by intermolecular epitope-spreading, initiating from a yet-to-be-discovered autoantigen. Although it is clear that autoantibodies to podocyte membrane proteins are elicited in idiopathic MN and contribute to the formation of the subepithelial deposits, many questions remain concerning the triggers for their development and their contribution toward proteinuria and progression of the disease.

  18. 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.

  19. 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.

  20. Is Grover's disease an autoimmune dermatosis?

    PubMed

    Phillips, Courtney; Kalantari-Dehaghi, Mina; Marchenko, Steve; Chernyavsky, Alex I; Galitovskiy, Valentin; Gindi, Vivian; Chun, Sookhee; Paslin, David; Grando, Sergei A

    2013-12-01

    Grover's disease (GD) is a transient or persistent, monomorphous, papulovesicular, asymptomatic or pruritic eruption classified as non-familial acantholytic disorder. Contribution of autoimmune mechanisms to GD pathogenesis remains controversial. The purpose of this study was to investigate antibody-mediated autoimmunity in 11 patients with GD, 4 of which were positive for IgA and/or IgG antikeratinocyte antibodies by indirect immunofluorescence. We used the most sensitive proteomic technique for an unbiased analysis of IgA- and IgG-autoantibody reactivities. Multiplex analysis of autoantibody responses revealed autoreactivity of all 11 GD patients with cellular proteins involved in the signal transduction events regulating cell development, activation, growth, death, adhesion and motility. Semiquantitative fluorescence analysis of cultured keratinocytes pretreated with sera from each patient demonstrated decreased intensity of staining for desmoglein 1 and/or 3 and PCNA, whereas 4 of 10 GD sera induced BAD expression, indicating that binding of autoantibodies to keratinocytes alters expression/function of their adhesion molecules and activates apoptosis. We also tested the ability of GD sera to induce visible alterations of keratinocyte shape and motility in vitro but found no specific changes. Thus, our results demonstrated that humoral autoimmunity in GD can be mediated by both IgA and IgG autoantibodies. At this point, however, it is impossible to conclude whether these autoantibodies cause or are caused by the disease. Antidesmoglein antibodies may be triggered by exposure to immune system of sequestered antigens due to disintegration of desmosomes during primary acantholysis. Clarifying aetiology of GD will help improve treatment, which currently is symptomatic and of marginal effectiveness.

  1. GM-CSF alters dendritic cells in autoimmune diseases.

    PubMed

    Li, Bao-Zhu; Ye, Qian-Ling; Xu, Wang-Dong; Li, Jie-Hua; Ye, Dong-Qing; Xu, Yuekang

    2013-11-01

    Autoimmune diseases arise from an inappropriate immune response against self components, including macromolecules, cells, tissues, organs etc. They are often triggered or accompanied by inflammation, during which the levels of granulocyte macrophage colony-stimulating factor (GM-CSF) are elevated. GM-CSF is an inflammatory cytokine that has profound impact on the differentiation of immune system cells of myeloid lineage, especially dendritic cells (DCs) that play critical roles in immune initiation and tolerance, and is involved in the pathogenesis of autoimmune diseases. Although GM-CSF was discovered decades ago, recent studies with some new findings have shed an interesting light on the old hematopoietic growth factor. In the inflammatory autoimmune diseases, GM-CSF redirects the normal developmental pathway of DCs, conditions their antigen presentation capacities and endows them with unique cytokine signatures to affect autoimmune responses. Here we review the latest advances in the field, with the aim of demonstrating the effects of GM-CSF on DCs and their influences on autoimmune diseases. The summarized knowledge will help to design DC-based strategies for the treatment of autoimmune diseases.

  2. 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

  3. Herpes simplex virus encephalitis is a trigger of brain autoimmunity.

    PubMed

    Armangue, Thaís; Leypoldt, Frank; Málaga, Ignacio; Raspall-Chaure, Miquel; Marti, Itxaso; Nichter, Charles; Pugh, John; Vicente-Rasoamalala, Monica; Lafuente-Hidalgo, Miguel; Macaya, Alfons; Ke, Michael; Titulaer, Maarten J; Höftberger, Romana; Sheriff, Heather; Glaser, Carol; Dalmau, Josep

    2014-02-01

    In 5 prospectively diagnosed patients with relapsing post-herpes simplex encephalitis (HSE), N-methyl-D-aspartate receptor (NMDAR) antibodies were identified. Antibody synthesis started 1 to 4 weeks after HSE, preceding the neurological relapse. Three of 5 patients improved postimmunotherapy, 1 spontaneously, and 1 has started to improve. Two additional patients with NMDAR antibodies, 9 with unknown neuronal surface antibodies, and 1 with NMDAR and unknown antibodies, were identified during retrospective assessment of 34 HSE patients; the frequency of autoantibodies increased over time (serum, p=0.004; cerebrospinal fluid, p=0.04). The 3 retrospectively identified NMDAR antibody-positive patients also had evidence of relapsing post-HSE. Overall, these findings indicate that HSE triggers NMDAR antibodies and potentially other brain autoimmunity.

  4. Vitiligo: How do oxidative stress-induced autoantigens trigger autoimmunity?

    PubMed

    Xie, Heng; Zhou, Fubo; Liu, Ling; Zhu, Guannan; Li, Qiang; Li, Chunying; Gao, Tianwen

    2016-01-01

    Vitiligo is a common depigmentation disorder characterized by a loss of functional melanocytes and melanin from epidermis, in which the autoantigens and subsequent autoimmunity caused by oxidative stress play significant roles according to hypotheses. Various factors lead to reactive oxygen species (ROS) overproduction in the melanocytes of vitiligo: the exogenous and endogenous stimuli that cause ROS production, low levels of enzymatic and non-enzymatic antioxidants, disturbed antioxidant pathways and polymorphisms of ROS-associated genes. These factors synergistically contribute to the accumulation of ROS in melanocytes, finally leading to melanocyte damage and the production of autoantigens through the following ways: apoptosis, accumulation of misfolded peptides and cytokines induced by endoplasmic reticulum stress as well as the sustained unfolded protein response, and an 'eat me' signal for phagocytic cells triggered by calreticulin. Subsequently, autoantigens presentation and dendritic cells maturation occurred mediated by the release of antigen-containing exosomes, adenosine triphosphate and melanosomal autophagy. With the involvement of inducible heat shock protein 70, cellular immunity targeting autoantigens takes the essential place in the destruction of melanocytes, which eventually results in vitiligo. Several treatments, such as narrow band ultraviolet, quercetin and α-melanophore-stimulating hormone, are reported to be able to lower ROS thereby achieving repigmentation in vitiligo. In therapies targeting autoimmunity, restore of regulatory T cells is absorbing attention, in which narrow band ultraviolet also plays a role.

  5. Kaleidoscope of autoimmune diseases in HIV infection.

    PubMed

    Roszkiewicz, Justyna; Smolewska, Elzbieta

    2016-11-01

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

  6. 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.

  7. Th17 cells in autoimmune diseases.

    PubMed

    Han, Lei; Yang, Jing; Wang, Xiuwen; Li, Dan; Lv, Ling; Li, Bin

    2015-03-01

    Th17 cells are a new subset of CD4(+) T cells involved in the clearance of extracellular pathogens and fungi. Accumulating evidence suggests that Th17 cells and their signature cytokines have a pivotal role in the pathogenesis of multiple autoimmune-mediated inflammatory diseases. Here, we summarize recent research progress on Th17 function in the development and pathogenesis of autoimmune diseases. We also propose to identify new small molecule compounds to manipulate Th17 function for potential therapeutic application to treat human autoimmune diseases, including rheumatoid arthritis, systemic lupus erythematosus, Sjögren's syndrome, inflammatory bowel disease, and multiple sclerosis.

  8. Prolactin and autoimmune diseases in humans.

    PubMed

    Chuang, Ellie; Molitch, Mark E

    2007-01-01

    Prolactin has been shown to have immunomodulatory as well as lactogenic effects. Generally less well known is that prolactin may also play a role in the activity of autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis. Studies have shown decreasing prolactin production to be beneficial in animal models of autoimmune disease. Thus far, double-blinded, placebo-controlled studies of dopamine agonist treatment in humans with autoimmune disease have been done only in lupus patients, and support the potential efficacy of such agents. Small, open-label trials have also suggested potential benefit in patients with rheumatoid arthritis, Reiter's syndrome, and psoriasis. More studies are required to further delineate the mechanisms by which prolactin affects autoimmune disease activity, to determine in which specific diseases prolactin plays a significant role, and to test the efficacy of prolactin-lowering agents as therapy for such diseases.

  9. Gastrointestinal Manifestations in Systemic Autoimmune Diseases

    PubMed Central

    COJOCARU, M.; COJOCARU, Inimioara Mihaela; SILOSI, Isabela; VRABIE, Camelia Doina

    2011-01-01

    ABSTRACT In an autoimmune disease, the immune system attacks and harms the body's own tissues. The systemic autoimmune diseases include collagen vascular diseases, the systemic vasculitides, Wegener granulomatosis, and Churg-Strauss syndrome. These disorders can involve any part of the gastrointestinal tract, hepatobiliary system and pancreas. They can cause a variety of gastrointestinal manifestations that are influenced by the pathophysiologic characteristics of the underlying disease process. There is a wide variation of gastrointestinal manifestations from these autoimmune disorders including, but not limited to: oral ulcers, dysphagia, gastroesophageal reflux disease, abdominal pain, constipation, diarrhea, fecal incontinence, pseudo-obstruction, perforation and gastrointestinal bleeding. Clinical workup should be initiated by the patient's subjective complaints. In this review, we analyze the effects of autoimmune diseases on the gastrointestinal tract. PMID:21977190

  10. [Hematopoietic stem cell transplantation in autoimmune diseases].

    PubMed

    Albarracín, Flavio; López Meiller, María José; Naswetter, Gustavo; Longoni, Héctor

    2008-01-01

    Transplantation of hematopoietic stem cells, which are capable of self renewal and reconstitution of all types of blood cells, can be a treatment for numerous potential lethal diseases, including leukemias and lymphomas. It may now be applicable for the treatment of severe autoimmune diseases, such as therapy-resistant multiple sclerosis, lupus and systemic sclerosis. Studies in animal models show that the transfer of hematopoietic stem cells can reverse autoimmunity. The outcome of ongoing clinical trials, as well as of studies in patients and animal models, will help to determine the role that stem-cell transplantation can play in the treatment of autoimmune diseases.

  11. Autoimmune liver disease: novelties in management.

    PubMed

    Hadzic, Nedim; Hierro, Loreto

    2014-06-01

    Autoimmune liver disease is the second commonest cause of chronic liver disease in teenagers. There are several forms including autoimmune hepatitis, autoimmune sclerosing cholangitis, primary sclerosing cholangitis and various overlap syndromes, classified on the basis of different serum antibody profiles, histological features and appearances on cholangiography. Treatment with immunosupressants is usually effective, but often required medium to long-term, raising concerns about side effects and adherence to therapy. For a minority of children presenting in acute liver failure or with difficult-to-treat disease liver transplantation is a possible option, although risk of recurrence in the grafted liver remains lifelong.

  12. Autoimmune blistering dermatoses as systemic diseases.

    PubMed

    Vassileva, Snejina; Drenovska, Kossara; Manuelyan, Karen

    2014-01-01

    Autoimmune blistering dermatoses are examples of skin-specific autoimmune disorders that can sometimes represent the cutaneous manifestation of a multiorgan disease due to potential common pathogenic mechanisms. As soon as a distinct autoimmune blistering dermatosis is diagnosed, it is imperative to consider its potential systemic involvement, as well as the autoimmune and inflammatory conditions that are frequently associated with it. In paraneoplastic pemphigus/paraneoplastic autoimmune multiorgan syndrome, the internal organs (particularly the lungs) are affected by the autoimmune injury. Pemphigus erythematosus may manifest with overlapping serologic and immunohistologic features of lupus erythematosus. In patients with bullous pemphigoid, there is a greater prevalence of neurologic disease, possibly caused by cross-reactivity of the autoantibodies with isoforms of bullous pemphigoid antigens expressed in the skin and brain. Anti-laminin 332 pemphigoid shows an increased risk for adenocarcinomas. Patients with anti-p200 pemphigoid often suffer from psoriasis. A rare form of pemphigoid with antibodies against the α5 chain of type IV collagen is characterized by underlying nephropathia. Particularly interesting is the association of linear IgA disease or epidermolysis bullosa acquisita with inflammatory bowel disease. Dermatitis herpetiformis is currently regarded as the skin manifestation of gluten sensitivity. Bullous systemic lupus erythematosus is part of the clinical spectrum of systemic lupus erythematosus, a prototypic autoimmune disease with multisystem involvement.

  13. Obstructive sleep apnea and autoimmune rheumatic disease: is there any link?

    PubMed

    Mirrakhimov, Aibek E

    2013-10-01

    The association between autoimmune rheumatic diseases and obstructive sleep apnea (OSA) is complex. Systemic inflammation secondary to OSA may underlie this association. It is possible that OSA-related inflammation may trigger the occurrence of autoimmune rheumatic disease in genetically susceptible individuals. On the other hand, autoimmune rheumatic diseases can lead to OSA or worsen preexisting OSA. Temporomandibular joint destruction, cervical spine subluxation and brainstem compression are the factors responsible for the above observation. Future studies are needed to clarify whether OSA is an independent risk factor for the development of autoimmune disease and whether OSA management will lead to a reduction in the incidence of autoimmune disease. On the other hand, it is important to treat autoimmune rheumatic disease promptly, to reduce the risk of complications, with OSA being one of these.

  14. Shaking Out Clues to Autoimmune Disease

    MedlinePlus

    ... Understanding Autoimmune Diseases Immune Cells References: Nature. 2013 Mar 6. doi: 10.1038/nature11981. [Epub ahead of print]. PMID: 23467089. Nature. 2013 Mar 6. doi: 10.1038/nature11984. [Epub ahead of ...

  15. SIALIC ACIDS AND AUTOIMMUNE DISEASE

    PubMed Central

    Mahajan, Vinay S.; Pillai, Shiv

    2016-01-01

    summary An important underlying mechanism that contributes to autoimmunity is the loss of inhibitory signaling in the immune system. Sialic acid-recognizing Ig superfamily lectins or Siglecs are a family of cell surface proteins largely expressed in hematopoietic cells. The majority of Siglecs are inhibitory receptors expressed in immune cells that bind to sialic acid containing ligands and recruit SH2-domain containing tyrosine phosphatases to their cytoplasmic tails. They deliver inhibitory signals that can contribute to the constraining of immune cells and thus protect the host from autoimmunity. The inhibitory functions of CD22/Siglec-2 and Siglec-G and their contributions to tolerance and autoimmunity, primarily in the B lymphocyte context, are considered in some detail in this review. The relevance to autoimmunity and unregulated inflammation of modified sialic acids, enzymes that modify sialic acid, and other sialic acid binding proteins are also reviewed. PMID:26683151

  16. Autoimmune thyroid disease in patients with rheumatic diseases.

    PubMed

    Robazzi, Teresa Cristina Martins Vicente; Adan, Luis Fernando Fernandes

    2012-01-01

    Thyroid function abnormalities and thyroid autoantibodies have been frequently described in patients with rheumatologic autoimmune diseases, such as Sjögren's syndrome, rheumatoid arthritis, systemic lupus erythematosus and scleroderma. Limited data are available regarding the prevalence and clinical characteristics of autoimmune thyroiditis in other rheumatologic disorders, such as rheumatic fever and juvenile systemic lupus erythematosus. The authors review the association of endocrine autoimmune and rheumatic autoimmune diseases, assessing various age groups and clinical conditions. The bibliographic survey was conducted through the search for scientific articles indexed in the general health sciences databases, such as Latin American and Caribbean Health Sciences Literature (LILACS), Medline/PubMed, and Scientific Electronic Library Online (SciELO). The following descriptors were used: "rheumatic autoimmune diseases and autoimmune thyroid diseases"; "thyroid disorders and rheumatic diseases"; "thyroiditis and rheumatic diseases"; "autoimmune diseases and thyroid"; and "pediatric rheumatic diseases and autoimmune thyroid diseases". This study showed that, despite contradictory results in the literature, there is a greater prevalence of the association between autoimmune thyroid diseases and rheumatic diseases, highlighting the possibility of common pathogenic mechanisms among them.

  17. Vitiligo disease triggers: psychological stressors preceding the onset of disease.

    PubMed

    Silverberg, Jonathan I; Silverberg, Nanette B

    2015-05-01

    Vitiligo is the loss of skin pigmentation caused by autoimmune destruction of melanocytes. Little is known about the impact of psychological stressors preceding vitiligo onset on symptoms associated with vitiligo and the extent of disease. We performed a questionnaire-based study of 1541 adults with vitiligo to evaluate the impact of psychological stressors in this patient population. Psychological stressors should be considered as potential disease triggers in vitiligo patients, and screening of vitiligo patients for psychological stressors and associated symptoms should be included in routine assessment.

  18. [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.

  19. Definition of human autoimmunity--autoantibodies versus autoimmune disease.

    PubMed

    Lleo, Ana; Invernizzi, Pietro; Gao, Bin; Podda, Mauro; Gershwin, M Eric

    2010-03-01

    The critical function of the immune system is to discriminate self from non-self. Tolerance against self-antigens is a highly regulated process and, in order to maintain it, the immune system must be able to distinguish self-reactive lymphocytes as they develop. The presence of autoantibodies is the consequence of breakdown of tolerance and, although they are an important serological feature of autoimmune diseases, their presence is not exclusive of these conditions. Antibodies against self-antigens are also found in cancer, during massive tissue damage and even in healthy subjects. Natural autoantibodies provide immediate protection against infection and also prevent inflammation by facilitating the clearance of oxidized lipids, oxidized proteins, and apoptotic cells; their role in development of autoimmunity is still unclear. Detection of serum autoantibodies in clinical practice has become more available to clinicians worldwide while providing a powerful diagnostic tool. This review discusses the clinical significance of autoantibodies, their pathogenic mechanisms in autoimmune diseases and, finally, illustrates the technology available for appropriate autoantibody detection.

  20. Acute recurrent pancreatitis: An autoimmune disease?

    PubMed Central

    Pezzilli, Raffaele

    2008-01-01

    In this review article, we will briefly describe the main characteristics of autoimmune pancreatitis and then we will concentrate on our aim, namely, evaluating the clinical characteristics of patients having recurrence of pain from the disease. In fact, the open question is to evaluate the possible presence of autoimmune pancreatitis in patients with an undefined etiology of acute pancreatitis and for this reason we carried out a search in the literature in order to explore this issue. In cases of recurrent attacks of pain in patients with “diopathic”pancreatitis, we need to keep in mind the possibility that our patients may have autoimmune pancreatitis. Even though the frequency of this disease seems to be quite low, we believe that in the future, by increasing our knowledge on the subject, we will be able to diagnose an ever-increasing number of patients having acute recurrence of pain from autoimmune pancreatitis. PMID:18286678

  1. 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)

  2. Antibodies as predictors of complex autoimmune diseases.

    PubMed

    Vojdani, A

    2008-01-01

    Emerging evidence has suggested environmental factors such as infections and xenobiotics and some dietary proteins and peptides in the pathogenesis of many autoimmune diseases. Considering the fact that autoantibodies can often be detected prior to the onset of a disease, in this study an enzyme immunoassay was used for measurement of antibodies against different highly purified antigens or synthetic peptides originating not only from human tissue, but also from cross-reactive epitopes of infectious agents, dietary proteins and xenobiotics. The measurement of antibodies against a panel of antigens allows for identification of patterns or antibody signatures, rather than just one or two markers of autoimmunity, thus establishing the premise for increased sensitivity and specificity of prediction, as well as positive predictive values. This panel of different autoantibodies was applied to 420 patients with different autoimmune diseases, including pernicious anemia, celiac disease, thyroiditis, lupus, rheumatoid arthritis, osteoarthritis, Addison's disease, type 1 diabetes, cardiovascular disease and autoimmunity, which are presented in this article. In all cases, the levels of these antibodies were significantly elevated in patients versus controls. Antibody patterns related to neuroautoimmune disorders, cancer, and patients with somatic hypermutation will be shown in a subsequent article. We believe that this novel 96 antigen-specific autoantibody or predictive antibody screen should be studied for its incorporation into routine medical examinations. Clinicians should be aware that the detection of antibodies should not automatically mean that a patient will definitely become ill, but would rather give a percentage of risk for autoimmune disease over subsequent months or years.

  3. Toll-Like Receptor Pathways in Autoimmune Diseases.

    PubMed

    Chen, Ji-Qing; Szodoray, Peter; Zeher, Margit

    2016-02-01

    Autoimmune diseases are a family of chronic systemic inflammatory disorders, characterized by the dysregulation of the immune system which finally results in the break of tolerance to self-antigen. Several studies suggest that Toll-like receptors (TLRs) play an essential role in the pathogenesis of autoimmune diseases. TLRs belong to the family of pattern recognition receptors (PRRs) that recognize a wide range of pathogen-associated molecular patterns (PAMPs). TLRs are type I transmembrane proteins and located on various cellular membranes. Two main groups have been classified based on their location; the extracelluar group referred to the ones located on the plasma membrane while the intracellular group all located in endosomal compartments responsible for the recognition of nucleic acids. They are released by the host cells and trigger various intracellular pathways which results in the production of proinflammatory cytokines, chemokines, as well as the expression of co-stimulatory molecules to protect against invading microorganisms. In particular, TLR pathway-associated proteins, such as IRAK, TRAF, and SOCS, are often dysregulated in this group of diseases. TLR-associated gene expression profile analysis together with single nucleotide polymorphism (SNP) assessment could be important to explain the pathomechanism driving autoimmune diseases. In this review, we summarize recent findings on TLR pathway regulation in various autoimmune diseases, including Sjögren's syndrome (SS), systemic lupus erythematosus (SLE), multiple sclerosis (MS), rheumatoid arthritis (RA), systemic sclerosis (SSc), and psoriasis.

  4. Emphysema: an autoimmune vascular disease?

    PubMed

    Voelkel, Norbert; Taraseviciene-Stewart, Laima

    2005-01-01

    We propose that an endogenous maintenance program controls lung cell turnover, apoptosis, and tissue repair, and that emphysema is a manifestation of the breakdown of the lung structure maintenance program. Emphysema can be induced experimentally in rats by three methods: blockade of vascular endothelial growth factor receptors using SU5416, a small molecule-tyrosine kinase inhibitor; methylprednisolone, which activates matrix metalloproteinase-9 and decreases Akt phosphorylation; and antibodies directed against endothelial cells (autoimmune emphysema). SU5416-induced emphysema is associated with lung induction of cytochrome P450 and oxidant stress, and a superoxide dismutase mimetic or N-acetylcysteine prevents this form of emphysema. A broad-spectrum metalloproteinase inhibitor prevents methylprednisolone-induced emphysema and, finally, autoimmune emphysema is associated with increased lung tissue metalloproteinase-9 expression and alveolar septal cell apoptosis. Athymic rats, which lack CD4+ T cells, are protected against autoimmune emphysema, whereas adoptive transfer of CD4+ T cells causes autoimmune emphysema in naive adult rats. It appears that vascular endothelial growth factor and signaling via its receptors plays a central role in the lung structural maintenance program, and oxidative stress, proteolysis, and apoptosis may coincide in the moment of lung cell destruction. Interestingly, the methylprednisolone model illustrates that inflammation is not necessary for the development of emphysema.

  5. Autoimmune liver disease in Noonan Syndrome.

    PubMed

    Loddo, Italia; Romano, Claudio; Cutrupi, Maria Concetta; Sciveres, Marco; Riva, Silvia; Salpietro, Annamaria; Ferraù, Valeria; Gallizzi, Romina; Briuglia, Silvana

    2015-03-01

    Noonan Syndrome (NS) is characterized by short stature, typical facial dysmorphology and congenital heart defects. The incidence of NS is estimated to be between 1:1000 and 1:2500 live births. The syndrome is transmitted as an autosomal dominant trait. In approximately 50% of cases, the disease is caused by missense mutations in the PTPN11 gene on chromosome 12, resulting in a gain of function of the non-receptor protein tyrosine phosphatase SHP-2 protein. Autoimmune Hepatitis (AIH) is a cryptogenic, chronic and progressive necroinflammatory liver disease. Common features of AIH are hypergammaglobulinemia (IgG), presence of circulating autoantibodies, histological picture of interface hepatitis and response to immunosuppressant drugs. Conventional treatment with Prednisone and Azathioprine is effective in most patients. We describe the case of a 6 years-old girl with Noonan Syndrome and Autoimmune Hepatitis type 1. Molecular analysis of PTPN11 gene showed heterozygous mutation c.923A>G (Asn308Ser) in exon 8. Though association between NS and autoimmune disorders is known, this is the second case of association between Noonan Syndrome and Autoimmune Hepatitis type 1 described in literature. In the management of NS, an accurate clinical evaluation would be recommended. When there is a clinical suspicion of autoimmune phenomena, appropriate laboratory tests should be performed with the aim of clarifying whether the immune system is involved in NS. We think that autoimmunity represents a characteristic of NS, even if the etiopathogenesis is still unknown.

  6. Local Cartilage Trauma as a Pathogenic Factor in Autoimmunity (One Hypothesis Based on Patients with Relapsing Polychondritis Triggered by Cartilage Trauma)

    PubMed Central

    Cañas, Carlos A.; Bonilla Abadía, Fabio

    2012-01-01

    In the recent years, it has been of great interest to study the binding mechanism between the innate and adaptive immune responses as interrelated processes for the development of multiple autoimmune diseases. Infection has been a well-known trigger of autoimmunity and trauma has been related as well too. Cryptogenic antigens release, recognition of pathogenic structure, and metabolic changes generated by both stimuli begin an inflammatory process which in turn activates the immune system amplifying T and B cell responses. The development of relapsing polychondritis after trauma may have a direct association with these events and in turn probably trigger autoimmune phenomena. PMID:22110903

  7. Retinal Mueller glial cells trigger the hallmark inflammatory process in autoimmune uveitis.

    PubMed

    Hauck, Stefanie M; Schoeffmann, Stephanie; Amann, Barbara; Stangassinger, Manfred; Gerhards, Hartmut; Ueffing, Marius; Deeg, Cornelia A

    2007-06-01

    Spontaneous equine recurrent uveitis (ERU) is an incurable autoimmune disease affecting the eye. Although retinal-autoantigen specific T-helper 1 cells have been demonstrated to trigger disease progression and relapses, the molecular processes leading to retinal degeneration and consequent blindness remain unknown. To elucidate such processes, we studied changes in the total retinal proteome of ERU-diseased horses compared to healthy controls. Severe changes in the retinal proteome were found for several markers for blood-retinal barrier breakdown and whose emergence depended upon disease severity. Additionally, uveitic changes in the retina were accompanied by upregulation of aldose 1-epimerase, selenium-binding protein 1, alpha crystallin A chain, phosphatase 2A inhibitor (SET), and glial fibrillary acidic protein (GFAP), the latter indicating an involvement of retinal Mueller glial cells (RMG) in disease process. To confirm this, we screened for additional RMG-specific markers and could demonstrate that, in uveitic retinas, RMG concomitantly upregulate vimentin and GFAP and downregulate glutamine synthetase. These expression patterns suggest for an activated state of RMG, which further downregulate the expression of pigment epithelium-derived factor (PEDF) and begin expressing interferon-gamma, a pro-inflammatory cytokine typical for T-helper 1 cells. We thus propose that RMG may play a fatal role in uveitic disease progression by directly triggering inflammatory processes through the expression and secretion of interferon-gamma.

  8. Acute rheumatic fever and streptococci: the quintessential pathogenic trigger of autoimmunity.

    PubMed

    Chakravarty, Soumya D; Zabriskie, John B; Gibofsky, Allan

    2014-07-01

    Acute rheumatic fever (ARF) is a non-suppurative complication of pharyngeal infection with group A streptococcus. Signs and symptoms of ARF develop 2 to 3 weeks following pharyngitis and include arthritis, carditis, chorea, subcutaneous nodules, and erythema marginatum. In developing areas of the world, ARF and rheumatic heart disease are estimated to affect nearly 20 million people and remain leading causes of cardiovascular death during the first five decades of life. ARF still represents one of the quintessential examples of a pathogenic trigger culminating in autoimmune manifestations. In this review, we will focus on the pathogenesis and etiology of ARF and its complications, along with diagnostic and treatment approaches to both ameliorate and prevent long-term sequelae of this potentially debilitating disease.

  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. Nanoparticle-based autoimmune disease therapy.

    PubMed

    Serra, Pau; Santamaria, Pere

    2015-09-01

    The goal of immunotherapy against autoimmunity is to block pathogenic inflammation without impairing immunity against infections and tumours. Regulatory T-cells (Tregs) play a central role in maintaining immune homeostasis, and autoimmune inflammation is frequently associated with decreased numbers and/or function of these T-cells. Therapies harnessing Tregs to treat autoimmune inflammation remain under-developed with caveats ranging from the lack of antigenic and disease specificity to the potential phenotypic and functional instability of in vitro-expanded Treg cells in vivo. Here, we review nanotechnology-based approaches designed to promote immune tolerance through various mechanisms, ranging from systemic or local suppression of antigen-presenting cells and deletion of antigen-specific T-cells, to the systemic expansion of antigen- and disease-specific Treg cells in vivo.

  11. Membranoproliferative glomerulonephritis associated with autoimmune diseases.

    PubMed

    Zand, Ladan; Fervenza, Fernando C; Nasr, Samih H; Sethi, Sanjeev

    2014-04-01

    Membranoproliferative glomerulonephritis (MPGN) has been classified based on its pathogenesis into immune complex-mediated and complement-mediated MPGN. The immune complex-mediated type is secondary to chronic infections, autoimmune diseases or monoclonal gammopathy. There is a paucity of data on MPGN associated with autoimmune diseases. We reviewed the Mayo Clinic database over a 10-year period and identified 12 patients with MPGN associated with autoimmune diseases, after exclusion of systemic lupus erythematosus. The autoimmune diseases included rheumatoid arthritis, primary Sjögren's syndrome, undifferentiated connective tissue disease, primary sclerosing cholangitis and Graves' disease. Nine of the 12 patients were female, and the mean age was 57.9 years. C4 levels were decreased in nine of 12 patients tested. The serum creatinine at time of renal biopsy was 2.2 ± 1.0 mg/dl and the urinary protein was 2,850 ± 3,543 mg/24 h. Three patients required dialysis at the time of renal biopsy. Renal biopsy showed an MPGN in all cases, with features of cryoglobulins in six cases; immunoglobulin (Ig)M was the dominant Ig, and both subendothelial and mesangial electron dense deposits were noted. Median follow-up was 10.9 months. Serum creatinine and proteinuria improved to 1.6 ± 0.8 mg/dl and 428 ± 677 mg/24 h, respectively, except in 3 patients with end-stage renal disease. In summary, this study describes the clinical features, renal biopsy findings, laboratory evaluation, treatment and prognosis of MPGN associated with autoimmune diseases.

  12. 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.

  13. Toll-like receptor mediated modulation of T cell response by commensal intestinal microbiota as a trigger for autoimmune arthritis.

    PubMed

    Rogier, Rebecca; Koenders, Marije I; Abdollahi-Roodsaz, Shahla

    2015-01-01

    In autoimmune diseases, a disturbance of the balance between T helper 17 (Th17) and regulatory T cells (Tregs) is often observed. This disturbed balance is also the case in rheumatoid arthritis (RA). Genetic predisposition to RA confers the presence of several polymorphisms mainly regulating activation of T lymphocytes. However, the presence of susceptibility factors is neither necessary nor sufficient to explain the disease development, emphasizing the importance of environmental factors. Multiple studies have shown that commensal gut microbiota is of great influence on immune homeostasis and can trigger the development of autoimmune diseases by favoring induction of Th17 cells over Tregs. However the mechanism by which intestinal microbiota influences the Th cell balance is not completely understood. Here we review the current evidence supporting the involvement of commensal intestinal microbiota in rheumatoid arthritis, along with a potential role of Toll-like receptors (TLRs) in modulating the relevant Th cell responses to trigger autoimmunity. A better understanding of TLR triggering by intestinal microbiota and subsequent T cell activation might offer new perspectives for manipulating the T cell response in RA patients and may lead to the discovery of new therapeutic targets or even preventive measures.

  14. GITR+ regulatory T cells in the treatment of autoimmune diseases.

    PubMed

    Petrillo, Maria Grazia; Ronchetti, Simona; Ricci, Erika; Alunno, Alessia; Gerli, Roberto; Nocentini, Giuseppe; Riccardi, Carlo

    2015-02-01

    Autoimmune diseases decrease life expectancy and quality of life for millions of women and men. Although treatments can slow disease progression and improve quality of life, all currently available drugs have adverse effects and none of them are curative; therefore, requiring patients to take immunosuppressive drugs for the remainder of their lives. A curative therapy that is safe and effective is urgently needed. We believe that therapies promoting the in vivo expansion of regulatory T cells (Tregs) or injection of in vitro expanded autologous/heterologous Tregs (cellular therapy) can alter the natural history of autoimmune diseases. In this review, we present data from murine and human studies suggesting that 1) glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR) plays a crucial role in thymic Treg (tTreg) differentiation and expansion; 2) GITR plays a crucial role in peripheral Treg (pTreg) expansion; 3) in patients with Sjögren syndrome and systemic lupus erythematosus, CD4(+)GITR(+) pTregs are expanded in patients with milder forms of the disease; and 4) GITR is superior to other cell surface markers to differentiate Tregs from other CD4(+) T cells. In this context, we consider two potential new approaches for treating autoimmune diseases consisting of the in vivo expansion of GITR(+) Tregs by GITR-triggering drugs and in vitro expansion of autologous or heterologous GITR(+) Tregs to be infused in patients. Advantages of such an approach, technical problems, and safety issues are discussed.

  15. Oral mucosal manifestations of autoimmune skin diseases.

    PubMed

    Mustafa, Mayson B; Porter, Stephen R; Smoller, Bruce R; Sitaru, Cassian

    2015-10-01

    A group of autoimmune diseases is characterised by autoantibodies against epithelial adhesion structures and/or tissue-tropic lymphocytes driving inflammatory processes resulting in specific pathology at the mucosal surfaces and the skin. The most frequent site of mucosal involvement in autoimmune diseases is the oral cavity. Broadly, these diseases include conditions affecting the cell-cell adhesion causing intra-epithelial blistering and those where autoantibodies or infiltration lymphocytes cause a loss of cell-matrix adhesion or interface inflammation. Clinically, patients present with blistering, erosions and ulcers that may affect the skin as well as further mucosal surfaces of the eyes, nose and genitalia. While the autoimmune disease may be suspected based on clinical manifestations, demonstration of tissue-bound and circulating autoantibodies, or lymphocytic infiltrates, by various methods including histological examination, direct and indirect immunofluorescence microscopy, immunoblotting and quantitative immunoassay is a prerequisite for definitive diagnosis. Given the frequency of oral involvement and the fact that oral mucosa is the initially affected site in many cases, the informed practitioner should be well acquainted with diagnostic and therapeutic aspects of autoimmune dermatosis with oral involvement. This paper reviews the pathogenesis and clinical presentation of these conditions in the oral cavity with a specific emphasis on their differential diagnosis and current management approaches.

  16. Vaccination with cytokines in autoimmune diseases.

    PubMed

    Delavallée, Laure; Assier, Eric; Denys, Anne; Falgarone, Géraldine; Zagury, Jean-François; Muller, Sylvianne; Bessis, Natacha; Boissier, Marie-Christophe

    2008-01-01

    Most autoimmune diseases have an unknown etiology, but all involve cytokines cascade in their development. At the present time, several cytokines have been identified as major targets in various autoimmune diseases, involving the development of monoclonal antibodies (MAbs) against those cytokines. Even if MAbs are indeed efficient, the passive immunotherapies also present some disadvantages and are expensive. To counter this, several strategies have been developed, including active immunotherapy, based on the vaccination principle. The aim of such a strategy is to induce a B cell response and to obtain autoantibodies able to neutralize the interaction of the self-cytokine with its receptor. To that purpose, cytokines (entire or peptide) are either coupled with a protein-carrier or virus-like particle, or modified with foreign Th cell epitopes. DNA vaccination can also be used with cytokine sequences. This review focuses on the different vaccination strategies with cytokines (including Tumor Necrosis Factor (TNF)alpha, Interleukin-1beta (IL-1beta), IL-17) in different autoimmune diseases in preclinical studies; the benefit/risk ratio of such a strategy and the present development of clinical trials in some autoimmune diseases are also discussed.

  17. Extrahepatic Autoimmune Diseases in Patients with Autoimmune Liver Diseases: A Phenomenon Neglected by Gastroenterologists

    PubMed Central

    Deng, Baoru

    2017-01-01

    Autoimmune liver diseases (AILDs) often coexist with other extrahepatic autoimmune diseases (EHAIDs). The spectrum of EHAIDs in patients with AILDs is similar, whereas the incidence is different. Notably, autoimmune thyroid disease and Sjogren's syndrome are the most common EHAIDs. Associated extrahepatic diseases may predate the appearance of AILDs or coincide with their onset. More frequently, they may appear during the course and even occur years after the diagnosis of AILDs. Importantly, associated EHAIDs may influence the natural course and prognosis of AILDs. To date, a definite pathophysiological pathway which contributes to the coexistence of AILDs and EHAIDs is still lacking. The current view of autoimmunity clustering involves a common susceptibility genetic background which applies to related pathologies. Herein, we review the current published researches regarding EHAIDs in patients with AILDs, particularly in relation to their clinical impact and pathophysiology. In managing patients with AILDs, gastroenterologists should be aware of the possibly associated EHAIDs to ensure a prompt diagnosis and better outcome. PMID:28191014

  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. 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

  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. NK cell subsets in autoimmune diseases.

    PubMed

    Zhang, Cai; Tian, Zhigang

    2017-03-09

    Natural killer (NK) cells are lymphocytes of the innate immune system. They not only exert cell-mediated cytotoxicity against tumor cells or infected cells, but also play regulatory role through promoting or suppressing functions of other immune cells by secretion of cytokines and chemokines. However, overactivation or dysfunction of NK cells may be associated with pathogenesis of some diseases. NK cells are found to act as a two edged weapon and play opposite roles with both regulatory and inducer activity in autoimmune diseases. Though the precise mechanisms for the opposite effects of NK cells has not been fully elucidated, the importance of NK cells in autoimmune diseases might be associated with different NK cell subsets, different tissue microenvironment and different stages of corresponding diseases. The local tissue microenvironment, unique cellular interactions and different stages of corresponding diseases shape the properties and function of NK cells. In this review, we focus on recent research on the features and function of different NK cell subsets, particularly tissue-resident NK cells in different tissues, and their potential role in autoimmune diseases.

  3. 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.

  4. 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

  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. 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

  7. 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

  8. [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.

  9. [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.

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

    PubMed

    Zhernakova, Alexandra; Withoff, Sebo; Wijmenga, Cisca

    2013-11-01

    Many endocrine diseases, including type 1 diabetes mellitus, Graves disease, Addison disease and Hashimoto disease, originate as an autoimmune reaction that affects disease-specific target organs. These autoimmune diseases are characterized by the development of specific autoantibodies and by the presence of autoreactive T cells. They are caused by a complex genetic predisposition that is attributable to multiple genetic variants, each with a moderate-to-low effect size. Most of the genetic variants associated with a particular autoimmune endocrine disease are shared between other systemic and organ-specific autoimmune and inflammatory diseases, such as rheumatoid arthritis, coeliac disease, systemic lupus erythematosus and psoriasis. Here, we review the shared and specific genetic background of autoimmune diseases, summarize their treatment options and discuss how identifying the genetic and environmental factors that predispose patients to an autoimmune disease can help in the diagnosis and monitoring of patients, as well as the design of new treatments.

  11. 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.

  12. Targeting Syk in Autoimmune Rheumatic Diseases

    PubMed Central

    Deng, Guo-Min; Kyttaris, Vasileios C.; Tsokos, George C.

    2016-01-01

    Spleen tyrosine kinase (Syk) is a member of the Src family of non-receptor tyrosine kinases, which associates directly with surface receptors, including B-cell receptor and Fcγ receptor, and is involved in a variety of signal transduction pathways. Rheumatoid arthritis (RA) and systemic lupus erythematosus are autoimmune diseases in which autoantibodies, immune complexes, and autoreactive T cells account for the expression of tissue inflammation and damage. Syk inhibitors efficiently suppress RA in patients albeit in the expression of unwanted side effects, including gastrointestinal effects, hypertension, and neutropenia. Syk inhibitors also inhibit clinical manifestations in lupus-prone mice. Here, we review the evidence that supports the use of Syk inhibitors to treat rheumatic and other autoimmune diseases. PMID:27014261

  13. B Cells with Regulatory Function in Animal Models of Autoimmune and Non-Autoimmune Diseases.

    PubMed

    Lin, Mei; Wang, Zuomin; Han, Xiaozhe

    2015-03-01

    Although the identification of B cell subsets with negative regulatory functions and the definition of their mechanisms of action are recent events, the important negative regulatory roles of B cells in immune responses are now broadly recognized. There is an emerging appreciation for the pivotal role played by B cells in several areas of human diseases including autoimmune diseases and non-autoimmune diseases such as parasite infections and cancer. The recent research advancement of regulatory B cells in human disease coincides with the vastly accelerated pace of research on the bridging of innate and adaptive immune system. Current study and our continued research may provide better understanding of the mechanisms that promote regulatory B10 cell function to counteract exaggerated immune activation in autoimmune as well as non-autoimmune conditions. This review is focused on the current knowledge of BREG functions studied in animal models of autoimmune and non-autoimmune diseases.

  14. Microbiota and autoimmune disease: the hosted self.

    PubMed

    Mathis, Diane; Benoist, Christophe

    2011-10-20

    The trillions of microbial symbionts normally hosted by mammals have important influences on the development and function of the immune system. We highlight recently discovered cellular and molecular mechanisms by which they impact autoimmune diseases--in particular, gut-distal disorders. Besides provoking a reconsideration of the definition of immunological "self" and "nonself," these new findings evoke exciting possibilities for the discovery of a whole new class of immunomodulatory molecules.

  15. MHC Genes Linked to Autoimmune Disease.

    PubMed

    Deitiker, Philip; Atassi, M Zouhair

    2015-01-01

    Autoimmune diseases (ADs), or autoinflammatoiy diseases, are growing in complexity as diagnoses improve and many factors escalate disease risk. Considerable genetic similarity is found among ADs, and they are frequently associated with major histocompatibility complex (MHC) genes. However, a given disease may be associated with more than one human leukocyte antigen (HLA) allotype, and a given HLA may be associated with more than one AD. The associations of non-MHC genes with AD present an additional problem, and the situation is further complicated by the role that other factors, such as age, diet, therapeutic drugs, and regional influences, play in disease. This review discusses some of the genetics and biochemistry of HLA-linked AD and inflammation, covering some of the best-studied examples and summarizing indicators for class I- and II-mediated disease. However, the scope of this review limits a detailed discussion of all known ADs.

  16. Coeliac disease in endocrine diseases of autoimmune origin.

    PubMed

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

    2012-01-01

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

  17. Renal involvement in autoimmune connective tissue diseases

    PubMed Central

    2013-01-01

    Connective tissue diseases (CTDs) are a heterogeneous group of disorders that share certain clinical presentations and a disturbed immunoregulation, leading to autoantibody production. Subclinical or overt renal manifestations are frequently observed and complicate the clinical course of CTDs. Alterations of kidney function in Sjögren syndrome, systemic scleroderma (SSc), auto-immune myopathies (dermatomyositis and polymyositis), systemic lupus erythematosus (SLE), antiphospholipid syndrome nephropathy (APSN) as well as rheumatoid arthritis (RA) are frequently present and physicians should be aware of that. In SLE, renal prognosis significantly improved based on specific classification and treatment strategies adjusted to kidney biopsy findings. Patients with scleroderma renal crisis (SRC), which is usually characterized by severe hypertension, progressive decline of renal function and thrombotic microangiopathy, show a significant benefit of early angiotensin-converting-enzyme (ACE) inhibitor use in particular and strict blood pressure control in general. Treatment of the underlying autoimmune disorder or discontinuation of specific therapeutic agents improves kidney function in most patients with Sjögren syndrome, auto-immune myopathies, APSN and RA. In this review we focus on impairment of renal function in relation to underlying disease or adverse drug effects and implications on treatment decisions. PMID:23557013

  18. Overlap syndromes among autoimmune liver diseases.

    PubMed

    Rust, Christian; Beuers, Ulrich

    2008-06-07

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

  19. Th17 cells in autoimmune demyelinating disease

    PubMed Central

    2010-01-01

    Recently published studies in multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE) have demonstrated an association between the development of demyelinating plaques and the accumulation of Th17 cells in the central nervous system and periphery. However, a causal relationship has been difficult to establish. In fact, in reports published thus far, interleukin (IL)-17A deficiency or neutralization in vivo attenuates, but does not completely abrogate, EAE. There is growing evidence that clinically similar forms of autoimmune demyelinating disease can be driven by myelin-specific T cells of distinct lineages with different degrees of dependence on IL-17A production to achieve their pathological effects. While such observations cast doubts about the potential therapeutic efficacy of Th17 blocking agents in MS, the collective data suggest that IL-17A expression in peripheral blood mononuclear cells could serve as a surrogate biomarker of neuroinflammation and plaque formation and be a useful outcome measure for future clinical trials. PMID:20195867

  20. Regulatory B cells in autoimmune diseases

    PubMed Central

    Yang, Min; Rui, Ke; Wang, Shengjun; Lu, Liwei

    2013-01-01

    B cells are generally considered to be positive regulators of the immune response because of their capability to produce antibodies, including autoantibodies. The production of antibodies facilitates optimal CD4+ T-cell activation because B cells serve as antigen-presenting cells and exert other modulatory functions in immune responses. However, certain B cells can also negatively regulate the immune response by producing regulatory cytokines and directly interacting with pathogenic T cells via cell-to-cell contact. These types of B cells are defined as regulatory B (Breg) cells. The regulatory function of Breg cells has been demonstrated in mouse models of inflammation, cancer, transplantation, and particularly in autoimmunity. In this review, we focus on the recent advances that lead to the understanding of the development and function of Breg cells and the implications of B cells in human autoimmune diseases. PMID:23292280

  1. Immuno- and genetic therapy in autoimmune diseases.

    PubMed

    Chernajovsky, Y; Dreja, H; Daly, G; Annenkov, A; Gould, D; Adams, G; Croxford, J L; Baker, D; Podhajcer, O L; Mageed, R A

    2000-06-01

    Animal models of autoimmune disease have been developed that mimic some aspects of the pathophysiology of human disease. These models have increased our understanding of possible mechanisms of pathogenesis at the molecular and cellular level and have been important in the testing, development and validation of new immunotherapies. The susceptibility to develop disease in the majority of these models is polygenic as is the case in humans. The exceptions to this rule are gene knock outs and transgenic models of particular genes which, in particular genetic backgrounds, have also contributed to the understanding of single gene function and their possible contribution to pathogenesis. Gene therapy approaches that target immune functions are being developed with encouraging results, despite the polygenic nature of these diseases. Basically this novel immuno-genetic therapy harnesses the knowledge of immunology with the myriad of biotechnological breakthroughs in vector design and delivery. Autoimmune disease is the result of genetic dysregulation which could be controlled by gene therapy. Here we summarize the genetic basis of these human diseases as well as some of the best characterized murine models. We discuss the strategies for their treatment using immuno- and gene therapy.

  2. CUTTING EDGE: THE ETIOLOGY OF AUTOIMMUNE THYROID DISEASES

    PubMed Central

    Eschler, Deirdre Cocks; Hasham, Alia; Tomer, Yaron

    2011-01-01

    Significant progress has been made in our understanding of the mechanisms leading to autoimmune thyroid diseases (AITD). For the first time we are beginning to unravel these mechanisms at the molecular level. AITD, including Graves’ disease (GD) and Hashimoto’s thyroiditis (HT), are common autoimmune diseases affecting the thyroid. They have a complex etiology that involves genetic and environmental influences. Seven genes have been shown to contribute to the etiology of AITD. The first AITD gene discovered, HLA-DR3, is associated with both GD and HT. More recently this association was dissected at the molecular level when it was shown that substitution of the neutral amino acids Ala or Gln with arginine at position beta 74 in the HLA-DR peptide binding pocket is the specific sequence change causing AITD. Non-MHC genes that confer susceptibility to AITD can be classified into two groups: 1) immune regulatory genes (e.g. CD40, CTLA-4, PTPN22); 2) thyroid specific genes -thyroglobulin, and TSH receptor genes. These genes interact with environmental factors, such as infection, likely through epigenetic mechanisms to trigger disease. In this review we summarize the latest findings on disease susceptibility and modulation by environmental factors. PMID:21234711

  3. Autoimmune neuropathies associated to rheumatic diseases.

    PubMed

    Martinez, Alberto R M; Faber, Ingrid; Nucci, Anamarli; Appenzeller, Simone; França, Marcondes C

    2017-04-01

    Systemic manifestations are frequent in autoimmune rheumatic diseases and include peripheral nervous system damage. Neuron cell body, axons and myelin sheath may all be affected in this context. This involvement results in severe and sometimes disabling symptoms. Sensory, motor and autonomic features may be present in different patterns that emerge as peculiar clinical pictures. Prompt recognition of these neuropathies is pivotal to guide treatment and reduce the risks of long term disability. In this review, we aim to describe the main immune-mediated neuropathies associated to rheumatic diseases: sensory neuronopathies, multiple mononeuropathies and chronic inflammatory demyelinating polyradiculoneuropathy, with an emphasis on clinical features and therapeutic options.

  4. The epidemiologic evidence linking autoimmune diseases and psychosis.

    PubMed

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

    2014-02-15

    This review summarizes the epidemiologic evidence linking autoimmune diseases and psychosis. The associations between autoimmune diseases and psychosis have been studied for more than a half century, but research has intensified within the last decades, since psychosis has been associated with genetic markers of the immune system and with excess autoreactivity and other immune alterations. A range of psychiatric disorders, including psychosis, have been observed to occur more frequently in some autoimmune diseases, such as systemic lupus erythematosus and multiple sclerosis. Many autoimmune diseases involve multiple organs and general dysfunction of the immune system, which could affect the brain and induce psychiatric symptoms. Most studies have been cross-sectional, observing an increased prevalence of a broad number of autoimmune diseases in people with psychotic disorders. Furthermore, there is some evidence of associations of psychosis with a family history of autoimmune disorders and vice versa. Additionally, several autoimmune diseases, individually and in aggregate, have been identified as raising the risk for psychotic disorders in longitudinal studies. The associations have been suspected to be caused by inflammation or brain-reactive antibodies associated with the autoimmune diseases. However, the associations could also be caused by shared genetic factors or common etiologic components such as infections. Infections can induce the development of autoimmune diseases and autoantibodies, possibly affecting the brain. Autoimmune diseases and brain-reactive antibodies should be considered by clinicians in the treatment of individuals with psychotic symptoms, and even if the association is not causal, treatment would probably still improve quality of life and survival.

  5. Stem cell transplantation for autoimmune diseases.

    PubMed

    Gratwohl, A; Passweg, J; Gerber, I; Tyndall, A

    2001-12-01

    Much progress has been made in the field of haemopoietic stem cell transplants (HSCTs) for severe autoimmune disorders. Theoretical considerations, animal data and anecdotal evidence suggested some time ago that intensive immunoablation followed by autologous HSCT could restore normal immune reactivity in patients with severe autoimmune disorders. Based on a concept statement issued in 1995, two European societies, the European League Against Rheumatism (EULAR) and the European Group for Blood and Marrow Transplantation (EBMT) began collecting phase I/II trial data in an international collaborative network. Sufficient information from more than 350 patients allows a preliminary assessment with level three evidence. Autologous HSCTs can induce remissions in all disease categories tested so far. Remissions can be transient or durable. HSCTs are associated with significant morbidity and mortality. Treatment-related mortality (TRM) is near 10% at 1 year and is associated with the intensity of the conditioning and the stage of the disease at the time of transplant. Marked interdisease differences exist. There are few data available in haematological autoimmune diseases, more in systemic sclerosis (SSc), systemic lupus erythematosus (SLE), juvenile idiopathic arthritis (JIA) and multiple sclerosis (MS). Patient selection has been recognized as a crucial element from the phase I-II trials. Patients with advanced disease, severely compromised organ function or irreversible organ damage should not be considered as candidates for HSCT. Prospective randomized studies should now determine the value of HSCT compared to standard therapy. Such trials are ongoing for patients with systemic sclerosis (ASTIS trial--Autologous Stem Cell Transplantation International Scleroderma Trial) or are planned for patients with multiple sclerosis (ASTIMS trial--Autologous Stem Cell Transplantation International Multiple Sclerosis Trial) and rheumatoid arthritis (ASTIRA trial--Autologous Stem

  6. 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

  7. T cells and autoimmune kidney disease.

    PubMed

    Suárez-Fueyo, Abel; Bradley, Sean J; Klatzmann, David; Tsokos, George C

    2017-03-13

    Glomerulonephritis is traditionally considered to result from the invasion of the kidney by autoantibodies and immune complexes from the circulation or following their formation in situ, and by cells of the innate and the adaptive immune system. The inflammatory response leads to the proliferation and dysfunction of cells of the glomerulus, and invasion of the interstitial space with immune cells, resulting in tubular cell malfunction and fibrosis. T cells are critical drivers of autoimmunity and related organ damage, by supporting B-cell differentiation and antibody production or by directly promoting inflammation and cytotoxicity against kidney resident cells. T cells might become activated by autoantigens in the periphery and become polarized to secrete inflammatory cytokines before entering the kidney where they have the opportunity to expand owing to the presence of costimulatory molecules and activating cytokines. Alternatively, naive T cells could enter the kidney where they become activated after encountering autoantigen and expand locally. As not all individuals with a peripheral autoimmune response to kidney antigens develop glomerulonephritis, the contribution of local kidney factors expressed or produced by kidney cells is probably of crucial importance. Improved understanding of the biochemistry and molecular biology of T cells in patients with glomerulonephritis offers unique opportunities for the recognition of treatment targets for autoimmune kidney disease.

  8.  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.

  9. Insights into IL-37, the role in autoimmune diseases.

    PubMed

    Xu, Wang-Dong; Zhao, Yi; Liu, Yi

    2015-12-01

    Autoimmune diseases are characterized by the impaired function and the destruction of tissues that are caused by an immune response in which aberrant antibodies are generated and attack the body's own cells and tissues. Interleukin (IL) -37, a new member of the IL-1 family, broadly reduces innate inflammation as well as acquired immune responses. Recently, studies have shown that expression of IL-37 was abnormal in autoimmune diseases, such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), inflammatory bowel disease (IBD), ankylosing spondylitis (AS), psoriasis, Graves' disease (GD). In addition, functional analysis indicated that IL-37 is negatively involved in the development and pathogenesis of these autoimmune disorders. The strong association of this cytokine with autoimmune diseases promotes us to systematically review what had been published recently on the crucial nature of IL-37 in relation to autoimmune diseases gaining attention for its regulatory capability in these autoimmune disorders.

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

    PubMed

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

    2016-08-01

    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.

  11. Immunogenetics of autoimmune thyroid diseases: A comprehensive review.

    PubMed

    Lee, Hanna J; Li, Cheuk Wun; Hammerstad, Sara Salehi; Stefan, Mihaela; Tomer, Yaron

    2015-11-01

    Both environmental and genetic triggers factor into the etiology of autoimmune thyroid disease (AITD), including Graves' disease (GD) and Hashimoto's thyroiditis (HT). Although the exact pathogenesis and causative interaction between environment and genes are unknown, GD and HT share similar immune-mediated mechanisms of disease. They both are characterized by the production of thyroid autoantibodies and by thyroidal lymphocytic infiltration, despite being clinically distinct entities with thyrotoxicosis in GD and hypothyroidism in HT. Family and population studies confirm the strong genetic influence and inheritability in the development of AITD. AITD susceptibility genes can be categorized as either thyroid specific (Tg, TSHR) or immune-modulating (FOXP3, CD25, CD40, CTLA-4, HLA), with HLA-DR3 carrying the highest risk. Of the AITD susceptibility genes, FOXP3 and CD25 play critical roles in the establishment of peripheral tolerance while CD40, CTLA-4, and the HLA genes are pivotal for T lymphocyte activation and antigen presentation. Polymorphisms in these immune-modulating genes, in particular, significantly contribute to the predisposition for GD, HT and, unsurprisingly, other autoimmune diseases. Emerging evidence suggests that single nucleotide polymorphisms (SNPs) in the immunoregulatory genes may functionally hinder the proper development of central and peripheral tolerance and alter T cell interactions with antigen presenting cells (APCs) in the immunological synapse. Thus, susceptibility genes for AITD contribute directly to the key mechanism underlying the development of organ-specific autoimmunity, namely the breakdown in self-tolerance. Here we review the major immune-modulating genes that are associated with AITD and their potential functional effects on thyroidal immune dysregulation.

  12. 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.

  13. [Assessment of endothelial function in autoimmune diseases].

    PubMed

    Benhamou, Y; Bellien, J; Armengol, G; Gomez, E; Richard, V; Lévesque, H; Joannidès, R

    2014-08-01

    Numerous autoimmune-inflammatory rheumatic diseases have been associated with accelerated atherosclerosis or other types of vasculopathy leading to an increase in cardiovascular disease incidence. In addition to traditional cardiovascular risk factors, endothelial dysfunction is an important early event in the pathogenesis of atherosclerosis, contributing to plaque initiation and progression. Endothelial dysfunction is characterized by a shift of the actions of the endothelium toward reduced vasodilation, a proinflammatory and a proadhesive state, and prothrombic properties. Therefore, assessment of endothelial dysfunction targets this vascular phenotype using several biological markers as indicators of endothelial dysfunction. Measurements of soluble adhesion molecules (ICAM-1, VCAM-1, E-selectin), pro-thrombotic factors (thrombomodulin, von Willebrand factor, plasminogen activator inhibitor-1) and inflammatory cytokines are most often performed. Regarding the functional assessment of the endothelium, the flow-mediated dilatation of conduit arteries is a non-invasive method widely used in pathophysiological and interventional studies. In this review, we will briefly review the most relevant information upon endothelial dysfunction mechanisms and explorations. We will summarize the similarities and differences in the biological and functional assessments of the endothelium in different autoimmune diseases.

  14. Epigenetic modifications and epigenetic based medication implementations of autoimmune diseases.

    PubMed

    Ahmadi, Majid; Gharibi, Tohid; Dolati, Sanam; Rostamzadeh, Davood; Aslani, Saeed; Baradaran, Behzad; Younesi, Vahid; Yousefi, Mehdi

    2017-03-01

    Recent genome-wide association studies have documented a number of genetic variants to explain mechanisms underlying autoimmune diseases. However, the precise etiology of autoimmune diseases remains largely unknown. Epigenetic mechanisms like alterations in the post-translational modification of histones and DNA methylation may potentially cause a breakdown of immune tolerance and the perpetuation of autoreactive responses. Recently, several studies both in experimental models and clinical settings proposed that the epigenome may hold the key to a better understanding of autoimmunity initiation and perpetuation. More specifically, data support the impact of epigenetic changes in autoimmune diseases, in some cases based on mechanistical observations. Epigenetic therapy already being employed in hematopoietic malignancies may also be associated with beneficial effects in autoimmune diseases. In this review, we will discuss on what we know and expect about the treatment of autoimmune disease based on epigenetic aberrations.

  15. 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

  16. Dry Eye as a Mucosal Autoimmune Disease

    PubMed Central

    Stern, Michael E.; Schaumburg, Chris S.; Pflugfelder, Stephen C.

    2013-01-01

    Dry eye is a common ocular surface inflammatory disease that significantly affects quality of life. Dysfunction of the lacrimal function unit (LFU) alters tear composition and breaks ocular surface homeostasis, facilitating chronic inflammation and tissue damage. Accordingly, the most effective treatments to date are geared towards reducing inflammation and restoring normal tear film. The pathogenic role of CD4+ T cells is well known, and the field is rapidly realizing the complexity of other innate and adaptive immune factors involved in the development and progression of disease. The data support the hypothesis that dry eye is a localized autoimmune disease originating from an imbalance in the protective immunoregulatory and proinflammatory pathways of the ocular surface. PMID:23360156

  17. Is narcolepsy a classical autoimmune disease?

    PubMed

    Arango, María-Teresa; Kivity, Shaye; Shoenfeld, Yehuda

    2015-02-01

    Narcolepsy is a neurological disorder characterized by excessive daytime sleepiness. It is caused by the loss of orexin producing neurons in the lateral hypothalamus. Current evidences suggest an autoimmune mediated process causing the specific loss of orexin neurons. The high association of the disease with the HLA DQB1*06:02, as well as the link with environmental factors and are important clues supporting this theory. Recently, the association between the occurrence of the disease and vaccination campaign after the 2009 H1N1 pandemic highlighted the importance to increase the knowledge in the Pandora box of the vaccines. This review discusses the last finding regarding the pathogenesis of the disease and its relationship with the H1N1 vaccines.

  18. 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

  19. Regulatory T cells and autoimmune disease.

    PubMed

    Paust, Silke; Cantor, Harvey

    2005-04-01

    Although T-cell clones bearing T-cell receptors with high affinity for self-peptide major histocompatibility complex (MHC) products are generally eliminated in the thymus (recessive tolerance), the peripheral T-cell repertoire remains strongly biased toward self-peptide MHC complexes and includes autoreactive T cells. A search for peripheral T cells that might exert dominant inhibitory effects on autoreactivity has implicated a subpopulation of CD4(+)CD25(+) T cells called regulatory T cells (Tregs). Here, we discuss the role of cytokines and costimulatory molecules in the generation, maintenance, and function of Tregs. We also summarize evidence for the involvement of Tregs in controlling autoimmune diseases, including type 1 diabetes, experimental autoimmune encephalomyelitis, and inflammatory bowel disease. Last, we discuss our recent definition of the potential role of B7 expressed on activated T-effector cells as a target molecule for Treg-dependent suppression. These observations suggest that the engagement of B7 on effector T cells transmits an inhibitory signal that blocks or attenuates effector T-cell function. We restrict our comments to the suppression mediated by cells within the CD4 lineage; the impact of the cells within the CD8 lineage that may suppress via engagement of Qa-1 on effector T cells is not addressed in this review.

  20. 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

  1. 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

  2. Ovarian autoimmune disease: clinical concepts and animal models.

    PubMed

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

    2014-11-01

    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.

  3. Genes, epigenetic regulation and environmental factors: which is the most relevant in developing autoimmune diseases?

    PubMed

    Costenbader, Karen H; Gay, Steffen; Alarcón-Riquelme, Marta E; Iaccarino, Luca; Doria, Andrea

    2012-06-01

    Autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis and inflammatory bowel disease, have complex pathogeneses and likely multifactorial etiologies. The current paradigm for understanding their development is that the disease is triggered in genetically-susceptible individuals by exposure to environmental factors. Some of these environmental factors have been specifically identified, while others are hypothesized and not yet proven, and it is likely that most have yet to be identified. One interesting hypothesis is that environmental effects on immune responses could be mediated by changes in epigenetic regulation. Major mechanisms of epigenetic gene regulation include DNA methylation and histone modification. In these cases, gene expression is modified without involving changes in DNA sequence. Epigenetics is a new and interesting research field in autoimmune diseases. We review the roles of genetic factors, epigenetic regulation and the most studied environmental risk factors such as cigarette smoke, crystalline silica, Epstein-Barr virus, and reproductive hormones in the pathogenesis of autoimmune disease.

  4. 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.

  5. Pharmacometabolomics-aided Pharmacogenomics in Autoimmune Disease

    PubMed Central

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

    2016-01-01

    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. PMID:27077110

  6. Frequency of rheumatic diseases in patients with autoimmune thyroid disease.

    PubMed

    Soy, Mehmet; Guldiken, Sibel; Arikan, Ender; Altun, Betul Ugur; Tugrul, Armagan

    2007-04-01

    We aimed to investigate the frequency of rheumatic diseases in patients suffering from autoimmune thyroid diseases (ATD). Sixty-five patients (56 F, 9 M), who were followed by diagnosis of ATD, were questioned and examined for the presence of rheumatic disease. Basic laboratory tests and antithyroid antibodies, antinuclear antibody and rheumatoid factor (RF) levels were also measured by appropriate methods. Various rheumatic diseases were detected in 40 (62%) of patients with ATD. The most frequent rheumatic conditions were fibromyalgia, recurrent aphthous stomatitis, osteoarthritis, keratoconjunctivitis sicca and xerostomia and carpal tunnel syndrome which were detected in 20 (31%), 13 (20%), 10 (15%), 9 (14%) and 8 (12%) of patients, respectively. Autoimmune diseases, except Sjogren's syndrome, which were detected in ten patients with ATD, are as follows-vitiligo: two; autoimmune hepatitis: two; oral lichen planus: one, ulcerative colitis: one, inflammatory arthritis in four patients (two of them had rheumatoid arthritis, one had psoriasis and psoriatic arthritis and one had mixed collagen tissue disease). RF was positive in two patients, one of them had rheumatoid arthritis and FANA was positive in six (9%) patients; all of them had hypothyroidism. The frequency of rheumatic diseases seems to be higher in patients suffering from ATD. Initial evaluation and a regular checking for rheumatic diseases in patients suffering from ATD were recommended.

  7. 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

  8. Siglec-H protects from virus-triggered severe systemic autoimmunity

    PubMed Central

    Schmitt, Heike; Koch, Julia

    2016-01-01

    It is controversial whether virus infections can contribute to the development of autoimmune diseases. Type I interferons (IFNs) are critical antiviral cytokines during virus infections and have also been implicated in the pathogenesis of systemic lupus erythematosus. Type I IFN is mainly produced by plasmacytoid dendritic cells (pDCs). The secretion of type I IFN of pDCs is modulated by Siglec-H, a DAP12-associated receptor on pDCs. In this study, we show that Siglec-H–deficient pDCs produce more of the type I IFN, IFN-α, in vitro and that Siglec-H knockout (KO) mice produce more IFN-α after murine cytomegalovirus (mCMV) infection in vivo. This did not impact control of viral replication. Remarkably, several weeks after a single mCMV infection, Siglec-H KO mice developed a severe form of systemic lupus–like autoimmune disease with strong kidney nephritis. In contrast, uninfected aging Siglec-H KO mice developed a mild form of systemic autoimmunity. The induction of systemic autoimmune disease after virus infection in Siglec-H KO mice was accompanied by a type I IFN signature and fully dependent on type I IFN signaling. These results show that Siglec-H normally serves as a modulator of type I IFN responses after infection with a persistent virus and thereby prevents induction of autoimmune disease. PMID:27377589

  9. 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

  10. Celiac disease and autoimmune-associated conditions.

    PubMed

    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.

  11. Selected Aspects in the Pathogenesis of Autoimmune Diseases.

    PubMed

    Nagy, György; Huszthy, Peter C; Fossum, Even; Konttinen, Yrjö; Nakken, Britt; Szodoray, Peter

    2015-01-01

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

  12. Erythrovirus B19 and autoimmune thyroid diseases. Review of the literature and pathophysiological hypotheses.

    PubMed

    Page, Cyril; Duverlie, Gilles; Sevestre, Henri; Desailloud, Rachel

    2015-01-01

    Erythrovirus B19 (EVB19) has been incriminated, over recent years, in the onset and/or pathogenesis of many diseases, especially autoimmune thyroid diseases. This review of the literature (published over the last 40 years using Pubmed and Science Direct search engines) was designed to define the role of EVB19, particularly in autoimmune thyroid diseases.Two cases of subacute thyroiditis, one case of Graves' disease (associated with type 1 diabetes and rheumatoid arthritis), and one case of Hashimoto's thyroiditis following acute EVB19 infection were reported. A retrospective case-control study in a pediatric population demonstrated the role of EVB19 in Hashimoto's thyroiditis. Four retrospective studies of pathology slides (including PCR, immunohistochemistry or in situ hybridization) and a prospective case-control study on pathology slides demonstrated the presence of EVB19 in thyroid tissue of patients with benign multinodular goiter, Graves' disease, autoimmune thyroiditis (including Hashimoto's thyroiditis), and thyroid cancer. EVB19 can be demonstrated in the thyroid gland in a wide range of diseases. Although acute EVB19 infection could theoretically trigger autoimmune thyroid disease, there is currently no evidence that EVB19 plays a specific role in the pathophysiology of autoimmune thyroid diseases.

  13. 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.

  14. Autoimmunity-Basics and link with periodontal disease.

    PubMed

    Kaur, Gagandeep; Mohindra, Kanika; Singla, Shifali

    2017-01-01

    Autoimmune reactions reflect an imbalance between effector and regulatory immune responses, typically develop through stages of initiation and propagation, and often show phases of resolution (indicated by clinical remissions) and exacerbations (indicated by symptomatic flares). The fundamental underlying mechanism of autoimmunity is defective elimination and/or control of self-reactive lymphocytes. Periodontal diseases are characterized by inflammatory conditions that directly affect teeth-supporting structures, which are the major cause of tooth loss. Several studies have demonstrated the involvement of autoimmune responses in periodontal disease. Evidence of involvement of immunopathology has been reported in periodontal disease. Bacteria in the dental plaque induce antibody formation. Autoreactive T-cells, natural killer cells, ANCA, heat shock proteins, autoantibodies, and genetic factors are reported to have an important role in the autoimmune component of periodontal disease. The present review describes the involvement of autoimmune responses in periodontal diseases and also the mechanisms underlying these responses.

  15. Postpartum autoimmune thyroid syndrome: a model of aggravation of autoimmune disease.

    PubMed

    Amino, N; Tada, H; Hidaka, Y

    1999-07-01

    Postpartum thyroid dysfunction is rather a common problem during the postpartum period being found in approximately 5% of mothers in the general population. It occurs from subclinical autoimmune thyroiditis that is aggravated after parturition and causes various types of thyroid dysfunction. Immune activity is physiologically suppressed during pregnancy so that the fetus is not rejected, and rebounds above the normal level after parturition. Graves' disease and Hashimoto's thyroiditis also spontaneously ameliorate during pregnancy, and are often aggravated after parturition. The high-risk mothers for postpartum thyroid dysfunction are well screened by antithyroid microsomal antibody (MCAb) and 60% to 70% of MCAb-positive mothers develop postpartum thyroid dysfunction, which is transient in most cases. New onset of Graves' disease may be screened by thyroid-stimulating antibody (TSAb) and 70% of TSAb-positive mothers develop either transient or persistent postpartum Graves' disease that usually occurs 3 to 6 months postpartum. Immune rebound after parturition may cause not only autoimmune thyroid diseases but other autoimmune diseases, which may be investigated with similar strategies to those in postpartum autoimmune thyroid disease. Thus, we found that postpartum onset of rheumatoid arthritis was found in 0.08% of women in the general population and could be partially predicted by measuring rheumatoid factors in early pregnancy. There are several case reports of other autoimmune diseases that develop after delivery; postpartum renal failure or postdelivery hemolytic-uremic syndrome, postpartum idiopathic polymyositis, postpartum syndrome with antiphospholipid antibodies, postpartum autoimmune myocarditis. Many other possible postpartum autoimmune diseases are still unexplored. Puerperal diseases should be carefully examined in relation to autoimmune abnormalities in the affected organs.

  16. Hot topics in autoimmune diseases: perspectives from the 2013 Asian Congress of Autoimmunity.

    PubMed

    Selmi, Carlo

    2014-08-01

    Our understanding of the pathogenic mechanisms and possible treatments of autoimmune diseases has significantly increased over the past decade. Nonetheless, numerous major issues remain open and such issues span from epidemiology to clinimetrics and from the role of infectious agents to the search for accurate biomarkers in paradigmatic conditions such as systemic lupus erythematosus, rheumatoid arthritis, and spondyloarthropathies. In the case of cardiovascular comorbidities of autoimmune diseases or, more generally, the pathogenesis of atherosclerosis, fascinating evidence points to a central role of autoimmunity and metabolic dysfunctions and a possible role of therapies targeting inflammation to ameliorate both conditions. Basic science and translational medicine contribute to identify common mechanisms that underlie different autoimmune diseases, as in the case of tumor necrosis factor alpha, and more recently vitamin D, autoantibodies, T and B regulatory cells, and microRNA. Finally, new therapies are expected to significantly change our approach to autoimmune diseases, as represented by the recent FDA approval of the first oral JAK inhibitor. The present article moves from the major topics that were discussed at the 2013 Asian Congress of Autoimmunity in Hong Kong to illustrate the most recent data from leading journals in autoimmunity and immunology.

  17. Epidemiologic studies of environmental agents and systemic autoimmune diseases.

    PubMed Central

    Mayes, M D

    1999-01-01

    Systemic lupus erythematosus and systemic scleroderma are autoimmune diseases thought to have an exogenous trigger. This review summarizes relevant case-control and cohort studies that investigated exogenous sex hormones, silica, silicone, solvents, pesticides, mercuric chloride, and hair dyes as putative risk factors for the development of these diseases. These studies indicate that estrogen replacement therapy in postmenopausal women increases the risk of developing lupus, scleroderma, and Raynaud disease, although the increase in risk is relatively modest. Oral contraceptives may also play a role in disease susceptibility in lupus but not apparently in scleroderma. Environmental endocrine modulators, in the form of pesticides, may represent another opportunity for estrogenlike effects to occur, but there is scant evidence that these agents play a role in human systemic autoimmune disease. Although exposure to silica dust increases the risk of scleroderma in men occupied in the industry, this does not explain most male scleroderma cases. When this exposure was investigated among women, no significant risk was found. Additionally, silicone in implanted devices as well as occupational exposure to silicone-containing compounds did not pose an increased risk among women for scleroderma. The role of solvent exposure has been investigated as a risk factor for scleroderma with mixed findings. One study suggested a potential role in male patients or in those individuals with Scl-70 antibody positivity either male or female. Two other studies were unable to corroborate this finding. Mercuric chloride causes antifibrillarin antibodies and immune complex glomerulonephritis in susceptible mouse strains. Antifibrillarin antibodies, but not glomerulonephritis, occur in a subset of scleroderma patients and preliminary evidence suggests that mercury levels may be higher in this group of individuals. Hair products have been studied as possibly raising the risk of developing lupus

  18. CNS autoimmune disease after Streptococcus pyogenes infections: animal models, cellular mechanisms and genetic factors

    PubMed Central

    Cutforth, Tyler; DeMille, Mellissa MC; Agalliu, Ilir; Agalliu, Dritan

    2016-01-01

    Streptococcus pyogenes infections have been associated with two autoimmune diseases of the CNS: Sydenham’s chorea (SC) and Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus infections (PANDAS). Despite the high frequency of pharyngeal streptococcus infections among children, only a small fraction develops SC or PANDAS. This suggests that several factors in combination are necessary to trigger autoimmune complications: specific S. pyogenes strains that induce a strong immune response toward the host nervous system; genetic susceptibility that predispose children toward an autoimmune response involving movement or tic symptoms; and multiple infections of the throat or tonsils that lead to a robust Th17 cellular and humoral immune response when untreated. In this review, we summarize the evidence for each factor and propose that all must be met for the requisite neurovascular pathology and behavioral deficits found in SC/PANDAS. PMID:27110222

  19. 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.

  20. 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

  1. 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.

  2. The prevalence of autoimmune disease in patients with esophageal achalasia.

    PubMed

    Booy, J D; Takata, J; Tomlinson, G; Urbach, D R

    2012-04-01

    Achalasia is a rare disease of the esophagus that has an unknown etiology. Genetic, infectious, and autoimmune mechanisms have each been proposed. Autoimmune diseases often occur in association with one another, either within a single individual or in a family. There have been separate case reports of patients with both achalasia and one or more autoimmune diseases, but no study has yet determined the prevalence of autoimmune diseases in the achalasia population. This paper aims to compare the prevalence of autoimmune disease in patients with esophageal achalasia to the general population. We retrospectively reviewed the charts of 193 achalasia patients who received treatment at Toronto's University Health Network between January 2000 and May 2010 to identify other autoimmune diseases and a number of control conditions. We determined the general population prevalence of autoimmune diseases from published epidemiological studies. The achalasia sample was, on average, 10-15 years older and had slightly more men than the control populations. Compared to the general population, patients with achalasia were 5.4 times more likely to have type I diabetes mellitus (95% confidence interval [CI] 1.5-19), 8.5 times as likely to have hypothyroidism (95% CI 5.0-14), 37 times as likely to have Sjögren's syndrome (95% CI 1.9-205), 43 times as likely to have systemic lupus erythematosus (95% CI 12-154), and 259 times as likely to have uveitis (95% CI 13-1438). Overall, patients with achalasia were 3.6 times more likely to suffer from any autoimmune condition (95% CI 2.5-5.3). Our findings are consistent with the impression that achalasia's etiology has an autoimmune component. Further research is needed to more conclusively define achalasia as an autoimmune disease.

  3. Serum autoantibodies for the diagnosis and management of autoimmune liver diseases.

    PubMed

    Achenza, Maria I S; Meda, Francesca; Brunetta, Enrico; Selmi, Carlo

    2012-12-01

    The spectrum of autoimmune liver diseases (AILD) includes primary biliary cirrhosis, primary sclerosing cholangitis and autoimmune hepatitis. The immunological mechanisms triggering the initiation and perpetuation of AILD remains unknown, while autoantigens are now recognized in most cases, and are generally nontraditional in their widespread distribution. Sensitive and specific methods for the detection of serum autoantibodies in patients affected by AILD represent a challenge for researchers and clinicians who desire to obtain an early and certain diagnosis as well as markers of disease control. To this regard, the use and interpretation of serum autoantibodies in AILD may be seen as paradigmatic for the large gaps in our knowledge based on the lack of true population-based studies. The present review article will critically discuss the available evidence on the use of autoantibody findings in the diagnosis or management of autoimmune liver disease.

  4. [Hodgkin disease and autoimmunity in children: 11 case reports].

    PubMed

    Jarrassé, C; Pagnier, A; Edan, C; Landman-Parker, J; Mazingue, F; Mansuy, L; Bertrand, Y; Paillard, C; Pellier, I; Margueritte, G; Plantaz, D

    2011-04-01

    The association of lymphoma and autoimmune manifestations has been predominantly studied in adults affected by non-Hodgkin lymphoma. Few publications exist in the literature concerning Hodgkin lymphoma, particularly in children and adolescents. The objectives of this study were to define the characteristics of the link between Hodgkin disease and autoimmunity in childhood. The present 25-year retrospective study was conducted in all centers affiliated with the French Society of Paediatric Oncology (SFCE). Eleven children with Hodgkin disease presented manifestations of disimmunity preceding or following their diagnosis. Four patients had thrombocytopenic purpura, the remaining 7 each had a different autoimmune pathology: lupus syndrome, antiphospholipid syndrome with transient ischemic attack, Evans syndrome, leukocytoclastic vasculitis, autoimmune hemolytic anemia, autoimmune thyroiditis, and juvenile idiopathic arthritis. Lymphoma relapse occurred in 3 patients. Two children died, death being directly attributed to the autoimmune disease in 1 case. Our data suggest that development of autoimmunity is related to significant morbidity. Possible pathophysiological mechanisms include lymphocyte proliferation secondary to chronic inflammation, cell-mediated immune deficiency in Hodgkin disease, molecular mimetics, and antineoplastic phenomena are discussed. A study with a larger patient population is needed to identify the group of children at high risk of autoimmunity for whom additional investigations and modified therapy may be indicated.

  5. Interleukin-28A enhances autoimmune disease in a retinal autoimmunity model.

    PubMed

    Ren, Xiangrong; Zhou, Hongyan; Liu, Xialin; Su, Shao Bo

    2014-12-01

    Interleukin-28A (IL-28A), a member of type III interferons (IFN-λs), promotes antiviral, antitumor and immune responses. However, its ability to regulate autoimmune diseases is poorly understood. In this study, we examined the effect of IL-28A on retinal antigen-induced experimental autoimmune uveoretinitis (EAU), a mouse model of human T-cell-mediated autoimmune eye disease. We found that administration of IL-28A enhanced EAU scores and autoimmune response parameters including delayed-type hypersensitivity (DTH), Ag-specific T cell proliferation and the production of Ag-specific IL-17 and IFN-γ in the priming phase. The effect of IL-28A was abrogated by administration of a neutralizing antibody against IL-28A. Our results suggest that IL-28A is capable of exacerbating a T-cell-mediated autoimmune disease. Thus, targeting IL-28A may provide a new therapeutic approach to T cell-mediated autoimmune diseases such as uveitis.

  6. Stem cell transplantation for rheumatic autoimmune diseases

    PubMed Central

    Hügle, Thomas; van Laar, Jacob M

    2008-01-01

    Immunoablative therapy and hematopoietic stem cell transplantation (HSCT) is an intensive treatment modality aimed at 'resetting' the dysregulated immune system of a patient with immunoablative therapy and allow outgrowth of a nonautogressive immune system from reinfused hematopoietic stem cells, either from the patient (autologous HSCT) or a healthy donor (allogeneic HSCT). HSCT has been shown to induce profound alterations of the immune system affecting B and T cells, monocytes, and natural killer and dendritic cells, resulting in elimination of autoantibody-producing plasma cells and in induction of regulatory T cells. Most of the available data have been collected through retrospective cohort analyses of autologous HSCT, case series, and translational studies in patients with refractory autoimmune diseases. Long-term and marked improvements of disease activity have been observed, notably in systemic sclerosis, systemic lupus erythematosus, and juvenile idiopathic arthritis, and treatment-related morbidity and mortality have improved due to better patient selection and modifications of transplant regimens. Treatment-related mortality has decreased to approximately 7%. Prospective, randomised, controlled clinical trials are ongoing or planned in systemic sclerosis, systemic lupus erythematosus, and several nonrheumatological conditions. PMID:18947373

  7. History and milestones of mouse models of autoimmune diseases.

    PubMed

    Yu, Xinhua; Huang, Qiaoniang; Petersen, Frank

    2015-01-01

    Autoimmune diseases are a group of disorders mediated by self-reactive T cells and/or autoantibodies. Mice, as the most widely used animal for modeling autoimmune disorders, have been extensively used in the investigation of disease pathogenesis as well as in the search for novel therapeutics. Since the first mouse model of multiple sclerosis was established more than 60 years ago, hundreds of mouse models have been established for tens of autoimmune diseases. These mouse models can be divided into three categories based on the approaches used for disease induction. The first one represents the induced models in which autoimmunity is initiated in mice by immunization, adoptive transfer or environmental factors. The second group is formed by the spontaneous models where mice develop autoimmune disorders without further induction. The third group refers to the humanized models in which mice bearing humanized cells, tissues, or genes, develop autoimmune diseases either spontaneously or by induction. This article reviews the history and highlights the milestones of the mouse models of autoimmune diseases.

  8. [Comorbid autoimmune pathology in patients treated with disease modifying drugs].

    PubMed

    Goncharova, Z A; Sizyakina, L P; Belovolova, R A; Megeryan, V A

    2016-01-01

    Because of intensive growth of the prevalence of multiple sclerosis (MS) and other autoimmune diseases (AID) during the last years, the comorbidity of MS and AID is not a rarity. In this literature review, the development of comorbid AID in patients with MS is considered to be the probable complication of disease modifying therapy with drugs of different groups. The authors present the own data on the prevalence of comorbid autoimmune pathology in patients with MS treated with disease modifying drugs.

  9. PI3K inhibitors as potential therapeutics for autoimmune disease.

    PubMed

    Ball, Jennifer; Archer, Sophie; Ward, Stephen

    2014-08-01

    Aberrant overactivation of the immune system can give rise to chronic and persistent self-attack, culminating in autoimmune disease. This is currently managed therapeutically using potent immunosuppressive and anti-inflammatory drugs. Class I phosphoinositide 3-kinases (PI3Ks) have been identified as ideal therapeutic targets for autoimmune diseases given their wide-ranging roles in immunological processes. Recent studies into the function of selective PI3K inhibitors in vitro and in vivo have yielded encouraging results, allowing progression into the clinic. Here, we review their recent progress across a range of autoimmune diseases.

  10. Stem cell autograft and allograft in autoimmune diseases.

    PubMed

    De Cata, Angelo; Matarangolo, Angela; Inglese, Michele; Rubino, Rosa; Mazzoccoli, Gianluigi

    2016-02-01

    Autoimmune diseases are characterized by an insufficiency of immune tolerance and, although treated with a number of useful drugs, may need more unconventional therapeutic strategies for their more severe presentations. Among such unconventional therapeutic approaches, stem cell autograft and allograft have been used, with the aim of stimulating disease remission by modifying the pathogenic mechanisms that induce anomalous responses against self-antigens. Autologous transplantation is performed with the purpose of retuning autoimmune cells, whereas allogeneic transplantation is performed with the purpose of replacing anomalous immune effectors and mediators. In this article, we comprehensively review up-to-date information on the autoimmune diseases for which the transplantation of stem cells is indicated.

  11. Accounting for chance in the calculus of autoimmune disease.

    PubMed

    Moore, Daniel J

    2010-02-01

    Discussions around the etiology of autoimmune disease routinely focus on the interplay between genes and the environment. In turn, efforts to ameliorate these diseases seek to modify genetic and environmental factors. However, there may be a third element that also accounts for the progression of autoimmunity. This article explores the role of chance, exemplified by the stochastic process of immune repertoire generation, in the evolution of autoimmunity. The presented modeling studies and concepts suggest that chance plays as significant a role as genes or environment. This hypothesis implies that a full understanding of the role of genes and environment will also require investigators to account for stochastic processes in building comprehensive disease models.

  12. P-glycoprotein in autoimmune rheumatic diseases.

    PubMed

    García-Carrasco, M; Mendoza-Pinto, C; Macias Díaz, S; Vera-Recabarren, M; Vázquez de Lara, L; Méndez Martínez, S; Soto-Santillán, P; González-Ramírez, R; Ruiz-Arguelles, A

    2015-07-01

    P-glycoprotein (Pgp) is a transmembrane protein of 170 kD encoded by the multidrug resistance 1 (MDR-1) gene, localized on chromosome 7. More than 50 polymorphisms of the MDR-1 gene have been described; a subset of these has been shown to play a pathophysiological role in the development of inflammatory bowel disease, femoral head osteonecrosis induced by steroids, lung cancer and renal epithelial tumors. Polymorphisms that have a protective effect on the development of conditions such as Parkinson disease have also been identified. P-glycoprotein belongs to the adenosine triphosphate binding cassette transporter superfamily and its structure comprises a chain of approximately 1280 aminoacid residues with an N-C terminal structure, arranged as 2 homologous halves, each of which has 6 transmembrane segments, with a total of 12 segments with 2 cytoplasmic nucleotide binding domains. Many cytokines like interleukin 2 and tumor necrosis factor alpha increase Pgp expression and activity. Pgp functions as an efflux pump for a variety of toxins in order to protect particular organs and tissues as the central nervous system. Pgp transports a variety of substrates including glucocorticoids while other drugs such as tacrolimus and cyclosporine A act as modulators of this protein. The most widely used method to measure Pgp activity is flow cytometry using naturally fluorescent substrates such as anthracyclines or rhodamine 123. The study of drug resistance and its association to Pgp began with the study of resistance to chemotherapy in the treatment of cancer and antiretroviral therapy for human immunodeficiency virus; however, the role of Pgp in the treatment of systemic lupus erythematosus, rheumatoid arthritis and psoriatic arthritis has been a focus of study lately and has emerged as an important mechanism by which treatment failure occurs. The present review analyzes the role of Pgp in these autoimmune diseases.

  13. [Low prevalence of autoimmune antiphospholipid antibodies in hepatic diseases].

    PubMed

    de Larrañaga, G F; Harris, N; Pierangeli, S S; Alonso, B S; Schroder, T; Fainboim, H

    2000-01-01

    Antiphospholipid antibodies (aPL) have been associated with different diseases. They are defined as a large family of immunoglobulins (Ig) of either alloantibodies or autoantibodies. The autoimmune antibodies are associated with venous and/or arterial thrombosis, thrombocytopenia and recurrent fetal loss in the so-called antiphospholipid syndrome or in systemic lupus erythematosus. These antibodies are directed against proteins or phospholipid-protein complexes. On the contrary, antiphospholipid antibodies (alloantibodies) which are found in infectious diseases sera (syphilis, HIV, and other viral diseases), disappear with illness remission and are directed to phospholipids alone (particularly cardiolipin) and are not associated with thrombosis or recurrent fetal loss. However, the role and type of aPL found during hepatic diseases is still unclear. To investigate the prevalence of autoimmune aPL (IgG and IgM) during different hepatic diseases, we have studied 128 patients with hepatitis C virus, hepatitis B virus and hepatic autoimmune diseases without treatment as well as 40 healthy control subjects. We have used a specific ELISA kit, that uses a mixture of phospholipid instead of cardiolipin alone, and allows a better detection of aPL of the autoimmune type. Our results show that autoimmune aPL are not significantly increased in viral hepatic diseases (2%) or autoimmune diseases of the liver (3%) when compared to the control group (0%).

  14. [Bullous autoimmune diseases of the oral mucosa].

    PubMed

    Vaillant, L

    1999-10-01

    Autoimmune bullous diseases (AIBD) are characterized by autoantibodies targeted against adhesion molecules, impairing their formation. According to localization criteria, pemphigus (intraepidermal blister and desmosomal involvement) and pemphigoid (subepidermal blister and dermoepidermal junction involvement) can be distinguished. In two-thirds of the cases, pemphigus vulgaris begins with oral lesions (mainly the buccal mucosa and palate, rarely the gingiva). Skin lesions are usual. Excepting paraneoplastic pemphigus (a recently individualized entity), oral lesions are uncommon in other types of pemphigus. Cicatricial pemphigoid mainly involves oral mucosa, frequently other mucous membranes, and rarely the skin. Gingival involvement is frequent. In case of desquamative gingivitis, the clip sign gives the diagnosis of cicatricial pemphigoid. Ocular involvement is frequent and causes blindness. Epidermolysis bullosa acquisita and IgA linear dermatosis are rare. Bullous pemphigoid and bullous lupus rarely involve the oral mucosa. Diagnosis of AIBD requires a biopsy within the mucosal membrane lesion for pathology examination and another biopsy in a lesion-free area for direct immunofluorescence detection of antibody fixation. Immunoelectron microscopy or immunoblast transfer may be needed for positive diagnosis. Corticosteroids are used to treat pemphigus and dapsone is used for cicatricial pemphigoid. Immunosuppressive therapy is rarely needed.

  15. 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.

  16. Autoimmune joint diseases in Late Medieval skeletal sample from Croatia.

    PubMed

    Rajić Sikanjić, Petra; Vlak, Dejana

    2010-01-01

    Analysis of 25 skeletons from Late Medieval cemetery Uzdolje-Grablje near Knin, Croatia, revealed three cases of systematic pathological changes to joints. Observed pathological lesions were examined macroscopically and radiologically and compared to the available paleopathological standards in order to formulate a differential diagnosis. In all three cases observed changes were most consistent with autoimmune joint diseases including ankylosing spondylitis, juvenile idiopathic arthritis and psoriatic arthritis. Based on published clinical studies, we suggest that the high prevalence of autoimmune diseases in our skeletal sample stems from the genetic basis of the autoimmunity, and that three individuals describe here are possibly closely related.

  17. Sexual dimorphism in autoimmunity

    PubMed Central

    Rubtsova, Kira; Marrack, Philippa; Rubtsov, Anatoly V.

    2015-01-01

    Autoimmune diseases occur when the immune system attacks and destroys the organs and tissues of its own host. Autoimmunity is the third most common type of disease in the United States. Because there is no cure for autoimmunity, it is extremely important to study the mechanisms that trigger these diseases. Most autoimmune diseases predominantly affect females, indicating a strong sex bias. Various factors, including sex hormones, the presence or absence of a second X chromosome, and sex-specific gut microbiota can influence gene expression in a sex-specific way. These changes in gene expression may, in turn, lead to susceptibility or protection from autoimmunity, creating a sex bias for autoimmune diseases. In this Review we discuss recent findings in the field of sex-dependent regulation of gene expression and autoimmunity. PMID:25915581

  18. [Congenital atrioventricular block and maternal autoimmune diseases].

    PubMed

    Herreman, G; Sauvaget, F; Généreau, T; Galezowski, N

    1990-01-01

    Congenital heart block is rare; it is acquired in utero, definitive and, more often than not, complete. It can be diagnosed by the appearance of fetal bradycardia around the 23rd week of gestation, during ultrasonographic monitoring of pregnancy. Heart block is usually associated with the presence of anti-Ro and/or anti-La antibodies in the mother's serum. These maternal immunological abnormalities can be isolated or associated with an autoimmune disease, usually systemic lupus erythematosus, but also Sjögren's syndrome, or more rarely still, an as yet unclassified connective tissue disease. Anti-Ro and anti-La antibodies cross the placental barrier and react with a fetal heart, leading to acute fetal myocarditis by the 17th week of gestation. When severe, it is lethal, otherwise it can result in degeneration and endocardial fibroelastosis, disrupting conduction and leading to congenital heart block. The ideal treatment would be prevention with corticosteroids. When the mother is Ro or La antibody-positive before pregnancy, elimination of these circulating antibodies can be attempted by treatment with 0.5 mg/kg body wt/d of prednisolone for 3 months. If the treatment is successful, corticotherapy can be prescribed early in the pregnancy to try to protect the fetus. However, there is not always a relationship between maternal anti-Ro antibodies and fetal heart block. If the Ro/La antibody-positive woman is already pregnant, but before her 17th week, it is possible to prescribe dexamethasone, which crosses the placenta and remains active, sometimes in association with plasmapheresis.

  19. 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.

  20. Biologics for the treatment of autoimmune renal diseases.

    PubMed

    Holdsworth, Stephen R; Gan, Poh-Yi; Kitching, A Richard

    2016-04-01

    Biological therapeutics (biologics) that target autoimmune responses and inflammatory injury pathways have a marked beneficial impact on the management of many chronic diseases, including rheumatoid arthritis, psoriasis, inflammatory bowel disease, and ankylosing spondylitis. Accumulating data suggest that a growing number of renal diseases result from autoimmune injury - including lupus nephritis, IgA nephropathy, anti-neutrophil cytoplasmic antibody-associated glomerulonephritis, autoimmune (formerly idiopathic) membranous nephropathy, anti-glomerular basement membrane glomerulonephritis, and C3 nephropathy - and one can speculate that biologics might also be applicable to these diseases. As many autoimmune renal diseases are relatively uncommon, with long natural histories and diverse outcomes, clinical trials that aim to validate potentially useful biologics are difficult to design and/or perform. Some excellent consortia are undertaking cohort studies and clinical trials, but more multicentre international collaborations are needed to advance the introduction of new biologics to patients with autoimmune renal disorders. This Review discusses the key molecules that direct injurious inflammation and the biologics that are available to modulate them. The opportunities and challenges for the introduction of relevant biologics into treatment protocols for autoimmune renal diseases are also discussed.

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

    PubMed

    Ahmad, Jowairiyya; Tagoe, Clement E

    2014-07-01

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

  2. 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

  3. Autoimmune disease and multiple autoantibodies in 42 patients with RASopathies.

    PubMed

    Quaio, Caio R D C; Carvalho, Jozélio F; da Silva, Clovis A; Bueno, Cleonice; Brasil, Amanda S; Pereira, Alexandre C; Jorge, Alexander A L; Malaquias, Alexsandra C; Kim, Chong A; Bertola, Débora R

    2012-05-01

    The association of RASopathies [Noonan syndrome (NS) and Noonan-related syndromes] and autoimmune disorders has been reported sporadically. However, a concomitant evaluation of autoimmune diseases and an assessment of multiple autoantibodies in a large population of patients with molecularly confirmed RASopathy have not been performed. The clinical and laboratory features were analyzed in 42 RASopathy patients, the majority of whom had NS and five individuals had Noonan-related disorders. The following autoantibodies were measured: Anti-nuclear antibodies, anti-double stranded DNA, anti-SS-A/Ro, anti-SS-B/La, anti-Sm, anti-RNP, anti-Scl-70, anti-Jo-1, anti-ribosomal P, IgG and IgM anticardiolipin (aCL), thyroid, anti-smooth muscle, anti-endomysial (AE), anti-liver cytosolic protein type 1 (LC1), anti-parietal cell (APC), anti-mitochondrial (AM) antibodies, anti-liver-kidney microsome type 1 antibodies (LKM-1), and lupus anticoagulant. Six patients (14%) fulfilled the clinical criteria for autoimmune diseases [systemic lupus erythematous, polyendocrinopathy (autoimmune thyroiditis and celiac disease), primary antiphospholipid syndrome (PAPS), autoimmune hepatitis, vitiligo, and autoimmune thyroiditis]. Autoimmune antibodies were observed in 52% of the patients. Remarkably, three (7%) of the patients had specific gastrointestinal and liver autoantibodies without clinical findings. Autoimmune diseases and autoantibodies were frequently present in patients with RASopathies. Until a final conclusion of the real incidence of autoimmunity in Rasopathy is drawn, the physicians should be alerted to the possibility of this association and the need for a fast diagnosis, proper referral to a specialist and ultimately, adequate treatment.

  4. Neuropathic Pain in Animal Models of Nervous System Autoimmune Diseases

    PubMed Central

    Tian, David H.; Perera, Chamini J.; Moalem-Taylor, Gila

    2013-01-01

    Neuropathic pain is a frequent chronic presentation in autoimmune diseases of the nervous system, such as multiple sclerosis (MS) and Guillain-Barre syndrome (GBS), causing significant individual disablement and suffering. Animal models of experimental autoimmune encephalomyelitis (EAE) and experimental autoimmune neuritis (EAN) mimic many aspects of MS and GBS, respectively, and are well suited to study the pathophysiology of these autoimmune diseases. However, while much attention has been devoted to curative options, research into neuropathic pain mechanisms and relief has been somewhat lacking. Recent studies have demonstrated a variety of sensory abnormalities in different EAE and EAN models, which enable investigations of behavioural changes, underlying mechanisms, and potential pharmacotherapies for neuropathic pain associated with these diseases. This review examines the symptoms, mechanisms, and clinical therapeutic options in these conditions and highlights the value of EAE and EAN animal models for the study of neuropathic pain in MS and GBS. PMID:23737643

  5. 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.

  6. Epigenetic control of autoimmune diseases: from bench to bedside.

    PubMed

    Picascia, Antonietta; Grimaldi, Vincenzo; Pignalosa, Orlando; De Pascale, Maria Rosaria; Schiano, Concetta; Napoli, Claudio

    2015-03-01

    Genome-wide association studies have revealed several genes predisposing to autoimmunity, however, concordance rates in monozygotic twins are significantly below 50% for several autoimmune diseases. The limited presence of a strong genetic association only in some patients supports that other non-genetic mechanisms are active in these pathologies. Epigenetic modifications such as DNA methylation, histone modification, and microRNA signaling regulate gene expression and are sensitive to external stimuli and they might be as bridging between genetic and environmental factors. Some evidence has highlighted the involvement of epigenetic alterations in the pathogenesis of various autoimmune diseases giving rise to great expectations among clinicians and researchers. The direct role of these alterations in the initiation/progression of autoimmune diseases is still unclear. The knowledge in depth of these pathogenic and epigenetic mechanisms will increase the possibility of the control and/or prevention of autoimmune diseases through the use of drugs that target epigenetic pathways. Moreover, we could use epigenetic-related biomarkers to follow this complicated framework (for example H3K4me3 and miRNA-155 are among those proposed biomarkers). This article reviews current understanding of the epigenetic involvement in the field of autoimmune diseases especially in systemic lupus erythematosus, rheumatoid arthritis, sclerosis multiple and type 1 diabetes.

  7. Autoimmune Thyroid Disease and Breast Cancer Prognosis

    PubMed Central

    Özmen, Tolga; Güllüoğlu, Bahadır Mahmut; Yegen, Cumhur Şevket; Soran, Atilla

    2015-01-01

    Objective The association of breast cancer and thyroid autoimmunity has been suggested by many studies in the literature, but the causality still needed to be proven. With this study we aimed to search the correlation between thyroid autoimmunity and breast cancer prognostic factors. Materials and Methods To this prospective cohort study 200 consecutive breast cancer patients, who were operated in our clinic were included. Patients’ serum thyroid hormone, anti-thyroglobuline (anti-TG) and anti-thyroid peroxidase (anti-TPO) levels and tumors’ prognostic parameters (tumor size, axillary involvement, histological grade, lymphovascular invasion, receptor status, Ki-67 proliferation index) were collected. The correlation between serum thyroid autoantibody levels and tumor’s prognostic factors were studied. Results The prevalence of thyroid autoimmunity (high levels of serum anti-TPO and/or anti-TG) was 18.5% (n=37). Patients with thyroid autoimmunity had a significant lower rate of axillary involvement and a lower rate of Ki-67 proliferation index (22% vs. 46% [p=0,007] and 12.73% vs. 20.72% [p=0.025], respectively) and were more commonly included to the “low-risk” group (<14%) according to their Ki-67 scores (68% vs. 46%; p=0.015). Other parameters did not differ between the two groups. Conclusion We found a favorable correlation between thyroid autoimmunity and axillary involvement and also Ki-67 proliferation index score, which are two crucial and strongly predictive parameters of breast cancer prognoses. This supports the idea of thyroid autoimmunity being a favorable prognostic parameter. Further studies are necessary to investigate the reasons of protective or predictive effect of high thyroid peroxidase levels in breast cancer patients.

  8. 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

  9. Autoimmune disease: A role for new anti-viral therapies?

    PubMed

    Dreyfus, David H

    2011-12-01

    Many chronic human diseases may have an underlying autoimmune mechanism. In this review, the author presents a case of autoimmune CIU (chronic idiopathic urticaria) in stable remission after therapy with a retroviral integrase inhibitor, raltegravir (Isentress). Previous reports located using the search terms "autoimmunity" and "anti-viral" and related topics in the pubmed data-base are reviewed suggesting that novel anti-viral agents such as retroviral integrase inhibitors, gene silencing therapies and eventually vaccines may provide new options for anti-viral therapy of autoimmune diseases. Cited epidemiologic and experimental evidence suggests that increased replication of epigenomic viral pathogens such as Epstein-Barr Virus (EBV) in chronic human autoimmune diseases such as rheumatoid arthritis (RA), systemic lupus Erythematosus (SLE), and multiple sclerosis (MS) may activate endogenous human retroviruses (HERV) as a pathologic mechanism. Memory B cells are the reservoir of infection of EBV and also express endogenous retroviruses, thus depletion of memory b-lymphocytes by monoclonal antibodies (Rituximab) may have therapeutic anti-viral effects in addition to effects on B-lymphocyte presentation of both EBV and HERV superantigens. Other novel anti-viral therapies of chronic autoimmune diseases, such as retroviral integrase inhibitors, could be effective, although not without risk.

  10. The Corrona US registry of rheumatic and autoimmune diseases.

    PubMed

    Kremer, Joel M

    2016-01-01

    The Corrona US national registry collects data concerning patient status from both the rheumatologist and patient at routine clinical encounters. Corrona has functioning disease registries in rheumatoid arthritis, psoriatic arthritis, spondyloarthropathies, psoriasis and inflammatory bowel disease. Corrona merges data concerning long-term effectiveness and safety, as well as comparative and cost effectiveness of agents to treat these autoimmune diseases.

  11. 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.

  12. Coeliac disease: a unique model for investigating broken tolerance in autoimmunity

    PubMed Central

    Hardy, Melinda Y; Tye-Din, Jason A

    2016-01-01

    Coeliac disease, a prevalent immune-mediated enteropathy driven by dietary gluten, provides an exceptional human model to dissect the genetic, environmental and immunologic factors operating in autoimmunity. Despite the causative antigen being an exogenous food protein, coeliac disease has many features in common with autoimmune disease including a strong HLA class II association and the presence of pathogenic CD4+ T cells and autoantibodies. CD8+ intraepithelial lymphocytes specifically target and destroy intestinal epithelium in response to stress signals and not a specific antigen. A unique feature of coeliac disease is the ability to remove gluten to induce disease remission and reintroduce it to trigger a memory response. This provides an unparalleled opportunity to study disease-relevant CD4+ T cells that have been expanded in vivo. As a result, the causative peptides have been characterised at a level unprecedented for any autoimmune disease. Despite the complexity of the gluten proteome, resistance to gastrointestinal proteolysis and susceptibility to post-translational modification by transglutaminase help shape a restricted repertoire of immunogenic gluten peptides that have high affinity for disease-associated HLA. The critical steps in coeliac disease pathogenesis have been broadly elucidated and provide the basis for experimental therapies in pre-clinical or clinical development. However, little is known about how and why tolerance to gluten sometimes breaks or fails to develop. Understanding the interactions between genes, the environment, gluten immunity and the microbiome may provide novel approaches for the prevention and treatment of disease. PMID:27990287

  13. Autoimmune lymphoproliferative syndrome-like disease with somatic KRAS mutation.

    PubMed

    Takagi, Masatoshi; Shinoda, Kunihiro; Piao, Jinhua; Mitsuiki, Noriko; Takagi, Mari; Matsuda, Kazuyuki; Muramatsu, Hideki; Doisaki, Sayoko; Nagasawa, Masayuki; Morio, Tomohiro; Kasahara, Yoshihito; Koike, Kenichi; Kojima, Seiji; Takao, Akira; Mizutani, Shuki

    2011-03-10

    Autoimmune lymphoproliferative syndrome (ALPS) is classically defined as a disease with defective FAS-mediated apoptosis (type I-III). Germline NRAS mutation was recently identified in type IV ALPS. We report 2 cases with ALPS-like disease with somatic KRAS mutation. Both cases were characterized by prominent autoimmune cytopenia and lymphoadenopathy/splenomegaly. These patients did not satisfy the diagnostic criteria for ALPS or juvenile myelomonocytic leukemia and are probably defined as a new disease entity of RAS-associated ALPS-like disease (RALD).

  14. 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.

  15. Molecular mimicry in autoimmune neurological disease after viral infection.

    PubMed

    Roep, Bart O

    2003-10-01

    Viral infections have been associated with the development of several neurological and neuroendocrine autoimmune diseases. Structural similarities between environmental proteins and self-proteins have long been proposed to be targets for immune cross reactivity associated with initiation of autoimmune diseases. This mechanism called molecular mimicry has also been put forward for immune mediated neurological diseases associated with viral infection. Although many potential candidates for cross reactivity have been put forward, only few have been substantiated on the molecular level. For the definition of cellular immune cross-reactivity, it proved critical to appreciate that recognition patterns of T-cells are not linear. Subsequent microarray studies unequivocally demonstrated functional mimicry of seemingly disparate amino acid sequences. This review summarises the present evidence for molecular mimicry in neurological autoimmune diseases and virus

  16. Targeting IL-10 in auto-immune diseases.

    PubMed

    Tian, Guo; Li, Jiao-Long; Wang, De-Guang; Zhou, Dian

    2014-09-01

    IL-10 is a multifunctional cytokine secreted by a variety of cells. It not only inhibits activation of monocyte/macrophage system and synthesis of monocyte cytokine and inflammatory cytokine but also promotes the proliferation and maturation of non-monocyte-dependent T cell, stimulating proliferation of antigen-specific B cell. Increasing evidence indicates that IL-10 plays an important role in both the onset and development of auto-immune diseases, such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), Sjogren's syndrome (SS), multiple sclerosis (MS), Crohn's disease (CD), and psoriasis. However, the exact mechanisms of IL-10 in auto-immune diseases remain unclear. In the present review, we will summarize the biological effects of IL-10, as well as its role and therapeutic potential in auto-immune diseases.

  17. Are individuals with an autoimmune disease at higher risk of a second autoimmune disorder?

    PubMed

    Somers, Emily C; Thomas, Sara L; Smeeth, Liam; Hall, Andrew J

    2009-03-15

    Limited evidence suggests that autoimmune diseases tend to co-occur, although data are needed to determine whether individuals with an existing autoimmune disorder are at increased risk of a second disorder. The authors conducted a series of population-based cohort studies, utilizing the United Kingdom General Practice Research Database, to assess intraindividual risks of coexistence of rheumatoid arthritis (RA), autoimmune thyroiditis (AIT), multiple sclerosis (MS), and insulin-dependent diabetes mellitus (IDDM) during 1990-1999. Sex-specific age- and calendar-period standardized incidence ratios (SIRs) were calculated for development of a second autoimmune disease among index populations including 22,888 RA, 26,198 AIT, 4,332 MS, and 6,170 IDDM patients compared with the general population. Among those with IDDM, adjusted AIT rates were higher than expected for both males (SIR = 646.0, 95% confidence interval (CI): 466, 873) and females (SIR = 409.6, 95% CI: 343, 485), as were RA rates for females (SIR = 181.6, 95% CI: 136, 238). Coexistence of AIT and RA was also shown for either disease sequence (sex-specific SIRs = 130.4-162.0). However, point estimates suggested an inverse relation between RA and MS, irrespective of diagnostic sequence. This study demonstrates coexistence of RA, AIT, and IDDM at higher than expected rates but reduced comorbidity between RA and MS.

  18. Autoantigen complementarity and its contributions to hallmarks of autoimmune disease.

    PubMed

    Pendergraft, William F; Badhwar, Anshul K; Preston, Gloria A

    2015-06-21

    The question considered is, "What causes the autoimmune response to begin and what causes it to worsen into autoimmune disease?" The theory of autoantigen complementarity posits that the initiating immunogen causing disease is a protein complementary (antisense) to the self-antigen, rather than a response to the native protein. The resulting primary antibody elicits an anti-antibody response or anti-idiotype, consequently producing a disease-inciting autoantibody. Yet, not everyone who developes self-reactive autoantibodies will manifest autoimmune disease. What is apparent is that manifestation of disease is governed by the acquisition of multiple immune-compromising traits that increase susceptibility and drive disease. Taking into account current cellular, molecular, and genetic information, six traits, or 'hallmarks', of autoimmune disease were proposed: (1) Autoreactive cells evade deletion, (2) Presence of asymptomatic autoantibodies, (3) Hyperactivity of Fc-FcR pathway, (4) Susceptibility to environmental impact, (5) Antigenic modifications of self-proteins, (6) Microbial Infections. Presented here is a discussion on how components delineated in the theory of autoantigen complementarity potentially promote the acquisition of multiple 'hallmarks' of disease.

  19. [Therapeutic intensification and autologous stem cell transplantation in autoimmune diseases].

    PubMed

    Marjanovic, Z; Gerber, I; Toledano, C; Hen-Solal, J; Damade, R; de Saint-Cyr, I; Sarrot-Reynauld, F; Ilié, D; Daneshpouy, M; Mounier, N; Ruivard, M; Tyndall, C; Vidal, E; Quere, I; Durand, J-M; Constans, J; Farge, D

    2005-02-26

    THE PATHOPHYSIOLOGY of most autoimmune diseases is often poorly understood. EXPERIMENTAL CONSIDERATIONS and clinical experience suggest that high doses immunoablation followed by stem cell transplantation is a therapeutic option to consider for certain severe autoimmune disorders. THE CONCEPT OF RESTORING NORMAL IMMUNE REACTIVITY must in part br true since current results of 466 transplants (445 autologous, 21 allogeneic) patients suffering from various autoimmune diseases show a beneficial outcome in approximately 2/3 of the patients. TO IMPROVE THE EFFICACY AND SAFETY OF SUCH AN AGGRESSIVE PROCEDURE in patients with potentially affected vital organs by the underlying autoimmune disease, it is especially important to follow international consensus guidelines and to centrally collect clinical data for in depth analysis in the EBMT International Stem Cell Project for Autoimmune Disease in Basel, Switzerland. PHASE III STUDIES ARE RUNNING FOR SYSTEMIC SCLEROSIS (Astis, Autologous Stem cell Transplantation International Rheumatoid Arthritis Trial) started in 2003. A STUDY PROJECT IS PLANNED FOR MULTIPLE SCLEROSIS (Astims, Autologous Stem cell Transplantation International Multiple Sclerosis).

  20. Biomarkers for cardiovascular risk assessment in autoimmune diseases.

    PubMed

    Teixeira, Priscila Camillo; Ferber, Philippe; Vuilleumier, Nicolas; Cutler, Paul

    2015-02-01

    Autoimmune diseases, such as antiphospholipid syndrome, systemic lupus erythematosus, and rheumatoid arthritis, are characterized by a high prevalence of cardiovascular (CV) disease (CVD), which constitutes the leading causes of morbidity and mortality among such patients. Although such effects are partly explained by a higher prevalence of traditional CV risk factors, many studies indicate that such factors do not fully explain the enhanced CV risk in these patients. In addition, risk stratification algorithms based upon traditional CV risk factors are not as predictive in autoimmune diseases as in the general population. For these reasons, the timely and accurate assessment of CV risk in these high-risk populations still remains an unmet clinical need. An enhanced contribution of different inflammatory components of the immune response, as well as autoimmune elements (e.g. autoantibodies, autoantigens, and cellular response), has been proposed to underlie the incremental CV risk observed in these populations. Recent advances in proteomic tools have contributed to the discovery of proteins involved in CVDs, including some that may be suitable to be used as biological markers. In this review we summarize the main markers in the field of CVDs associated with autoimmunity, as well as the recent advances in proteomic technology and their application for biomarker discovery in autoimmune disease.

  1. T follicular helper (Tfh) cells in autoimmune diseases.

    PubMed

    Nakayamada, Shingo; Tanaka, Yoshiya

    2016-01-01

      Systemic autoimmune diseases are characterized by multiple organ damages, whose pathogenesis caused by the activation of autoreactive T cells reacting against antigens of the body's own tissues and B cells producing autoantibodies. Following the animal studies, Tfh cells have been identified as a critical subset for the formation and function of B cell responses in humoral immunity, but also play an important role in autoimmunity. In fact, circulating Tfh cells are reported to increase and correlate with disease activity and autoantibody production in human autoimmune diseases. However, the evidence from human studies highlighted apparent differences between mouse and human Tfh cell differentiation. Furthermore, there is increased recognition of functional plasticity and diversity of Tfh cells. This may be advantageous in terms of host defense but needs to be borne in mind in thinking about effective therapies for autoimmune diseases. Thus, better understanding of the extrinsic and intrinsic signals that control plasticity and diversity of Tfh cells will have important therapeutic applications to control autoimmunity.

  2. Epigenetic Alterations in Cellular Immunity: New Insights into Autoimmune Diseases.

    PubMed

    Wang, Zijun; Lu, Qianjin; Wang, Zhihui

    2017-02-08

    Epigenetic modification is an additional regulator in immune responses as the genome-wide profiling somehow fails to explain the sophisticated mechanisms in autoimmune diseases. The effect of epigenetic modifications on adaptive immunity derives from their regulations to induce a permissive or negative gene expression. Epigenetic events, such as DNA methylation, histone modifications and microRNAs (miRNAs) are often found in T cell activation, differentiation and commitment which are the major parts in cellular immunity. Recognizing the complexity of interactions between epigenetic mechanisms and immune disturbance in autoimmune diseases is essential for the exploration of efficient therapeutic targets. In this review, we summarize a list of studies that indicate the significance of dysregulated epigenetic modifications in autoimmune diseases while focusing on T cell immunity.

  3. Therapeutic antibodies that target inflammatory cytokines in autoimmune diseases.

    PubMed

    Lai, Yuping; Dong, Chen

    2016-04-01

    Inflammatory cytokines are key regulators of immune responses. Persistent and excessive production of inflammatory cytokines underscores the development of autoimmune diseases. Therefore, neutralizing inflammatory cytokines or antagonizing their receptor function is considered as a useful therapeutic strategy to treat autoimmune diseases. To achieve the success of such a strategy, understanding of the complex actions of these cytokines and cytokine networks is required. In this review we focus on four inflammatory cytokines--tumor necrosis factor α (TNFα), interleukin-6 (IL-6), IL-23 and IL-17--and dissect how the dysregulation of these cytokines regulates autoimmune diseases. On the basis of pre-clinical and clinical data, we specifically discuss the therapeutic rationale for targeting these cytokines and describe the potential adverse effects.

  4. The roles of Egr-2 in autoimmune diseases.

    PubMed

    Zhang, Min; Wang, Ying; Wang, Jian-Shu; Liu, Jiao; Liu, Meng-Meng; Yang, Hai-Bing

    2015-01-01

    Being a member of the early growth response (Egr) family of transcription factors, Egr-2 is expressed in a variety of cell types of the immune system. Recent findings imply that Egr-2 is important in the development and function of T helper (Th) 17 cell, regulatory T (Treg) cell, as well as dendritic cell (DC). Although these cells perform significantly in the pathogenesis of autoimmune diseases, such as systemic lupus erythematosus, multiple sclerosis, and systemic sclerosis, the roles of Egr-2 in the pathogenesis of autoimmune diseases can not be neglected. In this article, we will discuss recent findings about the important roles of Egr-2 in immune cells and the possible pathological roles of Egr-2 in autoimmune diseases.

  5. Drug targets in the cytokine universe for autoimmune disease.

    PubMed

    Liu, Xuebin; Fang, Lei; Guo, Taylor B; Mei, Hongkang; Zhang, Jingwu Z

    2013-03-01

    In autoimmune disease, a network of diverse cytokines is produced in association with disease susceptibility to constitute the 'cytokine milieu' that drives chronic inflammation. It remains elusive how cytokines interact in such a complex network to sustain inflammation in autoimmune disease. This has presented huge challenges for successful drug discovery because it has been difficult to predict how individual cytokine-targeted therapy would work. Here, we combine the principles of Chinese Taoism philosophy and modern bioinformatics tools to dissect multiple layers of arbitrary cytokine interactions into discernible interfaces and connectivity maps to predict movements in the cytokine network. The key principles presented here have important implications in our understanding of cytokine interactions and development of effective cytokine-targeted therapies for autoimmune disorders.

  6. Haematopoietic stem cell gene therapy to treat autoimmune disease.

    PubMed

    Alderuccio, Frank; Siatskas, Christopher; Chan, James; Field, Judith; Murphy, Kim; Nasa, Zeyad; Toh, Ban-Hock

    2006-09-01

    Autoimmune diseases affect approximately 6% of the population and are characterised by a pathogenic immune response that targets self-antigens. Well known diseases of this nature include type 1 diabetes, systemic lupus erythematosus, rheumatoid arthritis and multiple sclerosis. Treatment is often restricted to replacement therapy or immunosuppressive regimes and to date there are no cures. The strategy of utilising autologous or allogeneic haematopoietic stem cell transplantation to treat autoimmunity and induce immunological tolerance has been trailed with various levels of success. A major issue is disease relapse as the autoimmune response is reinitiated. Cells of the immune system originate from bone marrow and have a central role in the induction of immunological tolerance. The ability to isolate and genetically manipulate bone marrow haematopoietic stem cells therefore makes these cells a suitable vehicle for driving ectopic expression of defined autoantigens and induction of immunological tolerance.

  7. Hypogonadism and the risk of rheumatic autoimmune disease.

    PubMed

    Baillargeon, Jacques; Al Snih, Soham; Raji, Mukaila A; Urban, Randall J; Sharma, Gulshan; Sheffield-Moore, Melinda; Lopez, David S; Baillargeon, Gwen; Kuo, Yong-Fang

    2016-12-01

    Testosterone deficiency has been linked with autoimmune disease and an increase in inflammatory markers, such as C-reactive protein (CRP), tumor necrosis factor, and interleukin-6 (IL-6). However, no large-scale longitudinal studies have examined this association. We examined whether untreated hypogonadism was associated with an increased risk of rheumatic autoimmune disease in a large nationally representative cohort. Using one of the nation's largest commercial insurance databases, we conducted a retrospective cohort study in which we identified 123,460 men diagnosed with hypogonadism between January 1, 2002 and December 31, 2014 and with no prior history of rheumatic autoimmune disease. We matched this cohort to 370,380 men without hypogonadism, at a 1 to 3 ratio, on age and index/diagnosis date. All patients were followed until December 31, 2014 or until they lost insurance coverage or were diagnosed with a rheumatic autoimmune disease. Cox proportional hazards regression was used to calculate adjusted hazard ratios (aHRs). Untreated hypogonadism was associated with an increased risk of developing any rheumatic autoimmune disease (HR = 1.33, 95 % CI = 1.28, 1.38), rheumatoid arthritis (HR = 1.31, 95 % CI = 1.22, 1.44), and lupus (HR = 1.58, 95 % CI = 1.28, 1.94). These findings persisted using latency periods of 1 and 2 years. Hypogonadism was not associated with the control outcome, epilepsy (HR = 1.04, 95 % CI = 0.96, 1.15). Patients diagnosed with hypogonadism who were not treated with testosterone had an increased risk of developing any rheumatic autoimmune disease, rheumatoid arthritis, and lupus. Future research should further examine this association, with particular attention to underlying mechanisms.

  8. Drug-induced autoimmune liver disease: A diagnostic dilemma of an increasingly reported disease.

    PubMed

    Castiella, Agustin; Zapata, Eva; Lucena, M Isabel; Andrade, Raúl J

    2014-04-27

    The aetiology of autoimmune hepatitis (AIH) is uncertain but the disease can be triggered in susceptible patients by external factors such as viruses or drugs. AIH usually develops in individuals with a genetic background mainly consisting of some risk alleles of the major histocompatibility complex (HLA). Many drugs have been linked to AIH phenotypes, which sometimes persist after drug discontinuation, suggesting that they awaken latent autoimmunity. At least three clinical scenarios have been proposed that refers to drug- induced autoimmune liver disease (DIAILD): AIH with drug-induced liver injury (DILI); drug induced-AIH (DI-AIH); and immune mediated DILI (IM-DILI). In addition, there are instances showing mixed features of DI-AIH and IM-DILI, as well as DILI cases with positive autoantibodies. Histologically distinguishing DILI from AIH remains a challenge. Even more challenging is the differentiation of AIH from DI-AIH mainly relying in histological features; however, a detailed standardised histologic evaluation of large cohorts of AIH and DI-AIH patients would probably render more subtle features that could be of help in the differential diagnosis between both entities. Growing information on the relationship of drugs and AIH is being available, being drugs like statins and biologic agents more frequently involved in cases of DIAILD. In addition, there is some evidence on the fact that patients diagnosed with DIAILD may have had a previous episode of hepatotoxicity. Further collaborative studies in DIAILD will strengthen the knowledge and understanding of this intriguing and complex disorder which might represent different phenotypes across the spectrum of disease.

  9. 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.

  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. HLA-G Molecules in Autoimmune Diseases and Infections

    PubMed Central

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

    2014-01-01

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

  12. Environmental Basis of Autoimmunity.

    PubMed

    Floreani, Annarosa; Leung, Patrick S C; Gershwin, M Eric

    2016-06-01

    The three common themes that underlie the induction and perpetuation of autoimmunity are genetic predisposition, environmental factors, and immune regulation. Environmental factors have gained much attention for their role in triggering autoimmunity, with increasing evidence of their influence as demonstrated by epidemiological studies, laboratory research, and animal studies. Environmental factors known to trigger and perpetuate autoimmunity include infections, gut microbiota, as well as physical and environmental agents. To address these issues, we will review major potential mechanisms that underlie autoimmunity including molecular mimicry, epitope spreading, bystander activation, polyclonal activation of B and T cells, infections, and autoinflammatory activation of innate immunity. The association of the gut microbiota on autoimmunity will be particularly highlighted by their interaction with pharmaceutical agents that may lead to organ-specific autoimmunity. Nonetheless, and we will emphasize this point, the precise mechanism of environmental influence on disease pathogenesis remains elusive.

  13. First-in-class inhibitor of the T cell receptor for the treatment of autoimmune diseases.

    PubMed

    Borroto, Aldo; Reyes-Garau, Diana; Jiménez, M Angeles; Carrasco, Esther; Moreno, Beatriz; Martínez-Pasamar, Sara; Cortés, José R; Perona, Almudena; Abia, David; Blanco, Soledad; Fuentes, Manuel; Arellano, Irene; Lobo, Juan; Heidarieh, Haleh; Rueda, Javier; Esteve, Pilar; Cibrián, Danay; Martinez-Riaño, Ana; Mendoza, Pilar; Prieto, Cristina; Calleja, Enrique; Oeste, Clara L; Orfao, Alberto; Fresno, Manuel; Sánchez-Madrid, Francisco; Alcamí, Antonio; Bovolenta, Paola; Martín, Pilar; Villoslada, Pablo; Morreale, Antonio; Messeguer, Angel; Alarcon, Balbino

    2016-12-21

    Modulating T cell activation is critical for treating autoimmune diseases but requires avoiding concomitant opportunistic infections. Antigen binding to the T cell receptor (TCR) triggers the recruitment of the cytosolic adaptor protein Nck to a proline-rich sequence in the cytoplasmic tail of the TCR's CD3ε subunit. Through virtual screening and using combinatorial chemistry, we have generated an orally available, low-molecular weight inhibitor of the TCR-Nck interaction that selectively inhibits TCR-triggered T cell activation with an IC50 (median inhibitory concentration) ~1 nM. By modulating TCR signaling, the inhibitor prevented the development of psoriasis and asthma and, furthermore, exerted a long-lasting therapeutic effect in a model of autoimmune encephalomyelitis. However, it did not prevent the generation of a protective memory response against a mouse pathogen, suggesting that the compound might not exert its effects through immunosuppression. These results suggest that inhibiting an immediate TCR signal has promise for treating a broad spectrum of human T cell-mediated autoimmune and inflammatory diseases.

  14. The contribution of thymic stromal abnormalities to autoimmune disease.

    PubMed

    Fletcher, Anne L; Calder, Adrienne; Hince, Melanie N; Boyd, Richard L; Chidgey, Ann P

    2011-01-01

    In essence, normal thymus function involves the production of a broad repertoire of αβT cells capable of responding to foreign antigens with low risk of autoreactivity. Thymic epithelial cells are an essential component of the thymic stromal microenvironment, promoting the growth and export of self-tolerant thymocytes. Autoimmune disease, resulting from a loss of self-tolerance, is clinically and genetically complex, and accordingly has many potential etiological origins. However, it is commonly linked to defects in the thymic epithelial microenvironment. The study of autoimmune-linked thymic stromal dysfunction has indisputably advanced our understanding of T cell tolerance; notably, a field-wide paradigm shift occurred when autoimmune regulator (Aire) was found to drive expression of a multitude of peripheral tissue-restricted antigens in medullary thymic epithelial cells. Many other associations with polygenically controlled autoimmune diseases have been reported but are more difficult to definitively dissect. Paradoxically, immunodeficiency and age-related immunosenescence are also linked with increased autoimmunity. Here we discuss the theoretical basis and the evidence gathered thus far to support these associations.

  15. The Influence and Role of Microbial Factors in Autoimmune Kidney Diseases: A Systematic Review.

    PubMed

    Kronbichler, Andreas; Kerschbaum, Julia; Mayer, Gert

    2015-01-01

    A better understanding of the pathophysiology of autoimmune disorders is desired to allow tailored interventions. Despite increased scientific interest a direct pathogenic factor in autoimmune renal disease has been described only in a minority like membranous nephropathy or ANCA-associated vasculitis. Nonetheless the initial step leading to the formation of these antibodies is still obscure. In this review we will focus on the possible role of microbial factors in this context. Staphylococcus aureus may be a direct pathogenetic factor in granulomatosis with polyangiitis (GPA). Chronic bacterial colonization or chronic infections of the upper respiratory tract have been proposed as trigger of IgA vasculitis and IgA nephropathy. Interventions to remove major lymphoid organs, such as tonsillectomy, have shown conflicting results but may be an option in IgA vasculitis. Interestingly no clear clinical benefit despite similar local colonization with bacterial strains has been detected in patients with IgA nephropathy. In systemic lupus erythematosus injection of bacterial lipopolysaccharide induced progressive lupus nephritis in mouse models. The aim of this review is to discuss and summarize the knowledge of microbial antigens in autoimmune renal disease. Novel methods may provide insight into the involvement of microbial antigens in the onset, progression, and prognosis of autoimmune kidney disorders.

  16. Possible pathogenic nature of the recently discovered TT virus: does it play a role in autoimmune rheumatic diseases?

    PubMed

    Gergely, Peter; Perl, Andras; Poór, Gyula

    2006-11-01

    Pathogenesis of viral origin has long been suggested in autoimmune rheumatic diseases. Beside the well-defined virus induced transient or chronic rheumatic diseases often resembling systemic autoimmune disorders such as rheumatoid arthritis, viruses can contribute to disease pathogenesis by several different pathomechanisms. TT virus is a recently discovered virus of extremely high genetic diversity which commonly infects humans. Despite accumulated evidence on the biological characteristics of TTV, its pathogenicity is still in question; many consider TTV as a harmless endosymbiont. The recent paper overviews the biology of TT virus and investigates the hypothesis that TTV might have a causative role in human diseases with special attention to the possibility that TTV might trigger autoimmunity in rheumatic disorders.

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

    PubMed Central

    Schwalfenberg, Gerry K.

    2012-01-01

    This paper looks at the environmental role of vitamin D and solar radiation as risk reduction factors in autoimmune disease. Five diseases are considered: multiple sclerosis, type 1 diabetes, rheumatoid arthritis, autoimmune disease of the thyroid, and inflammatory bowel disease. Clinical relevant studies and factors that may indicate evidence that autoimmune disease is a vitamin D-sensitive disease are presented. Studies that have resulted in prevention or amelioration of some autoimmune disease are discussed. An example of the utility of supplementing vitamin D in an unusual autoimmune disease, idiopathic thrombocytic purpura, is presented. PMID:22523507

  18. 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.

  19. Vaccine-related autoimmune hepatitis: the same disease as idiopathic autoimmune hepatitis? Two clinical reports and review.

    PubMed

    van Gemeren, Marline A J; van Wijngaarden, Peter; Doukas, Michael; de Man, Robert A

    2017-01-01

    Autoimmune hepatitis (AIH) develops in genetically predisposed individuals after an inciting or environmental trigger. These factors are unknown but may include viral infections, environmental toxins, drugs and vaccinations. Few reports are written about vaccination as potential trigger of autoimmune hepatitis. In this article, we additionally describe two vaccine-related cases of AIH. In both cases, long-term immune-suppressive therapy is demanded. Moreover, we present the cases of vaccine-related AIH from literature and compare these with idiopathic AIH and our own cases.

  20. Role of vitamin D in acquired immune and autoimmune diseases.

    PubMed

    Delvin, Edgard; Souberbielle, Jean-Claude; Viard, Jean-Paul; Salle, Bernard

    2014-08-01

    Vitamin D has been attributed roles in the pathogenesis and prevention of several diseases such as cancer, cardiovascular disease, multiple sclerosis, diabetes, autism and autoimmune diseases. The concomitant expression of the 25-hydroxyvitamin D3-1α-hydroxylase and of the vitamin D3 receptor in animal and human tissues and organs other than bone supports this paradigm. Translated into the clinical field, meta-analyses and systematic reviews have also revealed an association between vitamin D insufficiency or deficiency and non-osseous diseases. Although relying on the large databases, they are diverse in nature and involve participants of varying age and evolving in different environments. Furthermore, they do not allow any analysis of a possible causal relationship between vitamin D supplementation and clinical outcomes. Following a brief historical account, this review addresses these caveats, and gives examples of randomized controlled trials conducted in the fields of acquired immune and autoimmune diseases.

  1. 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.

  2. Omega-3 fatty acids in inflammation and autoimmune diseases.

    PubMed

    Simopoulos, Artemis P

    2002-12-01

    Among the fatty acids, it is the omega-3 polyunsaturated fatty acids (PUFA) which possess the most potent immunomodulatory activities, and among the omega-3 PUFA, those from fish oil-eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)--are more biologically potent than alpha-linolenic acid (ALA). Some of the effects of omega-3 PUFA are brought about by modulation of the amount and types of eicosanoids made, and other effects are elicited by eicosanoid-independent mechanisms, including actions upon intracellular signaling pathways, transcription factor activity and gene expression. Animal experiments and clinical intervention studies indicate that omega-3 fatty acids have anti-inflammatory properties and, therefore, might be useful in the management of inflammatory and autoimmune diseases. Coronary heart disease, major depression, aging and cancer are characterized by an increased level of interleukin 1 (IL-1), a proinflammatory cytokine. Similarly, arthritis, Crohn's disease, ulcerative colitis and lupus erythematosis are autoimmune diseases characterized by a high level of IL-1 and the proinflammatory leukotriene LTB(4) produced by omega-6 fatty acids. There have been a number of clinical trials assessing the benefits of dietary supplementation with fish oils in several inflammatory and autoimmune diseases in humans, including rheumatoid arthritis, Crohn's disease, ulcerative colitis, psoriasis, lupus erythematosus, multiple sclerosis and migraine headaches. Many of the placebo-controlled trials of fish oil in chronic inflammatory diseases reveal significant benefit, including decreased disease activity and a lowered use of anti-inflammatory drugs.

  3. [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

  4. Total Recovery from Monoclonal Gammopathy and Autoimmune Phenomena After Parathyroidectomy

    PubMed Central

    Cañas, Carlos A; Echeverri, Andrés F; Anaya, Juan-Manuel

    2012-01-01

    Based on the observation of a patient with a causal relationship between hyperparathyroidism and development of both autoimmune disease and paraproteinemia, we hypothesize a novel cause of autoimmunity triggered in the context of hyperparathyroidism. PMID:22870165

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

    ClinicalTrials.gov

    2016-12-12

    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; Gougerot-sjögren

  6. Association between thyroid autoimmunity and fibromyalgic disease severity.

    PubMed

    Bazzichi, Laura; Rossi, Alessandra; Giuliano, Tiziana; De Feo, Francesca; Giacomelli, Camillo; Consensi, Arianna; Ciapparelli, Antonio; Consoli, Giorgio; Dell'osso, Liliana; Bombardieri, Stefano

    2007-12-01

    Our objectives were to investigate thyroid abnormalities and autoimmunity in 120 patients affected by fibromyalgia (FM) and to study their relationships with clinical data and symptoms. Thyroid assessment by means of antithyroglobulin antibodies, antithyroid peroxidase antibodies, free triiodo-thyronine, free thyroxine, and thyroid stimulating hormone analyses was carried out. The clinical parameters "Fibromyalgia Impact Questionnaire", pain, tender points, fatigue, and other symptoms, and the presence of depression or anxiety disorders were evaluated. The basal thyroid hormone levels of FM patients were in the normal range, while 41% of the patients had at least one thyroid antibody. Patients with thyroid autoimmunity showed a higher percentage of dry eyes, burning, or pain with urination, allodynia, blurred vision, and sore throat. Correlations found between thyroid autoimmunity and age or with the presence of depression or anxiety disorders were not significant. However, in the cohort of post-menopausal patients, the frequency of thyroid autoimmunity was higher with respect to pre-menopausal patients. In conclusion, autoimmune thyroiditis is present in an elevated percentage of FM patients, and it has been associated with the presence of typical symptoms of the disease.

  7. 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

  8. Effect of TACI Signaling on Humoral Immunity and Autoimmune Diseases

    PubMed Central

    Zhang, Yi; Li, Jun; Zhang, Ya-Min; Zhang, Xiao-Ming; Tao, Juan

    2015-01-01

    Transmembrane activator and calcium-modulating cyclophilin ligand interactor (TACI) is one of the receptors of B cell activating factor of the tumor necrosis factor family (BAFF) and a proliferation-inducing ligand (APRIL). TACI is a regulator in the immune responses. TACI inhibits B cell expansion and promotes the differentiation and survival of plasma cells. The mechanisms underlying these effects probably involve changed expressions of some crucial molecules, such as B lymphocyte induced maturation protein-1 (Blimp-1) and inducible T-cell costimulator ligand (ICOSL) in B cells and/or plasma cells. However, abnormal TACI signaling may relate to autoimmune disorders. Common variable immune deficiency (CVID) patients with heterozygous mutations in TACI alleles increase susceptibility to autoimmune diseases. Taci−/− mice and BAFF transgenic mice both develop signs of human SLE. These findings that indicate inappropriate levels of TACI signaling may disrupt immune system balance, thereby promoting the development of autoimmune diseases. In this review, we summarize the basic characteristics of the TACI ligands BAFF and APRIL, and detail the research findings on the role of TACI in humoral immunity. We also discuss the possible mechanisms underlying the susceptibility of CVID patients with TACI mutations to autoimmune diseases and the role of TACI in the pathogenesis of SLE. PMID:25866827

  9. [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.

  10. Alcohol withdrawal syndrome--an auto-immune disease? A neuroimmunologic model for pathogenesis of alcohol withdrawal symptoms.

    PubMed

    Schubert, S

    1990-08-01

    A neuroimmunologic model of alcohol withdrawal symptoms is developed according to which these may be considered as an idiopathic auto-immune disease. During the alcohol abuse period of non-addicts, homeostasis may alter pathologically by gradual adaptation of the organism: auto-sensitisation develops and finally leads to the breakdown of auto-immune tolerance of the structural modifications set by alcohol withdrawal. The immunosystem regards the existing assimilation of alcohol as self, the withdrawal of alcohol as non-self. Alcohol withdrawal may be considered as an acknowledged physical stressor, and physical stressors as potential triggers of auto-immune diseases. Some so-called alcohol-induced diseases may originate in the pathogenic effects of preceding auto-immune responses to repeated alcohol withdrawals. Neuroimmunologic preconditions of potential auto-immune diseases exactly fit the alcohol withdrawal situation. Neuroimmunologic diseases themselves show close analogies respectively to alcohol withdrawal symptoms as well as to some alcohol-induced diseases. The myelin basis protein is assumed to be a potential auto-allergen. Finally withdrawal symptoms being the expression of physical dependence on alcohol, the model may highlight the very nature of physical dependence.

  11. 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.

  12. Effect of autoimmune diseases on risk and survival in histology-specific lung cancer.

    PubMed

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

    2012-12-01

    Patients with autoimmune diseases are at an increased risk of cancer due to underlying dysregulation of the immune system or treatment. Data on cancer incidence, mortality and survival after autoimmune diseases would provide further information on the clinical implications. We systematically analysed data on lung cancer in patients diagnosed with 33 different autoimmune diseases. Standardised incidence ratios (SIRs), standardised mortality ratios (SMRs) and hazard ratios (HRs) were calculated for subsequent incident lung cancers or lung cancer deaths up to 2008 in patients hospitalised for autoimmune disease after 1964. Increased risks of lung cancer were recorded for SIRs after 12 autoimmune diseases, SMRs after 11 autoimmune diseases and HRs after two autoimmune diseases. The highest SIRs and SMRs, respectively, were seen after discoid lupus erythematosus (4.71 and 4.80), polymyosistis/dermatomyositis (4.20 and 4.17), systemic lupus erythematosus (2.47 and 2.69), rheumatic fever (2.07 and 2.07) and systemic sclerosis (2.19 and 1.98). Autoimmune disease did not influence survival overall but some autoimmune diseases appeared to impair survival in small cell carcinoma. All autoimmune diseases that had an SIR >2.0 are known to present with lung manifestations, suggesting that the autoimmune process contributes to lung cancer susceptibility. The data on survival are reassuring that autoimmune diseases do not influence prognosis in lung cancer.

  13. [Type 1 diabetes-associated autoimmune diseases: screening, diagnostic principles and management].

    PubMed

    Witek, Przemysław R; Witek, Joanna; Pańkowska, Ewa

    2012-01-01

    Type 1 diabetes (T1DM) is often associated with autoimmune diseases such as: autoimmune thyroid disease (ATD), celiac disease (CD), autoimmune gastritis (AIG), pernicious anemia (PA) and vitiligo. Autoimmune thyroid disease is the most prevalent endocrinopathy among diabetic patients. Hypothyroidism, celiac disease or Addison's disease in patients with type 1 diabetes may deteriorate glycemic control and can lead to an increased rate of hypoglycemia. Autoimmune gastritis, pernicious anemia and celiac disease can cause malabsorption and anemia which additionally impair the quality of life in patients with T1DM. The presence of organ-specific autoantibodies can be used to screen patients who are at higher risk of developing autoimmune diseases. Such procedure can help to identify patients, who need to undergo treatment in order to decrease the rate of possible complications in the future. In this clinical review we present current opinions in terms of diagnosis, management and screening in the most common type 1 diabetes-associated autoimmune diseases.

  14. Serum IgG subclasses in autoimmune diseases.

    PubMed

    Zhang, Haoze; Li, Ping; Wu, Di; Xu, Dong; Hou, Yong; Wang, Qian; Li, Mengtao; Li, Yongzhe; Zeng, Xiaofeng; Zhang, Fengchun; Shi, Qun

    2015-01-01

    To characterize serum IgG subclass levels in several autoimmune diseases, including primary Sjogren syndrome (pSS), systemic sclerosis (SSc), systemic lupus erythematosus (SLE), and primary biliary cirrhosis (PBC). We aimed to analyze serum IgG subclass distribution and to test whether serum IgG4 levels are elevated in these diseases. Serum IgG subclass levels from 102 pSS, 102 SSc, 100 SLE, and 59 PBC patients, as well as 40 healthy controls (HCs), were measured using the immunonephelometric assay. The distribution of IgG subclasses among these autoimmune diseases was analyzed. In this cross-sectional study, serum IgG1 (IgG1/IgG) and/or IgG3 (IgG3/IgG) were significantly increased, compared with those in HCs. Only 6.34% of patients had levels of serum IgG4 >135 mg/dL. There were no significant differences in the frequency of elevated serum IgG4 levels between patients and HC. In pSS, serum IgG1 levels were much higher than those in other disease groups, whereas serum IgG2 and IgG3 levels were most prominently increased in PBC. A strikingly different serum IgG subclass distribution was detected in patients with autoimmune diseases compared with HCs. Serum IgG subclass levels also showed distinct characteristics among different autoimmune diseases. Serum IgG4 levels in these patients were lower or not much higher than those in HCs, which differed from IgG4-related diseases.

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

    PubMed

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

    2015-01-01

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

  16. Premature Ovarian Failure: An Association with Autoimmune Diseases

    PubMed Central

    Jha, Vandana; Goswami, Deepti

    2016-01-01

    Introduction Premature Ovarian Failure (POF) is the cessation of ovarian function before the age of 40 years. POF is reported to be associated with autoimmune diseases in 20-30% of cases. Aim Patients presenting with idiopathic POF were screened for the presence of autoimmune disorders. Materials and Methods Twenty patients with idiopathic POF were included in the study. Baseline investigation in all subjects included fasting serum FSH, LH, E2, progesterone, free T3, free T4, Thyroid-Stimulating Hormone (TSH) and Anti-Thyroperoxidase (anti-TPO) antibodies, testosterone and Dehydroepiandrosterone (DHEAS) levels. Fasting and post-glucose (2 hours after 75g of oral glucose) serum calcium and phosphate were estimated using appropriate assays in biochemistry laboratory. Results Seven patients (35%), who presented with secondary amenorrhea, had thyroid disorders and were already on thyroxine replacement therapy. One patient also had vitiligo. There was no history of adrenal disorder. Anti-TPO levels were elevated in two (10%) patients of secondary amenorrhea group. The levels of serum testosterone were low in three patients. Serum DHEAS levels were low in 13 patients. Blood sugar levels (fasting and 2 hour post 75g glucose load) and fasting insulin levels were normal. Serum calcium and phosphate levels were normal in all the patients. Conclusion Thyroid autoimmunity is the most common autoimmune disease associated with POF. The finding of low DHEAS in a large percentage of patients (65%), suggests possibility of adrenal dysfunction. This requires further testing for adrenal reserve and adrenal autoantibodies. PMID:27891401

  17. Malignancies in autoimmune rheumatic diseases - a mini-review.

    PubMed

    Szekanecz, Zoltán; Szekanecz, Eva; Bakó, Gyula; Shoenfeld, Yehuda

    2011-01-01

    Paraneoplastic symptoms, caused by a malignancy, but not directly related to invasion by the tumor or its metastases, are the result of a wide variety of tumor-derived biologic mediators like hormones, peptides, antibodies, cytotoxic lymphocytes, autocrine and paracrine mediators. Systemic inflammatory rheumatic diseases, such as rheumatoid arthritis, systemic lupus erythematosus, scleroderma or dermatomyositis, may increase the risk for the development of malignancies, predominantly lymphoproliferative disorders. Immunosuppressive drugs and biological agents may also be carcinogenic. However, sustained inflammatory activity seems to be the primary risk factor for malignancies in autoimmune diseases. Tumor-associated antigens may be produced by inflammatory cells and their production may be increased in rheumatoid arthritis and other autoimmune diseases.

  18. Cell therapy for autoimmune diseases: does it have a future?

    PubMed

    Radbruch, A; Thiel, A

    2004-11-01

    Almost all current therapeutic concepts in autoimmune diseases are based on the systemic suppression of immune functions and are not curative. The recent introduction of biologicals such as tumour necrosis factor blocking antibodies or receptors has added greater specificity to efficient management of disease by targeted suppression of rheumatic inflammation. It is evident, however, that only the elimination of the cells secreting inflammatory mediators, rather than the blockade of secreted molecules, will offer real specific therapeutic advantages in the future. Merely the elimination of such cells and also cells controlling the secreting effector cells could be curative and induce true long term remissions. We review here the state of the art and future therapeutic concepts that are based on the specific modulation of pathogenic cells that induce and sustain autoimmune inflammation. This sounds visionary, however, a variety of basic tools are at hand now. Thus, direct and specific cell therapy of rheumatic diseases will become a true alternative to conventional therapies.

  19. 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.

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

    PubMed

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

    2003-12-01

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

  1. Interleukin-23: as a drug target for autoimmune inflammatory diseases

    PubMed Central

    Tang, Chunlei; Chen, Shu; Qian, Hai; Huang, Wenlong

    2012-01-01

    Interleukin-23 (IL-23) is a member of the IL-12 family of cytokines with pro-inflammatory properties. Its ability to potently enhance the expansion of T helper type 17 (Th17) cells indicates the responsibility for many of the inflammatory autoimmune responses. Emerging data demonstrate that IL-23 is a key participant in central regulation of the cellular mechanisms involved in inflammation. Both IL-23 and IL-17 form a new axis through Th17 cells, which has evolved in response to human diseases associated with immunoactivation and immunopathogeny, including bacterial or viral infections and chronic inflammation. Targeting of IL-23 or the IL-23 receptor or IL-23 axis is a potential therapeutic approach for autoimmune diseases including psoriasis, inflammatory bowel disease, rheumatoid arthritis and multiple sclerosis. The current review focuses on the immunobiology of IL-23 and summarizes the most recent findings on the role of IL-23 in the pre-clinical and ongoing clinical studies. PMID:22044352

  2. 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.

  3. [Immunological Techniques that Support the Diagnosis of the Autoimmune Diseases].

    PubMed

    Hernández Ramírez, Diego F; Cabiedes, Javier

    2010-01-01

    During the past few years technological advance have been allowed the developing of techniques that help to the diagnosis of multiple diseases. In the case of the autoimmune diseases, immunological techniques are helpful since they allow the detection of multiple autoantibodies at the same time with small volumes of sample. Together with the development of the new techniques, sensitivity and specificity in the detection of the antibodies specificities' also have been increased, in such a way that the clinicians can count with tests that allow them to make early diagnoses with greater certainty and also to follow the course of the disease based on the variation of the antibodies presents in the patient's samples. It is important to emphasize that the new techniques of laboratory that are used for the support of the diagnosis of autoimmune diseases, no longer are exclusive for research laboratories but by their facility of standardization, quality control and reproducibility they can be used in clinical laboratory of medium and small sizes. In the present paper we describe those techniques with greater application in the clinical laboratory of autoimmune diseases.

  4. Refractive Surgery in Systemic and Autoimmune Disease

    PubMed Central

    AlKharashi, Majed; Bower, Kraig S.; Stark, Walter J.; Daoud, Yassine J.

    2014-01-01

    Patients with underlying systemic disease represent challenging treatment dilemma to the refractive surgeon. The refractive error in this patient population is accompanied by a systemic disease that may have an ocular or even a corneal component. The literature is rather sparse about the use of laser refractive surgery (LRS) and such procedure is not approved by the United States Food and Drug Administration (FDA) in this patient population. Patients with collagen vascular disease, diabetes mellitus (DM), allergic and atopic disease, or human immunodeficiency virus (HIV) are never ideal for LRS. Patients with uncontrolled systemic disease or ocular involvement of the disease should not undergo LRS. However, a patient with well-controlled and mild disease, no ocular involvement, and not on multidrug regimen may be a suitable candidate if they meet stringent criteria. There is a need for a large, multicenter, controlled trial to address the safety and efficacy of LRS in patients with systemic disease before such technology can be widely adopted by the refractive surgery community. PMID:24669141

  5. Antinuclear antibody testing in systemic autoimmune disease.

    PubMed

    Evans, J

    1998-12-01

    This article discusses the use and interpretation of antinuclear antibody (ANA) testing in connective tissue diseases. Methods of ANA detection are discussed and analyzed in detail as is the role of ANAs in systemic lupus, scleroderma, and polymyositis, connective tissue diseases with prominent pulmonary involvement.

  6. Association of the autoimmune disease scleroderma with an immunologic response to cancer.

    PubMed

    Joseph, Christine G; Darrah, Erika; Shah, Ami A; Skora, Andrew D; Casciola-Rosen, Livia A; Wigley, Fredrick M; Boin, Francesco; Fava, Andrea; Thoburn, Chris; Kinde, Isaac; Jiao, Yuchen; Papadopoulos, Nickolas; Kinzler, Kenneth W; Vogelstein, Bert; Rosen, Antony

    2014-01-10

    Autoimmune diseases are thought to be initiated by exposures to foreign antigens that cross-react with endogenous molecules. Scleroderma is an autoimmune connective tissue disease in which patients make antibodies to a limited group of autoantigens, including RPC1, encoded by the POLR3A gene. As patients with scleroderma and antibodies against RPC1 are at increased risk for cancer, we hypothesized that the "foreign" antigens in this autoimmune disease are encoded by somatically mutated genes in the patients' incipient cancers. Studying cancers from scleroderma patients, we found genetic alterations of the POLR3A locus in six of eight patients with antibodies to RPC1 but not in eight patients without antibodies to RPC1. Analyses of peripheral blood lymphocytes and serum suggested that POLR3A mutations triggered cellular immunity and cross-reactive humoral immune responses. These results offer insight into the pathogenesis of scleroderma and provide support for the idea that acquired immunity helps to control naturally occurring cancers.

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

    PubMed

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

    2016-10-07

    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.

  8. Twin studies in auto-immune disease.

    PubMed

    Leslie, R D; Hawa, M

    1994-01-01

    Immune-mediated diseases affect up to 5% of the population and are a major cause of morbidity and mortality. These diseases can be organ specific, such as insulin-dependent diabetes (IDDM) and non-organ specific, such as Rheumatoid Arthritis (RA). Identical and non-identical twins have been used to establish whether these diseases are determined by genetic or environmental factors. The results of these studies have been collated in a new section of the Mendel Institute in Rome. Diseases included in these studies included IDDM, RA, Systemic Lupus Erythematosus (SLE), Multiple Sclerosis (MS) and Myasthenia. Striking differences in concordance rates between identical and non-identical twins in all these studies suggest that genetic factors are important in causing these diseases. All the diseases are known to be associated with HLA genes on chromosome 6 which may account for some or all of the genetic susceptibility. However, in the majority of pairs the affected twin has an unaffected co-twin. These observations suggest that non-genetically determined factors, probably environmental factors and not somatic mutations, are critical. The study of unaffected co-twins, who are at high disease-risk, has allowed the identification of changes which precede and predict the clinical disease. The immune-mediated destruction in many of these diseases is probably caused by T-lymphocytes. Twin studies have shown the importance of genetic factors in determining T-cell responses. Identical twins should, therefore, provide the perfect test bed to assess the role of T-cells in immune-mediated diseases.

  9. Silica Triggers Inflammation and Ectopic Lymphoid Neogenesis in the Lungs in Parallel with Accelerated Onset of Systemic Autoimmunity and Glomerulonephritis in the Lupus-Prone NZBWF1 Mouse

    PubMed Central

    Bates, Melissa A.; Brandenberger, Christina; Langohr, Ingeborg; Kumagai, Kazuyoshi; Harkema, Jack R.; Holian, Andrij; Pestka, James J.

    2015-01-01

    Genetic predisposition and environmental factors influence the development of human autoimmune disease. Occupational exposure to crystalline silica (cSiO2) has been etiologically linked to increased incidence of autoimmunity, including systemic lupus erythematosus (SLE), but the underlying mechanisms are poorly understood. The purpose of this study was to test the hypothesis that early repeated short-term cSiO2 exposure will modulate both latency and severity of autoimmunity in the lupus-prone female NZBWF1 mouse. Weekly intranasal exposure to cSiO2 (0.25 and 1.0 mg) for 4 wk beginning at 9 wk of age both reduced latency and increased intensity of glomerulonephritis. cSiO2 elicited robust inflammatory responses in the lungs as evidenced by extensive perivascular and peribronchial lymphoplasmacytic infiltration consisting of IgG-producing plasma cells, and CD45R+ and CD3+ lymphocytes that were highly suggestive of ectopic lymphoid tissue (ELT). In addition, there were elevated concentrations of immunoglobulins and the cytokines MCP-1, TNF-α and IL-6 in bronchoalveolar lavage fluid. cSiO2-associated kidney and lung effects paralleled dose-dependent elevations of autoantibodies and proinflammatory cytokines in plasma. Taken together, cSiO2-induced pulmonary inflammation and ectopic lymphoid neogenesis in the NZBWF1 mouse corresponded closely to systemic inflammatory and autoimmune responses as well as the early initiation of pathological outcomes in the kidney. These findings suggest that following airway exposure to crystalline silica, in mice genetically prone to SLE, the lung serves as a platform for triggering systemic autoimmunity and glomerulonephritis. PMID:25978333

  10. [Silicone in autoimmune diseases and cancer].

    PubMed

    Elejabeitia, J

    1999-01-01

    In 1992 the Food and Drug Administration (FDA) announced the restriction of silicone gel-filled breast implants until research protocol studies evaluate the relationship of silicone to connective tissue diseases, and the association of the silicone implants with breast carcinoma. Since them comprehensive epidemiologic studies have concluded that there is no connection between breast implants and the known connective tissue diseases or between the implants and breast carcinoma. During the same year, The American College of Rheumatology said that it have not been demonstrated the relationship between silicone gel breast implants and any systemic disease. Although this, the FDA restriction continues.

  11. [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.

  12. Autoimmune Disease Manifestations in the Oral Cavity.

    PubMed

    Magliocca, Kelly R; Fitzpatrick, Sarah G

    2017-03-01

    Immune-related disorders of the oral cavity may occur as primary disease process, secondary to systemic disease or neoplasm, or as a reaction to medications and other agents. The entities represented within this group may vary significantly by severity, clinical presentation, microscopic presentation, and special testing results. The selected immune-related conditions of the oral cavity in this article are categorized and presented by their prototypical tissue reaction patterns: vesiculobullous, including acantholytic and subepithelial separation; psoriasiform; spongiotic; and lichenoid reaction patterns.

  13. [Involvement of Syk in pathology of systemic autoimmune disease].

    PubMed

    Iwata, Shigeru; Yamaoka, Kunihiro; Niiro, Hiroaki; Nakano, Kazuhisa; Wang, Sheau-Pey; Saito, Kazuyoshi; Akashi, Koichi; Tanaka, Yoshiya

    2012-01-01

    Biological products have proven its high efficacy on autoimmune disease such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Meanwhile, small molecular drugs have attracted attention over the years because of its availability of oral administration and cost effectiveness. Spleen tyrosine kinase (Syk) is a 72 kDa protein tyrosine kinase widely expressed on cells that are involved in the immune system and inflammation such as B cells, T cells, macrophages and synovial fibroblast. Syk is involved in intracellular signaling of the multi-chain immune receptors, including B cell receptor (BCR), ζchain of T-cell receptor (TCR), FcR and integrins, which contains the immune-receptor tyrosine-based activation motif (ITAM). Recently, Syk inhibitor fostamatinib has exerted potent therapeutic efficacy against autoimmune and allergic diseases such as rheumatoid arthritis (RA), bronchial asthma and thrombocytopenic purpura (ITP). Moreover, Syk blockade prevented the development of skin and kidney lesions in lupus-prone mice, however the mechanism of action is unclear. We have revealed that Syk-mediated BCR-signaling is prerequisite for optimal induction of toll-like receptor (TLR)-9, thereby allowing efficient propagation of CD40- and TLR9- signaling in human B cells. These results indicate that inhibition of Syk have a potential to regulate B-cell mediated inflammatory diseases such as SLE. We here document the in vitro and in vivo effects of a Syk inhibitor for the treatment of autoimmune diseases, mainly in RA and SLE.

  14. Epigenetics in autoimmune diseases: Pathogenesis and prospects for therapy.

    PubMed

    Zhang, Zimu; Zhang, Rongxin

    2015-10-01

    Epigenetics is the study of heritable changes in genome function without underlying modifications in their nucleotide sequence. Disorders of epigenetic processes, which involve DNA methylation, histone modification, non-coding RNA and nucleosome remodeling, may influence chromosomal stability and gene expression, resulting in complicated syndromes. In the past few years, it has been disclosed that identified epigenetic alterations give rise to several typical human autoimmune diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and multiple sclerosis (MS). These emerging epigenetic studies provide new insights into autoimmune diseases. The identification of specific epigenetic dysregulation may inspire more discoveries of other uncharacterized mechanisms. Further elucidation of the biological functions and clinical significance of these epigenetic alterations may be exploited for diagnostic biomarkers and therapeutic benefits.

  15. Are there environmental forms of systemic autoimmune diseases?

    PubMed Central

    Hess, E V

    1999-01-01

    A large number of drugs and an increasing number of environmental agents reportedly result in the appearance of a number of autoantibodies and in many instances in the appearance of a range of autoimmune clinical syndromes. The major disorders so recognized have marked resemblances to the autoimmune disease systemic lupus erythematosus. The commonly used term is drug-induced lupus; a better term is drug-related lupus. There is considerable interest at the present time in an increasing number of environmental agents. There have been two epidemics in recent years--one in Spain to a contaminant of rapeseed oil and one in the United States to a contaminant of l-tryptophan that caused an eosinophilic myositis. It is important for physicians and others involved in health care to recognize the potential associations of these diseases of unknown cause or causes. PMID:10502535

  16. 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.

  17. Phenomics in Autoimmune and Inflammatory Diseases

    ClinicalTrials.gov

    2016-12-12

    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

  18. B cell depletion for autoimmune diseases in paediatric patients.

    PubMed

    Jansson, Annette F; Sengler, Claudia; Kuemmerle-Deschner, Jasmin; Gruhn, Bernd; Kranz, A Birgitta; Lehmann, Hartwig; Kleinert, Daniela; Pape, Lars; Girschick, Hermann J; Foeldvari, Ivan; Haffner, Dieter; Haas, Johannes P; Moebius, Dagmar; Foell, Dirk; Peitz, Joachim; Grote, Veit

    2011-01-01

    Data on B cell depletion therapy in severe autoimmune diseases in paediatric patients are very limited. We conducted a retrospective cohort study and recruited patients who were treated with rituximab (RTX) and followed up for at least 6 months through the German societies of paediatric rheumatology and nephrology. The aim was to describe the spectrum of autoimmune disorders for which RTX was used and to describe the applied therapeutic regimens, the observed efficacy, as well as potential immunological side effects. The need to develop standard treatment guidelines for future trials should be discussed. Sixty-five patients were included. Nineteen patients suffered from systemic lupus erythematosus, 13 from vasculitic disorders, 12 from hematological autoimmune diseases, 5 from mixed connective tissue disorders, 4 from juvenile idiopathic arthritis, and 9 had other autoimmune diseases. Adverse, infusion-related events were reported in 12/65 (18%) patients. Considering laboratory and clinical parameters, 13 patients (22%) were in complete remission, 31 (52%) were in partial remission, 6 (10%) were unchanged and 10 (17%) had progressed after 6 months. In 46% of the patients, the steroid dose could be more than halved. IgG, IgM and IgA decreased from normal levels prior to RTX therapy to below normal levels at 6 months in 2/22 (9%), 10/21 (48%), and 4/22 (18%) patients, respectively. Immunoglobulin deficiency or prolonged CD20 depletion was reported in eight patients after an observation period longer than 12 months. RTX therapy led to a perceivable reduction in disease activity. However, long-term immunological alterations may occur in more than 10% of the patients. Guidelines and protocols for off-label therapy are desirable to document reasonable follow-up data. Controlled prospective studies for RTX therapies in children with standardised therapeutic and diagnostic protocols are urgently needed.

  19. Th17 Cells in Autoimmune and Infectious Diseases

    PubMed Central

    Zambrano-Zaragoza, José Francisco; Romo-Martínez, Enrique Jhonatan; Durán-Avelar, Ma. de Jesús; García-Magallanes, Noemí; Vibanco-Pérez, Norberto

    2014-01-01

    The view of CD4 T-cell-mediated immunity as a balance between distinct lineages of Th1 and Th2 cells has changed dramatically. Identification of the IL-17 family of cytokines and of the fact that IL-23 mediates the expansion of IL-17-producing T cells uncovered a new subset of Th cells designated Th17 cells, which have emerged as a third independent T-cell subset that may play an essential role in protection against certain extracellular pathogens. Moreover, Th17 cells have been extensively analyzed because of their strong association with inflammatory disorders and autoimmune diseases. Also, they appear to be critical for controlling these disorders. Similar to Th1 and Th2 cells, Th17 cells require specific cytokines and transcription factors for their differentiation. Th17 cells have been characterized as one of the major pathogenic Th cell populations underlying the development of many autoimmune diseases, and they are enhanced and stabilized by IL-23. The characteristics of Th17 cells, cytokines, and their sources, as well as their role in infectious and autoimmune diseases, are discussed in this review. PMID:25152827

  20. 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

  1. 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.

  2. Autoimmune diseases and HIV infection: A cross-sectional study.

    PubMed

    Virot, Emilie; Duclos, Antoine; Adelaide, Leopold; Miailhes, Patrick; Hot, Arnaud; Ferry, Tristan; Seve, Pascal

    2017-01-01

    To describe the clinical manifestations, treatments, prognosis, and prevalence of autoimmune diseases (ADs) in human immunodeficiency virus (HIV)-infected patients.All HIV-infected patients managed in the Infectious Diseases Department of the Lyon University Hospitals, France, between January 2003 and December 2013 and presenting an AD were retrospectively included.Thirty-six ADs were found among 5186 HIV-infected patients which represents a prevalence of 0.69% including immune thrombocytopenic purpura (n = 15), inflammatory myositis (IM) (n = 4), sarcoidosis (n = 4), Guillain-Barré syndrome (GBS) (n = 4), myasthenia gravis (n = 2), Graves' disease (n = 2), and 1 case of each following conditions: systemic lupus erythematosus, rheumatoid arthritis, autoimmune hepatitis, Hashimoto thyroiditis and autoimmune hemolytic anemia. One patient presented 2 ADs. Thirty patients were known to be HIV-infected when they developed an AD. The AD preceded HIV infection in 2 patients. GBS and HIV infection were diagnosed simultaneously in 3 cases. At AD diagnosis, CD4 T lymphocytes count were higher than 350/mm in 63% of patients, between 200 and 350/mm in 19% and less than 200/mm in 19%. Twenty patients benefited from immunosuppressant treatments, with a good tolerance.ADs during HIV infection are uncommon in this large French cohort. Immune thrombocytopenic purpura, sarcoidosis, IM, and GBS appear to be more frequent than in the general population. Immunosuppressant treatments seem to be effective and well tolerated.

  3. 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.

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

    PubMed Central

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

    2016-01-01

    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. PMID:27528673

  5. 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

  6. Th17 cells in autoimmune and infectious diseases.

    PubMed

    Zambrano-Zaragoza, José Francisco; Romo-Martínez, Enrique Jhonatan; Durán-Avelar, Ma de Jesús; García-Magallanes, Noemí; Vibanco-Pérez, Norberto

    2014-01-01

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

  7. Immunological GABAergic interactions and therapeutic applications in autoimmune diseases.

    PubMed

    Prud'homme, Gérald J; Glinka, Yelena; Wang, Qinghua

    2015-11-01

    Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the brain. However, it is also produced in other sites; notably by pancreatic β cells and immune cells. The function of GABA in the immune system is at an early stage of study, but it exerts inhibitory effects that are relevant to autoimmune diseases. The study of GABAergic interactions in the immune system has centered on three main aspects: 1) the expression of GABA and the relevant GABAergic molecular machinery; 2) the in vitro response of immune cells; and 3) therapeutic applications in autoimmune diseases. T cells and macrophages can produce GABA, and express all the components necessary for a GABAergic response. There are two types of GABA receptors, but lymphocytes appear to express only type A (GABAAR); a ligand-gated chloride channel. Other immune cells may also express the type B receptor (GABABR); a G-protein coupled receptor. Activation of GABA receptors on T cells and macrophages inhibits responses such as production of inflammatory cytokines. In T cells, GABA blocks the activation-induced calcium signal, and it also inhibits NF-κB activation. In preclinical models, therapeutic application of GABA, or GABAergic (agonistic) drugs, protects against type 1 diabetes (T1D), experimental autoimmune encephalomyelitis (EAE), collagen-induced arthritis (CIA) and contact dermatitis. In addition, GABA exerts anti-apoptotic and proliferative effects on islet β cells, which may be applicable to islet transplantation. Autoimmunity against glutamic acid decarboxylase 65 (GAD65; synthesizes GABA) occurs in T1D. Antigen therapy of T1D with GAD65 or proinsulin in mice has protective effects, which are markedly enhanced by combined GABA therapy. Clinically, autoantibodies against GAD65 and/or GABA receptors play a pathogenic role in several neurological conditions, including stiff person syndrome (SPS), some forms of encephalitis, and autoimmune epilepsy. GABAergic drugs are widely used in

  8. The complement system contributes to the pathology of experimental autoimmune encephalomyelitis by triggering demyelination and modifying the antigen-specific T and B cell response.

    PubMed

    Hundgeburth, Lorenz C; Wunsch, Marie; Rovituso, Damiano; Recks, Mascha S; Addicks, Klaus; Lehmann, Paul V; Kuerten, Stefanie

    2013-03-01

    So far, studies of the human autoimmune disease multiple sclerosis (MS) have largely been hampered by the absence of a pathogenic B cell component in its animal model, experimental autoimmune encephalomyelitis (EAE). To overcome this shortcoming, we have previously introduced the myelin basic protein (MBP)-proteolipid protein (PLP) MP4-induced EAE, which is B cell and autoantibody-dependent. Here we show that MP4-immunized wild-type C57BL/6 mice displayed a significantly lower disease incidence when their complement system was transiently depleted by a single injection of cobra venom factor (CVF) prior to immunization. Considering the underlying pathomechanism, our data suggest that the complement system is crucial for MP4-specific antibodies to trigger CNS pathology. Demyelinated lesions in the CNS were colocalized with complement depositions. In addition, B cell deficient JHT mice reconstituted with MP4-reactive serum showed significantly attenuated clinical and histological EAE after depletion of complement by CVF. The complement system was also critically involved in the generation of the MP4-specific T and B cell response: in MP4-immunized wild-type mice treated with CVF the MP4-specific cytokine and antibody response was significantly attenuated compared to untreated wild-type mice. Taken together, we propose two independent mechanisms by which the complement system can contribute to the pathology of autoimmune encephalomyelitis. Our data corroborate the role of complement in triggering antibody-dependent demyelination and antigen-specific T cell immunity and also provide first evidence that the complement system can modify the antigen-specific B cell response in EAE and possibly MS.

  9. Dephosphorylation of autoantigenic ribosomal P proteins during Fas-L induced apoptosis: a possible trigger for the development of the autoimmune response in patients with systemic lupus erythematosus

    PubMed Central

    Zampieri, S; Degen, W; Ghiradello, A; Doria, A; van Venrooij, W J

    2001-01-01

    OBJECTIVES—Autoimmune diseases are characterised by the production of autoantibodies against various autoantigens. In the past few years data have been published on a possible role of apoptosis in the development of autoimmunity. These include the finding that several autoantigens become modified (for example, by cleavage) during apoptosis, and the observation that these modified antigens are translocated to the cell surface. When the normal clearance of apoptotic cells somehow is disturbed, such modified antigens might become exposed to the immune system. Because acidic ribosomal P (phospho-) proteins targeted by autoantibodies in systemic lupus erythematosus (SLE) are also concentrated at the surface of apoptotic cells, this study aimed at investigating what modifications occur on these antigens during apoptosis.
METHODS—Apoptosis in Jurkat cells was induced by Fas ligand (Fas-L), and the fate of autoantigenic P proteins was analysed in both normal and apoptotic total cell extracts.
RESULTS—The autoantigenic P proteins were not cleaved but dephosphorylated during Fas-L induced apoptosis. This dephosphorylation was prevented when caspase activity was inhibited.
CONCLUSIONS—As has been shown for other autoantigens targeted by autoantibodies in SLE, P proteins also are modified during apoptosis. P1 and P2 are completely dephosphorylated while P0 is partly dephosphorylated. Because the epitope targeted by autoantibodies normally is phosphorylated, it is possible that the apoptotic dephosphorylation of the antigen might be the trigger for the development of the autoimmune response against P proteins.

 PMID:11114288

  10. Autoimmune thyroid disease: mechanism, genetics and current knowledge.

    PubMed

    Dong, Y H; Fu, D G

    2014-01-01

    Recent epidemiological studies recognized a steady increase in the incidence of different autoimmune endocrine disorders, including autoimmune thyroid disease (AITD). The etiology of AITD is multifactorial and involves genetic and environmental factors and apparently with a strong preponderance in females. There are mainly two types of AITD, Graves' disease and Hashimoto's disease and both of these show strong association in age groups above 45-50 years. Among environmental factors smoking and alcohol have significant effects, both protective as well as for aggravating the disease, even though the precise nature of these effects are not clearly known. There are elevated levels of circulating antibodies against the thyroid proteins, mainly thyroid oxidase, thyroglobulin and thyroid stimulating hormone receptor, in patients with Graves' disease or Hashimoto's disease. Linkage and association studies in AITD identified several major genes that are relevant for the onset of AITD, including the thyroid-specific genes, thyroglobulin and thyroid-stimulating hormone receptor and also many immune-regulatory genes. In this review we addressed many aspects of AITD including disease mechanisms, involved thyroid antigens, environmental factors and genetic factors.

  11. Autoimmune central diabetes insipidus in a patient with ureaplasma urealyticum infection and review on new triggers of immune response.

    PubMed

    Murdaca, Giuseppe; Russo, Rodolfo; Spanò, Francesca; Ferone, Diego; Albertelli, Manuela; Schenone, Angelo; Contatore, Miriam; Guastalla, Andrea; De Bellis, Annamaria; Garibotto, Giacomo; Puppo, Francesco

    2015-12-01

    Diabetes insipidus is a disease in which large volumes of dilute urine (polyuria) are excreted due to vasopressin (AVP) deficiency [central diabetes insipidus (CDI)] or to AVP resistance (nephrogenic diabetes insipidus). In the majority of patients, the occurrence of CDI is related to the destruction or degeneration of neurons of the hypothalamic supraoptic and paraventricular nuclei. The most common and well recognized causes include local inflammatory or autoimmune diseases, vascular disorders, Langerhans cell histiocytosis (LCH), sarcoidosis, tumors such as germinoma/craniopharyngioma or metastases, traumatic brain injuries, intracranial surgery, and midline cerebral and cranial malformations. Here we have the opportunity to describe an unusual case of female patient who developed autoimmune CDI following ureaplasma urealyticum infection and to review the literature on this uncommon feature. Moreover, we also discussed the potential mechanisms by which ureaplasma urealyticum might favor the development of autoimmune CDI.

  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.

  13. Does Vitamin D Affect Risk of Developing Autoimmune Disease?: A Systematic Review

    PubMed Central

    Kriegel, Martin A.; Manson, JoAnn E.; Costenbader, Karen H.

    2010-01-01

    Objectives We evaluated the epidemiologic evidence that vitamin D may be related to human autoimmune disease risk. Methods PubMed limited to English from inception through April 2010 was searched using keywords: “vitamin D”, “autoimmune” and autoimmune disease names. We summarized in vitro, animal, and genetic association studies of vitamin D in autoimmune disease pathogenesis. We sorted studies by design and disease and performed a systematic review of: a) cross-sectional data concerning vitamin D level and autoimmune disease; b) interventional data on vitamin D supplementation in autoimmune diseases and c) prospective data linking vitamin D level or intake to autoimmune disease risk. Results Vitamin D has effects on innate and acquired immune systems and vitamin D receptor polymorphisms have been associated with various autoimmune diseases. In experimental animal models, vitamin D supplementation can prevent or forestall autoimmune disease. We identified 76 studies in which vitamin D levels were studied in autoimmune disease patients, particularly with active disease, and compared to controls. Nineteen observational or interventional studies assessed the effect of vitamin D supplementation as therapy for various autoimmune diseases (excluding psoriasis and vitiligo) with a range of study approaches and results. The few prospective human studies performed conflict as to whether vitamin D level or intake is associated with autoimmune disease risk. No interventional trials have investigated whether vitamin D affects human autoimmune disease risk. Conclusions Cross-sectional data point to a potential role of vitamin D in autoimmune disease prevention, but prospective interventional evidence in humans is still lacking. PMID:21047669

  14. Does TSH Trigger the Anti-thyroid Autoimmune Processes? Observation on a Large Cohort of Naive Patients with Thyroid Hemiagenesis.

    PubMed

    Szczepanek-Parulska, Ewelina; Zybek-Kocik, Ariadna; Woliński, Kosma; Czarnocka, Barbara; Ruchała, Marek

    2016-08-01

    Thyroid hemiagenesis (THA) is a rare abnormality characterized by the absence of one thyroid lobe. Elevated thyroid stimulating hormone (TSH) level and higher incidence of thyroid diseases were reported in THA. The aim of the study is to evaluate the thyroid autoimmunity incidence in patients with THA and influence of higher than average TSH level on thyroid volume (TV) and its change with age. The study included a group of naive patients with THA and a control group of subjects with bilobate thyroid. All patients underwent clinical examination, thyroid ultrasound, scintiscan and laboratory tests. In the studied and control group the presence of thyroid autoantibodies (TAb) was evaluated. The THA group consisted of 65 patients. In THA group 53.85 % of patients were positive for TAb. Patients with positive TAb were older (46.0 ± 18.3 years) than those with negative (35.0 ± 19.8 years); p = 0.02. The incidence of TAb was lower in controls (13.85 %, p < 0.0001). In the study group, positive correlation between the age and TV (r = 0.46, p = 0.0001), and negative correlations between the age and TSH level (r = -0.31, p = 0.01), and TSH concentration and TV (r = -0.35, p = 0.004) were found. In a subgroup of 30 patients with THA negative for TAb, even stronger correlations were observed. The median single lobe volume and median TSH level were higher in patients with THA when compared to controls (13.60 vs 8.20 ml, p < 0.0001; 3.23 vs 1.48 µU/ml, p < 0.0001, respectively). Patients with THA constitute an in vivo model of long-term thyroid TSH overstimulation. Further studies are needed to reveal, whether TSH overstimulation may be the trigger for thyroid autoimmunity.

  15. Clinical characteristics of immune thrombocytopenia associated with autoimmune disease

    PubMed Central

    Liu, Yuan; Chen, Shiju; Sun, Yuechi; Lin, Qingyan; Liao, Xining; Zhang, Junhui; Luo, Jiao; Qian, Hongyan; Duan, Lihua; Shi, Guixiu

    2016-01-01

    Abstract To clarify clinical characteristics of immune thrombocytopenia (ITP) subsets associated with autoimmune diseases (AIDs). Five thousand five hundred twenty patients were reviewed retrospectively. One hundred four ITP patients were included for analysis. Clinical manifestations at first thrombocytopenic episode were recorded. Systemic lupus erythematosus (SLE) and primary Sjogren syndrome (pSS) accounted for a large part in AIDs associated with secondary ITP. SLE-ITP, pSS-ITP, and primary ITP (pITP) patients were different in several aspects in clinical and immunological characteristics. A subgroup of patients in pITP patients with some obvious autoimmune features (defined as AIF-ITP) such as positive ANA but failing to meet the diagnosis criteria now used for a specific kind of connective tissue diseases were also different with other pITP patients in some immunological features, indicating the difference in the pathogenesis mechanism of those autoimmune featured ITP patients. ITP patients were heterogeneous in clinical characteristics. Further study about the different pathogenesis of ITP subsets especially those AIF-ITP patients who only presented with thrombocytopenia will help us have a better understanding of pathogenesis of ITP and a better management of ITP patients. PMID:27977588

  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. [Equine exudative canker: an (auto-)immune disease?].

    PubMed

    Jongbloets, A M C; Sloet van Oldruitenborgh-Oosterbaan, M M; Meeus, P J H M; Back, W

    2005-02-15

    Equine canker is a chronic, hyperplastic, exudative pododermatitis affecting one or more feet. Although many causes and treatments have been suggested, the cause of the disease is still unknown and most probably multifactorial. Local treatments include radical surgical debridement of the diseased hoof tissue and application of caustic substances, antibiotics, and pressure bandaging. Nevertheless, the number of recurrences is high (45%). This article presents a 3-year-old New Forest pony-cross mare in which all horny structures (frogs, coronets, spurs, chestnuts) of all feet were affected. Bacteriological and fungal cultures of the frogs were found negative for the pathogens tested. Papilloma virus was not found. Clinical findings raised the hypothesis that the non-specific hyperplastic inflammation of these horn-like structures might have been caused by an (auto-)immune reaction. On the basis of the clinical findings, the pony was treated with surgical debridement of the frogs of a diagonal pair of feet and oral administration of prednisolone (1 mg/kg sid). The frogs, coronets, spurs, and chestnuts of all four feet healed completely within 8 weeks, thus making an (auto-)immune reaction more likely. In conclusion, this case report raised the hypothesis that an aspecific, hyperplastic inflammation of all four feet ('equine canker') and other horny structures may be caused by an (auto-)immune reaction, and that corticosteroids (prednisolone 1 mg/kg sid per os) are effective as treatment.

  18. 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.

  19. 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

  20. Prevalence of autoimmune disease in moyamoya disease patients in Western Chinese population.

    PubMed

    Chen, Jian-Bin; Liu, Yi; Zhou, Liang-Xue; Sun, Hong; He, Min; You, Chao

    2015-04-15

    The pathogenesis of moyamoya remains to be elucidated and an immunologic basis has been suggested. For gaining further insight into the pathogenesis of moyamoya, we explored the epidemiological characteristics of autoimmune disease in moyamoya disease (MMD) in Western Chinese population. Retrospective clinical characteristic analysis of patients with angiographically confirmed MMD was performed and compared with the general Chinese population. A significantly higher prevalence of autoimmune disease was observed, particularly type 1 diabetes mellitus (P<0.001, 7.0% vs 1.2%, χ(2) test) and Graves disease (P<0.001, 7.0% vs 0.34%, χ(2) test) in the general Chinese population. The overall prevalence of autoimmune disease in MMD was up to 31.0% (44/142). This study suggested higher overall prevalence of autoimmune disease in MMD in Western China when compared with the general Chinese population. The findings further supported that autoimmune abnormality might associate with MMD and autoimmune component to pathogenesis of moyamoya vasculopathy.

  1. 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.

  2. 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

  3. BAFF: a local and systemic target in autoimmune diseases

    PubMed Central

    Moisini, I; Davidson, A

    2009-01-01

    BAFF (B lymphocyte activating factor of the tumour necrosis factor family) is a vital homeostatic cytokine for B cells that helps regulate both innate and adaptive immune responses. Increased serum levels of BAFF are found in a number of different autoimmune diseases, and BAFF is found in inflammatory sites in which there is lymphoid neogenesis. BAFF antagonism has been used in several autoimmune disease models, resulting in B cell depletion, decreased activation of T cells and dendritic cells (DC) and a reduction in the overall inflammatory burden. BAFF, through its interaction with BAFF-R, is required for survival of late transitional, marginal zone and mature naive B cells, all of which are depleted by BAFF blockade. Through their interactions with TACI (transmembrane activator and calcium modulator and cyclophilin ligand interactor) and BCMA (B cell maturation protein), BAFF and its homologue APRIL (a proliferation-inducing ligand), support the survival of at least some subsets of plasma cells; blockade of both cytokines results in a decrease in serum levels of immunoglobulin (Ig)G. In contrast, neither BAFF nor APRIL is required for the survival or reactivation of memory B cells or B1 cells. BAFF also helps DC maturation and interleukin (IL)-6 release and is required for proper formation of a follicular dendritic cell (FDC) network within germinal centres, although not for B cell affinity maturation. The clinical efficacy of BAFF blockade in animal models of autoimmunity may be caused both by the decline in the number of inflammatory cells and by the inhibition of DC maturation within target organs. Blockade of BAFF and its homologue APRIL are being explored for human use; several Phase I and II clinical trials of BAFF inhibitors for autoimmunity have been completed and Phase III trials are in progress. PMID:19737141

  4. Autoimmunity in picornavirus infections

    PubMed Central

    Massilamany, Chandirasegaran; Koenig, Andreas; Reddy, Jay; Huber, Sally

    2015-01-01

    Enteroviruses are small, non-enveloped, positive-sense single-strand RNA viruses, and are ubiquitously found throughout the world. These viruses usually cause asymptomatic or mild febrile illnesses, but have a propensity to induce severe diseases including type 1 diabetes and pancreatitis, paralysis and neuroinflammatory disease, myocarditis, or hepatitis. This pathogenicity may result from induction of autoimmunity to organ-specific antigens. While enterovirus-triggered autoimmunity can arise from multiple mechanisms including antigenic mimicry and release of sequestered antigens, the recent demonstration of T cells expressing dual T cell receptors arising as a natural consequence of Theiler's virus infection is the first demonstration of this autoimmune mechanism. PMID:26554915

  5. Transition from an autoimmune-prone state to fatal autoimmune disease in CCR7 and RORγt double-deficient mice is dependent on gut microbiota.

    PubMed

    Wichner, Katharina; Fischer, André; Winter, Susann; Tetzlaff, Solveig; Heimesaat, Markus M; Bereswill, Stefan; Rehm, Armin; Lipp, Martin; Höpken, Uta E

    2013-12-01

    Autoimmunity is associated with a strong genetic component, but onset and persistence of clinically apparent autoimmune diseases often require an additional environmental trigger. The balance between immunity and tolerance is regulated by numerous molecular factors including nuclear hormone and homeostatic chemokine receptors. The nuclear hormone receptor RORγt and the chemokine receptor CCR7 are both essentially involved in functional lymphoid organogenesis and maintenance of lymphocyte homeostasis. Lack of one or the other impairs thymic T cell development and alters T cell homeostasis. Mice deficient for both, Ccr7(-/-)Rorγt(-/-), succumbed early to acute destructive inflammation, characterized by massive recruitment of inflammatory leukocytes, pro-inflammatory cytokine and autoantibody production, and wasting disease. Antibiotic-treatment of mice before disease onset reduced the overall gut microflora and abrogated the development of fatal mucosal inflammation. Hence, commensal bacteria and a confined tissue-specific inflammatory milieu serve as complementary trigger to initiate the lethal pathophysiologic process in Ccr7(-/-)Rorγt(-/-) mice.

  6. Transition of nodular toxic goiter to autoimmune hyperthyroidism triggered by 131I therapy.

    PubMed

    Nygaard, B; Faber, J; Veje, A; Hegedüs, L; Hansen, J M

    1999-05-01

    The use of 131I treatment in nodular toxic goiter is widely accepted. In this article, we describe transition of nodular toxic goiter into an autoimmune toxic goiter with development of thyrotropin receptor antibodies (TRAb) as a side effect of 131I treatment. In this retrospective study, 149 patients with nodular toxic goiter (100 with multinodular goiter, 49 with a solitary autonomously functioning toxic nodule) were studied. Of these 149 patients 100 became permanently euthryoid after 1 dose of 131I, and due to persistent hyperthyroidism, 32 patients needed 2-5 doses to became euthyroid. After becoming euthyroid, none of these 132 patients had relapse of hyperthyroidism in the follow-up period. Based on evaluation of the thyroid hormone variables, 17 of 149 patients had a distinctly different pattern in the changes in thyroid hormones. They developed an increase in FT4I 3-6 months posttreatment after an initial fall in FT4I. Twelve of these 17 patients were treated with antithyroid drugs before the initial 131I dose. On samples of frozen sera (-20 degrees C) anti-thyroid peroxidase (TPO) and TRAb were followed for 6 months after 131I treatment in these 17 patients. A similar follow-up was done in 20 patients (10 with and 10 without antithyroid drug pretreatment), randomly selected from the patients who did not relapse. In the remaining 112 patients, anti-TPO and TRAb levels were measured only before the 131I treatment. Of the 17 patients with relapse, 6 developed TRAb concomitant with recurrence of hyperthyroidism (4% of the study group). In 5 of the 17 patients TRAb values remained absent throughout the follow-up period. The remaining 6 patients had elevated TRAb values before 131I treatment. Among the 132 patients who did not relapse, an additional 7 cases with presence of TRAb were found. A total of 9% of the study group was found to have TRAb before 131I pretreatment. Anti-TPO was found in 20 of 149 patients (13%) before 131I treatment. Complications, either

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

    PubMed

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

    2016-08-01

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

  8. 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.

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

    PubMed Central

    2011-01-01

    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. PMID:22194706

  10. 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.

  11. Sclerostin serum levels in patients with systemic autoimmune diseases

    PubMed Central

    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; Centeno, Norberto Ortego

    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

  12. 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

  13. 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

  14. Systematics of the models of immune response and autoimmune disease

    NASA Astrophysics Data System (ADS)

    Chowdhury, Debashish; Stauffer, Dietrich

    1990-05-01

    A dynamical model of normal immune response has been formulated in terms of cellular automata by Kaufman et al. We generalize this model incorporating the antigens as a dynamical variable. This generalized model not only describes the kinetics of primary and secondary responses of humoral immunity, together with the appropriate memory cells, but also describes the vaccinated state as well as the states of low-dose and high-dose paralysis. Recently models of autoimmune response have also been developed in terms of discrete automata. But the models are underdetermined by the experimental facts, i.e., several models can account for the same set of observed biological facts. With an aim to find out how large this underdeterminacy is and how it can be reduced systematically, we have carried out an exhaustive computer-aided search of all those discrete three-cell and five-cell models of autoimmune response which at present cannot be ruled out by the existing biological informations. Out of the 325 possible five-cell models, only one fulfilled our criteria. We also carried out simulations of the dynamics of some of these models on a discrete lattice. We discuss the relevance of random interactions in the context of autoimmune disease.

  15. Serological aggravation of autoimmune thyroid disease in two cases receiving nivolumab.

    PubMed

    Narita, Tomohiko; Oiso, Naoki; Taketomo, Yasunori; Okahashi, Kazunori; Yamauchi, Kohei; Sato, Masako; Uchida, Shusuke; Matsuda, Hiromasa; Kawada, Akira

    2016-02-01

    Nivolumab, a blockade of programmed cell death 1, is now administrated for advanced malignant melanomas. Nivolumab-associated adverse events include organ-specific autoimmune disorders; autoimmune thyroid disease, vitiligo and insulin-dependent diabetes. However, predisposed persons are currently unknown. Here, we report serological aggravation of autoimmune thyroid disease in two cases receiving nivolumab: one with Hashimoto disease and another with probable subclinical Hashimoto disease. We should verify if nivolumab-related hypothyroidism and hyperthyroidism are predisposed to occur in euthyroid individuals with subclinical autoimmune thyroid disease.

  16. 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.

  17. The NLRP3 inflammasome in kidney disease and autoimmunity.

    PubMed

    Hutton, Holly L; Ooi, Joshua D; Holdsworth, Stephen R; Kitching, A Richard

    2016-09-01

    The NLRP3 inflammasome is an intracellular platform that converts the pro-inflammatory cytokines interleukin (IL)-1β and IL-18 to their active forms in response to 'danger' signals, which can be either host or pathogen derived, and mediates a form of inflammatory cell death called pyroptosis. This component of the innate immune system was initially discovered because of its role in rare autoinflammatory syndromes called cryopyrinopathies, but it has since been shown to mediate injurious inflammation in a broad range of diseases. Inflammasome activation occurs in both immune cells, primarily macrophages and dendritic cells, and in some intrinsic kidney cells such as the renal tubular epithelium. The NLRP3 inflammasome has been implicated in the pathogenesis of a number of renal conditions, including acute kidney injury, chronic kidney disease, diabetic nephropathy and crystal-related nephropathy. The inflammasome also plays a role in autoimmune kidney disease, as IL-1β and IL-18 influence adaptive immunity through modulation of T helper cell subsets, skewing development in favour of Th17 and Th1 cells that are important in the development of autoimmunity. Both IL-1 blockade and two recently identified specific NLRP3 inflammasome blockers, MCC950 and β-hydroxybutyrate, have shown promise in the treatment of inflammasome-mediated conditions. These targeted therapies have the potential to be of benefit in the growing number of kidney diseases in which the NLRP3 inflammasome has been implicated.

  18. Glutamic acid decarboxylase autoimmunity in Batten disease and other disorders.

    PubMed

    Pearce, David A; Atkinson, Mark; Tagle, Danilo A

    2004-12-14

    Degenerative diseases of the CNS, such as stiff-person syndrome (SPS), progressive cerebellar ataxia, and Rasmussen encephalitis, have been characterized by the presence of autoantibodies. Recent findings in individuals with Batten disease and in animal models for the disorder indicate that this condition may be associated with autoantibodies against glutamic acid decarboxylase (GAD), an enzyme that converts the excitatory neurotransmitter glutamate to the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). Anti-GAD autoantibodies could result in excess excitatory neurotransmitters, leading to the seizures and other symptoms observed in patients with Batten disease. The pathogenic potential of GAD autoantibodies is examined in light of what is known for other autoimmune disorders, such as multiple sclerosis, SPS, Rasmussen encephalitis, and type 1 diabetes, and may have radical implications for diagnosis and management of Batten disease.

  19. Autoimmune encephalopathies

    PubMed Central

    Leypoldt, Frank; Armangue, Thaís; Dalmau, Josep

    2014-01-01

    Over the last 10 years the continual discovery of novel forms of encephalitis associated with antibodies to cell-surface or synaptic proteins has changed the paradigms for diagnosing and treating disorders that were previously unknown or mischaracterized. We review here the process of discovery, the symptoms, and the target antigens of twelve autoimmune encephatilic disorders, grouped by syndromes and approached from a clinical perspective. Anti-NMDAR encephalitis, several subtypes of limbic encephalitis, stiff-person spectrum disorders, and other autoimmune encephalitides that result in psychosis, seizures, or abnormal movements are described in detail. We include a novel encephalopathy with prominent sleep dysfunction that provides an intriguing link between chronic neurodegeneration and cell-surface autoimmunity (IgLON5). Some of the caveats of limited serum testing are outlined. In addition, we review the underlying cellular and synaptic mechanisms that for some disorders confirm the antibody pathogenicity. The multidisciplinary impact of autoimmune encephalitis has been expanded recently by the discovery that herpes simplex encephalitis is a robust trigger of synaptic autoimmunity, and that some patients may develop overlapping syndromes, including anti-NMDAR encephalitis and neuromyelitis optica or other demyelinating diseases. PMID:25315420

  20. Autoimmunity to the alpha 3 chain of type IV collagen in glomerulonephritis is triggered by ‘autoantigen complementarity’

    PubMed Central

    Reynolds, John; Preston, Gloria A.; Pressler, Barrak M.; Hewins, Peter; Brown, Michael; Roth, Aleeza; Alderman, Elizabeth; Bunch, Donna; Jennette, J. Charles; Cook, H. Terence; Falk, Ronald J.; Pusey, Charles D.

    2015-01-01

    ‘Autoantigen complementarity’ is a theory proposing that the initiator of an autoimmune response is not necessarily the autoantigen or its molecular mimic, but may instead be a peptide that is ‘antisense/complementary’ to the autoantigen. We investigated whether such complementary proteins play a role in the immunopathogenesis of autoimmune glomerulonephritis. Experimental autoimmune glomerulonephritis, a model of anti-glomerular basement membrane (GBM) disease, can be induced in Wistar Kyoto (WKY) rats by immunization with the α3 chain of type IV collagen. In this study, WKY rats were immunized with a complementary α3 peptide (c-α3-Gly) comprised of amino acids that ‘complement’ the well characterized epitope on α3(IV)NC1, pCol(24–38). Within 8 weeks post-immunization, these animals developed cresentic glomerulonephritis, similar to pCol(24–38)-immunized rats, while animals immunized with scrambled peptide were normal. Anti-idiotypic antibodies to epitopes from c-α3-Gly-immunized animals were shown to be specific for α3 protein, binding in a region containing sense pCol(24–38) sequence. Interestingly, anticomplementary α3 antibodies were identified in sera from patients with anti-GBM disease, suggesting a role for ‘autoantigen complementarity’ in immunopathogenesis of the human disease. This work supports the idea that autoimmune glomerulonephritis can be initiated through an immune response against a peptide that is anti-sense or complementary to the autoantigen. The implications of this discovery may be far reaching, and other autoimmune diseases could be due to responses to these once unsuspected ‘complementary’ antigens. PMID:25841937

  1. Transient Expression of Transgenic IL-12 in Mouse Liver Triggers Unremitting Inflammation Mimicking Human Autoimmune Hepatitis.

    PubMed

    Gil-Farina, Irene; Di Scala, Marianna; Salido, Eduardo; López-Franco, Esperanza; Rodríguez-García, Estefania; Blasi, Mercedes; Merino, Juana; Aldabe, Rafael; Prieto, Jesús; Gonzalez-Aseguinolaza, Gloria

    2016-09-15

    The etiopathogenesis of autoimmune hepatitis (AIH) remains poorly understood. In this study, we sought to develop an animal model of human AIH to gain insight into the immunological mechanisms driving this condition. C57BL/6 mice were i.v. injected with adeno-associated viral vectors encoding murine IL-12 or luciferase under the control of a liver-specific promoter. Organ histology, response to immunosuppressive therapy, and biochemical and immunological parameters, including Ag-specific humoral and cellular response, were analyzed. Mechanistic studies were carried out using genetically modified mice and depletion of lymphocyte subpopulations. Adeno-associated virus IL-12-treated mice developed histological, biochemical, and immunological changes resembling type 1 AIH, including marked and persistent liver mononuclear cell infiltration, hepatic fibrosis, hypergammaglobulinemia, anti-nuclear and anti-smooth muscle actin Abs, and disease remission with immunosuppressive drugs. Interestingly, transgenic IL-12 was short-lived, but endogenous IL-12 expression was induced, and both IL-12 and IFN-γ remained elevated during the entire study period. IFN-γ was identified as an essential mediator of liver damage, and CD4 and CD8 T cells but not NK, NKT, or B cells were essential executors of hepatic injury. Furthermore, both MHC class I and MHC class II expression was upregulated at the hepatocellular membrane, and induction of autoreactive liver-specific T cells was detected. Remarkably, although immunoregulatory mechanisms were activated, they only partially mitigated liver damage. Thus, low and transient expression of transgenic IL-12 in hepatocytes causes loss of tolerance to hepatocellular Ags, leading to chronic hepatitis resembling human AIH type 1. This model provides a practical tool to explore AIH pathogenesis and novel therapies.

  2. Extraintestinal Crohn's disease mimicking autoimmune inner ear disease: a histopathological approach.

    PubMed

    Dettmer, M; Hegemann, I; Hegemann, S C A

    2011-01-01

    Patients with autoimmune inner ear disease develop rapidly progressive sensorineural hearing loss over a period of several weeks or months, often accompanied by vestibular loss. This disease can occur as a distinct clinical entity or in association with an underlying autoimmune disorder. Treatment comprises immunosuppression by corticosteroids, cytostatic drugs or tumor necrosis factor-α antagonists. We report histopathological and immunohistochemical findings of the inner ear of a patient with a granulomatous inner ear disease suffering from Crohn's disease that was nonresponsive to treatment and who underwent surgery for bilateral cochlear implants.

  3. Metabolite monitoring to guide thiopurine therapy in systemic autoimmune diseases.

    PubMed

    Chapdelaine, Aurélie; Mansour, Anne-Marie; Troyanov, Yves; Williamson, David R; Doré, Maxime

    2017-01-27

    6-Thioguanine nucleotide (6-TGN) is the active metabolite of thiopurine drugs azathioprine and 6-mercaptopurine. 6-Methylmercaptopurine (6-MMP) is an inactive and potentially hepatotoxic metabolite. A subgroup of patients (shunters) preferentially produce 6-MMP instead of 6-TGN, therefore displaying thiopurine resistance and risk for hepatotoxicity. Outside inflammatory bowel disease literature, few data exist regarding individualized thiopurine therapy based on metabolite monitoring. This study sought to describe metabolite monitoring in patients receiving weight-based thiopurine for systemic autoimmune diseases. Patients were enrolled using a laboratory database, and data were retrospectively collected. The correlation between the highest thiopurine dose (mg/kg) and the 6-TGN concentration (pmol/8 × 10(8) erythrocytes) was estimated with Pearson's correlation coefficient. Seventy-one patients with various systemic autoimmune conditions were enrolled. The correlation between the thiopurine dose and the 6-TGN level was weak for the overall patient sample (r = 0.201, p = 0.092) and for the subgroup of non-shunters (r = 0.278, p = 0.053). Subjects with 6-MMP levels >5700 pmol/8 × 10(8) erythrocytes had more hepatic cytolysis compared to subjects with 6-MMP <5700, OR = 4.36 (CI 95% 1.18-16.13, p = 0.027). Twenty-two patients (31%) were identified as shunters. Six shunters developed hepatotoxicity, five of which had 6-MMP concentration >5700. Eleven non-shunters had hepatotoxicity, one of which had 6-MMP >5700. Thiopurine metabolite monitoring shows wide variability in 6-TGN levels among patients treated with weight-based thiopurine for systemic autoimmune diseases. Thirty-one percent of the patients in our series fulfilled the shunter definition. Thiopurine metabolite monitoring and dose adjustment to improve maintenance of remission and avoid hepatotoxicity should be studied prospectively.

  4. The tumour necrosis factor/TNF receptor superfamily: therapeutic targets in autoimmune diseases

    PubMed Central

    Vinay, D S; Kwon, B S

    2011-01-01

    Autoimmune diseases are characterized by the body's ability to mount immune attacks on self. This results from recognition of self-proteins and leads to organ damage due to increased production of pathogenic inflammatory molecules and autoantibodies. Over the years, several new potential therapeutic targets have been identified in autoimmune diseases, notable among which are members of the tumour necrosis factor (TNF) superfamily. Here, we review the evidence that certain key members of this superfamily can augment/suppress autoimmune diseases. PMID:21401577

  5. 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.

  6. Peripheral nervous system manifestations in systemic autoimmune diseases.

    PubMed

    Cojocaru, Inimioara Mihaela; Cojocaru, Manole; Silosi, Isabela; Vrabie, Camelia Doina

    2014-09-01

    The peripheral nervous system refers to parts of the nervous system outside the brain and spinal cord. Systemic autoimmune diseases can affect both the central and peripheral nervous systems in a myriad of ways and through a heterogeneous number of mechanisms leading to many different clinical manifestations. As a result, neurological complications of these disorders can result in significant morbidity and mortality. The most common complication of peripheral nervous system (PNS) involvement is peripheral neuropathy, with symptoms of numbness, sensory paresthesias, weakness, or gait imbalance. The neuropathy may be multifocal and asymmetric or, less frequently, distal and symmetric.

  7. Autoimmune Hemolytic Anemia Triggered by Infection with Human Parvovirus B19 after Total Abdominal Colectomy for Ulcerative Colitis.

    PubMed

    Iida, Tomoya; Satoh, Shuji; Nakagaki, Suguru; Shimizu, Haruo; Kaneto, Hiroyuki

    2016-01-01

    A 50-year-old man was admitted to our hospital for an adhesive ileus 14 years after total abdominal colectomy for ulcerative colitis (UC). The ileus decreased with conservative treatment, however, autoimmune hemolytic anemia (AIHA) was diagnosed due to worsening anemia, a positive direct Coombs test, low haptoglobin, high lactase dehydrogenase, reticulocytosis, and an increase in the erythroblastic series in a bone-marrow examination. Human parvovirus B19 (PV-B19) IgM and PV-B19 DNA were present, indicating the development of AIHA triggered by an infection with PV-B19. The patient is currently being monitored after spontaneous remission. This is the first report of UC after total abdominal colectomy complicated by AIHA triggered by PV-B19 infection.

  8. 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

  9. Do we need autoimmune disease units in hospitals?

    PubMed

    Vasconcelos, Carlos

    2009-09-01

    Autoimmune diseases are increasing worldwide, and associated morbidity, mortality, and health care costs are high. Biological therapies, however, have brought physicians an extraordinary opportunity to change natural disease history, although these therapies can also have high associated iatrogenic costs. These factors point to the necessity of having physicians that are dedicated to autoimmunology. The question regarding the creation of a new specialty, the autoimmunologist, should be addressed after an inquiry into the current practice in this field of medicine. This includes many classical specialties, such as internal medicine, rheumatology, and neurology, as well as clinical immunology. In clinical immunology, not counting the specialists in allergology and clinical immunology that mainly work only with allergies, heterogeneity is high in clinical practice, as the European Union of Medical Specialists documented some years ago. I am, at least for now, in favor of the creation of a transversal competency to which the different physicians working in the area could apply to in order to standardize the clinical practice in autoimmunology. It will be necessary to define a core curriculum, and in the end we shall have classical specialists and clinical immunologists with or without the competency of autoimmunology. Of utmost importance is that this new field of medicine should not be translated, as in the past happened with other areas, by walls between medical specialties. Instead it should help standardize and harmonize clinical practice. The time for autoimmunology is now, and, indeed, hospitals must have autoimmune disease units.

  10. 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

  11. Mechanisms in endocrinology: autoimmune thyroid disease: old and new players.

    PubMed

    Effraimidis, Grigoris; Wiersinga, Wilmar M

    2014-06-01

    The last 10 years have seen some progress in understanding the etiology of autoimmune thyroid disease (AITD). The female preponderance can now be explained - at least in part - by fetal microchimerism and X-chromosome inactivation. The number of identified susceptibility genes for AITD is increasing (among others now including TSHR, TG, HLA, CTLA4, PTPN22, CD40, FCRL3, IL2RA, and FOXP3), but these genes together probably do not explain more than about 10% of the heritability of AITD. As twin studies indicate that genes contribute for 70% of AITD, it follows that there must be many more loci, each of them contributing a little. While the genetic studies have clarified why various autoimmune diseases so often cluster in the same patient, the molecular mechanism of action of these genetic polymorphisms (frequently located in introns) has hardly been explained. Polymorphisms in AITD susceptibility genes may become helpful in clinical practice, e.g. in assessing risk of recurrent Graves' hyperthyroidism (GH) after a course of antithyroid drugs. Moderate alcohol intake decreases the risk on overt GH and overt Hashimoto's hypothyroidism. Current smokers - as well known - are at increased risk for Graves' disease, but - surprisingly - at diminished risk for Hashimoto's thyroiditis. Low selenium and low vitamin D levels might increase the risk of developing AITD, but data are still inconclusive. Current options for preventive interventions in subjects at risk to develop AITD are very limited.

  12. Current and future immunomodulation strategies to restore tolerance in autoimmune diseases.

    PubMed

    Bluestone, Jeffrey A; Bour-Jordan, Hélène

    2012-11-01

    Autoimmune diseases reflect a breakdown in self-tolerance that results from defects in thymic deletion of potentially autoreactive T cells (central tolerance) and in T-cell intrinsic and extrinsic mechanisms that normally control potentially autoreactive T cells in the periphery (peripheral tolerance). The mechanisms leading to autoimmune diseases are multifactorial and depend on a complex combination of genetic, epigenetic, molecular, and cellular elements that result in pathogenic inflammatory responses in peripheral tissues driven by self-antigen-specific T cells. In this article, we describe the different checkpoints of tolerance that are defective in autoimmune diseases as well as specific events in the autoimmune response which represent therapeutic opportunities to restore long-term tolerance in autoimmune diseases. We present evidence for the role of different pathways in animal models and the therapeutic strategies targeting these pathways in clinical trials in autoimmune diseases.

  13. 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.

  14. 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

  15. 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.

  16. Updated assessment of the prevalence, spectrum and case definition of autoimmune disease.

    PubMed

    Hayter, Scott M; Cook, Matthew C

    2012-08-01

    Autoimmune diseases are heterogeneous with regard to prevalence, manifestations, and pathogenesis. The classification of autoimmune diseases has varied over time. Here, we have compiled a comprehensive up-to-date list of the autoimmune diseases, and have reviewed published literature to estimate their prevalence. We identified 81 autoimmune diseases. The overall estimated prevalence is 4.5%, with 2.7% for males and 6.4% for females. For specific diseases, prevalence ranges from 1% to <1/10(6). Considering all diseases in the class, the most common mean age-of-onset was 40-50 years. This list of autoimmune diseases has also yielded information about autoantigens. Forty-five autoimmune diseases have been associated with well-defined autoantigens. Of the diseases with known autoantigens, 33.3% had highly repetitive sequences, 35.6% had coiled-coil arrangements and 57.8% were associated with cellular membranes, which means that based on these structural motifs alone, autoantigens do not appear to be a random sample of the human proteome. Finally, we identified 19 autoimmune diseases that phenocopy diseases arising from germline mutations in the corresponding autoantigen. Collectively, our findings lead to a tentative proposal for criteria for assigning autoimmune pathogenesis to a particular disease.

  17. Increased prevalence of autoimmune disease in patients with unilateral compared with bilateral moyamoya disease.

    PubMed

    Chen, Jian-Bin; Liu, Yi; Zhou, Liang-Xue; Sun, Hong; He, Min; You, Chao

    2016-05-01

    OBJECT This study explored whether there were differences between the autoimmune disease prevalence rates in unilateral and bilateral moyamoya disease (MMD). METHODS The authors performed a retrospective review of data obtained from the medical records of their hospital, analyzing and comparing the clinical characteristics and prevalence rates of all autoimmune diseases that were associated with unilateral and bilateral MMD in their hospital from January 1995 to October 2014. RESULTS Three hundred sixteen patients with bilateral MMD and 68 with unilateral MMD were identified. The results indicated that patients with unilateral MMD were more likely to be female than were patients with bilateral MMD (67.6% vs 51.3%, p = 0.014, odds ratio [OR] 1.99). Overall, non-autoimmune comorbidities tended to be more prevalent in the unilateral MMD cases than in the bilateral MMD cases (17.6% vs 9.8%, p = 0.063, OR 1.97, chi-square test). Autoimmune thyroid disease and other autoimmune diseases also tended to be more prevalent in the unilateral MMD cases than in the bilateral MMD cases (19.1% vs 10.8%, p = 0.056, OR 1.96 and 8.8% vs 3.5%, p = 0.092, OR 2.77, respectively, chi-square test). The overall autoimmune disease prevalence in the unilateral MMD cases was significantly higher than in the bilateral MMD cases (26.5% vs 13.6%, p = 0.008, OR 2.29, 95% CI 1.22-4.28, chi-square test). Multiple logistic regression analysis showed that autoimmune disease was more likely to be associated with unilateral than with bilateral MMD (p = 0.039, OR 10.91, 95% CI 1.13-105.25). CONCLUSIONS This study indicated a higher overall autoimmune disease prevalence in unilateral than in bilateral MMD. Unilateral MMD may be more associated with autoimmune disease than bilateral MMD. Different pathogenetic mechanisms may underlie moyamoya vessel formation in unilateral and bilateral MMD.

  18. Autoimmunity as a Candidate for the Etiopathogenesis of Meniere's Disease: Detection of Autoimmune Reactions and Diagnostic Biomarker Candidate

    PubMed Central

    Kim, Sung Huhn; Kim, Jin Young; Lee, Hyun Jin; Gi, Mia; Kim, Bo Gyung; Choi, Jae Young

    2014-01-01

    Meniere's disease is an inner ear disorder that can manifest as fluctuating vertigo, sensorineural hearing loss, tinnitus, and aural fullness. However, the pathologic mechanism of Meniere's disease is still unclear. In this study, we evaluated autoimmunity as a potential cause of Meniere's disease. In addition we tried to find useful biomarker candidates for diagnosis. We investigated the protein composition of human inner ear fluid using liquid column mass spectrometry, the autoimmune reaction between circulating autoantibodies in patient serum and multiple antigens using the Protoarray system, the immune reaction between patient serum and mouse inner ear tissues using western blot analysis. Nine proteins, including immunoglobulin and its variants and interferon regulatory factor 7, were found only in the inner ear fluid of patients with Meniere's disease. Enhanced immune reactions with 18 candidate antigens were detected in patients with Meniere's disease in Protoarray analysis; levels of 8 of these antigens were more than 10-fold higher in patients than in controls. Antigen-antibody reactions between mouse inner ear proteins with molecular weights of 23–48 kDa and 63–75 kDa and patient sera were detected in 8 patients. These findings suggest that autoimmunity could be one of the pathologic mechanisms behind Meniere's disease. Multiple autoantibodies and antigens may be involved in the autoimmune reaction. Specific antigens that caused immune reactions with patient's serum in Protoarray analysis can be candidates for the diagnostic biomarkers of Meniere's disease. PMID:25330336

  19. Autoimmunity as a candidate for the etiopathogenesis of Meniere's disease: detection of autoimmune reactions and diagnostic biomarker candidate.

    PubMed

    Kim, Sung Huhn; Kim, Jin Young; Lee, Hyun Jin; Gi, Mia; Kim, Bo Gyung; Choi, Jae Young

    2014-01-01

    Meniere's disease is an inner ear disorder that can manifest as fluctuating vertigo, sensorineural hearing loss, tinnitus, and aural fullness. However, the pathologic mechanism of Meniere's disease is still unclear. In this study, we evaluated autoimmunity as a potential cause of Meniere's disease. In addition we tried to find useful biomarker candidates for diagnosis. We investigated the protein composition of human inner ear fluid using liquid column mass spectrometry, the autoimmune reaction between circulating autoantibodies in patient serum and multiple antigens using the Protoarray system, the immune reaction between patient serum and mouse inner ear tissues using western blot analysis. Nine proteins, including immunoglobulin and its variants and interferon regulatory factor 7, were found only in the inner ear fluid of patients with Meniere's disease. Enhanced immune reactions with 18 candidate antigens were detected in patients with Meniere's disease in Protoarray analysis; levels of 8 of these antigens were more than 10-fold higher in patients than in controls. Antigen-antibody reactions between mouse inner ear proteins with molecular weights of 23-48 kDa and 63-75 kDa and patient sera were detected in 8 patients. These findings suggest that autoimmunity could be one of the pathologic mechanisms behind Meniere's disease. Multiple autoantibodies and antigens may be involved in the autoimmune reaction. Specific antigens that caused immune reactions with patient's serum in Protoarray analysis can be candidates for the diagnostic biomarkers of Meniere's disease.

  20. Vaccines and autoimmunity.

    PubMed

    De Martino, M; Chiappini, E; Galli, L

    2013-01-01

    Vaccines have eradicated or controlled many infectious diseases, saving each year millions of lives and quality of life of many other millions of people. In spite of the success of vaccines over the last two centuries, parents (and also some health care workers) gloss over the devastating consequences of diseases, which are now avoided thanks to vaccines, and direct their attention to possible negative effects of immunization. Three immunological objections are raised: vaccines cause antigenic overload, natural immunity is safer and better than vaccine-induced immunity, and vaccines induce autoimmunity. The last point is examined in this review. Theoretically, vaccines could trigger autoimmunity by means of cytokine production, anti-idiotypic network, expression of human histocompatibility leukocyte antigens, modification of surface antigens and induction of novel antigens, molecular mimicry, bystander activation, epitope spreading, and polyclonal activation of B cells. There is strong evidence that none of these mechanisms is really effective in causing autoimmune diseases. Vaccines are not a source of autoimmune diseases. By contrast, absolute evidence exists that infectious agents can trigger autoimmune mechanisms and that they do cause autoimmune diseases.

  1. FOXP3(+) Treg Cells and Gender Bias in Autoimmune Diseases.

    PubMed

    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.

  2. New Autoantibody Detection Technologies Yield Novel Insights into Autoimmune Disease

    PubMed Central

    Burbelo, Peter D.; O’Hanlon, Terrance P.

    2014-01-01

    Purpose of review The purpose of this review is to highlight recent progress in autoantibody detection technologies and describe how these methods are providing novel information and insights into autoimmune disorders. Recent findings In recent years, alternative methods such as comprehensive phage display, fluid-phase immunoassays, and antigen microarrays have been developed for autoantigen discovery and profiling autoantibody responses. Compared to classic approaches such as Western blot and ELISA, these methods show improved diagnostic performance, the ability to measure antibody responses to multiple targets, and/or allow for more quantitative analyses. Specific notable findings include uncovering previously unrecognized autoantigens, the improved classification of patient clinical phenotypes, and the discovery of pathogenic autoantibodies promoting disease. Summary Advances in immunoassay technologies offer many opportunities for understanding the relationship between autoantibody detection and the myriad complex, clinical phenotypes characteristic of most autoimmune diseases. Further simplification and standardization of these technologies may allow routine integration into clinical practice with improved diagnostic and therapeutic outcomes. PMID:25203116

  3. 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

  4. New platform technology for comprehensive serological diagnostics of autoimmune diseases.

    PubMed

    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.

  5. 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

  6. 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

  7. Overexpression of Mcl-1 exacerbates lymphocyte accumulation and autoimmune kidney disease in lpr mice

    PubMed Central

    Anstee, Natasha S; Vandenberg, Cassandra J; Campbell, Kirsteen J; Hughes, Peter D; O'Reilly, Lorraine A; Cory, Suzanne

    2017-01-01

    Cell death by apoptosis has a critical role during embryonic development and in maintaining tissue homeostasis. In mammals, there are two converging apoptosis pathways: the ‘extrinsic' pathway, which is triggered by engagement of cell surface ‘death receptors' such as Fas/APO-1; and the ‘intrinsic' pathway, which is triggered by diverse cellular stresses, and is regulated by pro-survival and pro-apoptotic members of the Bcl-2 family of proteins. Pro-survival Mcl-1, which can block activation of the pro-apoptotic proteins, Bax and Bak, appears critical for the survival and maintenance of multiple haemopoietic cell types. To investigate the impact on haemopoiesis of simultaneously inhibiting both apoptosis pathways, we introduced the vavP-Mcl-1 transgene, which causes overexpression of Mcl-1 protein in all haemopoietic lineages, into Faslpr/lpr mice, which lack functional Fas and are prone to autoimmunity. The combined mutations had a modest impact on myelopoiesis, primarily an increase in the macrophage/monocyte population in Mcl-1tg/lpr mice compared with lpr or Mcl-1tg mice. The impact on lymphopoiesis was striking, with a marked elevation in all major lymphoid subsets, including the non-conventional double-negative (DN) T cells (TCRβ+CD4–CD8–B220+) characteristic of Faslpr/lpr mice. Of note, the onset of autoimmunity was markedly accelerated in Mcl-1tg/lpr mice compared with lpr mice, and this was preceded by an increase in immunoglobulin (Ig)-producing cells and circulating autoantibodies. This degree of impact was surprising, given the relatively mild phenotype conferred by the vavP-Mcl-1 transgene by itself: a two- to threefold elevation of peripheral B and T cells, no significant increase in the non-conventional DN T-cell population and no autoimmune disease. Comparison of the phenotype with that of other susceptible mice suggests that the development of autoimmune disease in Mcl-1tg/lpr mice may be influenced not only by Ig-producing cells but

  8. 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.

  9. [Hematopoietic stem cell transplantation in autoimmune diseases. Pros and cons

    PubMed

    Ferraccioli, G. F.

    2001-01-01

    New therapeutics have clearly advanced our chances of inducing remission in several aggressive autoimmune diseases like rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE). Despite this, subgroups of patients with RA or SLE or of other diseases like systemic sclerosis (SSc) or multiple sclerosis (MS) still present a poor response to conventional drugs. In this kind of patients, haematopoietic stem cell transplantation (HSCT) provided important clinical benefits in several studies. This might depend upon several possible mechanisms such as purging of autoreactive T cells during conditioning or changes of the TH1/TH2 biological milieu. An overview of the results obtained so far, the drawbacks and the perspectives in this field are presented.

  10. Recent Findings on Genetics of Systemic Autoimmune Diseases

    PubMed Central

    Delgado-Vega, Angélica; Sánchez, Elena; Löfgren, Sara; Castillejo-López, Casimiro; Alarcón-Riquelme, Marta E.

    2010-01-01

    Summary Association studies of over 1 million SNPs capturing most of the human genome common variation became possible thanks to the information provided by the HapMap International project and the development of high-throughput genotyping technologies at accessible prices. Genome-wide scans analyzing thousands of individuals have now identified most if not all of the major genes involved in susceptibility for several systemic autoimmune diseases. In particular, results for rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) are reviewed here. While most genes are shared between diseases, few seem to be unique reflecting that we still are long before knowing all genes, their interactions with other genes and the environment and their impact on biological functions. PMID:20933377

  11. Oxidative stress and nutritional prevention in autoimmune rheumatic diseases.

    PubMed

    Sukkar, Samir G; Rossi, Edoardo

    2004-03-01

    The hypothesis that oxidative stress favours flogistic and immune processes inducing autoimmune rheumatic diseases (ARDs) and their complications is still under discussion. In this review we take into consideration both the aetiopathological role of the diet in such diseases and the possible efficacy of dietary supports as adjuvants for the usual specific therapies. Moreover, we shall examine the hypothetical pathophysiological role of oxidative stress on ARDs and their complications, the methods for its evaluation and the possibility of intervening on oxidative pathways by means of nutritional modulation. It is possible that in the future we will be able to control connective pathology by associating an immuno-modulating therapy ('re-educating') with natural products having an anti-oxidant activity to current immunosuppressive treatment (which has potentially toxic effects).

  12. Osteopontin Bridging Innate and Adaptive Immunity in Autoimmune Diseases

    PubMed Central

    Raineri, Davide; Boggio, Elena; Favero, Francesco; Soluri, Maria Felicia

    2016-01-01

    Osteopontin (OPN) regulates the immune response at multiple levels. Physiologically, it regulates the host response to infections by driving T helper (Th) polarization and acting on both innate and adaptive immunity; pathologically, it contributes to the development of immune-mediated and inflammatory diseases. In some cases, the mechanisms of these effects have been described, but many aspects of the OPN function remain elusive. This is in part ascribable to the fact that OPN is a complex molecule with several posttranslational modifications and it may act as either an immobilized protein of the extracellular matrix or a soluble cytokine or an intracytoplasmic molecule by binding to a wide variety of molecules including crystals of calcium phosphate, several cell surface receptors, and intracytoplasmic molecules. This review describes the OPN structure, isoforms, and functions and its role in regulating the crosstalk between innate and adaptive immunity in autoimmune diseases. PMID:28097158

  13. 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.

  14. The Emerging Functions of Long Noncoding RNA in Immune Cells: Autoimmune Diseases.

    PubMed

    Sigdel, Keshav Raj; Cheng, Ao; Wang, Yin; Duan, Lihua; Zhang, YanLin

    2015-01-01

    The long noncoding RNAs (lncRNAs) are RNA transcripts more than 200 nucleotides in length, which do not encode proteins. The lncRNAs are emerging as an important regulator of biological process, such as chromatin remodeling, gene transcription, protein transport, and trafficking through diverse mechanisms. The lncRNAs play crucial role in various multigenetics human diseases including cancers and neurological diseases and currently its role in autoimmune diseases is attracting many researchers. Recent studies have reported that differentiation and activation of immune cells, T cells, B cells, macrophages, and NK cells have correlation with lncRNAs, which have also an essential role in autoimmune diseases such as rheumatoid arthritis and SLE. Therefore, elucidation of the roles of lncRNAs in autoimmunity could be beneficial to understand the pathogenesis of autoimmune diseases. In this review article we attempt to highlight the recent progress regarding lncRNAs studies and summarize its role in autoimmune diseases.

  15. Autoimmune bullous skin diseases. Part 1: Clinical manifestations.

    PubMed

    Kneisel, Andrea; Hertl, Michael

    2011-10-01

    Autoimmune bullous skin diseases are characterized by autoantibodies against adhesion molecules of the skin. Pemphigus is a disorder with an intraepidermal loss of adhesion and is characterized by fragile blisters and erosions. Pemphigus vulgaris often shows extensive lesions of the oral mucosa, while pemphigus foliaceus is commonly restricted to cutaneous involvement with puff pastry-like scale formation. Paraneoplastic pemphigus is obligatorily associated with malignancies and often presents as hemorrhagic stomatitis with multiforme-like exanthems. IgA pemphigus typically presents with pustules and annular plaques but not with mucosal involvement. The clinical spectrum of the pemphigoids includes tense blisters, urticarial plaques, and prurigo- like eczematous lesions. Pemphigoid gestationis mostly occurs during the last trimester of pregnancy and mucous membrane pemphigoid primarily involves the oral mucosa and conjunctivae and leads to scarring. Linear IgA bullous dermatosis manifests with tense blisters in a "cluster of jewels"-like pattern in childhood and is more heterogeneous in adulthood. Classical epidermolysis bullosa acquisita shows extensive skin fragility. Dermatitis herpetiformis is associated with gluten-sensitive enteropathy and manifests clinically with severe itching and papulovesicles on the extensor surfaces of the extremities and the lumbosacral area. The intention of the review is to demonstrate the heterogeneous clinical spectrum of autoimmune bullous disorders.

  16. 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...

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

    SciTech Connect

    Ikehara, S.; Yasumizu, R.; Inaba, M.; Izui, S.; Hayakawa, K.; Sekita, K.; Toki, J.; Sugiura, K.; Iwai, H.; Nakamura, T. )

    1989-05-01

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

  18. 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.

  19. 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

  20. 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

  1. 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

  2. Stem cell therapy in autoimmune rheumatic diseases: a comprehensive review.

    PubMed

    Liu, Bin; Shu, ShangAn; Kenny, Thomas P; Chang, Christopher; Leung, Patrick S C

    2014-10-01

    The clinical management of autoimmune rheumatic diseases (ARD) has undergone significant changes in the last few decades, leading to remarkable improvements in clinical outcomes of many patients with mild to moderate ARD. On the other hand, severe refractory ARD patients often have high morbidity and mortality. Extensive basic research and clinical evidence has opened the door to new encouraging perspectives, such as the establishment of a role of stem cell transplantation (SCT) in the strategic management of ARD. Given the great heterogeneity of ARD, it is difficult to assign an optimal SCT regimen to all ARD patients. SCT remains a challenging mode of therapy in ARD patients from the standpoints of both efficacy and safety. As the clinical data of SCT in ARD increases and as we improve our understanding of stem cell biology and the downstream effects on the immune system, the future is promising for the development of optimal personalized SCT regimens in ARD.

  3. Desmosomal cadherins and signaling: lessons from autoimmune disease.

    PubMed

    Spindler, Volker; Waschke, Jens

    2014-02-01

    Autoantibodies from patients suffering from the autoimmune blistering skin disease pemphigus can be applied as tools to study desmosomal adhesion. These autoantibodies targeting the desmosomal cadherins desmoglein (Dsg) 1 and Dsg3 cause disruption of desmosomes and loss of intercellular cohesion. Although pemphigus autoantibodies were initially proposed to sterically hinder desmosomes, many groups have shown that they activate signaling pathways which cause disruption of desmosomes and loss of intercellular cohesion by uncoupling the desmosomal plaque from the intermediate filament cytoskeleton and/or by interfering with desmosome turnover. These studies demonstrate that desmogleins serve as receptor molecules to transmit outside-in signaling and demonstrate that desmosomal cadherins have functions in addition to their adhesive properties. Two central molecules regulating cytoskeletal anchorage and desmosome turnover are p38MAPK and PKC. As cytoskeletal uncoupling in turn enhances Dsg3 depletion from desmosomes, both mechanisms reinforce one another in a vicious cycle that compromise the integrity and number of desmosomes.

  4. T helper 17 cell heterogeneity and pathogenicity in autoimmune disease

    PubMed Central

    Ghoreschi, Kamran; Laurence, Arian; Yang, Xiang-Ping; Hirahara, Kiyoshi; O’Shea, John J.

    2011-01-01

    Th17 cells have been proposed to represent a new CD4+ T cell lineage important for host defense against fungi and extracellular bacteria, and the development of autoimmune diseases. Precisely how these cells arise has been the subject of some debate with apparent species-specific differences in mice and men. Here, we describe evolving views of Th17 specification, highlighting the contribution of TGF-β and the opposing roles of STAT3 and STAT5. Increasing evidence points to heterogeneity and inherent phenotypic instability in this subset. Ideally, better understanding of expression and action of key transcription factors and the epigenetic landscape of Th17 can help explain the flexibility and diversity of IL-17-producing cells. PMID:21782512

  5. Prediction and Prevention of Autoimmune Disease in the 21st Century: A Review and Preview.

    PubMed

    Rose, Noel R

    2016-03-01

    Autoimmune diseases represent a family of at least 80 illnesses that share a common pathogenesis: an immune-mediated attack on the body's own organs. Collectively, autoimmune diseases affect some 20 million Americans, predominantly women. Many of these diseases are increasing in frequency in industrialized countries. Treatment of autoimmune diseases improved greatly during the second half of the 20th century but has been hampered because the diseases often progress before a clinical diagnosis is possible. Research in the 21st century is focusing on prospective prediction using the tools of systems biology.

  6. 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.

  7. A case of autoimmune urticaria accompanying autoimmune polyglandular syndrome type III associated with Hashimoto's disease, type 1 diabetes mellitus, and vitiligo.

    PubMed

    Kasznicki, Jacek; Drzewoski, Józef

    2014-01-01

    We present a case of autoimmune polyglandular syndrome type III (APS III) associated with Hashimoto's disease, type 1 diabetes mellitus, vitiligo and autoimmune urticaria. This rare genetic disorder occurs with unknown frequency in the Polish population. It is characterised by endocrine tissue destruction resulting in the malfunction of multiple organs.Several cases of APS III associated with organ-specific autoimmune diseases such as coeliac disease, hypogonadism and myasthenia gravis, as well as organ-nonspecific or systemic autoimmune diseases such as sarcoidosis, Sjögren syndrome, and rheumatoid arthritis have been described. To the best of our knowledge, we here describe the first case of APS III associated with autoimmune thyroiditis, type 1 diabetes mellitus, vitiligo and autoimmune urticaria in an adult patient.

  8. 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

  9. 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.

  10. Twin studies as a model for exploring the aetiology of autoimmune thyroid disease.

    PubMed

    Brix, Thomas Heiberg; Hegedüs, Laszlo

    2012-04-01

    Twins are an important resource for evaluating the relative contribution of genetic and environmental factors in determining a phenotype. During the last decades, a number of twin studies have investigated the aetiology of several phenotypes related to thyroid autoimmunity. Taken together, these studies have provided valid and unbiased information regarding the influence of genetic and environmental factors in the aetiology of autoimmune thyroid disease (AITD). The comparison of concordance rates between monozygotic (MZ) and dizygotic twins provides irrefutable evidence of a genetic component, and biometric twin modelling shows that approximately 75% of the total phenotypic variance in AITD is because of genetic effects. On the other hand, the lack of complete concordance in MZ twin pairs is proof of environmental and/or epigenetic factors also playing an important role. The impact of environmental triggers such as cigarette smoking, birth characteristics, infection with Yersinia enterocolitica, microchimerism and degree of X chromosome inactivation (XCI) has been evaluated by investigating AITD discordant twin pairs. These studies indicate that smoking, Y. enterocolitica infection and skewed XCI may be causally associated with clinically overt AITD, but not with the presence of thyroid autoantibodies in euthyroid subjects. Microchimerism, but not birth weight, might play a role in AITD. Twin studies offer several features that uniquely enhance our ability to localize genes and understand their function. Future twin studies should incorporate information on genetic, epigenetic and environmental variation thereby enhancing our ability to quantify the precise effect of specific risk factors.

  11. Autoimmune progesterone dermatitis: Case report with history of urticaria, petechiae and palpable pinpoint purpura triggered by medical abortion.

    PubMed

    Mbonile, Lumuli

    2016-03-17

    Autoimmune progesterone dermatitis (APD) is a rare autoimmune response to raised endogenous progesterone levels that occur during the luteal phase of the menstrual cycle. Cutaneous, mucosal lesions and other systemic manifestations develop cyclically during the luteal phase of the menstrual cycle when progesterone levels are elevated. APD symptoms usually start 3 - 10 days before menstruation and resolve 1 - 2 days after menstruation ceases. A 30-year-old woman presented with urticaria, petechiae and palpable pinpoint purpura lesions of the legs, forearms, neck and buttocks 1 week prior to her menses starting and 2 months after a medical abortion. She was diagnosed with allergic contact dermatitis and topical steroids were prescribed. Her skin conditions did not improve and were associated with her menstrual cycle. We performed an intradermal test using progesterone, which was positive. She was treated with oral contraceptive pills and the symptoms were resolved. This is a typical case of APD triggered by increased sensitivity to endogenous progesterone induced a few months after medical abortion.

  12. 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

  13. Low prevalence of hepatitis B virus infection in patients with autoimmune diseases in a Chinese patient population.

    PubMed

    Sui, M; Wu, R; Hu, X; Zhang, H; Jiang, J; Yang, Y; Niu, J

    2014-12-01

    Hepatitis B is a very common communicable disease in China but the prevalence of hepatitis B virus (HBV) infection in patients with autoimmune diseases is unknown. We retrospectively investigated the prevalence of autoimmune diseases in patients with HBV infection. The medical records of 4060 patients with autoimmune or nonautoimmune diseases were reviewed. A positive test result for hepatitis B surface antigen (HBsAg) was used to indicate the presence of HBV infection. Autoimmune diseases included autoimmune hepatitis, primary biliary cirrhosis, systemic lupus erythematosus and ulcerative colitis. Nonautoimmune conditions included inguinal hernia, appendicitis and pregnant or postpartum women. The proportion of autoimmune disease patients who were HBsAg positive (2.24%) was significantly lower than that of nonautoimmune disease patients who were HBsAg positive (4.58%; P = 0.0014). Regarding hepatic autoimmune diseases, the positivity rates for HBsAg in autoimmune hepatitis patients (0.83%) and primary biliary cirrhosis patients (1.02%) were both significantly lower than in nonautoimmune patients (4.58%; P = 0.006 and 0.004, respectively). Patients with hepatic autoimmune disease were significantly less likely to be HBsAg positive (0.93%) than patients with non-hepatic autoimmune disease (3.99%; P = 0.002). Patients with autoimmune diseases, especially those with hepatic autoimmune disease, may more efficiently clear HBV than patients with nonautoimmune diseases.

  14. Sex-specific environmental influences on the development of autoimmune diseases.

    PubMed

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

    2013-11-01

    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.

  15. Mammalian N-glycan branching protects against innate immune self-recognition and inflammation in autoimmune disease pathogenesis.

    PubMed

    Green, Ryan S; Stone, Erica L; Tenno, Mari; Lehtonen, Eero; Farquhar, Marilyn G; Marth, Jamey D

    2007-08-01

    Autoimmune diseases are prevalent and often life-threatening syndromes, yet the pathogenic triggers and mechanisms involved remain mostly unresolved. Protein asparagine linked- (N-) glycosylation produces glycan structures that substantially differ among the extracellular compartments of evolutionarily divergent organisms. Alpha-mannosidase-II (alphaM-II) deficiency diminishes complex-type N-glycan branching in vertebrates and induces an autoimmune disease in mice similar to human systemic lupus erythematosus. We found that disease pathogenesis provoking glomerulonephritis and kidney failure was nonhematopoietic in origin, independent of complement C3 and the adaptive immune system, mitigated by intravenous administration of immunoglobulin-G, and linked to chronic activation of the innate immune system. N-glycans produced in alphaM-II deficiency bear immune-stimulatory mannose-dependent ligands for innate immune lectin receptors, disrupting the phylogenic basis of this glycomic recognition mechanism. Thus, mammalian N-glycan branching safeguards against the formation of an endogenous immunologic signal of nonself that can provoke a sterile inflammatory response in the pathogenesis of autoimmune disease.

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

    PubMed

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

    2015-10-01

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

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

    PubMed Central

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

    2015-01-01

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

  18. Toxicities of Immunosuppressive Treatment of Autoimmune Neurologic Diseases

    PubMed Central

    Lallana, Enrico C; Fadul, Camilo E

    2011-01-01

    In parallel to our better understanding of the role of the immune system in neurologic diseases, there has been an increased availability in therapeutic options for autoimmune neurologic diseases such as multiple sclerosis, myasthenia gravis, polyneuropathies, central nervous system vasculitides and neurosarcoidosis. In many cases, the purported benefits of this class of therapy are anecdotal and not the result of good controlled clinical trials. Nonetheless, their potential efficacy is better known than their adverse event profile. A rationale therapeutic decision by the clinician will depend on a comprehensive understanding of the ratio between efficacy and toxicity. In this review, we outline the most commonly used immune suppressive medications in neurologic disease: cytotoxic chemotherapy, nucleoside analogues, calcineurin inhibitors, monoclonal antibodies and miscellaneous immune suppressants. A discussion of their mechanisms of action and related toxicity is highlighted, with the goal that the reader will be able to recognize the most commonly associated toxicities and identify strategies to prevent and manage problems that are expected to arise with their use. PMID:22379461

  19. 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.

  20. Vaccines, adjuvants and autoimmunity.

    PubMed

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

    2015-10-01

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

  1. 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

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

    PubMed

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

    2015-03-01

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

  3. CD24: from a Hematopoietic Differentiation Antigen to a Genetic Risk Factor for Multiple Autoimmune Diseases.

    PubMed

    Tan, Yixin; Zhao, Ming; Xiang, Bo; Chang, Christopher; Lu, Qianjin

    2016-02-01

    The autoantibody is an essential characteristic of inflammatory disorders, including autoimmune diseases. Although the exact pathogenic mechanisms of these diseases remain elusive, accumulated evidence has implicated that genetic factors play important roles in autoimmune inflammation. Among these factors, CD24 was first identified as a heat-stable antigen in 1978 and first successfully cloned in 1990. Thereafter, its functional roles have been intensively investigated in various human diseases, especially autoimmune diseases and cancers. It is currently known that CD24 serves as a costimulatory factor of T cells that regulate their homeostasis and proliferation, while in B cells, CD24 is functionally involved in cell activation and differentiation. CD24 can enhance autoimmune diseases in terms of its protective role in the clonal deletion of autoreactive thymocytes. Furthermore, CD24 deficiency has been linked to mouse experimental autoimmune encephalomyelitis. Finally, CD24 genetic variants, including single-nucleotide polymorphisms and deletions, are etiologically relevant to autoimmune diseases, such as multiple sclerosis and systemic lupus erythematosus. Therefore, CD24 is a promising biomarker and novel therapeutic target for autoimmune diseases.

  4. 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

  5. Autoimmune and infectious skin diseases that target desmogleins

    PubMed Central

    AMAGAI, Masayuki

    2010-01-01

    Desmosomes are intercellular adhesive junctions of epithelial cells that contain two major transmembrane components, the desmogleins (Dsg) and desmocollins (Dsc), which are cadherin-type cell–cell adhesion molecules and are anchored to intermediate filaments of keratin through interactions with plakoglobin and desmoplakin. Desmosomes play an important role in maintaining the proper structure and barrier function of the epidermis and mucous epithelia. Four Dsg isoforms have been identified to date, Dsg1–Dsg4, and are involved in several skin and heart diseases. Dsg1 and Dsg3 are the two major Dsg isoforms in the skin and mucous membranes, and are targeted by IgG autoantibodies in pemphigus, an autoimmune disease of the skin and mucous membranes. Dsg1 is also targeted by exfoliative toxin (ET) released by Staphylococcus aureus in the infectious skin diseases bullous impetigo and staphylococcal scalded skin syndrome (SSSS). ET is a unique serine protease that shows lock and key specificity to Dsg1. Dsg2 is expressed in all tissues possessing desmosomes, including simple epithelia and myocardia, and mutations in this gene are responsible for arrhythmogenic right ventricular cardiomyopathy/dysplasia. Dsg4 plays an important adhesive role mainly in hair follicles, and Dsg4 mutations cause abnormal hair development. Recently, an active disease model for pemphigus was generated by a unique approach using autoantigen-deficient mice that do not acquire tolerance against the defective autoantigen. Adoptive transfer of Dsg3−/− lymphocytes into mice expressing Dsg3 induces stable anti-Dsg3 IgG production with development of the pemphigus phenotype. This mouse model is a valuable tool with which to investigate immunological mechanisms of harmful IgG autoantibody production in pemphigus. Further investigation of desmoglein molecules will continue to provide insight into the unsolved pathophysiological mechanisms of diseases and aid in the development of novel therapeutic

  6. 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

  7. Venous thromboembolic disease in systemic autoimmune diseases: an association to keep in mind.

    PubMed

    Silvariño, Ricardo; Danza, Álvaro; Mérola, Valentina; Bérez, Adriana; Méndez, Enrique; Espinosa, Gerard; Cervera, Ricard

    2012-12-01

    Systemic autoimmune diseases are conditions of unknown etiology, characterized by the simultaneous or successive involvement of most organs and systems, as well as the presence of autoantibodies as biological markers. Venous thromboembolic disease has a higher incidence in this population when compared to healthy individuals. This responds to the increase in congenital and acquired risk factors in this group. One of the main risk factors is linked to the presence of antiphospholipid antibodies, whose prevalence is increased among patients with such conditions.

  8. 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.

  9. [Diagnosis of osteoporosis occurring in autoimmune thyroid gland disease].

    PubMed

    Radojković, Ivan; Radojković, Jana; Djurica, Snezana

    2005-10-01

    Osteoporosis or porotic bone is a general, systemic bone disease, which is manifested by fracture as its consequence. The main characteristic of this disease is the loss of bone microarchitecture, bone mass reduction, and its increased fragility. The result, thereof, is susceptibility to fracture. Etiology of osteoporosis is polymorph. Its socio-medical importance is enormous, since there is one osteoporotic fracture every 20 sec. worldwide. Million and six hundred thousand osteoporotic fractures occur annualy throughout the world. Thyroid gland is susceptible to autoimmune reactions that lead to autoimmune diseases, just like many other organs. The autoimmune disorder is a final consequence of a failure, in some instance, within the crucial mechanism of regulation of self tissue tolerance. The main goal is to prove the presence of osteoporosis, its inexpensive and quick diagnostics; to make a distinction among the causes that lead to it. In addition, to indicate the importance of osteoporosis that is caused by normal, metabolic processes which are an inevitable part of ageing. Diagnosis of osteoporosis can be done through laboratory, which is a tiresome, time consuming task. Measurements of BMD could be also performed by using new devices. Osteometers could be constructed on the basis of X-ray photon energy or US. Utilization most contemporary one uses laser beam, and it approximates the distance of additional tissue that also absorbs part of energy changing absorption of the reception unit and thus making the measurement results accurate. In diagnosing BMD by osteometer, one faces with certain difficulties. When axial quantitative CT is used, the value may be falsely lower, because of the loss of energy absorbed by aorta which is often calcified in elderly people. In devices with transversal scanning, of the same nature and technology, a part of the energy is being absorbed by transversal and spinal vertebrals. After the research, one may conclude that the most

  10. Tertiary lymphoid organs in systemic autoimmune diseases:  pathogenic or protective?

    PubMed Central

    Shipman, William D.; Dasoveanu, Dragos C.; Lu, Theresa T.

    2017-01-01

    Tertiary lymphoid organs are found at sites of chronic inflammation in autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis. These organized accumulations of T and B cells resemble secondary lymphoid organs and generate autoreactive effector cells. However, whether they contribute to disease pathogenesis or have protective functions is unclear. Here, we discuss how tertiary lymphoid organs can generate potentially pathogenic cells but may also limit the extent of the response and damage in autoimmune disease. PMID:28344775

  11. 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

  12. Clinical Presentation and Outcomes of Autoimmune Hepatitis in Inflammatory Bowel Disease.

    PubMed

    DeFilippis, Ersilia M; Kumar, Sonal

    2015-10-01

    Nearly one-third of patients with inflammatory bowel disease (IBD) have abnormal liver tests, which can be indicative of underlying hepatic disease. Primary sclerosing cholangitis has a clear association with ulcerative colitis, but other autoimmune disorders such as autoimmune hepatitis (AIH) have also been associated with IBD. AIH may also occur in the setting of an overlap syndrome or in the setting of medications, particularly tumor necrosis factor alpha inhibitors. Importantly, some studies have shown that IBD patients with AIH fail treatment more frequently than IBD patients without AIH. This review will focus on the clinical characteristics, diagnosis, and management of autoimmune hepatitis in inflammatory bowel disease patients.

  13. Gene Expression Profiles from Disease Discordant Twins Suggest Shared Antiviral Pathways and Viral Exposures among Multiple Systemic Autoimmune Diseases.

    PubMed

    Gan, Lu; O'Hanlon, Terrance P; Lai, Zhennan; Fannin, Rick; Weller, Melodie L; Rider, Lisa G; Chiorini, John A; Miller, Frederick W

    2015-01-01

    Viral agents are of interest as possible autoimmune triggers due to prior reported associations and widely studied molecular mechanisms of antiviral immune responses in autoimmunity. Here we examined new viral candidates for the initiation and/or promotion of systemic autoimmune diseases (SAID), as well as possible related signaling pathways shared in the pathogenesis of those disorders. RNA isolated from peripheral blood samples from 33 twins discordant for SAID and 33 matched, unrelated healthy controls was analyzed using a custom viral-human gene microarray. Paired comparisons were made among three study groups-probands with SAID, their unaffected twins, and matched, unrelated healthy controls-using statistical and molecular pathway analyses. Probands and unaffected twins differed significantly in the expression of 537 human genes, and 107 of those were associated with viral infections. These 537 differentially expressed human genes participate in overlapping networks of several canonical, biologic pathways relating to antiviral responses and inflammation. Moreover, certain viral genes were expressed at higher levels in probands compared to either unaffected twins or unrelated, healthy controls. Interestingly, viral gene expression levels in unaffected twins appeared intermediate between those of probands and the matched, unrelated healthy controls. Of the viruses with overexpressed viral genes, herpes simplex virus-2 (HSV-2) was the only human viral pathogen identified using four distinct oligonucleotide probes corresponding to three HSV-2 genes associated with different stages of viral infection. Although the effects from immunosuppressive therapy on viral gene expression remain unclear, this exploratory study suggests a new approach to evaluate shared viral agents and antiviral immune responses that may be involved in the development of SAID.

  14. Gene Expression Profiles from Disease Discordant Twins Suggest Shared Antiviral Pathways and Viral Exposures among Multiple Systemic Autoimmune Diseases

    PubMed Central

    Gan, Lu; O’Hanlon, Terrance P.; Lai, Zhennan; Fannin, Rick; Weller, Melodie L.; Rider, Lisa G.; Chiorini, John A.; Miller, Frederick W.

    2015-01-01

    Viral agents are of interest as possible autoimmune triggers due to prior reported associations and widely studied molecular mechanisms of antiviral immune responses in autoimmunity. Here we examined new viral candidates for the initiation and/or promotion of systemic autoimmune diseases (SAID), as well as possible related signaling pathways shared in the pathogenesis of those disorders. RNA isolated from peripheral blood samples from 33 twins discordant for SAID and 33 matched, unrelated healthy controls was analyzed using a custom viral-human gene microarray. Paired comparisons were made among three study groups—probands with SAID, their unaffected twins, and matched, unrelated healthy controls—using statistical and molecular pathway analyses. Probands and unaffected twins differed significantly in the expression of 537 human genes, and 107 of those were associated with viral infections. These 537 differentially expressed human genes participate in overlapping networks of several canonical, biologic pathways relating to antiviral responses and inflammation. Moreover, certain viral genes were expressed at higher levels in probands compared to either unaffected twins or unrelated, healthy controls. Interestingly, viral gene expression levels in unaffected twins appeared intermediate between those of probands and the matched, unrelated healthy controls. Of the viruses with overexpressed viral genes, herpes simplex virus-2 (HSV-2) was the only human viral pathogen identified using four distinct oligonucleotide probes corresponding to three HSV-2 genes associated with different stages of viral infection. Although the effects from immunosuppressive therapy on viral gene expression remain unclear, this exploratory study suggests a new approach to evaluate shared viral agents and antiviral immune responses that may be involved in the development of SAID. PMID:26556803

  15. C3 glomerulonephritis and autoimmune disease: more than a fortuitous association?

    PubMed

    Alexander, Mariam P; Fervenza, Fernando C; De Vriese, An S; Smith, Richard J H; Nasr, Samih H; Cornell, Lynn D; Herrera Hernandez, Loren P; Zhang, Yuzhou; Sethi, Sanjeev

    2016-04-01

    C3 glomerulonephritis (C3GN) results from genetic or acquired dysregulation of the alternative complement pathway. A subset of patients may have clinical and biochemical characteristics compatible with an autoimmune disorder. We studied a cohort of 85 patients with confirmed C3GN (2007-2014), of which ten patients (3 male, 7 female; mean age 38.5 years) had an associated autoimmune disorder. All patients had abnormal ANA titers, 6 also had positive ds-DNA titers. At the time of presentation with C3GN, all 7 female patients had autoimmune-related presentations. Of the 3 male patients, only 1 patient had autoimmune-related presentations. Kidney biopsy showed predominantly mesangial proliferative or membranoproliferative glomerulonephritis. In 5 patients, the alternative pathway was evaluated. All had allele variants/polymorphisms associated with C3GN. One patient was also positive for C3Nefs. Treatment varied form conservative management to the use of prednisone alone or with cytotoxic therapy. Mean serum creatinine decreased from 2.0 to 1.4 mg/dL while proteinuria decreased from 2300 to 994 mg/24 h in 8 patients with follow-up. The study highlights the association between C3GN and autoimmune disorders, particularly in female patients. The study suggests that an autoimmune milieu may act as a trigger for the development of C3GN in genetically susceptible patients. Short-term prognosis of C3GN associated with autoimmune disorders appears excellent.

  16. [The role of gender in the pathogenesis and development of autoimmune diseases].

    PubMed

    Tomczyńska, Małgorzata; Salata, Ireneusz; Saluk, Joanna

    2016-09-29

    Autoimmune diseases occur with greater frequency in women than in men, suggesting that the mechanism of pathogenesis is conditioned by gender. So far not defined clearly factors responsible for the development and course of these diseases depending on sex. However, it was found there is a clear sexual dimorphism of the immune system, which may determine the process of autoimmunity. The causes of the increased incidence of women in autoimmune diseases are attributed to the action of the hormones estrogen, which can promote the process of autoimmunity and enhance the clinical symptoms of the disease. As shown sex hormones have immunomodulatory activities on dendritic cells, macrophages, neutrophils, B and T cells. In the both situation the response to strange antigens and mechanism of autoimmunity sex hormones have been shown to play contributory roles in process of cytokine production, the expression of cytokine receptors and response of effector cells. According to recent research, the development of autoimmune diseases is determined by genetic factors. Changes in the autosomal genes X and Y chromosomes play an important role in the progression of autoimmune processes, especially that the X chromosome has genes responsible for the regulation of the immune system.

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

    PubMed

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

    2014-01-01

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

  18. Increased prevalence of autoimmune disease within C9 and FTD/MND cohorts

    PubMed Central

    Sturm, Virginia E.; Camsari, Gamze Balci; Karydas, Anna; Yokoyama, Jennifer S.; Grinberg, Lea T.; Boxer, Adam L.; Rosen, Howard J.; Rankin, Katherine P.; Gorno-Tempini, Maria Luisa; Coppola, Giovanni; Geschwind, Daniel H.; Rademakers, Rosa; Seeley, William W.; Graff-Radford, Neill R.; Miller, Bruce L.

    2016-01-01

    Objective: To determine the prevalence of autoimmune disease in symptomatic C9ORF72 (C9) mutation carriers and frontotemporal dementia with motor neuron disease (FTD/MND) cohorts. Methods: In this case-control study, we reviewed the clinical histories of 66 patients with FTD/MND and 57 symptomatic C9 carriers (24 overlapping cases), a total of 99 charts, for history of autoimmune disease. The prevalence of autoimmune disease in C9 and FTD/MND cohorts was determined by χ2 and Fisher exact comparisons between the combined C9 and FTD/MND group with normal control, Alzheimer disease, and progressive supranuclear palsy cohorts, as well as comparisons within C9 and FTD/MND cohorts. Results: Our combined C9 and FTD/MND cohort has a 12% prevalence of nonthyroid autoimmune disease. The prevalence of nonthyroid autoimmune disease in C9 and FTD/MND is similar to the rates in previously detailed progranulin and semantic variant primary progressive aphasia cohorts and elevated in comparison to previously collected normal control and typical Alzheimer disease cohorts, as well as a newly screened progressive supranuclear palsy cohort. Furthermore, the types of autoimmune disease in this combined C9 and FTD/MND cohort cluster within the same 3 categories previously described in progranulin and semantic variant primary progressive aphasia: inflammatory arthritides, cutaneous conditions, and gastrointestinal disorders. Conclusions: The association between selective autoimmune disease and neurodegenerative disorders unified by the underlying pathology frontotemporal lobar degeneration with TDP-43–positive inclusions (FTLD-TDP) extends to C9 and FTD/MND cohorts, providing further evidence that select autoimmune inflammation may be intrinsically linked to FTLD-TDP pathophysiology. PMID:27844039

  19. Promotion and prevention of autoimmune disease by CD8+ T cells.

    PubMed

    Gravano, David M; Hoyer, Katrina K

    2013-09-01

    Until recently, little was known about the importance of CD8+ T effectors in promoting and preventing autoimmune disease development. CD8+ T cells can oppose or promote autoimmune disease through activities as suppressor cells and as cytotoxic effectors. Studies in several distinct autoimmune models and data from patient samples are beginning to establish the importance of CD8+ T cells in these diseases and to define the mechanisms by which these cells influence autoimmunity. CD8+ effectors can promote disease via dysregulated secretion of inflammatory cytokines, skewed differentiation profiles and inappropriate apoptosis induction of target cells, and work to block disease by eliminating self-reactive cells and self-antigen sources, or as regulatory T cells. Defining the often major contribution of CD8+ T cells to autoimmune disease and identifying the mechanisms by which they alter the pathogenesis of disease is a rapidly expanding area of study and will add valuable information to our understanding of the kinetics, pathology and biology of autoimmune disease.

  20. 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.

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

    PubMed

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

    2007-12-01

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

  2. 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.

  3. Familial associations of lymphoma and myeloma with autoimmune diseases

    PubMed Central

    Hemminki, K; Försti, A; Sundquist, K; Sundquist, J; Li, X

    2017-01-01

    Many B-cell neoplasms are associated with autoimmune diseases (AIDs) but most evidence is based on a personal rather than a family history of AIDs. Here we calculated risks for non-Hodgkin lymphoma (NHL), Hodgkin lymphoma (HL) and multiple myeloma (MM) when family members were diagnosed with any of 44 different AIDs, or, independently, risk for AIDs when family members were diagnosed with a neoplasm. A total of 64 418 neoplasms and 531 155 AIDs were identified from Swedish nationwide health care records. NHL was associated with a family history of five AIDs, all increasing the risk, HL was associated with one AID increasing and three AIDs decreasing the risk while MM had no association. A family history of NHL was associated with eight, HL with seven and MM with seven different AIDs, nine increasing and 13 decreasing the risk. The present family data on B-cell neoplasms and AIDs show an approximately equal number of associations for risk increase and risk decrease, suggesting that inherited genes or gene-environment interactions may increase the risk or be protective. These results differed from published data on personal history of AID, which only report increased risks, often vastly higher and for different AIDs compared with the present data. PMID:28157190

  4. Paraneoplastic syndrome: a masquerade of autoimmune inner ear disease.

    PubMed

    Greene, Jacqueline J; Keefe, Michael W; Harris, Jeffrey P; Matsuoka, Akihiro J

    2015-01-01

    Rare and diagnostically challenging, paraneoplastic syndromes can appear months to years before detection of their underlying neoplasms and are associated with rapidly progressive neurologic deficits, including cochleovestibulopathy and death. Less than 20 cases of paraneoplastic cochleovestibulopathy have been reported in the online database PubMed. We present three recent cases: one patient with a history of B-cell follicular lymphoma who developed dermatomyositis and hearing loss before detection of lymphoma recurrence in his anterior chest wall, a second patient with sudden asymmetric hearing loss, found to have a 12-cm renal mass before death, and a third with fluctuating bilateral hearing loss who was ultimately found to have a thymoma. Although characterized as type VI (non-immune rapidly progressive sensorineural hearing loss) within the Harris autoimmune inner ear disease classification system, the mechanism of paraneoplastic cochleovestibulopathy is not well understood. Although specific anti-neuronal antibodies such as anti-Hu may be associated with other paraneoplastic neurologic disorders, these antibodies have limited diagnostic utility with paraneoplastic cochleovestibulopathy. Steroids have limited efficacy with regard to hearing recovery, whereas intravenous immunoglobulin has been shown to be of benefit. These recent cases demonstrate how auditory and vestibular deficits may be indicative of a rare but potentially life-threatening occult neoplasm where timely diagnosis is critical. We believe that understanding paraneoplastic cochleovestibulopathy is of interest across a broad range of clinical practices.

  5. Familial associations of lymphoma and myeloma with autoimmune diseases.

    PubMed

    Hemminki, K; Försti, A; Sundquist, K; Sundquist, J; Li, X

    2017-01-06

    Many B-cell neoplasms are associated with autoimmune diseases (AIDs) but most evidence is based on a personal rather than a family history of AIDs. Here we calculated risks for non-Hodgkin lymphoma (NHL), Hodgkin lymphoma (HL) and multiple myeloma (MM) when family members were diagnosed with any of 44 different AIDs, or, independently, risk for AIDs when family members were diagnosed with a neoplasm. A total of 64 418 neoplasms and 531 155 AIDs were identified from Swedish nationwide health care records. NHL was associated with a family history of five AIDs, all increasing the risk, HL was associated with one AID increasing and three AIDs decreasing the risk while MM had no association. A family history of NHL was associated with eight, HL with seven and MM with seven different AIDs, nine increasing and 13 decreasing the risk. The present family data on B-cell neoplasms and AIDs show an approximately equal number of associations for risk increase and risk decrease, suggesting that inherited genes or gene-environment interactions may increase the risk or be protective. These results differed from published data on personal history of AID, which only report increased risks, often vastly higher and for different AIDs compared with the present data.

  6. [The role of hereditary and environmental factors in autoimmune thyroid diseases].

    PubMed

    Balázs, Csaba

    2012-07-01

    Autoimmune thyroid diseases are the most common organ-specific autoimmune disorders affecting 5% to 10% of the population in Western countries. The clinical presentation varies from hyperthyroidism in Graves' disease to hypothyroidism in Hashimoto's thyroiditis. While the exact etiology of thyroid autoimmunity is not known, the interaction between genetic susceptibility and environmental factors appears to be of fundamental importance to initiate the process of thyroid autoimmunity. The identified autoimmune thyroid disease susceptibility genes include immune-modulating genes, such as the major histocompatibility complex, and thyroid-specific genes, including TSH receptor, thyroglobulin and thyroid peroxidase. The majority of the anti-TSH-receptor antibodies have a stimulating capacity and are responsible for hyperthyroidism. The anti-thyroglobulin- and anti-thyroid peroxidase antibodies belonging to the catalytic type of antibodies destroy the thyrocytes resulting in hypothyroidism. The appearance of anti-thyroid peroxidase antibodies precedes the induction of thyroiditis and the manifestation of hypothyroidism. The molecular analysis of thyroglobulin gene polymorphism is important in the mechanism of autoimmune thyroiditis. The autoantigen presentation by major histocompatibility complex molecules is a key point of the autoimmune mechanism. It has been shown that a HLA-DR variant containing arginine at position 74 of the DRβ1 chain confers a strong genetic susceptibility to autoimmune thyroid diseases, Graves' disease and Hashimoto's thyroiditis, while glutamine at position DRβ1-74 is protective. Human thyroglobulin 2098 peptide represents a strong and specific DRβ1-Arg74 binder, while a non-binding control peptide, thyroglobulin 2766 fails to induce this response. Moreover, thyroglobulin 2098 stimulated T-cells from individuals who were positive for thyroglobulin antibodies, demonstrating that thyroglobulin 2098 is an immunogenic peptide capable of being

  7. 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.

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

    PubMed

    Pellegrino, Paolo; Radice, Sonia; Clementi, Emilio

    2015-07-09

    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.

  9. Proapoptotic Bak and Bax guard against fatal systemic and organ-specific autoimmune disease

    PubMed Central

    Mason, Kylie D.; Lin, Ann; Robb, Lorraine; Josefsson, Emma C.; Henley, Katya J.; Gray, Daniel H. D.; Kile, Benjamin T.; Roberts, Andrew W.; Strasser, Andreas; Huang, David C. S.; Waring, Paul; O’Reilly, Lorraine A.

    2013-01-01

    Dysregulation of the “intrinsic” apoptotic pathway is associated with the development of cancer and autoimmune disease. Bak and Bax are two proapoptotic members of the Bcl-2 protein family with overlapping, essential roles in the intrinsic apoptotic pathway. Their activity is critical for the control of cell survival during lymphocyte development and homeostasis, best demonstrated by defects in thymic T-cell differentiation and peripheral lymphoid homeostasis caused by their combined loss. Because most bak−/−bax−/− mice die perinatally, the roles of Bax and Bak in immunological tolerance and prevention of autoimmune disease remain unclear. We show that mice reconstituted with a Bak/Bax doubly deficient hematopoietic compartment develop a fatal systemic lupus erythematosus-like autoimmune disease characterized by hypergammaglobulinemia, autoantibodies, lymphadenopathy, glomerulonephritis, and vasculitis. Importantly, these mice also develop a multiorgan autoimmune disease with autoantibodies against most solid glandular structures and evidence of glandular atrophy and necrotizing vasculitis. Interestingly, similar albeit less severe pathology was observed in mice containing a hematopoietic compartment deficient for only Bak, a phenotype reminiscent of the disease seen in patients with point mutations in BAK. These studies demonstrate a critical role for Bak and an ancillary role for Bax in safeguarding immunological tolerance and prevention of autoimmune disease. This suggests that direct activators of the intrinsic apoptotic pathway, such as BH3 mimetics, may be useful for treatment of diverse autoimmune diseases. PMID:23349374

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

    PubMed Central

    Rabin, R L; Levinson, A I

    2008-01-01

    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

  11. Type 1 autoimmune pancreatitis: case scenario and review of the disease.

    PubMed

    Donet, Jean A; Czul, Frank; Peña, Nathalie A; Barkin, Jamie S

    2016-01-01

    Autoimmune pancreatitis (AIP) is an uncommon disease that represents a diagnostic challenge unless it is considered as a cause of acute pancreatitis, pancreatic exocrine insufficiency and a pancreatic mass. This entity is under diagnosed and successful medical therapy is available. In this paper, we will describe a case of a 59 year-old, Hispanic woman diagnosed with autoimmune pancreatitis, a disease previously believed to affect typically older men. We will review the definition, types, clinical manifestations, radiological features, serology, histopathological findings, treatment strategies and diagnostic criteria of autoimmune pancreatitis.

  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. Serum Procalcitonin for Differentiating Bacterial Infection from Disease Flares in Patients with Autoimmune Diseases

    PubMed Central

    Joo, Kowoon; Lim, Mie-Jin; Kwon, Seong-Ryul; Yoon, Jiyeol

    2011-01-01

    Early differentiation between bacterial infections and disease flares in autoimmune disease patients is important due to different treatments. Seventy-nine autoimmune disease patients with symptoms suggestive of infections or disease flares were collected by retrospective chart review. The patients were later classified into two groups, disease flare and infection. C-reactive protein (CRP) and serum procalcitonin (PCT) levels were measured. The CRP and PCT levels were higher in the infection group than the disease flare group (CRP,11.96 mg/dL ± 9.60 vs 6.42 mg/dL ± 7.01, P = 0.003; PCT, 2.44 ng/mL ± 6.55 vs 0.09 ng/mL ± 0.09, P < 0.001). The area under the ROC curve (AUC; 95% confidence interval) for CRP and PCT was 0.70 (0.58-0.82) and 0.84 (0.75-0.93), which showed a significant difference (P < 0.05). The predicted AUC for the CRP and PCT levels combined was 0.83, which was not significantly different compared to the PCT level alone (P = 0.80). The best cut-off value for CRP was 7.18 mg/dL, with a sensitivity of 71.9% and a specificity of 68.1%. The best cut-off value for PCT was 0.09 ng/mL, with a sensitivity of 81.3% and a specificity of 78.7%. The PCT level had better sensitivity and specificity compared to the CRP level in distinguishing between bacterial infections and disease flares in autoimmune disease patients. The CRP level has no additive value when combined with the PCT level when differentiating bacterial infections from disease flares. PMID:21935268

  14. JAK-STAT Signaling as a Target for Inflammatory and Autoimmune Diseases: Current and Future Prospects.

    PubMed

    Banerjee, Shubhasree; Biehl, Ann; Gadina, Massimo; Hasni, Sarfaraz; Schwartz, Daniella M

    2017-04-01

    The Janus kinase/signal transduction and activator of transcription (JAK-STAT) signaling pathway is implicated in the pathogenesis of inflammatory and autoimmune diseases including rheumatoid arthritis, psoriasis, and inflammatory bowel disease. Many cytokines involved in the pathogenesis of autoimmune and inflammatory diseases use JAKs and STATs to transduce intracellular signals. Mutations in JAK and STAT genes cause a number of immunodeficiency syndromes, and polymorphisms in these genes are associated with autoimmune diseases. The success of small-molecule JAK inhibitors (Jakinibs) in the treatment of rheumatologic disease demonstrates that intracellular signaling pathways can be targeted therapeutically to treat autoimmunity. Tofacitinib, the first rheumatologic Jakinib, is US Food and Drug Administration (FDA) approved for rheumatoid arthritis and is currently under investigation for other autoimmune diseases. Many other Jakinibs are in preclinical development or in various phases of clinical trials. This review describes the JAK-STAT pathway, outlines its role in autoimmunity, and explains the rationale/pre-clinical evidence for targeting JAK-STAT signaling. The safety and clinical efficacy of the Jakinibs are reviewed, starting with the FDA-approved Jakinib tofacitinib, and continuing on to next-generation Jakinibs. Recent and ongoing studies are emphasized, with a focus on emerging indications for JAK inhibition and novel mechanisms of JAK-STAT signaling blockade.

  15. Animal Models used to Examine the Role of the Environment in the Development of Autoimmune Disease: Findings from an NIEHS Expert Panel Workshopa

    PubMed Central

    Germolec, Dori; Kono, Dwight H.; Pfau, Jean C.; Pollard, K. Michael

    2012-01-01

    Autoimmunity is thought to result from a combination of genetics, environmental triggers, and stochastic events. Environmental factors, such as chemicals, drugs or infectious agents, have been implicated in the expression of autoimmune disease, yet human studies are extremely limited in their ability to test isolated exposures to demonstrate causation or to assess pathogenic mechanisms. In this review we examine the research literature on the ability of chemical, physical and biological agents to induce and/or exacerbate autoimmunity in a variety of animal models. There is no single animal model capable of mimicking the features of human autoimmune disease, particularly as related to environmental exposures. An objective, therefore, was to assess the types of information that can be gleaned from the use of animal models, and how well that information can be used to translate back to human health. Our review notes the importance of genetic background to the types and severity of the autoimmune response following exposure to environmental factors, and emphasizes literature where animal model studies have led to increased confidence about environmental factors that affect expression of autoimmunity. A high level of confidence was reached if there were multiple studies from different laboratories confirming the same findings. Examples include mercury, pristane, and infection with Streptococcus or Coxsackie B virus. A second level of consensus identified those exposures likely to influence autoimmunity but requiring further confirmation. To fit into this category, there needed to be significant supporting data, perhaps by multiple studies from a single laboratory, or repetition of some but not all findings in multiple laboratories. Examples include silica, gold, TCE, TCDD, UV radiation, and Theiler’s murine encephalomyelitis virus. With the caveat that researchers must keep in mind the limitations and appropriate applications of the various approaches, animal models

  16. Animal models used to examine the role of the environment in the development of autoimmune disease: findings from an NIEHS Expert Panel Workshop.

    PubMed

    Germolec, Dori; Kono, Dwight H; Pfau, Jean C; Pollard, K Michael

    2012-12-01

    Autoimmunity is thought to result from a combination of genetics, environmental triggers, and stochastic events. Environmental factors, such as chemicals, drugs or infectious agents, have been implicated in the expression of autoimmune disease, yet human studies are extremely limited in their ability to test isolated exposures to demonstrate causation or to assess pathogenic mechanisms. In this review we examine the research literature on the ability of chemical, physical and biological agents to induce and/or exacerbate autoimmunity in a variety of animal models. There is no single animal model capable of mimicking the features of human autoimmune disease, particularly as related to environmental exposures. An objective, therefore, was to assess the types of information that can be gleaned from the use of animal models, and how well that information can be used to translate back to human health. Our review notes the importance of genetic background to the types and severity of the autoimmune response following exposure to environmental factors, and emphasizes literature where animal model studies have led to increased confidence about environmental factors that affect expression of autoimmunity. A high level of confidence was reached if there were multiple studies from different laboratories confirming the same findings. Examples include mercury, pristane, and infection with Streptococcus or Coxsackie B virus. A second level of consensus identified those exposures likely to influence autoimmunity but requiring further confirmation. To fit into this category, there needed to be significant supporting data, perhaps by multiple studies from a single laboratory, or repetition of some but not all findings in multiple laboratories. Examples include silica, gold, TCE, TCDD, UV radiation, and Theiler's murine encephalomyelitis virus. With the caveat that researchers must keep in mind the limitations and appropriate applications of the various approaches, animal models are

  17. 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

    2016-07-08

    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.

  18. [Pulmonary arterial hypertension: a flavor of autoimmunity].

    PubMed

    Perros, Frédéric; Humbert, Marc; Cohen-Kaminsky, Sylvia

    2013-01-01

    It is admitted that autoimmunity results from a combination of risks such as genetic background, environmental triggers, and stochastic events. Pulmonary arterial hypertension (PAH) shares with the so-called prototypic autoimmune diseases, genetic risk factors, female predominance and sex hormone influence, association with other chronic inflammatory and autoimmune diseases, defects in regulatory T cells function, and presence of autoantibodies. Case reports have been published indicating the beneficial effect of some immunosuppressive and anti-inflammatory therapies in PAH, supporting the potential role of immune mechanisms in the pathophysiology of the disease. In this review, we discuss the current knowledge on autoimmune mechanisms operating in PAH, especially mounting a local autoimmune response inside the pulmonary tissue, namely pulmonary lymphoid neogenesis. A better understanding of the role of autoimmunity in pulmonary vascular remodelling may help develop targeted immunomodulatory strategies in PAH.

  19. Paraproteins with antibody activity in acute viral hepatitis and chronic autoimmune liver diseases

    PubMed Central

    Roux, Maria E. B.; Florin-Christensen, A.; Arana, R. M.; Doniach, Deborah

    1974-01-01

    Of 27 patients with liver disease and cryoglobulinaemia 18 proved to have paraproteins. Six of these monoclonal immunoglobulins were shown to have antibody activity, directed to human gamma globulin, alpha1-fetoprotein, smooth muscle, and mitochondria. Eight of the patients suffered from acute viral hepatitis, five of whom were HB Ag positive; in all these cases the monoclonal spikes were transient and their antibody activities were directed against IgG in two cases and alpha1-fetoprotein in one. Seven of the patients had active chronic hepatitis and in these the paraproteinaemia persisted, though remaining quantitatively unchanged over several years. One of them had a cryoprecipitable monoclonal smooth muscle antibody. Three patients had primary biliary cirrhosis and in two of them monoclonal IgM mitochondrial antibodies were demonstrated. In three out of the 18 cases there was a double M-component. Since these monoclonal antibodies are directed to autoantigens not unlike the polyclonal ones usually seen in autoimmune hepatic diseases, it is suggested that the factor which triggers the uncontrolled plasma cell proliferation to produce paraproteins must meet cells from an already expanding clone. PMID:18668850

  20. Frequency of autoimmune diseases in those suffering from vitiligo in comparison with normal population.

    PubMed

    Nejad, Shahla Babaee; Qadim, Hamideh Herizchi; Nazeman, Leila; Fadaii, Roohollah; Goldust, Mohamad

    2013-06-15

    Vitiligo is more common in people with certain autoimmune diseases. Here we studied the association between vitiligo and autoimmune diseases. In this case control study, 86 patients with vitiligo were questioned about the location of vitiligo, family history, treatment and therapeutic response. All patients were examined both clinically and with laboratory tests to detect the presence of autoimmune disorders including autoimmune thyroid disease, pernicious anemia, insulin dependent diabetes, and Systemic Lupus Erythematic (SLE) and Addison disease. We compared the prevalence of autoimmune disorder in vitiligo patients with that in a group of age-and gender-matched normal population. Average age of disease onset was 21.8 +/- 11 years; 61% of patients were female and 39% were male. The most common locations of vitiligo were hands (33.7%) and face (32.1%). The most common pattern of onset was vulgaris type (40%). Nearly one-fourth of patients had a positive family history of vitiligo. Prevalence of thyroid disorders in vitiligo patients and control group was 21.1 and 7%, respectively. The difference was statistically significant (p = 0.008). The most common autoimmune disorder in patient with vitiligo was hypothyroidism. Family history had a poor prognostic effect on response to therapy.

  1. Autoimmune bullous diseases with skin and eye involvement: Cicatricial pemphigoid, pemphigus vulgaris, and pemphigus paraneoplastica.

    PubMed

    Broussard, Karen C; Leung, Theresa G; Moradi, Ahmadreza; Thorne, Jennifer E; Fine, Jo-David

    2016-01-01

    Autoimmune blistering diseases are a heterogeneous group of disorders that mostly affect the skin and mucous membranes. Occasionally, other organ systems may be involved, depending on the unique pathophysiology of each disease. Cicatricial pemphigoid, pemphigus vulgaris, and paraneoplastic pemphigus are distinct entities, but all have the potential to have cutaneous and ocular involvement. Awareness and early recognition of ocular involvement in these diseases is important given the increased risk for vision loss and blindness with delay in management. Several skin diseases may be associated with involvement of the external eye. The most common autoimmune diseases are cicatricial pemphigoid, pemphigus vulgaris, and paraneoplastic pemphigus.

  2. AAO: Autoimmune and Autoinflammatory (Disease) in Otology: What is New in Immune‐Mediated Hearing Loss

    PubMed Central

    Pathak, Shresh

    2016-01-01

    Objectives Autoinflammatory diseases are a family of immune‐mediated, rare diseases, some of which, exhibit sensorineural hearing loss (SNHL), suggesting potentially similar mechanisms of molecular pathogenesis between autoinflammatory‐mediated hearing loss and autoimmune inner ear disease (AIED) may exist. The purpose of this review is to compare the clinical features of autoimmune and autoinflammatory diseases that affect hearing, discuss the limitations of our knowledge, and highlight potential new disease mechanisms and therapeutics. Data sources Pubmed Literature Review; Google Scholar Literature review. Review methods A focused comparison of AIED with a number of autoinflammatory diseases that manifest with sensorineural hearing loss was performed. The pathogenesis of these diseases is reviewed in the context of the innate and adaptive immune system, cytokine expression and genetic polymorphisms. Results AIED, since first described by Cogan and Lehnhardt and first clinically characterized by McCabe, has remained an enigmatic disease, with limited advances in both new diagnostics and new therapeutics. Since the discovery of autoinflammatory diseases, a number of systemic autoimmune diseases have either been re‐classed as autoinflammatory diseases or identified to have features of autoinflammatory disease. Conclusion AIED has clinical features of both autoimmune and autoinflammatory disease. It is critical that autoinflammatory diseases be correctly identified, as failure to do so may result in systemic amyloidosis and kidney damage. PMID:27917401

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

    SciTech Connect

    Sakaguchi, N.; Sakaguchi, S. Scripps Research Institute, La Jolla, CA PRESTO, JRDC, Institute of Phical and Chemical Research, Tsukuba, Ibaraki ); Miyai, K. )

    1992-11-01

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

  4. New autoimmune diseases after cord blood transplantation: a retrospective study of EUROCORD and the Autoimmune Disease Working Party of the European Group for Blood and Marrow Transplantation.

    PubMed

    Daikeler, Thomas; Labopin, Myriam; Ruggeri, Annalisa; Crotta, Alessandro; Abinun, Mario; Hussein, Ayad Ahmed; Carlson, Kristina; Cornillon, Jérôme; Diez-Martin, Jose L; Gandemer, Virginie; Faraci, Maura; Lindemans, Caroline; O'Meara, Anne; Mialou, Valerie; Renard, Marleen; Sedlacek, Petr; Sirvent, Anne; Socié, Gérard; Sora, Federica; Varotto, Stefania; Sanz, Jaime; Voswinkel, Jan; Vora, Ajay; Yesilipek, M Akif; Herr, Andree-Laure; Gluckman, Eliane; Farge, Dominique; Rocha, Vanderson

    2013-02-07

    To describe the incidence, risk factors, and treatment of autoimmune diseases (ADs) occurring after cord blood transplantation (CBT), we analyzed both CBT recipients reported to EUROCORD who had developed at least 1 new AD and those who had not. Fifty-two of 726 reported patients developed at least 1 AD within 212 days (range, 27-4267) after CBT. Cumulative incidence of ADs after CBT was 5.0% +/- 1% at 1 year and 6.6% +/- 1% at 5 years. Patients developing ADs were younger and had more nonmalignant diseases (P < .001). ADs target hematopoietic (autoimmune hemolytic anemia, n = 20; Evans syndrome, n = 9; autoimmune thrombocytopenia, n = 11; and immune neutropenia, n = 1) and other tissues (thyroiditis, n = 3; psoriasis, n = 2; Graves disease, n 1; membranous glomerulonephritis, n = 2; rheumatoid arthritis, n = 1; ulcerative colitis, n = 1; and systemic lupus erythematosus, n = 1). Four patients developed 2 ADs (3 cases of immune thrombocytopenia followed by autoimmune hemolytic anemia and 1 Evans syndrome with rheumatoid arthritis). By multivariate analysis, the main risk factor for developing an AD was nonmalignant disease as an indication for CBT (P = .0001). Hematologic ADs were most often treated with steroids, rituximab, and cyclosporine. With a median follow-up of 26 months (range, 2-91), 6 of 52 patients died as a consequence of ADs. We conclude that CBT may be followed by potentially life-threatening, mainly hematologic ADs.

  5. Heterogeneity of autoimmune diseases: pathophysiologic insights from genetics and implications for new therapies.

    PubMed

    Cho, Judy H; Feldman, Marc

    2015-07-01

    Recent advances in genome-wide association studies (GWAS) across autoimmune and immune-mediated diseases have augmented our understanding of pathogenic mechanisms underlying these diseases. This has further highlighted their heterogeneous nature, both within and between diseases. Furthermore, varying responses to therapy have also served to underline the importance of this heterogeneity in the manner in which these diseases are diagnosed and treated. Here we discuss our current understanding of the shared pathways of autoimmunity, including the tumor necrosis factor (TNF), major histocompatibility complex (MHC), interleukin 23 receptor (IL23R) and protein tyrosine phosphatase non-receptor type 22 (PTPN22) pathways. In addition, we summarize effective specific therapies tested across major autoimmune diseases, highlighting the insight they have provided into disease mechanisms and their implications for potential future improvements.

  6. Cytokines and effector T cell subsets causing autoimmune CNS disease.

    PubMed

    Petermann, Franziska; Korn, Thomas

    2011-12-01

    Although experimental autoimmune encephalomyelitis (EAE) is limited in its potency to reproduce the entirety of clinical and histopathologic features of multiple sclerosis (MS), this model has been successfully used to prove that MS like autoimmunity in the CNS is orchestrated by autoantigen specific T cells. EAE was also very useful to refute the idea that IFN-γ producing T helper type 1 (Th1) cells were the sole players within the pathogenic T cell response. Rather, "new" T cell lineages such as IL-17 producing Th17 cells or IL-9 producing Th9 cells have been first discovered in the context of EAE. Here, we will summarize new concepts of early and late T cell plasticity and the cytokine network that shapes T helper cell responses and lesion development in CNS specific autoimmunity.

  7. Environmental chemicals and autoimmune disease: cause and effect.

    PubMed

    Hess, Evelyn V

    2002-12-27

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

  8. Nutrition and fasting mimicking diets in the prevention and treatment of autoimmune diseases and immunosenescence.

    PubMed

    Choi, In Young; Lee, Changhan; Longo, Valter D

    2017-01-27

    Complex and coordinated signals are necessary to initiate and sustain the activation, proliferation, and differentiation of lymphocytes. These signals, which are known to determine T-cell fate and function, also depend on the metabolic state of the organism. Recent studies indicate that both the type and levels of nutrients can influence the generation, survival and function of lymphocytes and therefore can affect several autoimmune diseases. Here, we review the dysregulation of lymphocytes during autoimmunity and aging, the mechanisms associated with loss of immune function, and how fasting mimicking diets and other dietary interventions affect autoimmunity and immunosenescence.

  9. Genome-wide genetic study in autoimmune disease-prone mice.

    PubMed

    Obata, Masaomi; Ohtsuji, Mareki; Iida, Yukiyasu; Shirai, Toshikazu; Hirose, Sachiko; Nishimura, Hioroyuki

    2014-01-01

    Mouse models of autoimmune diseases provide invaluable insights into the cellular and molecular bases of autoimmunity. Genetic linkage studies focusing on their abnormal quantitative phenotypes in relation to the loss of self-tolerance will lead to the identification of polymorphic genes that play pivotal roles in the genetic predisposition to autoimmunity. In this chapter, we first overview the basic concepts in the statistical genetics and then provide guides to genotyping microsatellite DNA markers and to quantitative trait loci mapping using a MAPMAKER program.

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

    PubMed

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

    2015-11-01

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

  11. 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.

  12. Dental care of patients with autoimmune vesiculobullous diseases: case reports and literature review.

    PubMed

    Fatahzadeh, Mahnaz; Radfar, Lida; Sirois, David A

    2006-01-01

    Dental management of patients with autoimmune vesiculobullous disorders is complicated because of prominent involvement of oral mucosa, increased risk of oral disease, and difficulty in rendering dental care. Although these diseases are relatively uncommon, dental practitioners should be familiar with the oral sequelae of these conditions and their management. Pemphigus vulgaris, cicatricial pemphigoid, and epidermolysis bullosa represent the most common autoimmune oral vesiculobullous diseases. This case-illustrated review summarizes the pathogenesis, diagnostic features, and natural history of oral vesiculobullous disorders, placing an emphasis on the treatment and prevention of associated oral disease aimed at maintaining a healthy, functional dentition.

  13. Mesenchymal stem cells in the treatment of inflammatory and autoimmune diseases in experimental animal models

    PubMed Central

    Klinker, Matthew W; Wei, Cheng-Hong

    2015-01-01

    Multipotent mesenchymal stromal cells [also known as mesenchymal stem cells (MSCs)] are currently being studied as a cell-based treatment for inflammatory disorders. Experimental animal models of human immune-mediated diseases have been instrumental in establishing their immunosuppressive properties. In this review, we summarize recent studies examining the effectiveness of MSCs as immunotherapy in several widely-studied animal models, including type 1 diabetes, experimental autoimmune arthritis, experimental autoimmune encephalomyelitis, inflammatory bowel disease, graft-vs-host disease, and systemic lupus erythematosus. In addition, we discuss mechanisms identified by which MSCs mediate immune suppression in specific disease models, and potential sources of functional variability of MSCs between studies. PMID:25914763

  14. 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

  15. Tolerance and short term efficacy of rituximab in 43 patients with systemic autoimmune diseases

    PubMed Central

    Gottenberg, J; Guillevin, L; Lambotte, O; Combe, B; Allanore, Y; Cantagrel, A; Larroche, C; Soubrier, M; Bouillet, L; Dougados, M; Fain, O; Farge, D; Kyndt, X; Lortholary, O; Masson, C; Moura, B; Remy, P; Thomas, T; Wendling, D; Anaya, J; Sibilia, J; Mariette, X; t for

    2005-01-01

    Objective: To assess the tolerance and efficacy of rituximab in patients with various autoimmune diseases seen in daily rheumatological practice. Methods: 866 rheumatology and internal medicine practitioners were contacted by email to obtain the files of patients treated with rituximab for systemic autoimmune diseases. Patients with lymphoma were analysed if the evolution of the autoimmune disease could be evaluated. Results: In all, 43 of 49 cases could be analysed, including 14 with rheumatoid arthritis (RA), 13 with systemic lupus erythematosus (SLE), six with primary Sjögren's syndrome (pSS), five with systemic vasculitis, and five with other autoimmune diseases. Rituximab was prescribed for lymphoma in two patients with RA and two with pSS. In the 39 other cases, rituximab was given because of the refractory character of the autoimmune disease. The mean follow up period was 8.3 months (range 2 to 26). There were 11 adverse events in 10 patients and treatment had to be discontinued in six. Efficacy was observed in 30 patients (70%): RA 11, SLE 9, pSS 5, vasculitis 2, antisynthetase syndromes 2, sarcoidosis 1. The mean decrease in corticosteroid intake was 9.5 mg/d (range 0 to 50) in responders. Seven patients experienced relapse after mean 8.1 months (5 to 15). Three patients died because of refractory autoimmune disease. Conclusions: Despite absence of marketing authorisation, rituximab is used to treat various refractory autoimmune diseases in daily rheumatological practice. This study showed good tolerance and short term clinical efficacy, with marked corticosteroid reduction in patients with SLE, pSS, vasculitis, and polymyositis. PMID:15550531

  16. Evaluation of Spleen Glucose Metabolism Using (18)F-FDG PET/CT in Patients with Febrile Autoimmune Disease.

    PubMed

    Ahn, Sung Soo; Hwang, Sang Hyun; Jung, Seung Min; Lee, Sang-Won; Park, Yong-Beom; Yun, Mijin; Song, Jason Jungsik

    2017-03-01

    The purpose of this study was to evaluate the clinical significance of (18)F-FDG uptake by the spleen in patients with autoimmune disease. Methods: We retrospectively reviewed Severance Hospital's electronic medical records of patients hospitalized for the evaluation of fever who underwent (18)F-FDG PET/CT. We found 91 patients with autoimmune diseases and 101 patients with localized infection. (18)F-FDG uptake was assessed by measuring SUV in the spleen and liver. The spleen-to-liver ratio of the SUVmean (SLRmean) was calculated. Clinical and laboratory parameters were collected and evaluated for association with SLRmean In-hospital mortality was defined as all-cause mortality during hospital admission for fever. Results: SLRmean was significantly higher in autoimmune disease than in localized infectious disease (1.28 ± 0.43 vs. 0.91 ± 0.21, P < 0.001). In autoimmune disease, SLRmean was correlated with monocytes, aspartate aminotransferase, alanine aminotransferase, albumin, and ferritin. Analysis of receiver-operating-characteristic curves revealed that in comparison with laboratory parameters, SLRmean had the highest performance in differentiating autoimmune from localized infectious disease. Multivariate logistic regression analysis demonstrated that high SLRmean and low platelets were significantly associated with in-hospital mortality in febrile autoimmune disease. Conclusion: These findings suggest that spleen glucose metabolism is increased in febrile autoimmune disease. Spleen (18)F-FDG uptake may provide information useful in differentiating febrile autoimmune disease from localized infectious disease and predicting clinical outcomes in febrile autoimmune disease.

  17. Common and specific signatures of gene expression and protein-protein interactions in autoimmune diseases.

    PubMed

    Tuller, T; Atar, S; Ruppin, E; Gurevich, M; Achiron, A

    2013-03-01

    The aim of this study is to understand intracellular regulatory mechanisms in peripheral blood mononuclear cells (PBMCs), which are either common to many autoimmune diseases or specific to some of them. We incorporated large-scale data such as protein-protein interactions, gene expression and demographical information of hundreds of patients and healthy subjects, related to six autoimmune diseases with available large-scale gene expression measurements: multiple sclerosis (MS), systemic lupus erythematosus (SLE), juvenile rheumatoid arthritis (JRA), Crohn's disease (CD), ulcerative colitis (UC) and type 1 diabetes (T1D). These data were analyzed concurrently by statistical and systems biology approaches tailored for this purpose. We found that chemokines such as CXCL1-3, 5, 6 and the interleukin (IL) IL8 tend to be differentially expressed in PBMCs of patients with the analyzed autoimmune diseases. In addition, the anti-apoptotic gene BCL3, interferon-γ (IFNG), and the vitamin D receptor (VDR) gene physically interact with significantly many genes that tend to be differentially expressed in PBMCs of patients with the analyzed autoimmune diseases. In general, similar cellular processes tend to be differentially expressed in PBMC in the analyzed autoimmune diseases. Specifically, the cellular processes related to cell proliferation (for example, epidermal growth factor, platelet-derived growth factor, nuclear factor-κB, Wnt/β-catenin signaling, stress-activated protein kinase c-Jun NH2-terminal kinase), inflammatory response (for example, interleukins IL2 and IL6, the cytokine granulocyte-macrophage colony-stimulating factor and the B-cell receptor), general signaling cascades (for example, mitogen-activated protein kinase, extracellular signal-regulated kinase, p38 and TRK) and apoptosis are activated in most of the analyzed autoimmune diseases. However, our results suggest that in each of the analyzed diseases, apoptosis and chemotaxis are activated via

  18. 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…

  19. Association of autoimmune diseases with lichen sclerosus in 532 male and female patients.

    PubMed

    Kreuter, Alexander; Kryvosheyeva, Yulia; Terras, Sarah; Moritz, Rose; Möllenhoff, Katrin; Altmeyer, Peter; Scola, Nina; Gambichler, Thilo

    2013-03-27

    Lichen sclerosus is a relatively common chronic inflammatory skin disease that predominantly affects the anogenital area. Accumulating evidence indicates that lichen sclerosus in women may be associated with other autoimmune disease, whereas this association seems to lack in male patients. We retrospectively evaluated the prevalence of autoimmune diseases and serological parameters indicative for autoimmunity in male and female patients with lichen sclerosus. Of the 532 patients (396 women, 136 men; 500 adults, 32 children; mean age: 49 years; range 1-89 years; female:male ratio 3:1), 452 (85%) had genital and 80 (15%) had extragenital disease. In women, lichen sclerosus was significantly more often associated with at least one autoimmune disease as compared to men (odds ratio [OR] 4.3, 95% confidence interval [CI] 1.9-9.6; p<0.0001). Moreover, female patients with lichen sclerosus had sinificantly more often associated autoimmune thyroid diseases (OR 4.7, 95% CI 1.8-11.9; p<0.0002), antithyroid-antibodies (OR 2.7, 95% CI 1.1-6.5; p=0.023), and elevated autoantibodies (OR 4.1, 95% CI 1.9-9.3; p<0.0001) as compared to male patients. This observation is suggestive for a different pathogenetic background in male and female patients.

  20. Roles of γδ T Cells in the Pathogenesis of Autoimmune Diseases

    PubMed Central

    Su, Dinglei; Shen, Minning; Li, Xia; Sun, Lingyun

    2013-01-01

    γ δ T cells are a minor population of T cells that express the TCR γδ chains, mainly distributed in the mucosal and epithelial tissue and accounting for less than 5% of the total T cells in the peripheral blood. By bridging innate and adaptive immunity, γδ T cells play important roles in the anti-infection, antitumor, and autoimmune responses. Previous research on γδ T cells was primarily concentrated on infectious diseases and tumors, whereas their functions in autoimmune diseases attracted much attention. In this paper, we summarized the various functions of γδ T cells in two prototypical autoimmune connective tissue diseases, that is, SLE and RA, elaborating on their antigen-presenting capacity, secretion of proinflammatory cytokines, immunomodulatory effects, and auxiliary function for B cells, which contribute to overproduction of proinflammatory cytokines and pathogenic autoantibodies, ultimately leading to the onset of these autoimmune diseases. Elucidation of the roles of γδ T cells in autoimmune diseases is not only conducive to in-depth understanding of the pathogenesis of these diseases, but also beneficial in providing theoretical support for the development of γδ T-cell-targeted therapy. PMID:23533458

  1. Comorbid autoimmune diseases in patients with sarcoidosis: A nationwide case-control study in Taiwan.

    PubMed

    Wu, Chi-Hung; Chung, Pei-I; Wu, Chen-Yi; Chen, Yen-Ta; Chiu, Yun-Wen; Chang, Yun-Ting; Liu, Han-Nan

    2017-04-01

    The association between sarcoidosis and autoimmune comorbidities has been reported, however, it has seldom been confirmed by a large nationwide study. Our study aimed to clarify the association between sarcoidosis and autoimmune comorbidities in the Taiwanese. A total of 1237 patients with sarcoidosis and 4948 age- and sex-matched control subjects were selected from the National Health Insurance Research Database of Taiwan from 1997 to 2010. Multiple logistic regressions were performed to calculate the odds of comorbidities between the two groups. The prevalence of sarcoidosis was 2.17/100 000 individuals in Taiwan. Sarcoidosis patients tended to run a higher risk of autoimmune comorbidities than the control group (17.6% vs 9.4%, P < 0.05). Autoimmune thyroid disease (adjusted odd ratio [aOR], 1.32; 95% confidence interval [CI], 1.05-1.64), Sjögren's syndrome (aOR, 11.6; 95% CI, 4.36-31.0) and ankylosing spondylitis (aOR, 3.80; 95% CI, 2.42-5.97) were significantly associated with sarcoidosis. The sex-stratified analyses were carried out to demonstrate a significant association of sarcoidosis with ankylosing spondylitis in both sexes, but with autoimmune thyroid disease in male patients and with Sjögren's syndrome female patients, respectively. Besides, the diagnosis of the autoimmune comorbidities strongly associated with sarcoidosis tended to be established after that of sarcoidosis. This study demonstrated that patients with sarcoidosis tended to have autoimmune thyroid disease, Sjögren's syndrome and ankylosing spondylitis, and the diagnosis of sarcoidosis usually preceded that of associated comorbidities. Clinicians should be alert to autoimmune comorbidities in patients with sarcoidosis.

  2. Clinical characteristics of patients with lymphoproliferative neoplasms in the setting of systemic autoimmune diseases.

    PubMed

    Suvajdzic, Nada; Djurdjevic, Predrag; Todorovic, Milena; Perunicic, Maja; Stojanović, Roksanda; Novkovic, Aleksandra; Mihaljevic, Biljana

    2012-09-01

    Clinical features of 40 lymphoproliferative neoplasm patients in the setting of systemic autoimmune diseases managed in the Clinic of Hematology during 1994-2006 were analyzed retrospectively. The classification of systemic autoimmune disease patients was as follows: 15 systemic lupus erythematosus--SLE, 11 rheumatoid arthritis--RA, 12 Sjögren's syndrome--SS, 1 scleroderma, and 1 dermatomyositis. Patients comprised 31 women and 9 men of mean age 55 years (range 33-76). Systemic autoimmune diseases preceeded the development of lymphoproliferative neoplasms in 37/40 (92.5%) patients. Mean latency period between the onset of systemic autoimmune diseases and lymphoproliferative neoplasms occurrence was significantly longer in RA (113 months) than in SLE (75 months) and SS patients (65 months)--P < 0.05. The most frequent lymphoproliferative neoplasms were non-Hodgkin's lymphoma--NHL (35/40; 88%), diffuse large B-cell lymphoma (DBCL)--12 (34%), follicular lymphoma (FC)--7 (20%), small lymphocytic (SL), and marginal zone lymphoma (MZL)--5 (14%) each. The primary site of NHL was extranodal in 18/35 (51.5%) cases. Advanced disease on diagnosis (III + IV clinical stages), constitutional symptoms, and bulky disease were diagnosed in 27/35 (77%), 26/35 (74%), and 3/35 (8.5%) patients, respectively. The overall survival (OS) was as follows (months): DBCL-12, FC-63, SLL-60, and MZL-48. There was no association between the lymphoproliferative neoplasm histological subtype and the systemic autoimmune diseases type or antirheumatic treatment P > 0.05. Our findings are in line with earlier reports showing a high proportion of patients with advanced disease, constitutional symptoms, extranodal manifestations, high grade histology, and low OS in the systemic autoimmune diseases setting.

  3. Hematopoietic cell transplantation for autoimmune disease: updates from Europe and the United States.

    PubMed

    Sullivan, Keith M; Muraro, Paolo; Tyndall, Alan

    2010-01-01

    Considerable advances have been made in our understanding of the immunobiology of autoimmune disease and its treatment with hematopoietic cell transplantation (HCT). In autoimmune disorders, the reconstituted immune system following lymphoablation and autologous HCT yields qualitative changes in immune defects and modifications in adaptive immune responses. Seminal experiments in animals demonstrated that allogeneic or autologous HCT could prevent progression or reverse organ damage from inherited (genetic) or acquired (antigen induced) autoimmune diseases. Convincing animal and clinical data now show that after HCT, the immune system is normalized and "reset". Following autologous transplantation, this resetting occurs via repertoire replacement. It is currently being studied whether and to what extent suppression of inflammation after HCT is due to reregulation of function or due to the eradication of disease associated T and/or B cell populations. There are now a number of published clinical reports with sufficient follow-up for determinations of safety and efficacy of HCT for autoimmune diseases. On behalf of colleagues in the European League Against Rheumatism (EULAR) and the European Group for Blood and Marrow Transplantation (EBMT), we review the experience with more than 1000 transplants for autoimmune disease in Europe along with the three major multinational randomized trials in for systemic sclerosis (SSc, the ASTIS study), multiple sclerosis (MS, the ASTIMS study), and Crohn's disease (CD, the ASTIC study). Completed phase II studies in the USA of transplantation for severe SSc, SLE and MS yield promising results. For individuals with SSc, there is dramatic improvement/resolution of dermal fibrosis and stabilization/improvement of pulmonary dysfunction reported up to 8 years after lymphoablative conditioning and autologous HCT. Currently, randomized phase III studies are recruiting subjects in the USA with SSc, MS and CD. In addition, 9 other phase I

  4. The contribution of natural selection to present-day susceptibility to chronic inflammatory and autoimmune disease

    PubMed Central

    Brinkworth, Jessica F; Barreiro, Luis B

    2015-01-01

    Chronic inflammatory and autoimmune diseases have been the focus of many genome-wide association studies (GWAS) because they represent a significant cause of illness and morbidity, and many are heritable. Almost a decade of GWAS studies suggests that the pathological inflammation associated with these diseases is controlled by a limited number of networked immune system genes. Chronic inflammatory and autoimmune diseases are enigmatic from an evolutionary perspective because they exert a negative affect on reproductive fitness. The persistence of these conditions may be partially explained by the important roles the implicated immune genes play in pathogen defense and other functions thought to be under strong natural selection in humans. The evolutionary reasons for chronic inflammatory and autoimmune disease persistence and uneven distribution across populations are the focus of this review. PMID:25458997

  5. The role of microRNAs in the pathogenesis of autoimmune diseases.

    PubMed

    Chen, Ji-Qing; Papp, Gábor; Szodoray, Péter; Zeher, Margit

    2016-12-01

    MicroRNAs (miRNAs) are single-stranded, endogenous non-coding small RNAs, ranging from 18 to 25 nucleotides in length. Growing evidence suggests that miRNAs are essential in regulating gene expression, cell development, differentiation and function. Autoimmune diseases are a family of chronic systemic inflammatory diseases. Recent findings on miRNA expression profiles have been suggesting their role as biomarkers in autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis and Sjögren's syndrome. In this review, we summarize the characteristics of miRNAs and their functional role in the immune system and autoimmune diseases including systemic lupus erythematosus, primary Sjögren's syndrome, rheumatoid arthritis, systemic sclerosis, multiple sclerosis and psoriasis; moreover, we depict the advantages of miRNAs in modern diagnostics.

  6. [Flu vaccine and auto-immune and/or inflammatory diseases].

    PubMed

    Duchet-Niedziolka, Paula; Hanslik, Thomas; Mouthon, Luc; Guillevin, Loïc; Launay, Odile

    2011-03-01

    Patients with systemic inflammatory and/or autoimmune diseases have an increased risk of infections particularly severe influenza infections. Annually vaccination can prevent these infections. Available data about the influenza vaccine in these patients show that, it remains well tolerated and effective even if the antibody response is lower compared to healthy controls. These data encourage to vaccine every year patients with systemic inflammatory and/or autoimmune diseases with influenza vaccine, particularly patients taking immunosuppressant drugs or having respiratory, cardiac or renal chronic diseases according to guidelines. More data are needed about the severity of influenza infection and the efficacy of influenza vaccination in patients with systemic inflammatory and/or autoimmune diseases to improve their vaccine coverage.

  7. The dual role of short fatty acid chains in the pathogenesis of autoimmune disease models

    PubMed Central

    Mizuno, Miho; Noto, Daisuke; Kaga, Naoko; Chiba, Asako; Miyake, Sachiko

    2017-01-01

    Autoimmune diseases are influenced by both genetic and environmental factors. The gut environment has attracted much attention as an essential component that modulates immune responses, and therefore immune-mediated disorders, such as autoimmune diseases. Growing evidence suggests that microbiota and their metabolites are critical factors for immune modulation. Recently, we reported that the microbiome in patients with multiple sclerosis, an autoimmune disease targeting the myelin sheath of the central nervous system, is characterized by a reduction of bacteria belonging to Clostridia clusters IV and XIVa, which are potent producers of short-chain fatty acids (SCFAs) by fermentation of indigestible carbohydrates. In the present study, we investigated the role of SCFAs in the regulation of inflammation. We demonstrated that oral administration of SCFAs ameliorated the disease severity of systemic autoimmune inflammatory conditions mediated by lymphocytes such as experimental autoimmune encephalitis and collagen-induced arthritis. Amelioration of disease was associated with a reduction of Th1 cells and an increase in regulatory T cells. In contrast, SCFAs contributed to the exaggeration of K/BxN serum transfer arthritis, representing the effector phase of inflammation in rheumatoid arthritis. An increased understanding of the effect of microbiota metabolites will lead to the effective treatment and prevention of systemic inflammatory disorders. PMID:28235016

  8. Biological effects of IL-21 on different immune cells and its role in autoimmune diseases.

    PubMed

    Gharibi, Tohid; Majidi, Jafar; Kazemi, Tohid; Dehghanzadeh, Rashedeh; Motallebnezhad, Morteza; Babaloo, Zohreh

    2016-02-01

    Interleukin-21 (IL-21) is a member of the common γ-chain cytokines with broad pleiotropic actions that affects different immune and nonimmune cells. IL-21 can affect differentiation, proliferation and function of T and B cells; it can also induce the maturation and enhance the cytotoxicity of CD8+ T cells and Natural killer (NK) cells. IL-21 exerts major effects on B-cell activation and differentiation or apoptosis during humoral immune responses and induces differentiation of naïve B cells and memory B cells into plasma cells. IL-21 also affects different subtypes of T cells including T helper-17 (TH17), T follicular helper (TFH) and regulatory T (Treg) cells and thereby promotes the development of autoimmune disorders and inflammatory diseases. Observations have shown that the blockade of IL-21 has therapeutic effects on various autoimmune diseases in animal models. A better understanding of the regulation of cell differentiation and stabilization by IL-21 in the context of each specific autoimmune disease or tissue-specific pathological microenvironments will be helpful in developing novel treatments to control autoimmune diseases. Herein, we review the biological effects of IL-21 on different immune cells and uncover the emerging role of this interesting cytokine in autoimmune diseases.

  9. COPA mutations impair ER-Golgi transport causing hereditary autoimmune-mediated lung disease and arthritis

    PubMed Central

    Watkin, Levi B.; Jessen, Birthe; Wiszniewski, Wojciech; Vece, Timothy; Jan, Max; Sha, Youbao; Thamsen, Maike; Santos-Cortez, Regie L. P.; Lee, Kwanghyuk; Gambin, Tomasz; Forbes, Lisa; Law, Christopher S.; Stray-Petersen, Asbjørg; Cheng, Mickie H.; Mace, Emily M.; Anderson, Mark S.; Liu, Dongfang; Tang, Ling Fung; Nicholas, Sarah K.; Nahmod, Karen; Makedonas, George; Canter, Debra; Kwok, Pui-Yan; Hicks, John; Jones, Kirk D.; Penney, Samantha; Jhangiani, Shalini N.; Rosenblum, Michael D.; Dell, Sharon D.; Waterfield, Michael R.; Papa, Feroz R.; Muzny, Donna M.; Zaitlen, Noah; Leal, Suzanne M.; Gonzaga-Jauregui, Claudia; Boerwinkle, Eric; Eissa, N. Tony; Gibbs, Richard A.; Lupski, James R.; Orange, Jordan S.; Shum, Anthony K.

    2015-01-01

    Advances in genomics have allowed unbiased genetic studies of human disease with unexpected insights into the molecular mechanisms of cellular immunity and autoimmunity1. We performed whole exome sequencing (WES) and targeted sequencing in patients with an apparent Mendelian syndrome of autoimmune disease characterized by high-titer autoantibodies, inflammatory arthritis and interstitial lung disease (ILD). In five families, we identified four unique deleterious variants in the Coatomer subunit alpha (COPA) gene all located within the same functional domain. We hypothesized that mutant COPA leads to a defect in intracellular transport mediated by coat protein complex I (COPI)2–4. We show that COPA variants impair binding of proteins targeted for retrograde Golgi to ER transport and demonstrate that expression of mutant COPA leads to ER stress and the upregulation of Th17 priming cytokines. Consistent with this pattern of cytokine expression, patients demonstrated a significant skewing of CD4+ T cells toward a T helper 17 (Th17) phenotype, an effector T cell population implicated in autoimmunity5,6. Our findings uncover an unexpected molecular link between a vesicular transport protein and a syndrome of autoimmunity manifested by lung and joint disease. These findings provide a unique opportunity to understand how alterations in cellular homeostasis caused by a defect in the intracellular trafficking pathway leads to the generation of human autoimmune disease. PMID:25894502

  10. TLR2 and TLR4 in autoimmune diseases: a comprehensive review.

    PubMed

    Liu, Yu; Yin, Heng; Zhao, Ming; Lu, Qianjin

    2014-10-01

    Autoimmune diseases are immune disorders characterized by T cell hyperactivity and B cell overstimulation leading to overproduction of autoantibodies. Although the pathogenesis of various autoimmune diseases remains to be elucidated, environmental factors have been thought to contribute to the initiation and maintenance of auto-respond inflammation. Toll-like receptors (TLRs) are pattern recognition receptors belonging to innate immunity that recognize and defend invading microorganisms. Besides these exogenous pathogen-associated molecular patterns, TLRs can also bind with damage-associated molecular patterns produced under strike or by tissue damage or cells apoptosis. It is believed that TLRs build a bridge between innate immunity and autoimmunity. There are five adaptors to TLRs including MyD88, TRIF, TIRAP/MAL, TRAM, and SARM. Upon activation, TLRs recruit specific adaptors to initiate the downstream signaling pathways leading to the production of inflammatory cytokines and chemokines. Under certain circumstances, ligation of TLRs drives to aberrant activation and unrestricted inflammatory responses, thereby contributing to the perpetuation of inflammation in autoimmune diseases. In the past, most studies focused on the intracellular TLRs, such as TLR3, TLR7, and TLR9, but recent studies reveal that cell surface TLRs, especially TLR2 and TLR4, also play an essential role in the development of autoimmune diseases and afford multiple therapeutic targets. In this review, we summarized the biological characteristics, signaling mechanisms of TLR2/4, the negative regulators of TLR2/4 pathway, and the pivotal function of TLR2/4 in the pathogenesis of autoimmune diseases including rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, Sjogren's syndrome, psoriasis, multiple sclerosis, and autoimmune diabetes.

  11. 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.

  12. 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

  13. To cardiovascular disease and beyond: new therapeutic perspectives of statins in autoimmune diseases and cancer.

    PubMed

    Lopez-Pedrera, Chary; Ruiz-Limon, Patricia; Valverde-Estepa, Araceli; Barbarroja, Nuria; Rodriguez-Ariza, Antonio

    2012-06-01

    Statins have been successfully used in patients with hypercholesterolemia and cardiovascular diseases, but there is increasing evidence that they exert effects by much exceeding the lowering of cholesterol levels. Statins have antiatherosclerotic, antiinflammatory, antioxidant, immunomodulatory and antithrombotic effects. These "pleiotropic" effects stem from their inhibition of prenylation of the small GTP-binding proteins Ras and Rho, and to the disruption, or depletion, of cholesterol rich membrane micro-domains (membrane rafts). Through these pathways statins modulate immune responses by altering cytokine levels and by affecting the function of cells involved in both innate and adaptive responses. Anti-inflammatory and immunosuppressory properties of statins provide the rationale for their potential application in conditions in which the inflammation and immune response represent key pathogenic mechanisms, such as antiphospholipid syndrome, rheumatoid arthritis and systemic lupus erythematosus. Reduction of atherosclerosis progression in autoimmunity is also a very important effect. Statins pathways of action in systemic autoimmune diseases, and their potential therapeutic use are discussed in this review. The inhibition of mevalonate pathway by statins impairs modification of Ras and Rho GTPases, which play key roles in signaling pathways related to tumor formation, metastasis and cell death. There is experimental and clinical evidence that statins may improve the therapeutic outcome of anticancer drugs. Thus, this review will also discuss recent insights into the molecular mechanisms underlying the anticancer effects of statins and their assessment as promising candidates for inclusion into current therapeutic regimens for the treatment of malignant diseases.

  14. 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.

  15. Cardiovascular involvement in pediatric systemic autoimmune diseases: the emerging role of noninvasive cardiovascular imaging.

    PubMed

    Mavrogeni, Sophie; Servos, George; Smerla, Roubini; Markousis-Mavrogenis, George; Grigoriadou, Georgia; Kolovou, Genovefa; Papadopoulos, George

    2015-01-01

    Cardiac involvement in pediatric systemic autoimmune diseases has a wide spectrum of presentation ranging from asymptomatic to severe clinically overt involvement. Coronary artery disease, pericardial, myocardial, valvular and rythm disturbances are the most common causes of heart lesion in pediatric systemic autoimmune diseases and cannot be explained only by the traditional cardiovascular risk factors. Therefore, chronic inflammation has been considered as an additive causative factor of cardiac disease in these patients. Rheumatic fever, juvenile idiopathic arthritis, systemic lupus erythematosus, ankylosing spondylitis/spondyloarthritides, juvenile scleroderma, juvenile dermatomyositis/polymyositis, Kawasaki disease and other autoimmune vasculitides are the commonest pediatric systemic autoimmune diseases with heart involvement. Noninvasive cardiovascular imaging is an absolutely necessary adjunct to the clinical evaluation of these patients. Echocardiography is the cornerstone of this assessment, due to excellent acoustic window in children, lack of radiation, low cost and high availability. However, it can not detect disease acuity and pathophysiologic background of cardiac lesions. Recently, the development of cardiovascular magnetic resonance imaging holds the promise for early detection of subclinical heart disease and detailed serial evaluation of myocardium (function, inflammation, stress perfusion-fibrosis) and coronary arteries (assessment of ectasia and aneurysms).

    .

  16. Coeliac disease in 2013: new insights in dietary-gluten-induced autoimmunity.

    PubMed

    Kaukinen, Katri; Mäki, Markku

    2014-02-01

    Coeliac disease comprises intolerance against dietary wheat, rye and barley gluten and is one of the most common food-related life-long disorders in Western countries. In 2013, new knowledge of the clinical diversity of coeliac disease and further details about the autoimmune aspects of this disorder have emerged.

  17. Experimental transmission of systemic AA amyloidosis in autoimmune disease and type 2 diabetes mellitus model mice

    PubMed Central

    Maeda, Mayuko; Murakami, Tomoaki; Muhammad, Naeem; Inoshima, Yasuo; Ishiguro, Naotaka

    2016-01-01

    AA amyloidosis is a protein misfolding disease characterized by extracellular deposition of amyloid A (AA) fibrils. AA amyloidosis has been identified in food animals, and it has been postulated that AA amyloidosis may be transmissible to different animal species. Since the precursor protein of AA fibrils is serum amyloid A (SAA), which is an inflammatory acute phase protein, AA amyloidosis is considered to be associated with inflammatory diseases such as rheumatoid arthritis. Chronic diseases such as autoimmune disease and type 2 diabetes mellitus could be potential factors for AA amyloidosis. In this study, to examine the relationship between the induction of AA amyloidosis and chromic abnormalities such as autoimmune disease or type 2 diabetes mellitus, amyloid fibrils from mice, cattle, or chickens were experimentally injected into disease model mice. Wild-type mice were used as controls. The concentrations of SAA, IL-6, and IL-10 in autoimmune disease model mice were higher than those of control mice. However, induction of AA amyloidosis in autoimmune disease and type 2 diabetes mellitus model mice was lower than that in control mice, and the amount of amyloid deposits in the spleens of both mouse models was lower than that of control mice according to Congo red staining and immunohistochemistry. These results suggest that factors other than SAA levels, such as an inflammatory or anti-inflammatory environment in the immune response, may be involved in amyloid deposition. PMID:27321428

  18. Allogeneic hematolymphoid microchimerism and prevention of autoimmune disease in the rat. A relationship between allo- and autoimmunity.

    PubMed Central

    Delaney, C P; Murase, N; Chen-Woan, M; Fung, J J; Starzl, T E; Demetris, A J

    1996-01-01

    Conventional allogeneic bone marrow transplantation after myeloablation can prevent experimental autoimmunity and has been proposed as treatment for humans. However, trace populations of donor hematolymphoid cells persisting in solid organ allograft recipients have been associated in some circumstances with therapeutic effects similar to replacement of the entire bone marrow. We therefore examined whether inducing hematolymphoid microchimerism without myeloablation could confer the ability to resist mercuric chloride (HgCl2)-induced autoimmunity. Brown-Norway (BN) rats were pretreated with a syngeneic or allogeneic bone marrow infusion under transient FK506 immunosuppression before receiving HgCl2. They were compared with BN rats receiving either no pretreatment (naive) or FK506 alone. Administration of HgCl2 to naive BN rats induced marked autoantibody production, systemic vasculitis and lymphocytic infiltration of the kidneys, liver and skin in all of the animals and a 47% mortality. In contrast, BN rats pretreated with HgCl2-resistant allogeneic Lewis bone marrow and transient FK506 showed less clinical disease and were completely protected from mortality. More specifically, IgG anti-laminin autoantibody production was decreased by 40% (P < 0.05), and there was less histopathological tissue injury (P < 0.005), less in vitro autoreactivity (P < 0.05), less of an increase in class II MHC expression on B cells (P < 0.01), and 22% less weight loss (P < 0.01), compared with controls. Protection from the experimental autoimmunity was associated with signs of low grade activation of the BN immune system, which included: increased numbers of circulating B and activated T cells before administration of HgCl2, and less autoreactivity and spontaneous proliferation in vitro after HgCl2. PMID:8550837

  19. 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

  20. Taming the TCR: antigen-specific immunotherapeutic agents for autoimmune diseases.

    PubMed

    Sauer, Evan L; Cloake, Nancy C; Greer, Judith M

    2015-01-01

    Current treatments for autoimmune diseases are typically non-specific anti-inflammatory agents that affect not only the autoreactive cells but also the parts of the immune system that are required to maintain health. There is a need for the development of antigen-specific therapeutic agents that can effectively prevent the autoimmune attack while leaving the rest of the immune system functioning as normal. The simplest way to achieve this is using the autoantigen itself as a tolerizing agent; however, there is some risk involved with administering a potentially pathogenic antigen. In this review, we focus instead on the development and use of modified T cell receptor (TCR) ligands, in which the peptide ligand is modified to change the response by the T cell from a disease inducing to a protective response, and still retain the antigen-specificity necessary to target the autoreactive T cells. We review the use of modified TCR ligands as therapeutic agents in animal models of autoimmunity and in human autoimmune disease, and finally consider how they need to be improved in order to use them effectively in patients with autoimmune disease.

  1. 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

  2. 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.

  3. Evidence for pathogenicity of autoreactive T cells in autoimmune bullous diseases shown by animal disease models.

    PubMed

    Ujiie, Hideyuki; Shimizu, Hiroshi

    2012-12-01

    Autoimmune bullous diseases (AIBDs) are characterized by blisters and erosions on the skin and/or mucous membranes, which are caused by autoantibodies directed to structural proteins of the epidermis and the epidermal basement membrane zone. This Viewpoint Essay discusses the contribution by autoreactive T cells to the pathogenesis of bullous pemphigoid, pemphigus and epidermolysis bullosa acquisita, with an emphasis on studies using active animal mouse models for these diseases. Previous studies have demonstrated that cytokines produced by autoreactive T cells, the interaction between antigen-specific T cells and B cells and the function of regulatory T cells are likely related to the pathogenesis of AIBDs. In interpreting the experimental results, the limitations of those animal models should be considered. Further understanding of the pathogenicity of autoreactive CD4(+) T cells may lead to disease-specific treatments.

  4. The association of other autoimmune diseases in patients with autoimmune thyroiditis: Review of the literature and report of a large series of patients.

    PubMed

    Fallahi, Poupak; Ferrari, Silvia Martina; Ruffilli, Ilaria; Elia, Giusy; Biricotti, Marco; Vita, Roberto; Benvenga, Salvatore; Antonelli, Alessandro

    2016-12-01

    We have evaluated prospectively the prevalence of other autoimmune disorders in outpatient clinic in 3069 consecutive patients with diagnosed chronic autoimmune thyroiditis (AT), with respect to two age- and sex-matched control groups: a) a control group of 1023 subjects, extracted from a random sample of the general population without thyroid disorders; b) 1023 patients with non-toxic multinodular goiter extracted from the same random sample of the general population, with similar iodine intake. The results of our study demonstrate a significant increase of the prevalence of autoimmune disorders in AT patients (with respect to both controls), for the following diseases: chronic autoimmune gastritis (CAG), vitiligo (Vit), rheumatoid arthritis, polymialgia rheumatica (Polym), celiac disease, diabetes, sjogren disease, multiple sclerosis, systemic lupus erythematosus, sarcoidosis, alopecia, psoriathic arthritis, systemic sclerosis, and HCV-related cryoglobulinemia. While the statistical analysis reached near the significance for Addison's disease and ulcerative colitis. Interestingly, the association of three autoimmune disorders was observed almost exclusively in AT patients, and the most frequent associations were AT+CAG+Vit and AT+CAG+Polym. We suggest that patients with AT who remain unwell, or who develop new not specific symptoms (despite adequate treatment) should be screened for other autoimmune disorders, avoiding the delay in the diagnosis of these disorders.

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

    PubMed Central

    Amador-Patarroyo, Manuel J.; Rodriguez-Rodriguez, Alberto; Montoya-Ortiz, Gladis

    2012-01-01

    The age at onset refers to the time period at which an individual experiences the first symptoms of a disease. In autoimmune diseases (ADs), these symptoms can be subtle but are very relevant for diagnosis. They can appear during childhood, adulthood or late in life and may vary depending on the age at onset. Variables like mortality and morbidity and the role of genes will be reviewed with a focus on the major autoimmune disorders, namely, systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), multiple sclerosis (MS), type 1 diabetes mellitus (T1D), Sjögren's syndrome, and autoimmune thyroiditis (AITD). Early age at onset is a worst prognostic factor for some ADs (i.e., SLE and T1D), while for others it does not have a significant influence on the course of disease (i.e., SS) or no unanimous consensus exists (i.e., RA and MS). PMID:22195277

  6. [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.

  7. 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.

  8. Systemic autoimmunity induced by the TLR7/8 agonist Resiquimod causes myocarditis and dilated cardiomyopathy in a new mouse model of autoimmune heart disease

    PubMed Central

    Hasham, Muneer G.; Baxan, Nicoleta; Stuckey, Daniel J.; Branca, Jane; Perkins, Bryant; Dent, Oliver; Duffy, Ted; Hameed, Tolani S.; Stella, Sarah E.; Bellahcene, Mohammed; Schneider, Michael D.; Harding, Sian E.; Rosenthal, Nadia

    2017-01-01

    ABSTRACT Systemic autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) show significant heart involvement and cardiovascular morbidity, which can be due to systemically increased levels of inflammation or direct autoreactivity targeting cardiac tissue. Despite high clinical relevance, cardiac damage secondary to systemic autoimmunity lacks inducible rodent models. Here, we characterise immune-mediated cardiac tissue damage in a new model of SLE induced by topical application of the Toll-like receptor 7/8 (TLR7/8) agonist Resiquimod. We observe a cardiac phenotype reminiscent of autoimmune-mediated dilated cardiomyopathy, and identify auto-antibodies as major contributors to cardiac tissue damage. Resiquimod-induced heart disease is a highly relevant mouse model for mechanistic and therapeutic studies aiming to protect the heart during autoimmunity. PMID:28250051

  9. 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 paracr