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Sample records for autoimmune disease triggered

  1. Is Bariatric Surgery a Trigger Factor for Systemic Autoimmune Diseases?

    PubMed

    Cañas, Carlos A; Echeverri, Andrés F; Ospina, Fabio E; Suso, Juan-Pablo; Agualimpia, Andrés; Echeverri, Alex; Bonilla-Abadía, Fabio; Tobón, Gabriel J

    2016-03-01

    Bariatric procedures are an effective option for weight loss and control of comorbidities in obese patients. Obesity is a proinflammatory condition in which some cytokines such as leptin, a proinflammatory protein, is elevated and adiponectin, an anti-inflammatory protein, is decreased. In patients undergoing weight reduction surgeries, these hormone levels behave paradoxically. It is not known whether bariatric surgery protects against development of autoinflammatory or autoimmune conditions; nevertheless, changes occurring in the immune system are incompletely understood. In this case series, we describe 4 patients undergoing bariatric surgery, who subsequently developed systemic autoimmune diseases. Patients in our case series were asymptomatic before surgery and developed an autoimmune disease within 11.2 months. Two women fulfilled criteria for systemic lupus erythematosus (one associated with antiphospholipid syndrome), and 2 men developed rheumatoid arthritis. A causal relationship is difficult to establish because factors that could trigger these diseases are multiple, including genetic susceptibility, time elapsed until achievement of ideal weight, and vitamin deficiencies, among others. However, clinicians must be attentive to this possible association. PMID:26906303

  2. Trigger of autoimmune diseases (SLE): identification of LINE transposition based novel therapeutic molecular targets.

    PubMed

    Tiwari, Anupama; Soni, Upendra Kumar

    2014-12-01

    Autoimmune diseases are the highly heterogeneous at cellular and molecular level. The causes and consequences of most of the autoimmune diseases are not well explored. However the researches focusing on the development of biomarkers for the diagnosis of autoimmune diseases are seems to be inadequate and given treatment are insufficient to control or cure the disease properly. It is a big obstacle to develop any therapy without knowing the actual cause and molecular event playing role in disease onset. In this article we are raising the involvement of LINE or other transposition as a first trigger and cause for autoimmune disease. Further we are proposing a novel hybrid aptamers based biocapturing model which would help in the investigation of genome-wide LINE transposition in pristane induced SLE mice model. Importantly the effect of new LINE movements at the expression pattern of neighboring genes would be used as novel molecular prognostic biomarkers for onset of SLE and related autoimmune diseases. We are also proposing that the differential expression either inductive or suppressive pattern of expected several candidate genes would be implicated in the defective biochemical or cellular defects, and targeted therapy would be employed to such life threatening disease. PMID:25468787

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

    PubMed Central

    Broccolo, Francesco; Fusetti, Lisa; Ceccherini-Nelli, Luca

    2013-01-01

    Human herpesvirus 6 (HHV-6) infection is common and has a worldwide distribution. Recently, HHV-6A and HHV-6B have been reclassified into two distinct species based on different biological features (genetic, antigenic, and cell tropism) and disease associations. A role for HHV-6A/B has been proposed in several autoimmune disorders (AD), including multiple sclerosis (MS), autoimmune connective tissue diseases, and Hashimoto's thyroiditis. The focus of this review is to discuss the above-mentioned AD associated with HHV-6 and the mechanisms proposed for HHV-6A/B-induced autoimmunity. HHV-6A/B could trigger autoimmunity by exposing high amounts of normally sequestered cell antigens, through lysis of infected cells. Another potential trigger is represented by molecular mimicry, with the synthesis of viral proteins that resemble cellular molecules, as a mechanism of immune escape. The virus could also induce aberrant expression of histocompatibility molecules thereby promoting the presentation of autoantigens. CD46-HHV-6A/B interaction is a new attractive mechanism proposed: HHV-6A/B (especially HHV-6A) could participate in neuroinflammation in the context of MS by promoting inflammatory processes through CD46 binding. Although HHV-6A/B has the ability to trigger all the above-mentioned mechanisms, more studies are required to fully elucidate the possible role of HHV-6A/B as a trigger of AD. PMID:24282390

  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. PMID:27396816

  5. 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

  6. Environmental Triggers of Autoimmune Thyroiditis

    PubMed Central

    Burek, C. Lynne; Talor, Monica V.

    2009-01-01

    Autoimmune thyroiditis is among the most prevalent of all the autoimmunities. Autoimmune thyroiditis is multifactorial with contributions from genetic and environmental factors. Much information has been published about the genetic predisposition to autoimmune thyroiditis both in experimental animals and humans. There is, in contrast, very little data on environmental agents that can serve as the trigger or autoimmunity in a genetically predisposed host. The best-established environmental factor is excess dietary iodine. Increased iodine consumption is strongly implicated as a trigger for thyroiditis, but only in genetically susceptible individuals. However, excess iodine is not the only environmental agent implicated as a trigger leading to autoimmune thyroiditis. There are a wide variety of other synthetic chemicals that affect the thyroid gland or have the ability to promote immune dysfunction in the host. These chemicals are released into the environment by design, such as in pesticides, or as a by-product of industry. Candidate pollutants include polyaromatic hydrocarbons, polybrominated biphenols, and polychlorinated biphenols, among others. Infections are also reputed to trigger autoimmunity and may act alone or in concert with environmental chemicals. We have utilized a unique animal model, the NOD.H2h4 mouse to explore the influence of iodine and other environmental factors on autoimmune thyroiditis. PMID:19818584

  7. Environmental triggers of autoimmune thyroiditis.

    PubMed

    Burek, C Lynne; Talor, Monica V

    2009-01-01

    Autoimmune thyroiditis is among the most prevalent of all the autoimmunities. Autoimmune thyroiditis is multifactorial with contributions from genetic and environmental factors. Much information has been published about the genetic predisposition to autoimmune thyroiditis both in experimental animals and humans. There is, in contrast, very little data on environmental agents that can serve as the trigger for autoimmunity in a genetically predisposed host. The best-established environmental factor is excess dietary iodine. Increased iodine consumption is strongly implicated as a trigger for thyroiditis, but only in genetically susceptible individuals. However, excess iodine is not the only environmental agent implicated as a trigger leading to autoimmune thyroiditis. There are a wide variety of other synthetic chemicals that affect the thyroid gland or have the ability to promote immune dysfunction in the host. These chemicals are released into the environment by design, such as in pesticides, or as a by-product of industry. Candidate pollutants include polyaromatic hydrocarbons, polybrominated biphenols, and polychlorinated biphenols, among others. Infections are also reputed to trigger autoimmunity and may act alone or in concert with environmental chemicals. We have utilized a unique animal model, the NOD.H2(h4) mouse to explore the influence of iodine and other environmental factors on autoimmune thyroiditis. PMID:19818584

  8. 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

  9. Molecular mimicry as an inducing trigger for CNS autoimmune demyelinating disease.

    PubMed

    Chastain, Emily M L; Miller, Stephen D

    2012-01-01

    Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) that affects about 0.1% of the worldwide population. This deleterious disease is marked by infiltration of myelin-specific T cells that attack the protective myelin sheath that surrounds CNS nerve axons. Upon demyelination, saltatory nerve conduction is disrupted, and patients experience neurologic deficiencies. The exact cause for MS remains unknown, although most evidence supports the hypothesis that both genetic and environmental factors contribute to disease development. Epidemiologic evidence supports a role for environmental pathogens, such as viruses, as potentially key contributors to MS induction. Pathogens can induce autoimmunity via several well-studied mechanisms with the most postulated being molecular mimicry. Molecular mimicry occurs when T cells specific for peptide epitopes derived from pathogens cross-react with self-epitopes, leading to autoimmune tissue destruction. In this review, we discuss an in vivo virus-induced mouse model of MS developed in our laboratory, which has contributed greatly to our understanding of the mechanisms underlying molecular mimicry-induced CNS autoimmunity. PMID:22168423

  10. 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.

  11. 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 diagnose ...

  12. Autoimmune Inner Ear Disease

    MedlinePlus

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

  13. Infections and autoimmune diseases.

    PubMed

    Bach, Jean-François

    2005-01-01

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

  14. American Autoimmune Related Diseases Association

    MedlinePlus

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

  15. Autoantibody-boosted T-cell reactivation in the target organ triggers manifestation of autoimmune CNS disease.

    PubMed

    Flach, Anne-Christine; Litke, Tanja; Strauss, Judith; Haberl, Michael; Gómez, César Cordero; Reindl, Markus; Saiz, Albert; Fehling, Hans-Jörg; Wienands, Jürgen; Odoardi, Francesca; Lühder, Fred; Flügel, Alexander

    2016-03-22

    Multiple sclerosis (MS) is caused by T cells that are reactive for brain antigens. In experimental autoimmune encephalomyelitis, the animal model for MS, myelin-reactive T cells initiate the autoimmune process when entering the nervous tissue and become reactivated upon local encounter of their cognate CNS antigen. Thereby, the strength of the T-cellular reactivation process within the CNS tissue is crucial for the manifestation and the severity of the clinical disease. Recently, B cells were found to participate in the pathogenesis of CNS autoimmunity, with several diverse underlying mechanisms being under discussion. We here report that B cells play an important role in promoting the initiation process of CNS autoimmunity. Myelin-specific antibodies produced by autoreactive B cells after activation in the periphery diffused into the CNS together with the first invading pathogenic T cells. The antibodies accumulated in resident antigen-presenting phagocytes and significantly enhanced the activation of the incoming effector T cells. The ensuing strong blood-brain barrier disruption and immune cell recruitment resulted in rapid manifestation of clinical disease. Therefore, myelin oligodendrocyte glycoprotein (MOG)-specific autoantibodies can initiate disease bouts by cooperating with the autoreactive T cells in helping them to recognize their autoantigen and become efficiently reactivated within the immune-deprived nervous tissue. PMID:26957602

  16. Autoimmunity in neuromuscular disease.

    PubMed

    Newsom-Davis, J

    1988-01-01

    A number of confounding factors can be identified from the search for autoimmune mechanisms over the last 2 decades that may be relevant for future studies. (1) An apparently homogeneous clinical disorder may represent more than one disease process and thereby imply antibody/antigen heterogeneity as, for example, in MG with and without detectable anti-AChR antibodies. In some cases, physiologic studies allow the different forms of the disease to be distinguished as in AIDP and acute inflammatory axonal polyneuropathy. (2) A homogeneous disorder (e.g., LEMS) may have at least two different triggering mechanisms (SCLC and an unknown stimulus). (3) Antigen density may be too low to be detected by the immunohistologic techniques available, as initially occurred in MG and LEMS. (4) Autoantibodies may be detected that are irrelevant to the primary disease, such as anti-striated muscle antibodies in MG. (5) Poor antibody cross-reactivity between species may mean that the pathogenic antibody is undetected in binding assays or in experimental passive transfer studies. For example, anti-AChR antibody in MG shows less than 5% reactivity with Torpedo AChR. (6) A poor regenerative capacity of the target antigen may mean that reduction of circulating autoantibodies by either plasma exchange or ISD treatment is not associated with detectable clinical improvement, as may be the case in SSN in which DRG cells appear to be the target. TABLE 5 summarizes the extent to which the data reviewed have established a role for pathogenic antibodies in the light of the postulates for autoimmunity set out earlier and ranks the disorders accordingly. Only in MG with detectable anti-AChR antibody are all the postulates met, including definition of the antigen, experimental passive transfer by the IgG fraction of MG sera, active immunization of experimental animals, and propagation. In both LEMS and the IgM kappa anti-MAG demyelinating neuropathy the antigen is known, although better

  17. Autoimmune liver disease panel

    MedlinePlus

    ... common of these diseases are autoimmune hepatitis and primary biliary cirrhosis. This group of tests helps your health care ... anti-mitochondrial antibodies, you are likely to have primary biliary cirrhosis. If the immune proteins are high and albumin ...

  18. 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 ...

  19. A Potential Link between Environmental Triggers and Autoimmunity.

    PubMed

    Vojdani, Aristo

    2014-01-01

    Autoimmune diseases have registered an alarming rise worldwide in recent years. Accumulated evidence indicates that the immune system's ability to distinguish self from nonself is negatively impacted by genetic factors and environmental triggers. Genetics is certainly a factor, but since it normally takes a very long time for the human genetic pattern to change enough to register on a worldwide scale, increasingly the attention of studies has been focused on the environmental factors of a rapidly changing and evolving civilization. New technology, new industries, new inventions, new chemicals and drugs, and new foods and diets are constantly and rapidly being introduced in this fast-paced ever-changing world. Toxicants, infections, epitope spreading, dysfunctions of immune homeostasis, and dietary components can all have an impact on the body's delicate immune recognition system. Although the precise etiology and pathogenesis of many autoimmune diseases are still unknown, it would appear from the collated studies that there are common mechanisms in the immunopathogenesis of multiple autoimmune reactivities. Of particular interest is the citrullination of host proteins and their conversion to autoantigens by the aforementioned environmental triggers. The identification of these specific triggers of autoimmune reactivity is essential then for the development of new therapies for autoimmune diseases. PMID:24688790

  20. Epigenetics and Autoimmune Diseases

    PubMed Central

    Quintero-Ronderos, Paula; Montoya-Ortiz, Gladis

    2012-01-01

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

  1. Sirolimus for Autoimmune Disease of Blood Cells

    ClinicalTrials.gov

    2016-04-22

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

  2. Autoimmunity in Addison's disease.

    PubMed

    Martín Martorell, P; Roep, B O; Smit, J W A; Martorell, P M

    2002-08-01

    Addison's disease has a low incidence and is most frequently the result of an autoimmune disease in developed countries. Addison's disease can present as an isolated entity or in combination with other autoimmune diseases: Addison's disease can be part of the distinct polyglandular autoimmune syndromes APS I and II. Autoantibodies in patients with isolated Addison's disease are directed against the enzymes involved in steroid synthesis, P45oc21, P45oscc and P45oc17. Addison's disease, both isolated and in the context of APS II, has been associated with the haplotype HLA-A1, -B8 and DR3. The value of the increased expression of these molecules on adrenocortical cells could point towards an infectious pathogenesis. Given the prevalence, up to 80 %, of autoantibodies in Addison's disease as well as the high predictive value for developing the disease when antibodies are present (41% in three years), we advise screening high-risk populations, such as patients with other autoimmune endocrinopathies or their relatives for the presence of these antibodies. The adrenocortical function of patients positive for antibodies should be followed yearly. PMID:12430572

  3. Helicobacter pylori and skin autoimmune diseases.

    PubMed

    Magen, Eli; Delgado, Jorge-Shmuel

    2014-02-14

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

  4. 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

  5. [Diagnostics of autoimmune diseases].

    PubMed

    Beleznay, Zsuzsanna; Regenass, Stephan

    2008-09-01

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

  6. Autoimmune liver disease, autoimmunity and liver transplantation.

    PubMed

    Carbone, Marco; Neuberger, James M

    2014-01-01

    Primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH) represent the three major autoimmune liver diseases (AILD). PBC, PSC, and AIH are all complex disorders in that they result from the effects of multiple genes in combination with as yet unidentified environmental factors. Recent genome-wide association studies have identified numerous risk loci for PBC and PSC that host genes involved in innate or acquired immune responses. These loci may provide a clue as to the immune-based pathogenesis of AILD. Moreover, many significant risk loci for PBC and PSC are also risk loci for other autoimmune disorders, such type I diabetes, multiple sclerosis and rheumatoid arthritis, suggesting a shared genetic basis and possibly similar molecular pathways for diverse autoimmune conditions. There is no curative treatment for all three disorders, and a significant number of patients eventually progress to end-stage liver disease requiring liver transplantation (LT). LT in this context has a favourable overall outcome with current patient and graft survival exceeding 80% at 5years. Indications are as for other chronic liver disease although recent data suggest that while lethargy improves after transplantation, the effect is modest and variable so lethargy alone is not an indication. In contrast, pruritus rapidly responds. Cholangiocarcinoma, except under rigorous selection criteria, excludes LT because of the high risk of recurrence. All three conditions may recur after transplantation and are associated with a greater risk of both acute cellular and chronic ductopenic rejection. It is possible that a crosstalk between alloimmune and autoimmune response perpetuate each other. An immunological response toward self- or allo-antigens is well recognised after LT in patients transplanted for non-autoimmune indications and sometimes termed "de novo autoimmune hepatitis". Whether this is part of the spectrum of rejection or an autoimmune

  7. Environmental Exposures and Autoimmune Thyroid Disease

    PubMed Central

    2010-01-01

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

  8. Avenues to autoimmune arthritis triggered by diverse remote inflammatory challenges.

    PubMed

    Chevalier, Nina; Tan, Jian K; Mason, Linda J; Robert, Remy; McKenzie, Craig I; Lim, Florence; Wong, Connie H; Macia, Laurence; Thorburn, Alison N; Russ, Brendan E; Masters, Seth L; Mackay, Charles R

    2016-09-01

    Environmental factors contribute to development of autoimmune diseases. For instance, human autoimmune arthritis can associate with intestinal inflammation, cigarette smoking, periodontal disease, and various infections. The cellular and, molecular pathways whereby such remote challenges might precipitate arthritis or flares remain unclear. Here, we used a transfer model of self-reactive arthritis-inducing CD4(+) cells from KRNtg mice that, upon transfer, induce a very mild form of autoinflammatory arthritis in recipient animals. This model enabled us to identify external factors that greatly aggravated disease. We show that several distinct challenges precipitated full-blown arthritis, including intestinal inflammation through DSS-induced colitis, and bronchial stress through Influenza infection. Both triggers induced strong IL-17 expression primarily in self-reactive CD4(+) cells in lymph nodes draining the site of inflammation. Moreover, treatment of mice with IL-1β greatly exacerbated arthritis, while transfer of KRNtg CD4(+) cells lacking IL-1R significantly reduced disease and IL-17 expression. Thus, IL-1β enhances the autoaggressive potential of self-reactive CD4(+) cells, through increased Th17 differentiation, and this influences inflammatory events in the joints. We propose that diverse challenges that cause remote inflammation (lung infection or colitis, etc.) result in IL-1β-driven Th17 differentiation, and this precipitates arthritis in genetically susceptible individuals. Thus the etiology of autoimmune inflammatory arthritis likely relates to diverse triggers that converge to a common pathway involving IL-1β production and Th17 cell distribution. PMID:27427404

  9. Human autoimmune diseases: a comprehensive update.

    PubMed

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

    2015-10-01

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

  10. [Hydroxychloroquine for autoimmune diseases].

    PubMed

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

    2016-02-01

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

  11. 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

  12. Autoimmune muscle disease.

    PubMed

    Mammen, Andrew

    2016-01-01

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

  13. Autoimmune diseases and myelodysplastic syndromes.

    PubMed

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

    2016-05-01

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

  14. 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

  15. Melanocyte antigen triggers autoimmunity in human psoriasis.

    PubMed

    Arakawa, Akiko; Siewert, Katherina; Stöhr, Julia; Besgen, Petra; Kim, Song-Min; Rühl, Geraldine; Nickel, Jens; Vollmer, Sigrid; Thomas, Peter; Krebs, Stefan; Pinkert, Stefan; Spannagl, Michael; Held, Kathrin; Kammerbauer, Claudia; Besch, Robert; Dornmair, Klaus; Prinz, Jörg C

    2015-12-14

    Psoriasis vulgaris is a common T cell-mediated inflammatory skin disease with a suspected autoimmune pathogenesis. The human leukocyte antigen (HLA) class I allele, HLA-C*06:02, is the main psoriasis risk gene. Epidermal CD8(+) T cells are essential for psoriasis development. Functional implications of HLA-C*06:02 and mechanisms of lesional T cell activation in psoriasis, however, remained elusive. Here we identify melanocytes as skin-specific target cells of an HLA-C*06:02-restricted psoriatic T cell response. We found that a Vα3S1/Vβ13S1 T cell receptor (TCR), which we had reconstituted from an epidermal CD8(+) T cell clone of an HLA-C*06:02-positive psoriasis patient specifically recognizes HLA-C*06:02-positive melanocytes. Through peptide library screening, we identified ADAMTS-like protein 5 (ADAMTSL5) as an HLA-C*06:02-presented melanocytic autoantigen of the Vα3S1/Vβ13S1 TCR. Consistent with the Vα3S1/Vβ13S1-TCR reactivity, we observed numerous CD8(+) T cells in psoriasis lesions attacking melanocytes, the only epidermal cells expressing ADAMTSL5. Furthermore, ADAMTSL5 stimulation induced the psoriasis signature cytokine, IL-17A, in CD8(+) T cells from psoriasis patients only, supporting a role as psoriatic autoantigen. This unbiased analysis of a TCR obtained directly from tissue-infiltrating CD8(+) T cells reveals that in psoriasis HLA-C*06:02 directs an autoimmune response against melanocytes through autoantigen presentation. We propose that HLA-C*06:02 may predispose to psoriasis via this newly identified autoimmune pathway. PMID:26621454

  16. Melanocyte antigen triggers autoimmunity in human psoriasis

    PubMed Central

    Arakawa, Akiko; Siewert, Katherina; Stöhr, Julia; Besgen, Petra; Kim, Song-Min; Rühl, Geraldine; Nickel, Jens; Vollmer, Sigrid; Thomas, Peter; Krebs, Stefan; Pinkert, Stefan; Spannagl, Michael; Held, Kathrin; Kammerbauer, Claudia; Besch, Robert; Dornmair, Klaus

    2015-01-01

    Psoriasis vulgaris is a common T cell–mediated inflammatory skin disease with a suspected autoimmune pathogenesis. The human leukocyte antigen (HLA) class I allele, HLA-C*06:02, is the main psoriasis risk gene. Epidermal CD8+ T cells are essential for psoriasis development. Functional implications of HLA-C*06:02 and mechanisms of lesional T cell activation in psoriasis, however, remained elusive. Here we identify melanocytes as skin-specific target cells of an HLA-C*06:02–restricted psoriatic T cell response. We found that a Vα3S1/Vβ13S1 T cell receptor (TCR), which we had reconstituted from an epidermal CD8+ T cell clone of an HLA-C*06:02–positive psoriasis patient specifically recognizes HLA-C*06:02–positive melanocytes. Through peptide library screening, we identified ADAMTS-like protein 5 (ADAMTSL5) as an HLA-C*06:02–presented melanocytic autoantigen of the Vα3S1/Vβ13S1 TCR. Consistent with the Vα3S1/Vβ13S1-TCR reactivity, we observed numerous CD8+ T cells in psoriasis lesions attacking melanocytes, the only epidermal cells expressing ADAMTSL5. Furthermore, ADAMTSL5 stimulation induced the psoriasis signature cytokine, IL-17A, in CD8+ T cells from psoriasis patients only, supporting a role as psoriatic autoantigen. This unbiased analysis of a TCR obtained directly from tissue-infiltrating CD8+ T cells reveals that in psoriasis HLA-C*06:02 directs an autoimmune response against melanocytes through autoantigen presentation. We propose that HLA-C*06:02 may predispose to psoriasis via this newly identified autoimmune pathway. PMID:26621454

  17. 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

  18. Sensory Neuronopathy and Autoimmune Diseases

    PubMed Central

    Martinez, Alberto R. M.; Nunes, Marcelo B.; Nucci, Anamarli; França, Marcondes C.

    2012-01-01

    Sensory neuronopathies (SNs) are a specific subgroup of peripheral nervous system diseases characterized by primary degeneration of dorsal root ganglia and their projections. Multifocal sensory symptoms often associated to ataxia are the classical features of SN. Several different etiologies have been described for SNs, but immune-mediated damage plays a key role in most cases. SN may herald the onset of some systemic autoimmune diseases, which further emphasizes how important the recognition of SN is in clinical practice. We have thus reviewed available clinical, neurophysiological, and therapeutic data on autoimmune disease-related SN, namely, in patients with Sjögren's syndrome, autoimmune hepatitis, and celiac disease. PMID:22312482

  19. Progesterone and Autoimmune Disease

    PubMed Central

    Hughes, Grant C.

    2011-01-01

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

  20. Epigenetic alterations underlying autoimmune diseases.

    PubMed

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

    2016-03-01

    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. PMID:26761426

  1. Smoke and autoimmunity: The fire behind the disease.

    PubMed

    Perricone, Carlo; Versini, Mathilde; Ben-Ami, Dana; Gertel, Smadar; Watad, Abdulla; Segel, Michael J; Ceccarelli, Fulvia; Conti, Fabrizio; Cantarini, Luca; Bogdanos, Dimitrios P; Antonelli, Alessandro; Amital, Howard; Valesini, Guido; Shoenfeld, Yehuda

    2016-04-01

    The association between smoke habit and autoimmunity has been hypothesized a long time ago. Smoke has been found to play a pathogenic role in certain autoimmune disease as it may trigger the development of autoantibodies and act on pathogenic mechanism possibly related with an imbalance of the immune system. Indeed, both epidemiological studies and animal models have showed the potential deleterious effect caused by smoke. For instance, smoke, by provoking oxidative stress, may contribute to lupus disease by dysregulating DNA demethylation, upregulating immune genes, thereby leading to autoreactivity. Moreover, it can alter the lung microenvironment, facilitating infections, which, in turn, may trigger the development of an autoimmune condition. This, in turn, may result in a dysregulation of immune system leading to autoimmune phenomena. Not only cigarette smoke but also air pollution has been reported as being responsible for the development of autoimmunity. Large epidemiological studies are needed to further explore the accountability of smoking effect in the pathogenesis of autoimmune diseases. PMID:26772647

  2. American Autoimmune Related Diseases Association

    MedlinePlus

    ... Statistics Your source for autoimmune related disease information. **We need your input** We want to know of your experiences with Non- ... email address with us. Please be assured that we will always keep your email private. We will ...

  3. Autoimmune Thyroid Diseases in Children

    PubMed Central

    Cappa, Marco; Bizzarri, Carla; Crea, Francesca

    2011-01-01

    The two major autoimmune thyroid diseases (ATDs) include Graves' disease (GD) and autoimmune thyroiditis (AT); both of which are characterized by infiltration of the thyroid by T and B cells reactive to thyroid antigens, by the production of thyroid autoantibodies and by abnormal thyroid function (hyperthyroidism in GD and hypothyroidism in AT). While the exact etiology of thyroid autoimmunity is not known, it is believed to develop when a combination of genetic susceptibility and environmental encounters leads to breakdown of tolerance. It is important to recognize thyroid dysfunction at an early stage by maintaining an appropriate index of suspicion. PMID:21209713

  4. Chronic autoimmune thyroid disease.

    PubMed

    Litta Modignani, R; Barantani, E; Mazzolari, M; Pincetti Nervi, M; Macchi, R

    1991-01-01

    A total of 67 patients with chronic autoimmune thyroid disease were followed, mainly as outpatients, for a period of a few months to over 15 years. The diagnosis was euthyroidism (n = 16, 23.8%), subclinical hypothyroidism (n = 20, 29.8%), primary hypothyroidism (n = 28, 41.7%) or hashitoxicosis (n = 3, 4.47%). Patients with goiters fit Hashimoto's original description of "struma lymphomatosa". The diagnosis was made on clinical grounds and the usual laboratory hormonal tests. Histological examination was carried out at surgery or by fine needle aspiration in 35 patients (52.2%), and a clinical diagnosis was made in 32 (47.7%). Three patients had juvenile Hashimoto's thyroiditis. Most patients were in the fourth, fifth or sixth decade (64.8%), and of these 12 (18%) had subclinical hypothyroidism, which should be suspected when thyrotropin (TSH) is twice the upper normal limit. In these cases thyrotropin releasing hormone (TRH) testing and evaluation of anti-thyroglobulin antibodies (TgAb) and anti-microsomal antigen antibodies (MsAb) are mandatory. Hypothyroidism with few symptoms develops insidiously in young or elderly patients; the most sensitive test is TSH assay in conjunction with tests for TgAb and MsAb. L-thyroxine administration may be harmful in older patients with late diagnosed primary hypothyroidism. Thyroid supplementation is suggested for patients with subclinical hypothyroidism if TSH values are above 10 mU/L; otherwise they should be followed up annually, as should patients with positive thyroid autoantibodies who are still euthyroid. PMID:1804288

  5. Estrogens and autoimmune diseases.

    PubMed

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

    2006-11-01

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

  6. Autoimmune hepatitis triggered by Brucella infection or doxycycline or both.

    PubMed

    Selimoglu, M A; Ertekin, V

    2003-09-01

    Autoimmune hepatitis is a disorder of unknown aetiology in which progressive destruction of the hepatic parenchyma occurs, often progressing to cirrhosis. Hepatitis A, Ebstein-Barr virus and measles virus have been identified as triggers for autoimmune hepatitis in susceptible individuals. There are also reports about herbal medicine and minocycline. A case with autoimmune hepatitis triggered by Brucella infection or doxycycline, or both, is presented. An 11-year-old female patient treated with six weeks of doxycycline and three weeks of streptomycine for brucellosis presented with histologically proven autoimmune hepatitis (AH) and responded to corticosteroid treatment. Since neither brucellosis nor doxcycyline as triggering factors for AH have been described so far, these two entities are discussed and the literature reviewed. PMID:14529072

  7. 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. PMID:26168705

  8. [Retinoid therapy for autoimmune diseases].

    PubMed

    Fukasawa, Hiroshi; Kagechika, Hiroyuki; Shudo, Koichi

    2006-06-01

    Retinoid is a collective term for compounds which bind to and activate retinoic acid receptors (RARalpha, beta, gamma and RXRalpha, beta, gamma), members of nuclear hormone receptor superfamily. The most important endogeneous retinoid is all-trans-retinoic acid (ATRA) which is an RARalpha, beta and gamma ligand. ATRA and its mimics have been in clinical use for treatment of acute promyelocytic leukemia (APL) and some skin diseases. Many synthetic retinoids have been developed and attempts to improve their medicinal properties have been made. Among them, tamibarotene (Am80) is an RARalpha- and RARbeta-specific (but RARgamma- and RXRs-nonbinding) synthetic retinoid that is effective in the treatment of psoriasis patients and relapsed APL. Experimentally, this compound is also active in animal models of rheumatoid arthritis and experimental autoimmune encephalomyelitis. On this background, possible application of retinoids for the treatment of autoimmune diseases was discussed. In particular, Th1 dominant autoimmune diseases may be the targets of the retinoids. PMID:16819260

  9. [Infectious agents and autoimmune diseases].

    PubMed

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

    1992-01-01

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

  10. Genetic susceptibility to autoimmune liver disease.

    PubMed

    Mattner, Jochen

    2011-01-27

    Autoimmune hepatitis (AIH), primary sclerosing cholangitis (PSC) and primary biliary cirrhosis (PBC) are considered as putative autoimmune diseases of the liver. Whereas strong evidence that bacterial infection may trigger PBC exists, the etiologies for PSC and AIH remain unknown. Although there have been significant discoveries of genetic polymorphisms that may underlie the susceptibility to these liver diseases, their associations with environmental triggers and the subsequent implications have been difficult to elucidate. While single nucleotide polymorphisms within the negative costimulatory molecule cytotoxic T lymphocyte antigen 4 (CTLA-4) have been suggested as genetic susceptibility factors for all three disorders, we discuss the implications of CTLA-4 susceptibility alleles mainly in the context of PBC, where Novosphingobium aromaticivorans, an ubiquitous alphaproteobacterium, has recently been specifically associated with the pathogenesis of this devastating liver disease. Ultimately, the discovery of infectious triggers of PBC may expand the concept of genetic susceptibility in immune-mediated liver diseases from the concept of aberrant immune responses against self-antigens to insufficient and/or inappropriate immunological defense mechanisms allowing microbes to cross natural barriers, establish infection and damage respective target organs. PMID:21307981

  11. Celiac disease and autoimmune thyroid disease.

    PubMed

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

    2007-10-01

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

  12. 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

  13. 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. PMID:24763536

  14. Therapy of autoimmune bullous diseases

    PubMed Central

    Mutasim, Diya F

    2007-01-01

    Autoimmune bullous diseases result from an immune response to molecular components of the desmosome or basement membrane. Bullous diseases are associated with a high degree of morbidity and occasional mortality. Therapy of bullous diseases consists of suppressing the immune system, controlling inflammation and improving healing of erosions. The therapeutic agents used in the treatment of bullous diseases may be associated with high morbidity and occasional mortality. Successful treatment requires understanding of the pathophysiology of the disease process and the pharmacology of the drugs being used. PMID:18360613

  15. Progranulin antibodies in autoimmune diseases.

    PubMed

    Thurner, Lorenz; Preuss, Klaus-Dieter; Fadle, Natalie; Regitz, Evi; Klemm, Philipp; Zaks, Marina; Kemele, Maria; Hasenfus, Andrea; Csernok, Elena; Gross, Wolfgang L; Pasquali, Jean-Louis; Martin, Thierry; Bohle, Rainer Maria; Pfreundschuh, Michael

    2013-05-01

    Systemic vasculitides constitute a heterogeneous group of diseases. Autoimmunity mediated by B lymphocytes and their humoral effector mechanisms play a major role in ANCA-associated vasculitis (AAV) as well as in non-ANCA associated primary systemic vasculitides and in the different types of autoimmune connective tissue disorders and rheumatoid arthritis. In order to detect autoantibodies in systemic vasculitides, we screened protein macroarrays of human cDNA expression libraries with sera from patients with ANCA-associated and ANCA-negative primary systemic vasculitides. This approach led to the identification of antibodies against progranulin, a 88 kDA secreted glycoprotein with strong anti-inflammatory activity in the course of disease of giant-cell arteritis/polymyalgia rheumatica (14/65), Takayasu's arteritis (4/13), classical panarteritis nodosa (4/10), Behcet's disease (2/6) and in the course of disease in granulomatosis with polyangiitis (31/75), Churg-Strauss syndrome (7/23) and in microscopic polyangiitis (7/19). In extended screenings the progranulin antibodies were also detected in other autoimmune diseases such as systemic lupus erythematosus (39/91) and rheumatoid arthritis (16/44). Progranulin antibodies were detected only in 1 of 97 healthy controls. Anti-progranulin positive patients with systemic vasculitides, systemic lupus erythematosus or rheumatoid arthritis had significant lower progranulin plasma levels, indicating a neutralizing effect. In light of the anti-inflammatory effects of progranulin, progranulin antibodies might exert pro-inflammatory effects thus contributing to the pathogenesis of the respective autoimmune diseases and might serve as a marker for disease activity. This hypothesis is supported by the fact that a positive progranulin antibody status was associated with active disease in granulomatosis with polyangiitis. PMID:23149338

  16. Associated Autoimmune Diseases

    MedlinePlus

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

  17. Propylthiouracil-induced autoimmune disease

    PubMed Central

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

    2015-01-01

    Hyperthyroidism is a condition characterized by excessive production of thyroid hormones. Propylthiouracil (PTU) is commonly used as first line drug in the management of hyperthyroidism. This is a case report of 24-year-old female, a known case of hyperthyroidism since 4 years, who came with a history of fever and myalgia since 3 days and dyspnea with coughing out of blood since 1 day. Patient was taking PTU (100 mg per day) since 4 years for hyperthyroidism. Patient was immediately intubated for type-II respiratory failure. Diagnosed to be having PTU-induced autoimmune disease. PTU was stopped and treated with methylprednisolone and cyclophosphamide. Clinical features improved over a period of 8 days and discharged home successfully. Having a high suspicion for the onset of autoimmune disease in hyperthyroidism patients who are on PTU therapy and timely treatment with immunosuppressants and supportive care along with the withdrawal of the drug can make a difference in morbidity and mortality. PMID:26321810

  18. Shaking Out Clues to Autoimmune Disease

    MedlinePlus

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

  19. Questions and Answers on Autoimmunity and Autoimmune Diseases

    MedlinePlus

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

  20. Viral triggers for autoimmunity: is the 'glass of molecular mimicry' half full or half empty?

    PubMed

    Christen, Urs; Hintermann, Edith; Holdener, Martin; von Herrath, Matthias G

    2010-02-01

    In this review we want to consider some of the requirements for autoimmune disease to develop and how this may be reproduced in animal models. Besides a genetic predisposition, environmental triggering factors seem to play a central role in the etiology of many autoimmune diseases. In theory, a structural similarity or identity between the host and an invading pathogen might cause the immune system of the host to react not only to the pathogen but also to self-components. However, in order for such a process of molecular mimicry to induce autoimmunity the mechanisms of maintaining tolerance or ignorance to the self-components need to be circumvented. Subsequently, in order to advance autoimmunity to overt autoimmune disease the frequency and avidity of autoaggressive lymphocytes has to be of sufficient magnitude. Intuitively, one would assume that tolerance might be stronger to identical structures than to structures that just share a certain degree of similarity. Self-reactive lymphocytes with high-avidity are more likely to be deleted or functionally silenced by central and/or peripheral tolerance mechanisms. Thus, perfect mimicry between identical structures might fail in inducing autoimmunity because of efficient tolerance mechanisms. In contrast, imperfect mimicry between similar but not identical structures might on one hand circumvent tolerance but on the other hand result in the generation of lymphocytes with only low- to intermediate avidity. Here we examine animal models that use the concept of molecular mimicry as a potential mechanism for inducing or accelerating autoimmunity. We focus on the RIP-LCMV model for type 1 diabetes and the novel cytochrome P450 2D6 (CYP2D6) model for autoimmune hepatitis, which use either identical or similar triggering and target antigens. PMID:19716269

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

    PubMed

    Rahat, Michal A; Shakya, Jivan

    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

  2. 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

  3. Immunomodulatory vaccines against autoimmune diseases.

    PubMed

    Sela, Michael

    2006-01-01

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

  4. Immunomodulatory vaccination in autoimmune disease.

    PubMed

    Urbanek-Ruiz, Irene; Ruiz, Pedro J; Steinman, Lawrence; Fathman, C Garrison

    2002-06-01

    The development of vaccines is arguably the most significant achievement in medicine to date. The practice of innoculation with the fluid from a sore to protect from a disease actually dates back to ancient China; however, with the introduction of Jenner's smallpox vaccine, and greater understanding of the immune system, vaccines have become specific and systematic. Traditional vaccines have used killed pathogens (hepatitis A and the Salk polio vaccines), immunogenic subunits of a given pathogen (hepatitis B subunit vaccine), or live attenuated pathogens (measles, mumps, rubella, Sabin polio vaccines) to generate protective immunity. Currently, a new generation of vaccines that use the genetic material of a pathogen to elicit protective immunity are being developed. Although the most widespread and successful use of vaccines today remains in the arena of infectious diseases, manipulations of immune responses to protect against cancers, neurologic diseases, and autoimmunity are being explored rigorously. PMID:12092460

  5. 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

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

    PubMed

    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 possibility

  7. Rett syndrome: An autoimmune disease?

    PubMed

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

    2016-04-01

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

  8. Amplification of autoimmune disease by infection

    PubMed Central

    Posnett, David N; Yarilin, Dmitry

    2005-01-01

    Reports of infection with certain chronic persistent microbes (herpesviruses or Chlamydiae) in human autoimmune diseases are consistent with the hypothesis that these microbes are reactivated in the setting of immunodeficiency and often target the site of autoimmune inflammation. New experimental animal models demonstrate the principle. A herpesvirus or Chlamydia species can be used to infect mice with induced transient autoimmune diseases. This results in increased disease severity and even relapse. The evidence suggests that the organisms are specifically imported to the inflammatory sites and cause further tissue destruction, especially when the host is immunosuppressed. We review the evidence for the amplification of autoimmune inflammatory disease by microbial infection, which may be a general mechanism applicable to many human diseases. We suggest that patients with autoimmune disorders receiving immunosuppressing drugs should benefit from preventive antiviral therapy. PMID:15743493

  9. Molecular diagnosis of autoimmune blistering diseases.

    PubMed

    Tsuruta, Daisuke; Dainichi, Teruki; Hamada, Takahiro; Ishii, Norito; Hashimoto, Takashi

    2013-01-01

    Autoimmune bullous diseases are the best-characterized autoimmune skin diseases. Molecular diagnosis of these diseases has become possible due to the identification of their target autoantigens over the past three decades. In this review, we summarize methodology for categorizing autoimmune bullous diseases by means of combinations of direct and indirect immunofluorescence techniques using normal human skin sections, rat bladder sections and COS7 cells transfected with desmocollins 1-3 encoded vectors, enzyme-linked immunosorbent assays and immunoblotting with normal human epidermal extracts, dermal extracts, purified proteins from cell cultures and recombinant proteins. PMID:23325635

  10. Phosphodiesterase 4-targeted treatments for autoimmune diseases

    PubMed Central

    2013-01-01

    Advancements in phosphodiesterase (PDE)-targeted therapies have shown promise in recent years for treating patients with a variety of autoimmune diseases. This review summarizes the development of PDE4 inhibitors and the associated literature with a focus on treatments for autoimmune diseases. After the initial investigations of the prototypic PDE inhibitor, rolipram, more selective inhibitors targeting the PDE4 isozyme have been developed. With phase II and phase III clinical trials currently underway to evaluate the safety and efficacy of the latest generation of PDE4 inhibitors, namely apremilast, a new class of treatments may be around the corner for patients suffering from chronic, autoimmune diseases. PMID:23557064

  11. 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. PMID:26387449

  12. Sialic acids and autoimmune disease.

    PubMed

    Mahajan, Vinay S; Pillai, Shiv

    2016-01-01

    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

  13. Epidemiology of Autoimmune Diseases in Denmark

    PubMed Central

    Eaton, William W.; Rose, Noel R.; Kalaydjian, Amanda; Pedersen, Marianne G.; Mortensen, Preben Bo

    2007-01-01

    An epidemiologic study of the autoimmune diseases taken together has not been done heretofore. The National Patient Register of Denmark is used to estimate population prevalence of 31 possible or probable autoimmune diseases. Record linkage is used to estimate 465 pairwise comorbidities in individuals among the 31 diseases, and familial aggregation among sibs, parents and offspring. The prevalence of any of the 31 diseases in the population is more than 5%. Within individuals, there is extensive comorbidity across the 31 diseases. Within families, aggregation is strongest for individual diseases, and weak across diseases. These data confirm the importance of the autoimmune diseases as a group, and suggest that common etiopathologies exist among them. PMID:17582741

  14. Role of neutrophils in systemic autoimmune diseases

    PubMed Central

    2013-01-01

    Neutrophils have emerged as important regulators of innate and adaptive immune responses. Recent evidence indicates that neutrophils display marked abnormalities in phenotype and function in various systemic autoimmune diseases, and may play a central role in initiation and perpetuation of aberrant immune responses and organ damage in these conditions. This review discusses the putative roles that neutrophils and aberrant neutrophil cell death play in the pathogenesis of various systemic autoimmune diseases, including systemic lupus erythematosus, small vessel vasculitis and rheumatoid arthritis. PMID:24286137

  15. Pregnancy and autoimmune connective tissue diseases.

    PubMed

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

    2016-02-01

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

  16. [Autoimmune connective tissue diseases and vaccination].

    PubMed

    Więsik-Szewczyk, Ewa; Jahnz-Różyk, Karina

    2015-01-01

    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. PMID:27259225

  17. 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)

  18. MicroRNA in autoimmunity and autoimmune diseases

    PubMed Central

    Pauley, Kaleb M.; Cha, Seunghee; Chan, Edward K.L.

    2009-01-01

    MicroRNAs (miRNAs) are small conserved non-coding RNA molecules that post-transcriptionally regulate gene expression by targeting the 3′ untranslated region (UTR) of specific messenger RNAs (mRNAs) for degradation or translational repression. miRNA-mediated gene regulation is critical for normal cellular functions such as the cell cycle, differentiation, and apoptosis, and as much as one-third of human mRNAs may be miRNA targets. Emerging evidence has demonstrated that miRNAs play a vital role in the regulation of immunological functions and the prevention of autoimmunity. Here we review the many newly discovered roles of miRNA regulation in immune functions and in the development of autoimmunity and autoimmune disease. Specifically, we discuss the involvement of miRNA regulation in innate and adaptive immune responses, immune cell development, T regulatory cell stability and function, and differential miRNA expression in rheumatoid arthritis and systemic lupus erythematosus. PMID:19303254

  19. 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. PMID:25687121

  20. Cardiovascular disease in autoimmune rheumatic diseases.

    PubMed

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

    2013-08-01

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

  1. 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. PMID:25595571

  2. Neuromyelitis optica spectrum disorders without and with autoimmune diseases

    PubMed Central

    2014-01-01

    Background Neuromyelitis optica spectrum disorder (NMOSD) can coexist with non-organ-specific or organ-specific autoimmune diseases. The aim of this study was to investigate and compare the features between NMOSD without and with autoimmune diseases, and NMOSD with non-organ-specific and organ-specific autoimmune diseases. Methods One hundred and fifty five NMOSD patients without autoimmune diseases (n = 115) and with autoimmune diseases (n = 40) were enrolled. NMOSD with autoimmune diseases were divided by organ-specific autoimmune diseases. The clinical, laboratory and magnetic resonance imaging features between two groups were assessed. Results Motor deficit was less frequent in NMOSD patients with non-organ-specific autoimmune diseases (p = 0.024). Cerebrospinal fluid white blood cell and protein, serum C-reactive protein and immunoglobulin G were lower in NMOSD patients without autoimmune diseases, while several autoantibodies seropositivity and thyroid indexes were significantly higher in NMOSD patients with autoimmune diseases (p < 0.05). No difference was found in other clinical and laboratory characteristics between different NMOSD subtypes (p > 0.05). NMOSD patients with autoimmune diseases had higher brain abnormalities than NMOSD without autoimmune diseases (p < 0.001). Conclusions The characteristics between NMOSD without and with autoimmune diseases were similar. NMOSD with autoimmune diseases have high frequency of brain abnormalities. PMID:25135481

  3. Epigenetics changes associated to environmental triggers in autoimmunity.

    PubMed

    Cañas, Carlos A; Cañas, Felipe; Bonilla-Abadía, Fabio; Ospina, Fabio E; Tobón, Gabriel J

    2016-02-01

    Autoimmune diseases (AIDs) are chronic conditions initiated by the loss of immunological tolerance to self-antigens and represent a heterogeneous group of disorders that affect specific target organs or multiple organs in different systems. While the pathogenesis of AID remains unclear, its aetiology is multifunctional and includes a combination of genetic, epigenetic, immunological and environmental factors. In AIDs, several epigenetic mechanisms are defective including DNA demethylation, abnormal chromatin positioning associated with autoantibody production and abnormalities in the expression of RNA interference (RNAi). It is known that environmental factors may interfere with DNA methylation and histone modifications, however, little is known about epigenetic changes derived of regulation of RNAi. An approach to the known environmental factors and the mechanisms that alter the epigenetic regulation in AIDs (with emphasis in systemic lupus erythematosus, the prototype of systemic AID) are showed in this review. PMID:26369426

  4. Molecular Mimicry as a Mechanism of Autoimmune Disease

    PubMed Central

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

    2012-01-01

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

  5. Macrophage activation syndrome in autoimmune disease.

    PubMed

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

    2010-01-01

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

  6. Fibrosis in autoimmune and cholestatic liver disease.

    PubMed

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

    2011-04-01

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

  7. 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.

  8. 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. PMID:26117595

  9. The immunofluorescence techniques in the diagnosis of endocrine autoimmune diseases.

    PubMed

    Betterle, Corrado; Zanchetta, Renato

    2012-08-01

    In the study of autoimmune diseases, the laboratory plays a very important role. We describe the immunofluorescence techniques (direct, indirect, complement-fixing, double) for determining the presence of autoantibodies and their role in the autoimmune endocrine diseases. PMID:26000129

  10. Apoptosis in autoimmune and non-autoimmune thyroid disease.

    PubMed

    Ludgate, M; Jasani, B

    1997-06-01

    The elimination of autoreactive T cells in the thymus involves the process of programmed cell death. Animal model studies, using the lpr and gld strains of mice, have identified FAS receptor (FAS) and FAS ligand (FAS-L) as important components of this mechanism. Whether FAS and FAS-L are also implicated in the autoimmune destruction of a target organ, such as the thyroid, remain hypothetical. An accompanying paper in this issue has addressed the question by FACS and immunocytochemical analysis of FAS expression and apoptosis in thyrocytes grown in culture and in intact thyroid tissues obtained from Hashimoto's thyroiditis, multinodular goitre and Graves' disease. The overall results suggest that the degree of FAS expression on target cells may determine their sensitivity to T-cell mediated cytotoxicity in the absence of perforin or granzyme directed apoptosis mechanisms. PMID:9274519

  11. MicroRNAs in Autoimmune Diseases

    PubMed Central

    Qu, Zigang; Li, Wenhui; Fu, Baoquan

    2014-01-01

    Autoimmune diseases (ADs) are featured by body's immune responses being directed towards its own specific target organs or multiple organ systems, causing persistent inflammation and consequent tissue damage. miRNAs are small noncoding RNAs in a size of approximately 22 nt that play important regulatory roles in many organisms by cleavage or translational inhibition of targeted mRNAs. Many miRNAs are reported to be differentially expressed in ADs and may play a pivotal role in regulating immune responses and autoimmunity. In this review, current research progress in the miRNAs in ADs was elucidated. PMID:24991561

  12. 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

  13. 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

  14. 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

  15. Complicating autoimmune diseases in myasthenia gravis: a review

    PubMed Central

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

    2015-01-01

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

  16. [Glycosylation of autoantibodies in autoimmunes diseases].

    PubMed

    Goulabchand, R; Batteux, F; Guilpain, P

    2013-12-01

    Protein glycosylation is one of the most common post-translational modifications, involved in the well described protein biosynthesis process. Protein glycosylation seems to play a major role in the pathogenesis of auto-immune diseases. Herein are described the main alterations of autoantibody glycosylation associated with autoimmunes diseases such as rheumatoid arthritis, IgA glomerulonephritis, Schoenlein-Henoch purpura, Sjögren's syndrome, systemic scleroderma, systemic lupus erythematosus, myasthenia gravis and granulomatosis with polyangiitis (Wegener). Molecular identification of altered immunoglobulin glycosylation could lead to a better understanding of the pathogenesis of those diseases, might allow an evaluation of their biological activity and could even be a new therapeutic target. PMID:24139501

  17. 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

  18. Achalasia and thyroid disease: possible autoimmune connection?

    PubMed

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

    2012-12-01

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

  19. Activation of benign autoimmunity as both tumor and autoimmune disease immunotherapy: a comprehensive review.

    PubMed

    Cohen, Irun R

    2014-11-01

    Here, I consider how benign autoimmunity, the immunological homunculus, can be used to reinstate the healthy regulation of inflammation in both autoimmune diseases and in tumor immunotherapy. Different autoimmune diseases manifest clinically distinct phenotypes, but, in general, they all result from the transition of benign, healthy recognition of key body molecules into a damaging effector reaction. Tumors, in contrast to autoimmune diseases, grow by subverting the immune system into supporting and protecting the growing tumor from immune surveillance. Therefore our therapeutic aim in autoimmune disease is to induce the immune system to down-regulate the specific autoimmune effector reaction that causes the disease; in tumor immunotherapy, on the contrary, we aim to deprive the growing tumor of its illicit activation of immune suppression and to unleash an autoimmune disease targeted to the tumor. The recent success of anti-PD1 and anti-CTLR4 treatments exemplify the reinstatement of tumor autoimmunity subsequent to inhibition of immune suppression. With regard to the therapy of autoimmune diseases, I cite examples of immune system down-regulation of autoimmune diseases by T cell vaccination or HSP60 peptide treatment. Inducing the immune system to regulate itself is safer than global immune suppression and may be more effective in the long run. PMID:24924121

  20. Autoimmune Inner Ear Disease (AIED)

    MedlinePlus

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

  1. 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

  2. [Vaccinations in patients with autoimmune diseases].

    PubMed

    Bühler, Silja; Hatz, Christoph

    2016-01-01

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

  3. 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

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

    PubMed

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

    2011-08-11

    To specify the incidence and risk factors for secondary autoimmune diseases (ADs) after HSCT for a primary AD, we retrospectively analyzed AD patients treated by HSCT reported to EBMT from 1995 to 2009 with at least 1 secondary AD (cases) and those without (controls). After autologous HSCT, 29 of 347 patients developed at least 1 secondary AD within 21.9 (0.6-49) months and after allogeneic HSCT, 3 of 16 patients. The observed secondary ADs included: autoimmune hemolytic anemia (n = 3), acquired hemophilia (n = 3), autoimmune thrombocytopenia (n = 3), antiphospholipid syndrome (n = 2), thyroiditis (n = 12), blocking thyroid-stimulating hormone receptor antibody (n = 1), Graves disease (n = 2), myasthenia gravis (n = 1), rheumatoid arthritis (n = 2), sarcoidosis (n = 2), vasculitis (n = 1), psoriasis (n = 1), and psoriatic arthritis (n = 1). After autologous HSCT for primary AD, the cumulative incidence of secondary AD was 9.8% ± 2% at 5 years. Lupus erythematosus as primary AD, and antithymocyte globulin use plus CD34(+) graft selection were important risk factors for secondary AD by multivariate analysis. With a median follow-up of 6.2 (0.54-11) years after autologous HSCT, 26 of 29 patients with secondary AD were alive, 2 died during their secondary AD (antiphospholipid syndrome, hemophilia), and 1 death was HSCT-related. This European multicenter study underlines the need for careful management and follow-up for secondary AD after HSCT. PMID:21596847

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

    PubMed Central

    Lin, Mei; Wang, Zuomin; Han, Xiaozhe

    2015-01-01

    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. PMID:26236565

  6. Environmentally induced autoimmune diseases: potential mechanisms.

    PubMed Central

    Rao, T; Richardson, B

    1999-01-01

    Environmental and other xenobiotic agents can cause autoimmunity. Examples include drug-induced lupus, toxic oil syndrome, and contaminated l-tryptophan ingestion. Numerous mechanisms, based on (italic)in vitro(/italic) evidence and animal models, have been proposed to explain how xenobiotics induce or accelerate autoimmunity. The majority of these can be divided into three general categories. The first is those inhibiting the processes involved in establishing tolerance by deletion. Inhibiting deletion can result in the release of newly generated autoreactive cells into the periphery. The second mechanism is the modification of gene expression in the cells participating in the immune response, permitting lymphocytes to respond to signals normally insufficient to initiate a response or allowing the antigen-presenting cells to abnormally stimulate a response. Abnormal gene expression can thus disrupt tolerance maintained by suppression or anergy, permitting activation of autoreactive cells. The third is the modification of self-molecules such that they are recognized by the immune system as foreign. Examples illustrating these concepts are presented, and related mechanisms that have the potential to similarly affect the immune system are noted. Some mechanisms appear to be common to a variety of agents, and different mechanisms appear to produce similar diseases. However, evidence that any of these mechanisms are actually responsible for xenobiotic-induced human autoimmune disease is still largely lacking, and the potential for numerous and as yet unidentified mechanisms also exists. PMID:10502539

  7. The Dopaminergic System in Autoimmune Diseases

    PubMed Central

    Pacheco, Rodrigo; Contreras, Francisco; Zouali, Moncef

    2014-01-01

    Bidirectional interactions between the immune and the nervous systems are of considerable interest both for deciphering their functioning and for designing novel therapeutic strategies. The past decade has brought a burst of insights into the molecular mechanisms involved in neuroimmune communications mediated by dopamine. Studies of dendritic cells (DCs) revealed that they express the whole machinery to synthesize and store dopamine, which may act in an autocrine manner to stimulate dopamine receptors (DARs). Depending on specific DARs stimulated on DCs and T cells, dopamine may differentially favor CD4+ T cell differentiation into Th1 or Th17 inflammatory cells. Regulatory T cells can also release high amounts of dopamine that acts in an autocrine DAR-mediated manner to inhibit their suppressive activity. These dopaminergic regulations could represent a driving force during autoimmunity. Indeed, dopamine levels are altered in the brain of mouse models of multiple sclerosis (MS) and lupus, and in inflamed tissues of patients with inflammatory bowel diseases or rheumatoid arthritis (RA). The distorted expression of DARs in peripheral lymphocytes of lupus and MS patients also supports the importance of dopaminergic regulations in autoimmunity. Moreover, dopamine analogs had beneficial therapeutic effects in animal models, and in patients with lupus or RA. We propose models that may underlie key roles of dopamine and its receptors in autoimmune diseases. PMID:24711809

  8. 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

  9. Targeting the Fc receptor in autoimmune disease

    PubMed Central

    Li, Xinrui; Kimberly, Robert P

    2014-01-01

    Introduction The Fc receptors and their interaction with immunoglobulin and innate immune opsonins such as CRP are key players in humoral and cellular immune responses. As the effector mechanism for some therapeutic monoclonal antibodies and often a contributor to the pathogenesis and progression of autoimmunity, FcRs are promising targets for treating autoimmune diseases. Areas covered This review discusses the nature of different Fc receptors and the various mechanisms of their involvement in initiating and modulating immunocyte functions and their biological consequences. It describes a range of current strategies in targeting Fc receptors and manipulating their interaction with specific ligands while presenting the pros and cons of these approaches. This review also discusses potential new strategies including regulation of FcR expression and receptor cross-talk. Expert opinion Fc receptors are appealing targets in the treatment of inflammatory autoimmune diseases. However, there are still knowledge limitations and technical challenges, the most important being a better understanding of the individual roles of each of the Fc receptors and enhancement of the specificity in targeting particular cell types and specific Fc receptors. PMID:24521454

  10. Fetal microchimeric cells in autoimmune thyroid diseases

    PubMed Central

    Lepez, Trees; Vandewoestyne, Mado; Deforce, Dieter

    2013-01-01

    Autoimmune thyroid diseases (AITD) show a female predominance, with an increased incidence in the years following parturition. Fetal microchimerism has been suggested to play a role in the pathogenesis of AITD. However, only the presence of fetal microchimeric cells in blood and in the thyroid gland of these patients has been proven, but not an actual active role in AITD. Is fetal microchimerism harmful for the thyroid gland by initiating a Graft versus Host reaction (GvHR) or being the target of a Host versus Graft reaction (HvGR)? Is fetal microchimerism beneficial for the thyroid gland by being a part of tissue repair or are fetal cells just innocent bystanders in the process of autoimmunity? This review explores every hypothesis concerning the role of fetal microchimerism in AITD. PMID:23723083

  11. 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. PMID:22744631

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

    PubMed Central

    Dow, Coad Thomas

    2012-01-01

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

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

    PubMed

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

    2016-01-01

    The prevalence of celiac disease autoimmunity or tissue transglutaminase autoantibodies (TGA) amongst patients with type 1 diabetes (T1D) and autoimmune thyroid disease (AITD) in the Chinese population remains unknown. This study examined the rate of celiac disease autoimmunity amongst patients with T1D and AITD in the Chinese population. The study included 178 patients with type 1 diabetes and 119 with AITD where 36 had both T1D and AITD, classified as autoimmune polyglandular syndrome type 3 variant (APS3v). The study also included 145 patients with type 2 diabetes (T2D), 97 patients with non-autoimmune thyroid disease (NAITD), and 102 healthy controls. Serum islet autoantibodies, thyroid autoantibodies and TGA were measured by radioimmunoassay. TGA positivity was found in 22% of patients with either type 1 diabetes or AITD, much higher than that in patients with T2D (3.4%; p< 0.0001) or NAITD (3.1%; P < 0.0001) or healthy controls (1%; p<0.0001). The patients with APS3v having both T1D and AITD were 36% positive for TGA, significantly higher than patients with T1D alone (p = 0.040) or with AITD alone (p = 0.017). T1D and AITD were found to have a 20% and 30% frequency of overlap respectively at diagnosis. In conclusion, TGA positivity was high in the Chinese population having existing T1D and/or AITD, and even higher when both diseases were present. Routine TGA screening in patients with T1D or AITD will be important to early identify celiac disease autoimmunity for better clinical care of patients. PMID:27427767

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

    PubMed Central

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

    2016-01-01

    The prevalence of celiac disease autoimmunity or tissue transglutaminase autoantibodies (TGA) amongst patients with type 1 diabetes (T1D) and autoimmune thyroid disease (AITD) in the Chinese population remains unknown. This study examined the rate of celiac disease autoimmunity amongst patients with T1D and AITD in the Chinese population. The study included 178 patients with type 1 diabetes and 119 with AITD where 36 had both T1D and AITD, classified as autoimmune polyglandular syndrome type 3 variant (APS3v). The study also included 145 patients with type 2 diabetes (T2D), 97 patients with non-autoimmune thyroid disease (NAITD), and 102 healthy controls. Serum islet autoantibodies, thyroid autoantibodies and TGA were measured by radioimmunoassay. TGA positivity was found in 22% of patients with either type 1 diabetes or AITD, much higher than that in patients with T2D (3.4%; p< 0.0001) or NAITD (3.1%; P < 0.0001) or healthy controls (1%; p<0.0001). The patients with APS3v having both T1D and AITD were 36% positive for TGA, significantly higher than patients with T1D alone (p = 0.040) or with AITD alone (p = 0.017). T1D and AITD were found to have a 20% and 30% frequency of overlap respectively at diagnosis. In conclusion, TGA positivity was high in the Chinese population having existing T1D and/or AITD, and even higher when both diseases were present. Routine TGA screening in patients with T1D or AITD will be important to early identify celiac disease autoimmunity for better clinical care of patients. PMID:27427767

  15. Role of Helicobacter pylori infection in autoimmune systemic rheumatic diseases.

    PubMed

    Radić, Mislav

    2014-09-28

    The relationship between infection and autoimmunity has been increasingly defined over the last 20 years. The systemic rheumatic diseases are characterized by dysregulation of the immune system resulting in a loss of tolerance to self-antigen. The exact etiology for the majority of these diseases is unknown; however, a complex combination of host and environmental factors are believed to play a pivotal role. Helicobacter pylori (H. pylori) is one of the most widely studied infectious agents proposed as agents triggering autoimmune response. The persistent presence of H. pylori in the gastric mucosa results in chronic immune system activation with ongoing cytokine signaling, infiltration of gastric mucosa by neutrophils, macrophages, lymphocytes, as well as production of antibodies and effector T-cells. Various mechanisms have been proposed in an attempt to explain the extra-intestinal manifestations of H. pylori infections. These include: molecular mimicry, endothelial cell damage, superantigens and microchimerism. I performed a systematic literature review using the keywords "rheumatoid arthritis", "Sjögren's syndrome", "systemic sclerosis", "systemic lupus erythematosus", "Helicobacter pylori" and "pathogenesis". A systematic literature search was carried out in MEDLINE; EMBASE; Cochrane Library and ACR/EULAR meeting abstracts. In systemic rheumatic diseases H. pylori infection prevalence alone should not be expected to provide sufficient evidence for or against a pathologic role in the disease. In this article I review studies examining the potential involvement of H. pylori infection in autoimmune systemic rheumatic diseases. Further studies of the immunological response to H. pylori and its role in the pathogenesis of systemic rheumatic diseases are warranted. PMID:25278681

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

    PubMed

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

    2016-01-01

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

  17. 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

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

    PubMed

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

    2016-01-01

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

  19. Role of extracellular vesicles in autoimmune diseases.

    PubMed

    Turpin, Delphine; Truchetet, Marie-Elise; Faustin, Benjamin; Augusto, Jean-François; Contin-Bordes, Cécile; Brisson, Alain; Blanco, Patrick; Duffau, Pierre

    2016-02-01

    Extracellular vesicles (EVs) consist of exosomes released upon fusion of multivesicular bodies with the cell plasma membrane and microparticles shed directly from the cell membrane of many cell types. EVs can mediate cell-cell communication and are involved in many processes including inflammation, immune signaling, angiogenesis, stress response, senescence, proliferation, and cell differentiation. Accumulating evidence reveals that EVs act in the establishment, maintenance and modulation of autoimmune processes among several others involved in cancer and cardiovascular complications. EVs could also present biomedical applications, as disease biomarkers and therapeutic targets or agents for drug delivery. PMID:26554931

  20. Treating prolactinoma can prevent autoimmune diseases.

    PubMed

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

    2015-04-01

    Prolactin (PRL) is a pleiotropic hormone; in addition to a wide variety of endocrine effects, PRL also exhibits immunostimulating effects. Therefore, there is increasing evidence linking PRL with a large number of systemic and organ specific autoimmune diseases. Herein, we report the case of an adolescent girl diagnosed with multiple sclerosis (MS) occurring in the context of untreated prolactinoma evolving since childhood. This raises the exciting question of the involvement of PRL in the pathogenesis of MS. It is likely that early treatment of hyperprolactinemia in this case would have significantly reduced the risk of developing MS or even prevented its occurrence. PMID:25468803

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

    PubMed Central

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

    2016-01-01

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

  2. Immune-Neuroendocrine Interactions and Autoimmune Diseases

    PubMed Central

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

    2006-01-01

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

  3. 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

  4. 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. PMID:25447795

  5. A Genomic Approach to Human Autoimmune Diseases

    PubMed Central

    Pascual, Virginia; Chaussabel, Damien; Banchereau, Jacques

    2010-01-01

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

  6. 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

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

    PubMed Central

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

    2015-01-01

    Systemic autoimmune diseases are a group of heterogeneous disorders caused by both genetic and environmental factors. Although numerous causal genes have been identified by genome-wide association studies (GWAS), these susceptibility genes are correlated to a relatively low disease risk, indicating that environmental factors also play an important role in the pathogenesis of disease. The intestinal microbiome, as the main symbiotic ecosystem between the host and host-associated microorganisms, has been demonstrated to regulate the development of the body’s immune system and is likely related to genetic mutations in systemic autoimmune diseases. Next-generation sequencing (NGS) technology, with high-throughput capacity and accuracy, provides a powerful tool to discover genomic mutations, abnormal transcription and intestinal microbiome identification for autoimmune diseases. In this review, we briefly outlined the applications of NGS in systemic autoimmune diseases. This review may provide a reference for future studies in the pathogenesis of systemic autoimmune diseases. PMID:26432094

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

    PubMed

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

    2015-08-01

    Systemic autoimmune diseases are a group of heterogeneous disorders caused by both genetic and environmental factors. Although numerous causal genes have been identified by genome-wide association studies (GWAS), these susceptibility genes are correlated to a relatively low disease risk, indicating that environmental factors also play an important role in the pathogenesis of disease. The intestinal microbiome, as the main symbiotic ecosystem between the host and host-associated microorganisms, has been demonstrated to regulate the development of the body's immune system and is likely related to genetic mutations in systemic autoimmune diseases. Next-generation sequencing (NGS) technology, with high-throughput capacity and accuracy, provides a powerful tool to discover genomic mutations, abnormal transcription and intestinal microbiome identification for autoimmune diseases. In this review, we briefly outlined the applications of NGS in systemic autoimmune diseases. This review may provide a reference for future studies in the pathogenesis of systemic autoimmune diseases. PMID:26432094

  9. 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. PMID:27077110

  10. 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

  11. 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

  12. New Genetic Insights from Autoimmune Thyroid Disease

    PubMed Central

    Davies, Terry F.; Latif, Rauf; Yin, Xiaoming

    2012-01-01

    The autoimmune thyroid diseases (AITDs) (Graves' disease and Hashimoto's thyroiditis) are complex genetic diseases which most likely have more than 20 genes contributing to the clinical phenotypes. To date, the genes known to be contributing fall into two categories: immune regulatory genes (including HLA, CTLA4, PTPN22, CD40, CD25, and FCRL3) and thyroid-specific genes (TG and TSHR). However, none of these genes contribute more than a 4-fold increase in risk of developing one of these diseases, and none of the polymorphisms discovered is essential for disease development. Hence, it appears that a variety of different gene interactions can combine to cause the same clinical disease pattern, but the contributing genes may differ from patient to patient and from population to population. Furthermore, this possible mechanism leaves open the powerful influence of the environment and epigenetic modifications of gene expression. For the clinician, this means that genetic profiling of such patients is unlikely to be fruitful in the near future. PMID:22530160

  13. 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

  14. Vitamin D and autoimmune thyroid diseases: facts and unresolved questions.

    PubMed

    Bizzaro, Giorgia; Shoenfeld, Yehuda

    2015-02-01

    Vitamin D deficiency (levels lower than 20 ng/ml) is becoming a global health problem, since it is increasingly represented even among healthy subjects. Vitamin D, as an environmental factor, is involved in many biological processes, like perception of chronic pain and response to infections. In recent years, evidence has emerged pointing to an involvement of vitamin D in the development of many autoimmune diseases, and a severe vitamin D deficiency has been especially demonstrated in patients affected with autoimmune thyroid disease (AITD). Low levels of vitamin D were found associated with antithyroid antibody presence, abnormal thyroid function, increased thyroid volume, increased TSH levels, and adverse pregnancy outcome in women with AITD. Vitamin D mediates its effect through binding to vitamin D receptor (VDR), which is harbored on many human immune cells, and in this way is able to modulate immune cells activity, triggering both innate and adaptive immune responses. As VDR gene polymorphisms were found to associate with AITD, the evidence links vitamin D deficiency to AITD either through gene polymorphism or by environmental factors (lack of dietary uptake and sun exposure). Vitamin D supplementation may be offered to AITD patients, but further research is needed to define whether it should be introduced in clinical practice. PMID:25407646

  15. Novel Therapies for Thyroid Autoimmune Diseases.

    PubMed

    Fallahi, Poupak; Ferrari, Silvia Martina; Elia, Giusy; Nasini, Francesco; Colaci, Michele; Giuggioli, Dilia; Vita, Roberto; Benvenga, Salvatore; Ferri, Clodoveo; Antonelli, Alessandro

    2016-06-01

    C-X-C chemokine receptor (CXCR)3 and its interferon(IFN)γ-dependent chemokines (CXCL10, CXCL9, CXCL11) are implicated in the immune-pathogenesis of autoimmune thyroiditis (AT), Graves disease (GD) and Graves Ophthalmopathy (GO). In tissue, recruited Th1 lymphocytes produce IFNγ, enhancing the tissue secretion of IFNγ-inducible chemokines, initiating and perpetuating the autoimmune process. Patients with AT (with hypothyroidism), and with GO and GD, particularly in the active phase, have high IFNγ-inducible chemokines. Peroxisome proliferator-activated receptor (PPAR)γ or -α agonists and methimazole exert an immune-modulation on CXCR3 chemokines in AT, GD and GO. Other studies are ongoing to evaluate new molecules acting as antagonists of CXCR3, or blocking CXCL10, in Hashimoto thyroiditis (HT), GD and GO. Recently, novel molecules targeting the various agents involved in the pathogenesis of GO, such as rituximab, have been proposed as an alternative to corticosteroids. However, randomized and controlled studies are needed to generalize these interesting results. PMID:26900630

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

    PubMed Central

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

    1998-01-01

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

  17. Selected Aspects in the Pathogenesis of Autoimmune Diseases

    PubMed Central

    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. PMID:26300591

  18. Recurrence of autoimmune liver diseases after liver transplantation

    PubMed Central

    Faisal, Nabiha; Renner, Eberhard L

    2015-01-01

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

  19. Ocular Involvement in Systemic Autoimmune Diseases.

    PubMed

    Generali, Elena; Cantarini, Luca; Selmi, Carlo

    2015-12-01

    Eye involvement represents a common finding in patients with systemic autoimmune diseases, particularly rheumatoid arthritis, Sjogren syndrome, seronegative spondyloarthropathy, and antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. The eye is a privileged immune site but commensal bacteria are found on the ocular surface. The eye injury may be inflammatory, vascular or infectious, as well as iatrogenic, as in the case of hydroxychloroquine, chloroquine, corticosteroids, and bisphosphonates. Manifestations may affect different components of the eye, with episcleritis involving the episclera, a thin layer of tissue covering the sclera; scleritis being an inflammation of the sclera potentially leading to blindness; keratitis, referring to corneal inflammation frequently associated with scleritis; and uveitis as the inflammation of the uvea, including the iris, ciliary body, and choroid, subdivided into anterior, posterior, or panuveitis. As blindness may result from the eye involvement, clinicians should be aware of the possible manifestations and their management also independent of the ophthalmologist opinion as the therapeutic approach generally points to the underlying diseases. In some cases, the eye involvement may have a diagnostic implication, as for episcleritis in rheumatoid arthritis, or acute anterior uveitis in seronegative spondyloarthritis. Nonetheless, some conditions lack specificity, as in the case of dry eye which affects nearly 30 % of the general population. The aim of this review is to elucidate to non-ophthalmologists the major ocular complications of rheumatic diseases and their specific management and treatment options. PMID:26494481

  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. Modelling autoimmune rheumatic disease: a likelihood rationale.

    PubMed

    Ulvestad, E

    2003-07-01

    Immunoglobulins (Igs) and autoantibodies are commonly tested in sera from patients with suspected rheumatic disease. To evaluate the clinical utility of the tests in combination, we investigated sera from 351 patients with autoimmune rheumatic disease (ARD) rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and Sjögren's syndrome (SS) and 96 patients with nonautoimmune rheumatic disease (NAD) (fibromyalgia, osteoarthritis, etc.). Antinuclear antibodies (ANA), rheumatoid factor (RF), antibodies against DNA and extractable nuclear antigens (anti-ENA), IgG, IgA and IgM were measured for all patients. Logistic regression analysis of test results was used to calculate each patient's probability for belonging to the ARD or NAD group as well as likelihood ratios for disease. Test accuracy was investigated using receiver-operating characteristic (ROC) plots and nonparametric ROC analysis. Neither concentrations of IgG, IgA, IgM, anti-DNA nor anti-ENA gave a significant effect on diagnostic outcome. Probabilities for disease and likelihood ratios calculated by combining RF and ANA performed significantly better at predicting ARD than utilization of the diagnostic tests in isolation (P < 0.001). At a cut-off level of P = 0.73 and likelihood ratio = 1, the logistic model gave a specificity of 93% and a sensitivity of 75% for the differentiation between ARD and NAD. When compared at the same level of specificity, ANA gave a sensitivity of 37% and RF gave a sensitivity of 56.6%. Dichotomizing ANA and RF as positive or negative did not reduce the performance characteristics of the model. Combining results obtained from serological analysis of ANA and RF according to this model will increase the diagnostic utility of the tests in rheumatological practice. PMID:12828565

  2. Autoimmune thyroid disease in systemic lupus erythematosus

    PubMed Central

    Pyne, D; Isenberg, D

    2002-01-01

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

  3. Measurement of disease severity in cutaneous autoimmune diseases

    PubMed Central

    2013-01-01

    The development of disease-specific outcome instruments for several autoimmune skin diseases including cutaneous lupus erythematosus (CLE), dermatomyositis, vitiligo, pemphigus and alopecia areata has facilitated the objective assessment of disease in clinical trials. Validation of these instruments provides reliable tools to measure disease severity and therapeutic effect in clinical studies. However, the existence of multiple outcome measures for each disease and the lack of uniformity between studies has created a challenge in comparing results across trials. Efforts to address this issue include the Core Outcome Measures in Effectiveness Trials (COMET) initiative and international meetings directed at reaching a consensus. Other challenges with the use of outcome measures include difficulties measuring change in mild disease, measuring response in topical studies, and capturing disease activity in skin with extensive post-inflammatory hyperpigmentation. PMID:23755366

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

    PubMed

    Schmitt, Heike; Sell, Sabrina; Koch, Julia; Seefried, Martina; Sonnewald, Sophia; Daniel, Christoph; Winkler, Thomas H; Nitschke, Lars

    2016-07-25

    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

  5. Vaccine against autoimmune disease: antigen-specific immunotherapy✩

    PubMed Central

    Anderson, Robert P; Jabri, Bana

    2013-01-01

    Recent interest in testing whether the success of antigen-specific immunotherapy (ASIT) for autoimmune diseases in mice can be translated to humans has highlighted the need for better tools to study and understand human autoimmunity. Clinical development of ASIT for allergy has been instructive, but limited understanding of CD4 T cell epitope/determinant hierarchies hampers the rational design and monitoring of ASIT. Definitive identification of pathogenic T cell epitopes as is now known in celiac disease and recent initiatives to optimize immune monitoring will facilitate rational design, monitoring and mechanistic understanding of ASIT for human autoimmune diseases. PMID:23478068

  6. Chronic Obstructive Pulmonary Disease: Evidence for an Autoimmune Component

    PubMed Central

    Stefanska, Anna M; Walsh, Patrick T

    2009-01-01

    Chronic obstructive pulmonary disease (COPD) is characterized by an irreversible limitation on pulmonary airflow associated with chronic inflammation and mucous hypersecretion (chronic bronchitis) and/or the pathological destruction of alveolar airspaces leading to emphysema. COPD, predominantly as a result of tobacco smoke exposure, represents the fourth leading cause of mortality worldwide and its prevalence is increasing. Despite this, much of the basic mechanisms which contribute to disease progression remain to be elucidated and current therapeutic approaches are, for the most part, based upon alleviating patient symptoms (bronchodilators) as opposed to treating the underlying pathological mechanisms triggered in response to cigarette smoke exposure. The classic disease paradigm suggests that an imbalance of pulmonary matrix proteases versus anti-proteases underlies the tissue destruction and inflammation associated with COPD. However, there is a growing appreciation of the complex and multifaceted nature of the pathological mechanisms associated with disease progression. Recently, there has been mounting evidence indicating that COPD patients exhibit many of the characteristics of a classical autoimmune response. We will discuss current evidence in support of this paradigm and outline how future therapeutic approaches may be tailored to address this. PMID:19403056

  7. Role of “Western Diet” in Inflammatory Autoimmune Diseases

    PubMed Central

    Manzel, Arndt; Muller, Dominik N.; Hafler, David A.; Erdman, Susan E.; Linker, Ralf A.; Kleinewietfeld, Markus

    2014-01-01

    Developed societies, although having successfully reduced the burden of infectious disease, constitute an environment where metabolic, cardiovascular, and autoimmune diseases thrive. Living in westernized countries has not fundamentally changed the genetic basis on which these diseases emerge, but has strong impact on lifestyle and pathogen exposure. In particular, nutritional patterns collectively termed the “Western diet”, including high-fat and cholesterol, high-protein, high-sugar, and excess salt intake, as well as frequent consumption of processed and ‘fast foods’, promote obesity, metabolic syndrome, and cardiovascular disease. These factors have also gained high interest as possible promoters of autoimmune diseases. Underlying metabolic and immunologic mechanisms are currently being intensively explored. This review discusses the current knowledge relative to the association of “Western diet” with autoimmunity, and highlights the role of T cells as central players linking dietary influences to autoimmune pathology. PMID:24338487

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

    PubMed Central

    Hirsch, Darren Lowell; Ponda, Punita

    2015-01-01

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

  9. 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. PMID:25712147

  10. Acute myeloid leukemia developing in patients with autoimmune diseases

    PubMed Central

    Ramadan, Safaa M.; Fouad, Tamer M; Summa, Valentina; Hasan, Syed KH; Lo-Coco, Francesco

    2012-01-01

    Therapy-related acute myeloid leukemia is an unfortunate complication of cancer treatment, particularly for patients with highly curable primary malignancies and favorable life expectancy. The risk of developing therapy-related acute myeloid leukemia also applies to patients with non-malignant conditions, such as autoimmune diseases treated with cytotoxic and/or immunosuppressive agents. There is considerable evidence to suggest that there is an increased occurrence of hematologic malignancies in patients with autoimmune diseases compared to the general population, with a further increase in risk after exposure to cytotoxic therapies. Unfortunately, studies have failed to reveal a clear correlation between leukemia development and exposure to individual agents used for the treatment of autoimmune diseases. Given the dismal outcome of secondary acute myeloid leukemia and the wide range of available agents for treatment of autoimmune diseases, an increased awareness of this risk and further investigation into the pathogenetic mechanisms of acute leukemia in autoimmune disease patients are warranted. This article will review the data available on the development of acute myeloid leukemia in patients with autoimmune diseases. Possible leukemogeneic mechanisms in these patients, as well as evidence supporting the association of their primary immunosuppressive status and their exposure to specific therapies, will also be reviewed. This review also supports the idea that it may be misleading to label leukemias that develop in patients with autoimmune diseases who are exposed to cytotoxic agents as ‘therapy-related leukemias’. A better understanding of the molecular defects in autoimmune disease patients who develop acute leukemia will lead to a better understanding of the association between these two diseases entities. PMID:22180424

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

    PubMed

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

    2016-03-01

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

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

    MedlinePlus

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

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

    PubMed

    Margo, Curtis E; Harman, Lynn E

    2016-01-01

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

  14. Role of myeloid-derived suppressor cells in autoimmune disease

    PubMed Central

    Crook, Kristen R; Liu, Peng

    2015-01-01

    Myeloid-derived suppressor cells (MDSCs) represent an important class of immunoregulatory cells that can be activated to suppress T cell functions. These MDSCs can inhibit T cell functions through cell surface interactions and the release of soluble mediators. MDSCs accumulate in the inflamed tissues and lymphoid organs of patients with autoimmune diseases. Much of our knowledge of MDSC function has come from studies involving cancer models, however many recent studies have helped to characterize MDSC involvement in autoimmune diseases. MDSCs are a heterogeneous group of immature myeloid cells with a number of different functions for the suppression of T cell responses. However, we have yet to fully understand their contributions to the development and regulation of autoimmune diseases. A number of studies have described beneficial functions of MDSCs during autoimmune diseases, and thus there appears to be a potential role for MDSCs in the treatment of these diseases. Nevertheless, many questions remain as to the activation, differentiation, and inhibitory functions of MDSCs. This review aims to summarize our current knowledge of MDSC subsets and suppressive functions in tissue-specific autoimmune disorders. We also describe the potential of MDSC-based cell therapy for the treatment of autoimmune diseases and note some of hurdles facing the implementation of this therapy. PMID:25621222

  15. 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

  16. Hypoxia-inducible factor 1 in autoimmune diseases.

    PubMed

    Deng, Wei; Feng, Xuebing; Li, Xia; Wang, Dandan; Sun, Lingyun

    2016-05-01

    Autoimmune disorders are a complicated and varied group of diseases arising from inappropriate immune responses. Recent studies have demonstrated that ongoing inflammatory and immune responses are associated with increased oxygen consumption, a process resulting in localized tissue hypoxia within inflammatory lesions ("inflammatory hypoxia"), in which hypoxia-inducible factor 1 (HIF-1), an oxygen-sensitive transcription factor that allows adaptation to hypoxia environments, has been shown to play an important function. HIF-1 is a regulator of angiogenesis and immune system. Besides, HIF-1-mediated metabolic shift and fibrosis may also play crucial roles in some autoimmune disorders. Firstly, we briefly summarize the role of HIF-1 in angiogenesis, immune responses and fibrosis. Secondly, we will show the major recent findings demonstrating a role for HIF-1 signaling in autoimmune disorders, including rheumatoid arthritis, inflammatory bowel disease, psoriasis, systemic sclerosis and multiple sclerosis. The growing evidences may prompt HIF-1 to be a new target for treatment of autoimmune diseases. PMID:27071377

  17. Immunogenetics of autoimmune diseases in Asian Indians.

    PubMed

    Mehra, N K; Kaur, Gurvinder; Kanga, Uma; Tandon, Nikhil

    2002-04-01

    The HLA class II molecules play a critical role in the processing and presentation of specific peptides derived from autoantigens of pancreatic beta cells or gluten for T cell scrutiny in IDDM and CD. In the present study, extended DR3-positive haplotypes associated with autoimmunity in northern Indian patients have been reported. The haplotype A26-B8-DR3 was the most common autoimmunity-favoring haplotype encountered among these patients. This association is, indeed, unique to Indian autoimmune patients, as it replaces the otherwise most commonly associated Caucasian haplotype A1-B8-DR3 (AH8.1) in this population. Further, CD patients revealed 100% association with DQB1*0201 along with DQA*0501 (97%) either in cis or trans configuration. PMID:12021136

  18. Extracorporeal photopheresis for the treatment of autoimmune diseases.

    PubMed

    Adamski, Jill; Kinard, Theresa; Ipe, Tina; Cooling, Laura

    2015-04-01

    The immune system is tasked with the unique challenge of recognizing foreign pathogens and damaged cells while at the same time preserving and protecting the integrity of "self". When this process fails, severe consequences including cancer and autoimmunity are the end result. Current therapies aimed at treating autoimmune disorders result in generalized immunosuppression and place the patient at increased risk for infection and malignancy. ECP is a potential therapeutic intervention that recapitulates natural physiologic processes of tolerance induction to restore immune homeostasis. Several clinical trials suggest that ECP may be used to treat a broad spectrum of autoimmune diseases. PMID:25886694

  19. 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. PMID:21871974

  20. Epigenetic mechanisms in systemic lupus erythematosus and other autoimmune diseases

    PubMed Central

    Hedrich, Christian M.; Tsokos, George C.

    2011-01-01

    The pathogenic origin of autoimmune diseases can be traced to both genetic susceptibility and epigenetic modifications arising from exposure to the environment. Epigenetic modifications influence gene-expression and alter cellular functions without modifying the genomic sequence. CpG-DNA methylation, histone-tail modifications, and micro-RNAs (miRNAs) are the main epigenetic mechanisms of gene regulation. Understanding the molecular mechanisms that are involved in the pathophysiology of autoimmune diseases is essential for the introduction of effective, target-directed, and tolerated therapies. In this review, we summarize recent findings that signify the importance of epigenetic modifications in autoimmune disorders while focusing on systemic lupus erythematosus (SLE). We discuss future directions in basic research, autoimmune diagnostics, and applied therapy. PMID:21885342

  1. Molecular Mechanisms for Contribution of MHC Molecules to Autoimmune Diseases

    PubMed Central

    Sollid, Ludvig M.; Pos, Wouter; Wucherpfennig, Kai W.

    2014-01-01

    It will soon be 50 years since the first MHC associations with human disease were described. These seminal studies opened a flourishing area of research, yet much remains to be discovered. Genome-wide association studies of autoimmune diseases have demonstrated that the MHC region has effect sizes that supersede those for any non-MHC locus for most diseases. Thus, an understanding of how particular MHC alleles confer susceptibility will be essential for a comprehensive understanding of autoimmune disease pathogenesis. Here we review recent exciting findings in this important field. PMID:25216261

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

    PubMed Central

    Brooks, Wesley H.; Renaudineau, Yves

    2015-01-01

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

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

    PubMed

    Coit, Patrick; Sawalha, Amr H

    2016-09-01

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

  4. TREG-cell therapies for autoimmune rheumatic diseases.

    PubMed

    Miyara, Makoto; Ito, Yoshinaga; Sakaguchi, Shimon

    2014-09-01

    Naturally occurring Foxp3(+)CD25(+)CD4(+) regulatory T (TREG) cells maintain immunological self-tolerance and prevent a variety of autoimmune diseases, including rheumatic diseases such as rheumatoid arthritis and systemic lupus erythematosus. In animal models of rheumatic disease, autoimmune responses can be controlled by re-establishing the T-cell balance in favour of TREG cells. Here we discuss three potential strategies for the clinical use of TREG cells to treat autoimmune rheumatic disease: expansion of self-antigen-specific natural TREG cells in vivo; propagation of antigen-specific natural TREG cells ex vivo, by in vitro antigenic stimulation, and subsequent transfer back into the host; or conversion of antigen-specific conventional T cells into TREG cells in vivo or ex vivo. These strategies require depletion of the effector T cells that mediate autoimmunity before initiating TREG-cell-based therapies. Immunotherapies that target TREG cells, and the balance of TREG cells and autoreactive T cells, are therefore an important modality for the treatment of autoimmune rheumatic disease. PMID:24980140

  5. Case study: a new infection-triggered, autoimmune subtype of pediatric OCD and Tourette's syndrome.

    PubMed

    Allen, A J; Leonard, H L; Swedo, S E

    1995-03-01

    A review of clinical observations and literature reports leads to the hypothesis that, via a process analogous to Sydenham's chorea, infections with group A beta-hemolytic streptococci, among others, may trigger autoimmune responses that cause or exacerbate some cases of childhood-onset obsessive-compulsive disorder (OCD) or tic disorders (including Tourette's syndrome). If this hypothesis is correct, then immunological treatments should lead to decreased symptoms in some cases. Four cases with abrupt, severe onset or worsening of OCD or tics are presented from an open treatment study. All were boys aged 10 to 14 years. One had OCD, one had Tourette's syndrome, and two had both OCD and Tourette's syndrome. Clinically and on standardized rating scales, their symptoms were in the moderate to very severe range. Two had evidence of recent group A beta-hemolytic streptococci infections, and the others had histories of recent viral illnesses. Two were treated with plasmapheresis, one with intravenous immunoglobulin, and one with immunosuppressive doses of prednisone. All had a clinically significant response immediately after treatment. Diagnostic criteria are provided that describe these cases of pediatric, infection-triggered, autoimmune neuropsychiatric disorders (PITANDs). Suggestions are made regarding the evaluation and management of patients who may have this condition. PMID:7896671

  6. Is Tourette's syndrome an autoimmune disease?

    PubMed

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

    2002-01-01

    We provide a review of recent research findings which support the involvement of autoimmunity in childhood-onset tic disorders, in particular the presence of antineuronal autoantibodies, D8/17 B lymphocyte overexpression, a marker of chorea associated with streptococcal infection, and possible beneficial effects of immunomodulatory intervention. One of the most controversial areas in this field is the validity of the proposed PANDAS concept. Some researchers have delineated a putatively unique subgroup of patients, from the spectrum of illness encompassing Tourette's syndrome and obsessive-compulsive disorder (OCD), whose tics and obsessive-compulsive symptoms are shown to arise in response to beta-hemolytic streptococcal infections. They designated it by the term pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS). Herein we additionally present pros and cons concerning the concept of PANDAS. Finally, recommendations for future research directions are given. PMID:12082557

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

    PubMed

    Mantegazza, Adriana R; Marks, Michael S

    2016-07-12

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

  8. 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. PMID:27181228

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

    PubMed

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

    1992-01-01

    Interest in T-lymphocyte subsets has arisen because of their involvement in the autoimmune process. Contradictory results have been published in the literature about the number of peripheral blood lymphocyte subsets in autoimmune diseases. In order to investigate the number and distribution of peripheral blood lymphocyte subsets in autoimmune thyroid disease, the levels of total T-lymphocytes (CD3), T-helper (CD4) and T-suppressor/cytotoxic (CD8) lymphocytes were determined in 44 patients with Graves' disease (1), multinodular goiter (2) and Hashimoto's thyroiditis (3). All patients had high levels of antithyroglobulin and thyroid antiperoxidase (antimicrosomal) antibodies. The T subset levels were related to the functional thyroid status, measured as serum free thyroxine (FT4) and thyrotropin (TSH). Our data show the existence of a strong influence of functional status on CD3, CD4 and CD8 levels, as reflected in the significant correlations obtained with FT4 (negative) and TSH (positive). A significant decrease in all populations was observed in Graves' disease hyperthyroid patients. A decrease in the CD4/CD8 ratio in Hashimoto's thyroiditis hypothyroid patients was observed, in contrast to an increase in the ratio in autoimmune hyperthyroid patients. This points to the CD4/CD8 ratio as a differential characteristic between the two autoimmune (hypothyroid and hyperthyroid) entities, independent of free thyroxine levels. No significant correlation was found between antithyroid antibody levels and peripheral blood T-lymphocyte subsets or serum levels of FT4 and TSH. PMID:1342892

  10. Cumulative Childhood Stress and Autoimmune Diseases in Adults

    PubMed Central

    Dube, Shanta R.; Fairweather, DeLisa; Pearson, William S.; Felitti, Vincent J.; Anda, Robert F.; Croft, Janet B.

    2012-01-01

    Objective To examine whether childhood traumatic stress increased the risk of developing autoimmune diseases as an adult. Methods Retrospective cohort study of 15,357 adult health maintenance organization members enrolled in the Adverse Childhood Experiences (ACEs) Study from 1995 to 1997 in San Diego, California, and eligible for follow-up through 2005. ACEs included childhood physical, emotional, or sexual abuse; witnessing domestic violence; growing up with household substance abuse, mental illness, parental divorce, and/or an incarcerated household member. The total number of ACEs (ACE Score range = 0–8) was used as a measure of cumulative childhood stress. The outcome was hospitalizations for any of 21 selected autoimmune diseases and 4 immunopathology groupings: T- helper 1 (Th1) (e.g., idiopathic myocarditis); T-helper 2 (Th2) (e.g., myasthenia gravis); Th2 rheumatic (e.g., rheumatoid arthritis); and mixed Th1/Th2 (e.g., autoimmune hemolytic anemia). Results Sixty-four percent reported at least one ACE. The event rate (per 10,000 person-years) for a first hospitalization with any autoimmune disease was 31.4 in women and 34.4 in men. First hospitalizations for any autoimmune disease increased with increasing number of ACEs (p < .05). Compared with persons with no ACEs, persons with ≥2 ACEs were at a 70% increased risk for hospitalizations with Th1, 80% increased risk for Th2, and 100% increased risk for rheumatic diseases (p < .05). Conclusions Childhood traumatic stress increased the likelihood of hospitalization with a diagnosed autoimmune disease decades into adulthood. These findings are consistent with recent biological studies on the impact of early life stress on subsequent inflammatory responses. PMID:19188532

  11. Dendritic cells in autoimmune thyroid disease.

    PubMed

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

    1987-01-01

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

  12. 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.

  13. 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

  14. Clinical aspects of indirect immunofluorescence for autoimmune diseases.

    PubMed

    Ghanadan, Alireza; Saghazadeh, Amene; Jahanzad, Issa; Rezaei, Nima

    2015-05-01

    Because the most common term used in conversations considering autoimmunity is autoantibodies, it is well-expected that the indirect immunofluorescence assay, which detects antibodies directed against various antigens, is one of our most impressive techniques for investigating autoimmune diseases (AIDs). Roughly speaking, the current literature corroborates that this immunopathologic investigation means that autoantibodies detection makes a considerable contribution to both diagnostic and prognostic aspects of AIDs in the clinical setting. However, it varies between different AIDs, autoantibodies, ethnicities or detection methodologies. Directly focusing on the indirect immunofluorescence assay, we present evidence to support this multidimensional variation regarding the subject via reviewing briefly the best-investigated autoantibodies in the well-documented AIDs, including vasculitis, inflammatory bowel disease, scleroderma, autoimmune hepatitis, primary biliary cirrhosis, systemic lupus erythematosus and Sjögren's syndrome. PMID:25786676

  15. 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

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

    PubMed

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

    2016-06-01

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

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

    PubMed

    Strickland, D K; Ware, R E

    1995-09-01

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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  20. 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.

  1. Cannabinoids and autoimmune diseases: A systematic review.

    PubMed

    Katchan, Valeria; David, Paula; Shoenfeld, Yehuda

    2016-06-01

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

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

    PubMed

    Kerr, Jonathan R

    2016-04-01

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

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

    PubMed Central

    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. PMID:26078982

  4. 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. PMID:25998909

  5. 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.

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

    PubMed

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

    2012-02-01

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

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

    PubMed

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

    2016-01-01

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

  8. Contribution of MicroRNAs to autoimmune diseases.

    PubMed

    Garo, Lucien P; Murugaiyan, Gopal

    2016-05-01

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

  9. Autoimmune enteropathy: not all flat mucosa mean coeliac disease

    PubMed Central

    Volta, Umberto; Mumolo, Maria Gloria; Caio, Giacomo; Boschetti, Elisa; Latorre, Rocco; Giancola, Fiorella; Paterini, Paola; Giorgio, Roberto De

    2016-01-01

    A 62-year-old woman complaining of severe malabsorption was diagnosed with celiac disease based on the findings of flat, small intestinal mucosa and HLA-DQ2 positivity, although celiac serology was negative. This diagnosis was questioned due to the lack of clinical and histological improvement after a long period of strict gluten-free diet. The detection of enterocyte autoantibodies guided to the correct diagnosis of autoimmune enteropathy, leading to a complete recovery of the patient following an appropriate immunosuppressive treatment. Autoimmune enteropathy should be considered in the differential diagnosis of malabsorption with severe villous atrophy, including those cases with negative celiac-related serology. PMID:27099674

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

    ClinicalTrials.gov

    2016-04-18

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

  11. [Auto-immune liver diseases and their treatment].

    PubMed

    Hess, J; Thorens, J; Pache, I; Troillet, F X; Moradpour, D; Gonvers, J J

    2005-01-19

    There are three main types of auto-immune liver disease, auto-immune hepatitis, primary biliary cirrhosis and primary sclerosing cholangitis. In the case of auto-immune hepatitis, prednisone therapy, with or without azathioprine, can improve quality of life and halt progression to cirrhosis. If there is no response or if the therapy is poorly tolerated, mycophenolate mofetil or cyclosporin should be considered. Ursodeoxycholic acid (UDCA), at a dosage of 13 to 15 mg/kg/day slows the progression of fibrosis in patients with primary biliary cirrhosis. Pruritus may be treated with cholestyramine, rifampicin or opiate antagonists. Ursodeoxycholic acid at a dosage of 20 to 30 mg/kg/day will slow the evolution of fibrosis. PMID:15770819

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

    PubMed Central

    Picchianti-Diamanti, Andrea; Rosado, Maria Manuela; Scarsella, Marco; Laganà, Bruno; D’Amelio, Raffaele

    2014-01-01

    Autoimmune diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and psoriatic arthritis (PsA) are chronic inflammatory disorders of unknown etiology characterized by a wide range of abnormalities of the immune system that may compromise the function of several organs, such as kidney, heart, joints, brain and skin. Corticosteroids (CCS), synthetic and biologic immunosuppressive agents have demonstrated the capacity to improve the course of autoimmune diseases. However, a significant number of patients do not respond or develop resistance to these therapies over time. P-glycoprotein (P-gp) is a transmembrane protein that pumps several drugs out of the cell, including CCS and immunosuppressants; thus, its over-expression or hyper-function has been proposed as a possible mechanism of drug resistance in patients with autoimmune disorders. Recently, different authors have demonstrated that P-gp inhibitors, such as cyclosporine A (CsA) and its analogue Tacrolimus, are able to reduce P-gp expression and or function in SLE, RA and PsA patients. These observations suggest that P-gp antagonists could be adopted to revert drug resistance and improve disease outcome. The complex inter-relationship among drug resistance, P-gp expression and autoimmunity still remains elusive. PMID:24658440

  13. 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

  14. [Intravenous immunoglobulin in treatment of autoimmune neurological diseases in children].

    PubMed

    Bembeeva, R Ts; Zavadenko, N N

    2015-01-01

    Though the mechanisms of action of intravenous immunoglobulins (IVIG) are not completely understood, these drugs are widely used in treatment of autoimmune diseases. In this review, we have analyzed the literature on the use of IVIG in the treatment of autoimmune diseases of the nervous system in children and discuss the management of patients basing on the recommendation of the European Federation of Neurological Societies. The efficacy of IVIG in children has been shown as first line treatment in Guillain-Barre syndrome, chronic inflammatory demyelinating polyneuropathy, multifocal motor neuropathy, dermatomyositis as a second-line drug in the combination with prednisolone or immunosuppressors in patients refractory to treatment with corticosteroids and cytostatics, myasthenic crisis in myasthenia gravis, exacerbations and short-term treatment of severe forms, non-responsiveness to acetylcholinesterase inhibitors, multiple sclerosis as second or third line of treatment in patients with relapsing-remitting course with intolerance to standard immunomodulatory therapy, acute multiple encephalomyelitis with no response to the treatment with high doses of corticosteroids, paraneoplastic syndromes, pharmacoresistant epilepsy and autoimmune encephalitis. Because the right choice of the drug plays a key role, in particular, in children, that determines the efficacy and safety of the treatment, we present the main approaches to the choice of the drug and schemes of treatment of autoimmune diseases of the nervous system in children. PMID:26356621

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

    PubMed

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

    2015-01-20

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

  16. [Immunopathogenesis of cytotoxic antibody-mediated autoimmune diseases].

    PubMed

    Morenz, J

    1980-01-15

    This review deals with autoantibodies, autoantigens, immunopathogenetic mechanisms and their consequences in autoimmune diseases caused by cytotoxic antibodies. Findings demonstrating the pathogenicity and pathogenic potency of antibodies, the involvement of complement and polymorphonuclears, and the chain of events leading from the start of immune reactions to clinical signs and symptoms are stressed. It is shown that the immunopathogenesis of this group of diseases can be deduced from only a few related immune mechanisms while the heterogeneity of clinical syndromes can be explained primarily by the function and localization of autoantigens. Questions still open and findings not yet understood are pointed out. From the progress of immunology in recent years further diseases can be expected to be recognized as type II autoimmune diseases in the years ahead notably by the combined application of immunological and physiological or pharmacological methods. PMID:6996350

  17. Low Serum Hepcidin in Patients with Autoimmune Liver Diseases

    PubMed Central

    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. PMID:26270641

  18. 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

  19. [Wounds in autoimmune bullous dermatoses and systemic connective tissue diseases].

    PubMed

    Marinović, Branka; Jukić, Ines Lakos; Lipozencić, Jasna

    2012-10-01

    Autoimmune bullous dermatoses are a group of skin and/or mucous membrane diseases characterized by blisters and erosions, which are the results of autoantibodies directed to structural components of desmosomes and structural proteins of the basement membrane zone. In this group of diseases, the diagnosis is based on history, clinical presentation, histopathologic findings, findings of direct and indirect immunofluorescence, and specific evidence of circulating antibodies by the enzyme linked immunosorbent assay (ELISA) method. Connective tissue diseases are a heterogeneous group of diseases with some common pathogenetic mechanisms and frequent involvement of the skin. This group of diseases commonly includes lupus erythematosus, dermatomyositis/polymyositis, localized and systemic scleroderma. As most of the diseases in this group have positive one of the antinuclear antibodies, in clinical practice these diseases are often called autoimmune connective tissue diseases. In the group of autoimmune bullous dermatoses, wounds occur as the result of breaking of blisters, and consequently affect the epidermis alone or epidermis and upper dermis, while in the group of systemic diseases of connective tissue, wounds occur in advanced stages of disease as a result of vascular tissue damage, causing necrosis of tissue and wounds. When wounds in these diseases last for a longer period (longer than 3 months), they are considered as chronic wounds and in these cases it is necessary to determine the reason for slow healing. In patients with wounds as a symptom of disease, besides systemic therapy, special attention should be paid to local therapy in order to prevent superinfection and accelerate epithelialization and wound healing. PMID:23193815

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

    PubMed

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

    2016-06-01

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

  1. 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. PMID:25444650

  2. New tools for classification and monitoring of autoimmune diseases

    PubMed Central

    Maecker, Holden T.; Lindstrom, Tamsin M.; Robinson, William H.; Utz, Paul J.; Hale, Matthew; Boyd, Scott D.; Shen-Orr, Shai S.; Fathman, C. Garrison

    2012-01-01

    Rheumatologists see patients with a range of autoimmune diseases. Phenotyping these diseases for diagnosis, prognosis and selection of therapies is an ever increasing problem. Advances in multiplexed assay technology at the gene, protein, and cellular level have enabled the identification of `actionable biomarkers'; that is, biological metrics that can inform clinical practice. Not only will such biomarkers yield insight into the development, remission, and exacerbation of a disease, they will undoubtedly improve diagnostic sensitivity and accuracy of classification, and ultimately guide treatment. This Review provides an introduction to these powerful technologies that could promote the identification of actionable biomarkers, including mass cytometry, protein arrays, and immunoglobulin and T-cell receptor high-throughput sequencing. In our opinion, these technologies should become part of routine clinical practice for the management of autoimmune diseases. The use of analytical tools to deconvolve the data obtained from use of these technologies is also presented here. These analyses are revealing a more comprehensive and interconnected view of the immune system than ever before and should have an important role in directing future treatment approaches for autoimmune diseases. PMID:22647780

  3. [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. PMID:11256005

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

    PubMed

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

    2016-06-13

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

  5. Interleukin 6 in autoimmune and inflammatory diseases: a personal memoir

    PubMed Central

    HIRANO, Toshio

    2010-01-01

    In this review, the author discusses the research that led to the identification and characterization of interleukin 6 (IL-6), including his own experience isolating IL-6, and the roles this cytokine has on autoimmune and inflammatory diseases. The cDNAs encoding B-cell stimulatory factor 2 (BSF-2), interferon (IFN)-β2 and a 26-kDa protein were independently cloned in 1986, which in turn led to the identification of each. To resolve the confusing nomenclature, these identical molecules were named IL-6. Characterization of IL-6 revealed a multifunctional cytokine that is involved in not only immune responses but also hematopoiesis, inflammation, and bone metabolism. Moreover, IL-6 makes significant contributions to such autoimmune and inflammatory diseases as rheumatoid arthritis (RA). IL-6 activates both the STAT3 and SHP2/Gab/MAPK signaling pathways via the gp130 signal transducer. F759 mice, which contain a single amino-acid substitution in gp130 (Y759F) and show enhanced STAT3 activation, spontaneously develop a RA-like arthritis as they age. F759 arthritis is dependent on CD4+ T cells, IL-6, and IL-17A, and is enhanced by the pX gene product from human T cell leukemia virus 1 (HTLV-1). Arthritis development in these mice requires that the F759 mutation is present in nonhematopoietic cells, but not in immune cells, highlighting the important role of the interaction between nonimmune tissues and the immune system in this disease. Furthermore, this interaction is mediated by the IL-6 amplifier through STAT3 and NF-κB. Ultimately, this model may represent a general etiologic process underlying other autoimmune and inflammatory diseases. More importantly, the understanding of IL-6 has paved the way for new therapeutic approaches for RA and other autoimmune and inflammatory diseases. PMID:20689230

  6. IL-10 Modulates Th17 Pathogenicity during Autoimmune Diseases

    PubMed Central

    Guo, Beichu

    2016-01-01

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

  7. Commensal Flora, is it an Unwelcomed Companion as a Triggering Factor of Autoimmune Pancreatitis?

    PubMed Central

    Haruta, Ikuko; Shimizu, Kyoko; Yanagisawa, Naoko; Shiratori, Keiko; Yagi, Junji

    2012-01-01

    The etiopathogenesis of many autoimmune disorders has not been identified. The aim of this paper is to focus on the involvement of bacterial exposure, as an environmental factor, in the pathogenesis of autoimmune pancreatitis (AIP), which is broadly categorized as autoimmune disorders involving pancreatic lesions. Avirulent and/or commensal bacteria, which may have an important role(s) as initiating/progressing factors in the pathogenesis of autoimmune disorder AIP, will be emphasized. PMID:22485093

  8. 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.

  9. 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

  10. Phenomics in Autoimmune and Inflammatory Diseases

    ClinicalTrials.gov

    2016-04-18

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

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

    PubMed Central

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

    2006-01-01

    Background Autoimmune diseases are disorders caused by an immune response directed against the body's own organs, tissues and cells. In practice more than 80 clinically distinct diseases, among them systemic lupus erythematosus and rheumatoid arthritis, are classified as autoimmune diseases. Although their etiology is unclear these diseases share certain similarities at the molecular level i.e. susceptibility regions on the chromosomes or the involvement of common genes. To gain an overview of these related diseases it is not feasible to do a literary review but it requires methods of automated analyses of the more than 500,000 Medline documents related to autoimmune disorders. Results In this paper we present the first version of the Autoimmune Disease Database which to our knowledge is the first comprehensive literature-based database covering all known or suspected autoimmune diseases. This dynamically compiled database allows researchers to link autoimmune diseases to the candidate genes or proteins through the use of named entity recognition which identifies genes/proteins in the corresponding Medline abstracts. The Autoimmune Disease Database covers 103 autoimmune disease concepts. This list was expanded to include synonyms and spelling variants yielding a list of over 1,200 disease names. The current version of the database provides links to 541,690 abstracts and over 5,000 unique genes/proteins. Conclusion The Autoimmune Disease Database provides the researcher with a tool to navigate potential gene-disease relationships in Medline abstracts in the context of autoimmune diseases. PMID:16803617

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

    PubMed

    Urboniene, Daiva; Sakalauskas, Raimundas; Sitkauskiene, Brigita

    2005-01-01

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

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

    PubMed

    Fatimah, Nafeesah; Ussaid, Ahmad; Rasheed, Aflak

    2016-08-01

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

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

    PubMed Central

    Fatimah, Nafeesah; Ussaid, Ahmad; Rasheed, Aflak

    2016-01-01

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

  15. Therapeutic targeting of B cells for rheumatic autoimmune diseases.

    PubMed

    Engel, Pablo; Gómez-Puerta, José A; Ramos-Casals, Manuel; Lozano, Francisco; Bosch, Xavier

    2011-03-01

    Autoreactive B cells are characterized by their ability to secrete autoantibodies directed against self-peptides. During the last decade, it has become increasingly apparent that B lymphocytes not only produce autoantibodies but also exert important regulatory roles independent of their function as antibody-producing cells. This is especially relevant in the context of autoimmunity, because autoreactive B cells have been shown to possess the ability to activate pathogenic T cells, to produce pro-inflammatory cytokines, and to promote the formation of tertiary lymphoid tissue in target organs. The production of monoclonal antibodies against B-cell-surface molecules has facilitated the characterization of several distinct B lymphocyte subsets. These cell-surface molecules have not only served as useful cell differentiation markers but have also helped to unravel the important biological functions of these cells. Some of these molecules, all of which are expressed on the cell surface, have proven to be effective therapeutic targets. In both animal models and in clinical assays, the efficient elimination of B lymphocytes has been shown to be useful in the treatment of rheumatoid arthritis and other autoimmune diseases. The treatment of most rheumatic autoimmune diseases relies mainly on the use of cytotoxic immunosuppressants and corticosteroids. Although this has resulted in improved disease survival, patients may nonetheless suffer severe adverse events and, in some cases, their relapse rate remains high. The increasing need for safer and more effective drugs along with burgeoning new insights into the pathogenesis of these disorders has fueled interest in biological agents; clinical trials involving the B-cell depletion agent rituximab have been especially promising. This article reviews the current knowledge of B-cell biology and pathogenesis as well as the modern therapeutic approaches for rheumatic autoimmune diseases focusing in particular on the targeting of B

  16. Sclerosing cholangitis associated with Crohn's disease and autoimmune haemolytic anaemia.

    PubMed Central

    Eilam, O.; Goldin, E.; Shouval, D.; Gimon, T.; Brautbar, C.

    1993-01-01

    A middle-aged man was found to have autoimmune haemolytic anaemia. Seven years after the first manifestations of the anaemia, he developed jaundice without haemolysis and a diagnosis of primary sclerosing cholangitis was made by endoscopic retrograde cholangiography. Crohn's colitis was later confirmed by X-rays and colonoscopy. This association is unique to the best of our knowledge and suggests that genetic and immunological mechanisms may be involved in the pathogenesis of these diseases. Images Figure 1 PMID:8234117

  17. Interferon regulatory factor 5 in human autoimmunity and murine models of autoimmune disease.

    PubMed

    Eames, Hayley L; Corbin, Alastair L; Udalova, Irina A

    2016-01-01

    Interferon regulatory factor 5 (IRF5) has been demonstrated as a key transcription factor of the immune system, playing important roles in modulating inflammatory immune responses in numerous cell types including dendritic cells, macrophages, and B cells. As well as driving the expression of type I interferon in antiviral responses, IRF5 is also crucial for driving macrophages toward a proinflammatory phenotype by regulating cytokine and chemokine expression and modulating B-cell maturity and antibody production. This review highlights the functional importance of IRF5 in a disease setting, by discussing polymorphic mutations at the human Irf5 locus that lead to susceptibility to systemic lupus erythematosus, rheumatoid arthritis, and inflammatory bowel disease. In concordance with this, we also discuss lessons in IRF5 functionality learned from murine in vivo models of autoimmune disease and inflammation and hypothesize that modulation of IRF5 activity and expression could provide potential therapeutic benefits in the clinic. PMID:26207886

  18. Biologic therapy for autoimmune diseases: an update

    PubMed Central

    2013-01-01

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

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

    PubMed

    Jiao, Guohui; Wang, Bangmao

    2016-01-01

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

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

    PubMed

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

    2016-08-30

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

  1. 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

  2. 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. PMID:25152827

  3. 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

  4. 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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

    Jacob, Louis; Dauvilliers, Yves

    2014-12-01

    Narcolepsy type 1 (also named narcolepsy-cataplexy or hypocretin deficiency syndrome) is a rare sleep disorder characterized by excessive daytime sleepiness and cataplexy, plus frequently hypnagogic hallucinations, sleep paralysis and nocturnal sleep disturbances. Narcolepsy type 1 is an immune system-associated disease linked with the destruction of 70.000-90.000 hypocretin neurons notably involved in wakefulness. Among narcoleptic patients, 98% are positive for HLA-DQB1*06:02, a HLA class II allele, against 20-25% in general population. Individuals carrying HLA-DQB1*06:02 have an extraordinary risk to develop narcolepsy (odd ratio: 251). Other genes involved in CD4+ T cells and immune system activation as T-cell receptor α are also associated with narcolepsy. The development of the disease is linked with environmental factors such as influenza and streptococcal infections. Narcolepsy type 1 incidence also increased in Europe following the use of Pandemrix, a 2009 H1N1 AS03-adjuvanted vaccine manufactured by GlaxoSmithKline. Interestingly, such increase was not observed with Arepanrix, another vaccine developed by GSK very similar to Pandemrix. PMID:25537044

  7. 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. PMID:26709064

  8. CNS disease triggering Takotsubo stress cardiomyopathy.

    PubMed

    Finsterer, Josef; Wahbi, Karim

    2014-12-15

    There are a number of hereditary and non-hereditary central nervous system (CNS) disorders, which directly or indirectly affect the heart (brain-heart disorders). The most well-known of these CNS disorders are epilepsy, stroke, infectious or immunological encephalitis/meningitis, migraine, and traumatic brain injury. In addition, a number of hereditary and non-hereditary neurodegenerative disorders may impair cardiac functions. Affection of the heart may manifest not only as arrhythmias, myocardial infarction, autonomic impairment, systolic dysfunction/heart failure, arterial hypertension, or pulmonary hypertension, but also as stress cardiomyopathy (Takotsubo syndrome, TTS). CNS disease triggering TTS includes subarachnoid bleeding, epilepsy, ischemic stroke, intracerebral bleeding, migraine, encephalitis, traumatic brain injury, PRES syndrome, or ALS. Usually, TTS is acutely precipitated by stress triggered by various different events. TTS is one of the cardiac abnormalities most frequently induced by CNS disorders. Appropriate management of TTS from CNS disorders is essential to improve the outcome of affected patients. PMID:25213573

  9. Multisensory body representation in autoimmune diseases.

    PubMed

    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

  10. 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

  11. AID in aging and autoimmune diseases

    PubMed Central

    FRASCA, DANIELA; ANDRISANI, GIANLUCA; DIAZ, ALAIN; FELICE, CARLA; GUIDI, LUISA; BLOMBERG, BONNIE B.

    2016-01-01

    The aim of this study was to evaluate the quality of B cell responses in patients with Inflammatory Bowel Disease (IBD) and healthy individuals of different ages, vaccinated with the pandemic (p)2009 influenza vaccine. The in vivo response was measured by the hemagglutination inhibition (HAI) assay, which represents the most established correlate with vaccine protectiveness. The in vitro response was measured by activation-induced cytidine deaminase (AID) in cultures of vaccine-stimulated PBMC. Both responses are somewhat impaired in IBD patients undergoing anti-TNF-α treatment but these are much more decreased in IBD patients undergoing treatment with anti-TNF-α and immunosuppressive (IS) drugs. These latter patients had in vivo and in vitro B cell responses similar to those of elderly individuals. Moreover, as we have previously demonstrated in healthy subjects, the in vitro response to the polyclonal stimulus CpG may be used as a biomarker for subsequent vaccine response and AID activation is correlated with the serum response in IBD patients, as it is in healthy individuals. These results altogether indicate that IBD patients on anti-TNF-α and IS have significantly impaired in vivo and in vitro B cell responses, as compared to those on monotherapy. This is the first report to demonstrate that B cell defects, as measured by the autonomous AID reporter, in IBD patients contribute to reduced humoral responses to the influenza vaccine, as we have previously shown for elderly individuals. PMID:23190037

  12. 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

  13. 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

  14. Seven newly identified loci for autoimmune thyroid disease.

    PubMed

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

    2012-12-01

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

  15. Epstein-Barr virus in systemic autoimmune diseases.

    PubMed

    Draborg, Anette Holck; Duus, Karen; Houen, Gunnar

    2013-01-01

    Systemic autoimmune diseases (SADs) are a group of connective tissue diseases with diverse, yet overlapping, symptoms and autoantibody development. The etiology behind SADs is not fully elucidated, but a number of genetic and environmental factors are known to influence the incidence of SADs. Recent findings link dysregulation of Epstein-Barr virus (EBV) with SAD development. EBV causes a persistent infection with a tight latency programme in memory B-cells, which enables evasion of the immune defence. A number of immune escape mechanisms and immune-modulating proteins have been described for EBV. These immune modulating functions make EBV a good candidate for initiation of autoimmune diseases and exacerbation of disease progression. This review focuses on systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and Sjögren's syndrome (SS) and sum up the existing data linking EBV with these diseases including elevated titres of EBV antibodies, reduced T-cell defence against EBV, and elevated EBV viral load. Together, these data suggest that uncontrolled EBV infection can develop diverse autoreactivities in genetic susceptible individuals with different manifestations depending on the genetic background and the site of reactivation. PMID:24062777

  16. 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. PMID:27312321

  17. Targeting interleukin-6 in inflammatory autoimmune diseases and cancers.

    PubMed

    Yao, Xin; Huang, Jiaqi; Zhong, Haihong; Shen, Nan; Faggioni, Raffaella; Fung, Michael; Yao, Yihong

    2014-02-01

    Interleukin-6 (IL-6) is a pleiotropic cytokine with significant functions in the regulation of the immune system. As a potent pro-inflammatory cytokine, IL-6 plays a pivotal role in host defense against pathogens and acute stress. However, increased or deregulated expression of IL-6 significantly contributes to the pathogenesis of various human diseases. Numerous preclinical and clinical studies have revealed the pathological roles of the IL-6 pathway in inflammation, autoimmunity, and cancer. Based on the rich body of studies on biological activities of IL-6 and its pathological roles, therapeutic strategies targeting the IL-6 pathway are in development for cancers, inflammatory and autoimmune diseases. Several anti-IL-6/IL-6 receptor monoclonal antibodies developed for targeted therapy have demonstrated promising results in both preclinical studies and clinical trials. Tocilizumab, an anti-IL-6 receptor antibody, is effective in the treatment of various autoimmune and inflammatory conditions notably rheumatoid arthritis. It is the only IL-6 pathway targeting agent approved by the regulatory agencies for clinical use. Siltuximab, an anti-IL-6 antibody, has been shown to have potential benefits treating various human cancers either as a single agent or in combination with other chemotherapy drugs. Several other anti-IL-6-based therapies are also under clinical development for various diseases. IL-6 antagonism has been shown to be a potential therapy for these disorders refractory to conventional drugs. New strategies, such as combination of IL-6 blockade with inhibition of other signaling pathways, may further improve IL-6-targeted immunotherapy of human diseases. PMID:24076269

  18. 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

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

    PubMed

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

    2016-01-01

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

  20. 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

  1. Origin of B-Cell Neoplasms in Autoimmune Disease

    PubMed Central

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

    2016-01-01

    Autoimmune diseases (ADs) are associated with a number of B-cell neoplasms but the associations are selective in regard to the type of neoplasm and the conferred risks are variable. So far no mechanistic bases for these differential associations have been demonstrated. We speculate that developmental origin of B-cells might propose a mechanistic rationale for their carcinogenic response to autoimmune stimuli and tested the hypothesis on our previous studies on the risks of B-cell neoplasms after any of 33 ADs. We found that predominantly germinal center (GC)-derived B-cells showed multiple associations with ADs: diffuse large B cell lymphoma associated with 15 ADs, follicular lymphoma with 7 ADs and Hodgkin lymphoma with 11 ADs. Notably, these neoplasms shared significant associations with 5 ADs (immune thrombocytopenic purpura, polymyositis/dermatomyositis, rheumatoid arthritis, Sjogren syndrome and systemic lupus erythematosis). By contrast, primarily non-GC neoplasms, acute lymphocytic leukemia, chronic lymphocytic leukemia and myeloma associated with 2 ADs only and mantle cell lymphoma with 1 AD. None of the neoplasms shared associated ADs. These data may suggest that autoimmune stimulation critically interferes with the rapid cell division, somatic hypermutation, class switch recombination and immunological selection of maturing B-cell in the GC and delivers damage contributing to transformation. PMID:27355450

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

    PubMed

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

    2016-01-01

    Autoimmune diseases (ADs) are associated with a number of B-cell neoplasms but the associations are selective in regard to the type of neoplasm and the conferred risks are variable. So far no mechanistic bases for these differential associations have been demonstrated. We speculate that developmental origin of B-cells might propose a mechanistic rationale for their carcinogenic response to autoimmune stimuli and tested the hypothesis on our previous studies on the risks of B-cell neoplasms after any of 33 ADs. We found that predominantly germinal center (GC)-derived B-cells showed multiple associations with ADs: diffuse large B cell lymphoma associated with 15 ADs, follicular lymphoma with 7 ADs and Hodgkin lymphoma with 11 ADs. Notably, these neoplasms shared significant associations with 5 ADs (immune thrombocytopenic purpura, polymyositis/dermatomyositis, rheumatoid arthritis, Sjogren syndrome and systemic lupus erythematosis). By contrast, primarily non-GC neoplasms, acute lymphocytic leukemia, chronic lymphocytic leukemia and myeloma associated with 2 ADs only and mantle cell lymphoma with 1 AD. None of the neoplasms shared associated ADs. These data may suggest that autoimmune stimulation critically interferes with the rapid cell division, somatic hypermutation, class switch recombination and immunological selection of maturing B-cell in the GC and delivers damage contributing to transformation. PMID:27355450

  3. 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

  4. Autoimmunity in picornavirus infections.

    PubMed

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

    2016-02-01

    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. 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. PMID:27011059

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

    PubMed

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

    2015-09-01

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

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

    PubMed Central

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

    2015-01-01

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

  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. PMID:23352967

  9. 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

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

    PubMed

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

    2015-01-01

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

  11. 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

  12. 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

  13. Single Nucleotide Polymorphism Clustering in Systemic Autoimmune Diseases.

    PubMed

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

    2016-01-01

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

  14. Current and Future Immunomodulation Strategies to Restore Tolerance in Autoimmune Diseases

    PubMed Central

    Bluestone, Jeffrey A.; Bour-Jordan, Hélène

    2012-01-01

    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. PMID:23125012

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

    PubMed

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

    2016-12-01

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

  16. 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. PMID:26975391

  17. Pregnancy-Related Challenges in Systemic Autoimmune Diseases.

    PubMed

    Taraborelli, Mara; Erkan, Doruk

    2015-01-01

    The awareness of pregnancy-related physiologic changes and complications is critical for the appropriate assessment and management of pregnant patients with systemic autoimmune diseases. The overlapping features of physiologic and pathological changes, selected autoantibodies, and the use of potentially teratogenic medications can complicate their management during pregnancy. While pregnancy in lupus patients presents an additional risk to an already complex situation, in patients with no disease activity, the risk of a future pregnancy-related complication is relatively low. Anti-Ro and anti-La antibodies increase the risk of neonatal lupus erythematosus, eg, photosensitive rash and irreversible congenital heart block. Antiphospholipid antibodies increase the risk of pregnancy morbidity, eg, fetal loss and early preeclampsia. Pregnancy usually has a positive effect on rheumatoid arthritis; however, a disease flare is common during the postpartum period. Both the rheumatologist and the obstetrician should partner throughout the pregnancy to manage patients for successful outcomes. PMID:26339942

  18. 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.

  19. 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. PMID:26406790

  20. 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

  1. [Assessment of association between autoimmune thyroid disease and chronic urticaria].

    PubMed

    Feibelmann, Taciana C M; Gonçalves, Fabrícia Torres; Daud, Mariana Salomão; Jorge, André de Sousa; Mantese, Sônia A O; Jorge, Paulo Tannús

    2007-10-01

    Several studies found a higher prevalence of Autoimmune Thyroid Disease (ATD) in patients with Chronic Urticaria (CU). This relationship may be due to the possible autoimmune etiology in up to one third of the cases of Chronic Idiopathic Urticaria (CIU). However, the frequency of ATD ranged from 1.14% to 28.6%. The study began by determining whether there is an association between ATD and CU, in a population seen at the same clinic. We compared the frequency of anti-thyroid antibodies and thyroid dysfunction in 49 patients with CIU (group 1) and 112 controls (group 2). In order to support the result found, we studied the prevalence of CIU in 60 patients with ATD (group 3) and compared with 29 patients who had non-immune thyroid disease (NITD) (group 4). We did not find a statistical difference for the presence of anti-thyroid antibodies or thyroid dysfunction between groups 1 and 2 (12.24% x 9.82% and 12.24% x 7.14%, respectively). The same occurred for the presence of CIU among groups 3 and 4 (3.33% x 3.44%). In our study it was not possible to demonstrate a relationship between ATD and CIU, which means that different populations may present a higher or lower degree of association between these illnesses. PMID:18157382

  2. Immunopathology: autoimmune glial diseases and differentiation from multiple sclerosis.

    PubMed

    Popescu, Bogdan F Gh; Lucchinetti, Claudia F

    2016-01-01

    While multiple sclerosis (MS) is often referred to as an autoimmune inflammatory demyelinating disease, neuromyelitis optica (NMO) is currently the only proven and well-characterized autoimmune disease affecting the glial cells. The target antigen is the water channel aquaporin-4 (AQP4), expressed on astrocytes, and antibodies against AQP4 (AQP4-IgG) are present in the serum of NMO patients. Clinical, serologic, cerebrospinal fluid, and neuroimaging criteria help differentiate NMO from other central nervous system inflammatory demyelinating disorders. Pathologically, the presence of dystrophic astrocytes, myelin vacuolation, granulocytic inflammatory infiltrates, vascular hyalinization, macrophages containing glial fibrillary acidic protein-positive debris and/or the absence of Creutzfeldt-Peters cells is more characteristic, but not specific, for NMO. These findings should prompt the neuropathologist to perform AQP4 immunohistochemistry, and recommend serologic testing for AQP4-IgG to exclude a diagnosis of NMO/NMO spectrum disorder (NMOSD). Loss of AQP4 on biopsied active demyelinating lesions and/or seropositivity for AQP4-IgG may confirm the diagnosis of NMO/NMOSD, which is important because treatments that are suitable for MS can aggravate NMO. Few other putative glial antigens have been postulated, but their pathogenic role remains to be demonstrated. PMID:27112673

  3. 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

  4. Impaired hapten sensitization in patients with autoimmune disease

    PubMed Central

    Bangsgaard, N; Engkilde, K; Menné, T; Løvendorf, M; Jacobsen, G K; Olsen, J; Skov, L

    2011-01-01

    An inverse relation between contact allergy and autoimmune diseases is suggested from epidemiological studies. The aim of this study was to investigate susceptibility and reactivity in patients with psoriasis, patients with diabetes and healthy controls in an experimental sensitization study. We sensitized 68 adult individuals (23 patients with psoriasis, 22 patients with diabetes and 23 healthy controls) with diphenylcyclopropenone (DPCP) and assessed challenge responses with visual scoring and ultrasound. Skin biopsies from challenged skin were investigated for differences in down-regulatory mechanisms with immunohistochemistry and gene-expression profiles using microarray technology. The sensitization ratios were 26%, 36% and 65% for the psoriatic, diabetic and healthy groups, respectively. Logistic regression analysis gave an odds ratio (OR) for a patient with psoriasis or diabetes type I of being sensitized to 0·18 [95% confidence interval (CI): 0·039–0·85], P = 0·031 and 0·74 (95% CI: 0·548–1·008), P = 0·056, respectively. A high degree of forkhead box P3-positive (FoxP3+) cells were found in biopsies of positively challenged reactions, but only limited numbers in negatively challenged reactions, with no difference among the groups. No specific mRNA expression was found in the challenged skin of negative elicitation reactions, also indicating no sign of active down-regulation. The study contibutes strongly to the evidence of a decreased susceptibility to develop contact allergy in individuals with autoimmune diseases such as psoriasis. PMID:21668897

  5. Impaired hapten sensitization in patients with autoimmune disease.

    PubMed

    Bangsgaard, N; Engkilde, K; Menné, T; Løvendorf, M; Jacobsen, G K; Olsen, J; Skov, L

    2011-09-01

    An inverse relation between contact allergy and autoimmune diseases is suggested from epidemiological studies. The aim of this study was to investigate susceptibility and reactivity in patients with psoriasis, patients with diabetes and healthy controls in an experimental sensitization study. We sensitized 68 adult individuals (23 patients with psoriasis, 22 patients with diabetes and 23 healthy controls) with diphenylcyclopropenone (DPCP) and assessed challenge responses with visual scoring and ultrasound. Skin biopsies from challenged skin were investigated for differences in down-regulatory mechanisms with immunohistochemistry and gene-expression profiles using microarray technology. The sensitization ratios were 26%, 36% and 65% for the psoriatic, diabetic and healthy groups, respectively. Logistic regression analysis gave an odds ratio (OR) for a patient with psoriasis or diabetes type I of being sensitized to 0·18 [95% confidence interval (CI): 0·039-0·85], P = 0·031 and 0·74 (95% CI: 0·548-1·008), P = 0·056, respectively. A high degree of forkhead box P3-positive (FoxP3(+) ) cells were found in biopsies of positively challenged reactions, but only limited numbers in negatively challenged reactions, with no difference among the groups. No specific mRNA expression was found in the challenged skin of negative elicitation reactions, also indicating no sign of active down-regulation. The study contibutes strongly to the evidence of a decreased susceptibility to develop contact allergy in individuals with autoimmune diseases such as psoriasis. PMID:21668897

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

    PubMed Central

    Wen, Zhonghui

    2004-01-01

    The pathogenesis of Crohn's disease (CD) and ulcerative colitis (UC), the two main forms of inflammatory bowel disease (IBD), is still unclear, but both autoimmune and immune-mediated phenomena are involved. Autoimmune phenomena include the presence of serum and mucosal autoantibodies against intestinal epithelial cells in either form of IBD, and against human tropomyosin fraction five selectively in UC. In addition, perinuclear antineutrophil cytoplasmic antibodies (pANCA) are common in UC, whereas antibodies against Saccharomyces cerevisiae (ASCA) are frequently found in CD. Immune-mediate phenomena include a variety of abnormalities of humoral and cell-mediated immunity, and a generalized enhanced reactivity against intestinal bacterial antigens in both CD and UC. It is currently believed that loss of tolerance against the indigenous enteric flora is the central event in IBD pathogenesis. Various complementary factors probably contribute to the loss of tolerance to commensal bacteria in IBD. They include defects in regulatory T-cell function, excessive stimulation of mucosal dendritic cells, infections or variants of proteins critically involved in bacterial antigen recognition, such as the products of CD-associated NOD2/CARD15 mutations. PMID:15559364

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

    PubMed

    Berrih-Aknin, S

    1995-04-01

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

  8. 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

  9. 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. PMID:26003843

  10. Autoimmune Hemolytic Anemia and Hodgkin's Disease: An Unusual Pediatric Association

    PubMed Central

    Gomes, Maria Miguel; Oliva, Tereza; Pinto, Armando

    2016-01-01

    Autoimmune hemolytic anemia (AIHA) is a recognized complication of lymphoproliferative disorders. AIHA associated with Hodgkin's disease (HD) is uncommon especially in the pediatric population. The diagnosis of AIHA is usually associated with HD at the time of initial presentation or during the course of disease, but it could precede it by years to months. In adults the association of AIHA and HD is more frequent in advanced stages and in the nodular sclerosis and mixed cellularity type HD. Warm immune hemolytic anemia is mainly controlled with steroids and chemotherapy. We report a case of a pediatric patient with direct antiglobulin positive test at the diagnosis of a late relapse of stage III B mixed cellularity type HD. PMID:26904342

  11. GCN2 kinase plays an important role triggering the remission phase of experimental autoimmune encephalomyelitis (EAE) in mice.

    PubMed

    Orsini, Heloisa; Araujo, Leandro P; Maricato, Juliana T; Guereschi, Marcia G; Mariano, Mario; Castilho, Beatriz A; Basso, Alexandre S

    2014-03-01

    Experimental autoimmune encephalomyelitis (EAE) has been widely employed as a model to study multiple sclerosis (MS) and indeed has allowed some important advances in our comprehension of MS pathogenesis. Several pieces of evidence suggest that infiltrating Th1 and Th17 lymphocytes are important players leading to CNS demyelination and lesion during the peak of murine EAE. Subsequently, effector T cell responses rapidly decline and the recovery phase of the disease strongly correlates with the expression of anti-inflammatory cytokines and the enrichment of Foxp3+ regulatory T (Treg) cells within the target organ. However, the mechanisms leading to the increased presence of Treg cells and to the remission phase of the disease are still poorly understood. Recent researches demonstrated that chemically induced amino-acid starvation response might suppress CNS immune activity. Here we verified an important participation of the general control nonrepressible 2 (GCN2), a key regulator kinase of the amino-acid starvation response, in the development of the remission phase of EAE in C57BL/6 mice. By immunizing wild type C57BL/6 (WT) and GCN2 knock-out mice (GCN2 KO) with myelin oligodendrocyte glycoprotein peptide (MOG35-55), it was noticed that GCN2 KO mice did not develop the remission phase of the disease and this was associated with higher levels of CNS inflammation and increased presence of effector T cells (Th1/Th17). These animals also showed lower frequency of Treg cells within the CNS as compared to WT animals. Higher expression of indoleamine 2,3-dioxygenase (IDO) and higher frequency of plasmacytoid dendritic cells (pDCs) were found at the peak of the disease in the CNS of WT animals. Our results suggest that the GCN2 kinase-dependent sensing of IDO activity represents an important trigger to the EAE remission phase. The IDO-mediated immunoregulatory events may include the arresting of effector T cell responses and the differentiation/expansion of Treg cells

  12. 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.

  13. Population Based Study of 12 Autoimmune Diseases in Sardinia, Italy: Prevalence and Comorbidity

    PubMed Central

    Sardu, Claudia; Cocco, Eleonora; Mereu, Alessandra; Massa, Roberta; Cuccu, Alessandro; Marrosu, Maria Giovanna; Contu, Paolo

    2012-01-01

    Background The limited availability of prevalence data based on a representative sample of the general population, and the limited number of diseases considered in studies about co-morbidity are the critical factors in study of autoimmune diseases. This paper describes the prevalence of 12 autoimmune diseases in a representative sample of the general population in the South of Sardinia, Italy, and tests the hypothesis of an overall association among these diseases. Methods Data were obtained from 21 GPs. The sample included 25,885 people. Prevalence data were expressed with 95% Poisson C.I. The hypothesis of an overall association between autoimmune diseases was tested by evaluating the co-occurrence within individuals. Results Prevalence per 100,000 are: 552 rheumatoid arthritis, 124 ulcerative colitis, 15 Crohn's disease, 464 type 1 diabetes, 81 systemic lupus erythematosus, 124 celiac disease, 35 myasthenia gravis, 939 psoriasis/psoriatic arthritis, 35 systemic sclerosis, 224 multiple sclerosis, 31 Sjogren's syndrome, and 2,619 autoimmune thyroiditis . An overall association between autoimmune disorders was highlighted. Conclusions The comparisons with prevalence reported in current literature do not show outlier values, except possibly for a few diseases like celiac disease and myasthenia gravis. People already affected by a first autoimmune disease have a higher probability of being affected by a second autoimmune disorder. In the present study, the sample size, together with the low overall prevalence of autoimmune diseases in the population, did not allow us to examine which diseases are most frequently associated with other autoimmune diseases. However, this paper makes available an adequate control population for future clinical studies aimed at exploring the co-morbidity of specific pairs of autoimmune diseases. PMID:22396771

  14. Autoimmune hepatitis

    MedlinePlus

    ... diseases. These include: Graves disease Inflammatory bowel disease Rheumatoid arthritis Scleroderma Sjogren syndrome Systemic lupus erythematosus Thyroiditis Type 1 diabetes Ulcerative colitis Autoimmune hepatitis may occur in family ...

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

    PubMed Central

    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. PMID:26090502

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

    PubMed Central

    Hew, Meilyn; O’Connor, Kevin; Edel, Michael J.; Lucas, Michaela

    2015-01-01

    The ability to generate inducible pluripotent stem cells (iPSCs) and the potential for their use in treatment of human disease is of immense interest. Autoimmune diseases, with their limited treatment choices are a potential target for the clinical application of stem cell and iPSC technology. IPSCs provide three potential ways of treating autoimmune disease; (i) providing pure replacement of lost cells (immuno-reconstitution); (ii) through immune-modulation of the disease process in vivo; and (iii) for the purposes of disease modeling in vitro. In this review, we will use examples of systemic, system-specific and organ-specific autoimmunity to explore the potential applications of iPSCs for treatment of autoimmune diseases and review the evidence of iPSC technology in auto-immunity to date. PMID:26239553

  17. 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. PMID:27511737

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

    PubMed Central

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

    2014-01-01

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

  19. Extracorporeal photopheresis as a therapy for autoimmune diseases.

    PubMed

    Kuzmina, Zoya; Stroncek, David; Pavletic, Steven Z

    2015-08-01

    Systemic autoimmune diseases (AID) have multiorgan, heterogeneous clinical presentations and are characterized by dysregulation of the immune system, immunodeficiency, irreversible organ damage and increased morbidity and mortality. Preventing or decreasing flares of AID correlate with durable disease control, significant reduction of inflammation and prevention of disability or therapy-related toxicity. There is an urgent need for better treatment of severe, therapy-refractory AID. Extracorporeal photopheresis (ECP) is a cell-based immunomodulatory treatment which has been extensively used in variety of autoimmune disorders for the last two decades. ECP treatment is FDA approved for the treatment of cutaneous T-cell lymphoma (CTCL) with particularly promising results seen in graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (HCT). Prolonged therapy is safe, well tolerated and allows reduction of systemic immunosuppression in therapy-refractory patients. Both clinical and experimental evidence suggest that ECP mechanism of action is characterized by apoptosis and phagocytosis of activated cells by antigen-presenting cells (APC), secretion of anti-inflammatory cytokines and stimulation of regulatory T cells (Tregs). The focus of this paper is to review the current evidence of ECP use in the treatment of AID. Here, we summarize the experience of nine major AID from 65 published reports. The key findings demonstrate substantial evidence of ECP feasibility, safety and in some AID also promising efficacy. However, the role of ECP in AID therapy is not established as most published studies are retrospective with limited number of patients and the trials are small or poorly standardized. The available data support future investigations of ECP as a therapeutic modality for the treatment of AID in well-designed prospective clinical studies. J PMID:25546289

  20. 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.

  1. 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...

  2. Autoimmune diseases, gastrointestinal disorders and the microbiome in schizophrenia: More than a gut feeling

    PubMed Central

    Severance, Emily G.; Yolken, Robert H.; Eaton, William W.

    2014-01-01

    Autoimmunity, gastrointestinal (GI) disorders and schizophrenia have been associated with one another for a long time. This paper reviews these connections and provides a context by which multiple risk factors for schizophrenia may be related. Epidemiological studies strongly link schizophrenia with autoimmune disorders including enteropathic celiac disease. Exposure to wheat gluten and bovine milk casein also contribute to non-celiac food sensitivities in susceptible individuals. Co-morbid GI inflammation accompanies humoral immunity to food antigens, occurs early during the course of schizophrenia and appears to be independent from antipsychotic-generated motility effects. This inflammation impacts endothelial barrier permeability and can precipitate translocation of gut bacteria into systemic circulation. Infection by the neurotropic gut pathogen, Toxoplasma gondii, will elicit an inflammatory GI environment. Such processes trigger innate immunity, including activation of complement C1q, which also functions at synapses in the brain. The emerging field of microbiome research lies at the center of these interactions with evidence that the abundance and diversity of resident gut microbiota contribute to digestion, inflammation, gut permeability and behavior. Dietary modifications of core bacterial compositions may explain inefficient gluten digestion and how immigrant status in certain situations is a risk factor for schizophrenia. Gut microbiome research in schizophrenia is in its infancy, but data in related fields suggest disease-associated altered phylogenetic compositions. In summary, this review surveys associative and experimental data linking autoimmunity, GI activity and schizophrenia, and proposes that understanding of disrupted biological pathways outside of the brain can lend valuable information regarding pathogeneses of complex, polygenic brain disorders. PMID:25034760

  3. Autoimmune diseases, gastrointestinal disorders and the microbiome in schizophrenia: more than a gut feeling.

    PubMed

    Severance, Emily G; Yolken, Robert H; Eaton, William W

    2016-09-01

    Autoimmunity, gastrointestinal (GI) disorders and schizophrenia have been associated with one another for a long time. This paper reviews these connections and provides a context by which multiple risk factors for schizophrenia may be related. Epidemiological studies strongly link schizophrenia with autoimmune disorders including enteropathic celiac disease. Exposure to wheat gluten and bovine milk casein also contribute to non-celiac food sensitivities in susceptible individuals. Co-morbid GI inflammation accompanies humoral immunity to food antigens, occurs early during the course of schizophrenia and appears to be independent from antipsychotic-generated motility effects. This inflammation impacts endothelial barrier permeability and can precipitate translocation of gut bacteria into systemic circulation. Infection by the neurotropic gut pathogen, Toxoplasma gondii, will elicit an inflammatory GI environment. Such processes trigger innate immunity, including activation of complement C1q, which also functions at synapses in the brain. The emerging field of microbiome research lies at the center of these interactions with evidence that the abundance and diversity of resident gut microbiota contribute to digestion, inflammation, gut permeability and behavior. Dietary modifications of core bacterial compositions may explain inefficient gluten digestion and how immigrant status in certain situations is a risk factor for schizophrenia. Gut microbiome research in schizophrenia is in its infancy, but data in related fields suggest disease-associated altered phylogenetic compositions. In summary, this review surveys associative and experimental data linking autoimmunity, GI activity and schizophrenia, and proposes that understanding of disrupted biological pathways outside of the brain can lend valuable information regarding pathogeneses of complex, polygenic brain disorders. PMID:25034760

  4. 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

  5. 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

  6. Proteins derived from neutrophil extracellular traps may serve as self-antigens and mediate organ damage in autoimmune diseases

    PubMed Central

    Knight, Jason S.; Carmona-Rivera, Carmelo; Kaplan, Mariana J.

    2012-01-01

    Neutrophils are the most abundant leukocytes in circulation and represent one of the first lines of defense against invading pathogens. Neutrophils possess a vast arsenal of antimicrobial proteins, which can be released from the cell by a death program termed NETosis. Neutrophil extracellular traps (NETs) are web-like structures consisting of decondensed chromatin decorated with granular and cytosolic proteins. Both exuberant NETosis and impaired clearance of NETs have been implicated in the organ damage of autoimmune diseases, such as systemic lupus erythematosus (SLE), small vessel vasculitis (SVV), and psoriasis. NETs may also represent an important source of modified autoantigens in SLE and SVV. Here, we review the autoimmune diseases linked to NETosis, with a focus on how modified proteins externalized on NETs may trigger loss of immune tolerance and promote organ damage. PMID:23248629

  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. PMID:26984090

  8. [The management of autoimmune liver diseases: from the consensus to the guideline].

    PubMed

    Ma, X

    2016-01-20

    Autoimmune liver disease is an aberrant autoimmunity-mediated liver injury, its early diagnosis and management can significantly improve the prognosis of patients and their quality of life. Most recently, the 3 societies of Hepatology, Gastroenterology and Infectious Diseases of the Chinese Medical Association jointly released 4 consensuses about the diagnosis and management of autoimmune liver diseases. This academic milestone in the Chinese hepatology field should have major impact on the standardization and improvement of autoimmune liver disease management in China. We urgently need to carry out the joint clinical studies, in particular, multicenter randomized control prospective trials, to clarify the clinical and pathological features of Chinese patients with autoimmune liver diseases. We hope more and more original findings in China may promote the transition from the consensuses to guidelines in the near future. PMID:26983383

  9. 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. PMID:25146442

  10. Cardiac autoimmunity in HIV related heart muscle disease

    PubMed Central

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

    1998-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2016-08-01

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

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

    PubMed

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

    2015-12-15

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

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

    PubMed Central

    Zhang, Peng

    2015-01-01

    Background Thymoma is thymic epithelial cell tumor. Studies have shown that thymoma associated with autoimmune disorders and possible mechanisms of autoimmune diseases is the central immune tolerance and peripheral tolerance obstacles have resulted in the breaking of the autoimmune response activation and immune tolerance. Tc17 cells and Th17 cells have been shown play an important role in tumor and autoimmune diseases’ development process. This study test the distribution of Tc17cells in thymoma and the expression of RORγt in thymus of thymoma patients with myasthenia gravis (MG) or other autoimmune diseases, the frequency of Th17/Tc17 in PBMCs, to explore the expression of Th17/Tc17 cells in thymoma accompany with autoimmune diseases or autoimmune disorders. Methods In this study, grouped as follows: (I) thymoma non gravis group (Tm groups); (II) thymoma with MG group thymoma with MG (MG group); (III) thymoma with MG associated with other autoimmune diseases group or anti- nuclear antibodies abnormal elevation of the group (AD group), to analyze the basic differences between the groups. In this study, we examined the RT-PCR to detect RORγt in the thymoma tissue, immunohistochemical double staining method to detect Tc17 cells expression and localization in the thymoma tissue distribution expression Th17/Tc17 in PBMCs by flow cytometry [Interleukin (IL)-17-producing CD8+ cells as Thl7 cells and IL-17-producing CD4+ cells as Tcl7 cells], analysis of differential expression of three in each group thymoma; and explore of Th17/Tc17 expression. Results (I) Tm groups and AD group serum CD8+ cells was statistically significant (P<0.05), Tm groups and MG group serum CD4+ cells/CD8+ cells was statistically significant (P<0.05); Tm and MG/AD group serum, C3 statistically significant (P<0.05); Tm and MG/AD group serum, CRP statistically significant (P<0.05); Tm groups and AD group serum IgE cells was statistically significant (P<0.05); (II) in thymoma tissus, the level of

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

    PubMed

    Tyndall, Alan; van Laar, Jacob M

    2016-06-01

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

  16. [Aplastic anemia combined with an autoimmune disease (eosinophilic fasciitis or glomerulonephritis)].

    PubMed

    Stebler, C; Tichelli, A; Gratwohl, A; Dazzi, H; Nissen, C; Steiger, U; Speck, B

    1991-06-01

    We describe 3 patients with aplastic anemia and an autoimmune disease. Two had eosinophilic fasciitis and 1 glomerulonephritis. In all patients both diseases were successfully treated by immunosuppressive therapy. Pathophysiological aspects of this association are discussed. PMID:1857945

  17. 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

  18. 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

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

    PubMed Central

    de Campos, Fernando Peixoto Ferraz

    2015-01-01

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

  20. Autoimmunity and the basal ganglia: new insights into old diseases.

    PubMed

    Dale, R C

    2003-03-01

    Sydenham's chorea (SC) occurs weeks or months after Group A streptococcal infection, and is characterized by involuntary, purposeless movements of the limbs, in addition to behavioural alteration. There is a body of evidence which suggests that SC is an immune-mediated brain disorder with regional localization to the basal ganglia. Recent reports have suggested that the spectrum of post-streptococcal CNS disease is broader than chorea alone, and includes other hyperkinetic movement disorders (tics, dystonia and myoclonus). In addition, there are high rates of behavioural sequelae, particularly emotional disorders such as obsessive-compulsive disorder, anxiety and depression. These findings have lead to the hypothesis that similar immune-mediated basal ganglia processes may be operating in common neuropsychiatric disease such as tic disorders, Tourette syndrome and obsessive-compulsive disorder. This review analyses the historical aspects of post-streptococcal CNS disease, and the recent immunological studies which have addressed the hypothesis that common neuropsychiatric disorders may be secondary to basal ganglia autoimmunity. PMID:12615982

  1. Immunoproteomics technologies in the discovery of autoantigens in autoimmune diseases.

    PubMed

    Ganesan, Vinitha; Ascherman, Dana P; Minden, Jonathan S

    2016-05-01

    Proteomics technologies are often used for the identification of protein targets of the immune system. Here, we discuss the immunoproteomics technologies used for the discovery of autoantigens in autoimmune diseases where immune system dysregulation plays a central role in disease onset and progression. These autoantigens and associated autoantibodies can be used as potential biomarkers for disease diagnostics, prognostics and predicting/monitoring drug responsiveness (theranostics). Here, we compare a variety of methods such as mass spectrometry (MS)-based [serological proteome analysis (SERPA), antibody mediated identification of antigens (AMIDA), circulating immune complexome (CIC) analysis, surface enhanced laser desorption/ionization-time of flight (SELDI-TOF)], nucleic acid based serological analysis of antigens by recombinant cDNA expression cloning (SEREX), phage immunoprecipitation sequencing (PhIP-seq) and array-based immunoscreening (proteomic microarrays), luciferase immunoprecipitation systems (LIPS), nucleic acid programmable protein array (NAPPA) methods. We also review the relevance of immunoproteomic data generated in the last 10 years, with a focus on the aforementioned MS based methods. PMID:27115324

  2. Epigenetics of autoantigens: new opportunities for therapy of autoimmune diseases.

    PubMed

    Radic, Marko; Muller, Sylviane

    2013-01-01

    The field of epigenetics requires that traditional divisions between scientific disciplines give way to cross-fertilization of concepts and ideas from different areas of investigation. Such is the case with research in autoimmunity. Recent discoveries of stimuli that induce autoimmunity reveal that epigenetic marks of autoantigens are recognized by autoreactive B and T cell receptors. Thus, insights into the initiation of autoimmunity, its prevention and therapy will arise from understanding the biochemistry, cell biology and microbiology of autoantigen epigenetics. Here, we highlight potential benefits from the inhibition of a histone modifying enzyme and the administration of a phosphorylated, spliceosome-derived peptide, in the treatment of autoimmunity. PMID:25512708

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

    PubMed

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

    2016-05-01

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

  4. Was the appearance of surfactants in air breathing vertebrates ultimately the cause of decompression sickness and autoimmune disease?

    PubMed

    Arieli, Ran

    2015-01-15

    All air breathing vertebrates are endowed with pulmonary surfactants, surface-active lipoprotein complexes formed by type II alveolar cells. Surfactants are deposited in clearly defined areas on the luminal aspect of blood vessels, producing hydrophobic spots. Gas nanobubbles measuring 5-100nm form spontaneously on the smooth hydrophobic spot from dissolved gas. Bubbles nucleate and grow at these spots after decompression from high pressure. Proteins with hydrophobic regions circulating in the blood will adhere to the gas phase-plasma interface. Deformation of their secondary and tertiary configuration will present them as foreign molecules or autoantigens. Components of the intact protein which are also present in a deformed protein may be recognized as foreign too. This process is proposed as the trigger for autoimmune diseases. The presence of autoimmune disease in air breathing vertebrates, increased autoimmunity and the elevated risk of decompression sickness with age, as well as variable sensitivity to both diseases, can be matched with the appearance of surfactant spots. Eliminating these spots may provide protection against both diseases. PMID:25462836

  5. 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

  6. Microbiome and mucosal inflammation as extra-articular triggers for rheumatoid arthritis and autoimmunity

    PubMed Central

    Brusca, Samuel B; Abramson, Steven B; Scher, Jose U

    2014-01-01

    Purpose of Review Despite progress towards understanding the molecular pathogenesis of Rheumatoid Arthritis (RA), its etiology remains elusive. Genes are important but rather insufficient to explain the majority of RA cases. This review describes novel data supporting the microbiome and its interactions with the human host as potential en(‘in’)vironmental factors in RA pathogenesis. Recent Findings Animal models of inflammatory arthritis have shown that the presence of bacteria in mucosal surfaces is sufficient to alter local and systemic host immune responses and elicit joint inflammation. Human RA studies have focused on three mucosal sites: the gut, the gingival, and the respiratory tree. The oral microbiome, and specifically Porphyromonas gingivalis (P. gingivalis), has long been implicated. Novel sequencing technologies have allowed investigations into the role of the gut microbiome in the development of autoimmune arthritis. Most recently, the pulmonary parenchyma has also been described as yet another possible mucosal site of initiation of autoimmunity in RA. Summary Emerging data implicates the microbiome in RA pathogenesis. Mucosal sites exposed to a high load of bacterial antigens - such as the periodontium, lung, and gut - may represent the initial site of autoimmune generation. If validated, these findings could lead to the discovery of potential biomarkers and therapeutic approaches in the pre-clinical and clinical phases of RA. PMID:24247114

  7. 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

  8. Immunoblot assay for detection of autoantibodies in autoimmune disease.

    PubMed

    Capín, N G; Rodriguez, M R; Lavalle, C M; Ortiz-Ortiz, L

    1992-01-01

    When detecting antinuclear antibodies (ANA) a similar indirect immunofluorescence (IIF) pattern may be produced by antibodies which correspond to different antigenic specificity or to diverse autoimmune disorders. To circumvent this problem, we used an immunoblotting against total antigen from HEp-2 cells (TA-HEp-2-C) which proved to be more specific and sensitive than IIF, since it detected up to 40 antigenic bands and an immunoblot pattern characteristic of each individual and unrelated to the fluorescence patterns of ANA. The analysis of immunoblot patterns is of great diagnostic value, since in patients with systemic lupus erythematosus (SLE) the antigenic zone is found between 21 and 48 kDa, whereas in other rheumatic diseases with or without positive ANA antibodies by IIF it is found between 14 and 21 kDa. Bands which appear after 50 kDa may or may not have pathological significance since they are present in most normal individuals. The use of reference sera allowed the identification in the extract of previously described antigens relevant to these diseases. Some patients showed bands which have yet to be reported and may be clinically significant on their own or in association with other autoantibodies. The long-term follow-up of these immunoblot patterns may prove to be of prognostic importance. PMID:1403353

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

    PubMed

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

    2006-01-01

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

  10. Genetics of autoimmune diseases: insights from population genetics

    PubMed Central

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

    2015-01-01

    Human genetic diversity is the result of population genetic forces. This genetic variation influences disease risk and contributes to health disparities. Autoimmune diseases (ADs) are a family of complex heterogeneous disorders with similar underlying mechanisms characterized by immune responses against self. Collectively, ADs are common, exhibit gender and ethnic disparities, and increasing incidence. As natural selection is an important influence on human genetic variation, and immune function genes are enriched for signals of positive selection, it is thought that the prevalence of AD risk alleles seen in different population is partially the result of differing selective pressures (for example, due to pathogens). With the advent of high-throughput technologies, new analytical methodologies and large-scale projects, evidence for the role of natural selection in contributing to the heritable component of ADs keeps growing. This review summarizes the genetic regions associated with susceptibility to different ADs and concomitant evidence for selection, including known agents of selection exerting selective pressure in these regions. Examples of specific adaptive variants with phenotypic effects are included as an evidence of natural selection increasing AD susceptibility. Many of the complexities of gene effects in different ADs can be explained by population genetics phenomena. Integrating AD susceptibility studies with population genetics to investigate how natural selection has contributed to genetic variation that influences disease risk will help to identify functional variants and elucidate biological mechanisms. As such, the study of population genetics in human population holds untapped potential for elucidating the genetic causes of human disease and more rapidly focusing to personalized medicine. PMID:26223182

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

    PubMed

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

    2007-10-01

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

  13. Contributions of neutrophils to the adaptive immune response in autoimmune disease

    PubMed Central

    Pietrosimone, Kathryn M; Liu, Peng

    2016-01-01

    Neutrophils are granulocytic cytotoxic leukocytes of the innate immune system that activate during acute inflammation. Neutrophils can also persist beyond the acute phase of inflammation to impact the adaptive immune response during chronic inflammation. In the context of the autoimmune disease, neutrophils modulating T and B cell functions by producing cytokines and chemokines, forming neutrophil extracellular traps, and acting as or priming antigen presentation cells. Thus, neutrophils are actively involved in chronic inflammation and tissue damage in autoimmune disease. Using rheumatoid arthritis as an example, this review focuses on functions of neutrophils in adaptive immunity and the therapeutic potential of these cells in the treatment of autoimmune disease and chronic inflammation. PMID:27042404

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

    PubMed Central

    2012-01-01

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

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

    PubMed

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

    2011-04-01

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

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

    PubMed Central

    2013-01-01

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

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

    PubMed

    Tavakolpour, Soheil; Rahimzadeh, Ghazal

    2016-09-01

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

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

    PubMed Central

    Ivarsson, Anneli; Högberg, Lotta; Svensson, Johan; Carlsson, Annelie

    2014-01-01

    Objectives. Studies have suggested a correlation between untreated celiac disease and risk for other autoimmune diseases. We investigated the prevalence of thyroid autoimmunity in 12-year-old children (i) with symptomatic celiac disease diagnosed and treated with a gluten-free diet, (ii) with screening-detected untreated celiac disease, and (iii) without celiac disease. Methods. Blood samples from 12632 children were collected. All celiac disease cases, previously diagnosed and newly screening-detected, were identified. Per case, 4 referents were matched. Blood samples were analyzed for autoantibodies against thyroid peroxidase (TPOAb). The cut-off value for TPO positivity was set to 100 U/mL. Results. Altogether, 335 celiac disease cases were found. In the entire celiac disease group, 7.2% (24/335) had elevated titers of TPOAb compared to 2.8% (48/1695) of the referents. Among the previously diagnosed celiac disease cases, 7.5% (7/93, OR 2.8, 95% CI 1.2–6.4) was TPOAb positive and among screening-detected cases, 7.0% (17/242, OR 2.6, 95% CI 1.5–4.6) was TPOAb positive. Conclusion. Children with celiac disease showed a higher prevalence of thyroid autoimmunity. We could not confirm the hypothesis that untreated celiac disease is associated with increased risk of developing thyroid autoimmunity. Early initiation of celiac disease treatment might not lower the risk for other autoimmune diseases. PMID:24592326

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

    PubMed

    Mbonile, Lumuli

    2016-04-01

    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. PMID:27032848

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

    PubMed

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

    2014-01-01

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

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

    PubMed

    Maritsi, Despoina N; Zarganis, Diagoras; Metaxa, Zoi; Papaioannou, Georgia; Vartzelis, George

    2013-01-01

    We present a case of a seven-year-old immunocompetent female patient who developed systemic symptoms mimicking an autoimmune rather than an infectious disease. The patient presented with rash, biquotidian fever, night sweats, and arthralgias. There was no antecedent history of cat contact. Investigations showed increased inflammatory markers, leukocytosis, thrombocytosis, hypercalcemia, and raised angiotensin-converting enzyme. Interferon-gamma releasing assay for tuberculosis infection was negative. Abdominal imaging demonstrated multifocal lesions of the liver and spleen (later proved to be granulomata), chest X-ray showed enlarged hilar lymph nodes, and ophthalmology review revealed uveitis. Clinical, laboratory, and imaging features pointed towards sarcoidosis. Subsequently, raised titers (IgM 1 : 32, IgG 1 : 256) against Bartonella confirmed the diagnosis of B. henselae infection. She was treated with gentamycin followed by ciprofloxacin; repeat investigations showed complete resolution of findings. The presence of hepatic and splenic lesions in children with bartonellosis is well documented. Our case, however, exhibited certain unusual findings such as the coexistence of acute ocular and systemic involvement in an immunocompetent host. Serological testing is an inexpensive and effective way to diagnose bartonellosis in immunocompetent patients; we suggest that bartonella serology is included in the baseline tests performed on children with prolonged fever even in the absence of contact with cats in countries where bartonellosis is prevalent. PMID:23424700

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

    PubMed

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

    2015-01-01

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

  3. [Chronic urticaria from the aspect of autoimmune diseases].

    PubMed

    Jovanović, M; Lenert, P; Poljacki, M; Mitić, I; Duran, V

    1995-01-01

    At some time in their lives one in a five persons is affected by urticaria and/or angioedema. The cause of urticaria may never be found in up to one quarter of patients with acute urticaria and in up to 90-95% with chronic urticaria. In this study we present results of our compounded approach (clinical follow up, laboratory findings, allergological testing) to patients with chronic urticaria and autoimmune diseases that progressed into chronic urticaria or started before the onset of the chronic urticaria. Our first case was a 56 year old woman with a 10 month history of chronic urticaria, angioedema and chronic gastritis before the diagnoses of insulin dependent Diabetes mellitus and Hypothyreoidismus primarius were established. Allergological testing reveals specific clinical significant immediate reaction to Balsam Peru. After adequate substitutional therapy was advocated and with specific clinical avoidance of offended allergen, remission was obtained. The second case was a 46 year old female suffering from chronic urticaria (with clinical features of urticaria like vasculitis) associated with hypocomplementemia (particularly C4 depressed) with negative antinuclear antibodies but positive circulating immune complexes after a 2 year follow up the patient developed Systemic lupus erythematosus. The third case was a 63 year old woman who developed chronic urticaria 3 years after total thyroidectomy, with pathological finding of Thyroiditis lymphocytaria-Hashimoto; after the allergological testing, positive lymphocyte transformation test revealed allergical sensitization to Vobenol was substituted with Thyvoral, complete remission was obtained. PMID:7565341

  4. [Oral symptoms of immunologic disorders. Part I. Systemic autoimmune diseases].

    PubMed

    Márton, Krisztina

    2003-02-01

    Polysystemic autoimmune diseases often cause orofacial and stomatognathic symptoms. Inflammation of the temporomandibular joint only rarely and slightly reduces the range of mouth opening (rheumatoid arthritis), which is much more restricted in systemic sclerosis due to fibrosis of perioral soft tissues. Weakness of masticatory and pharyngeal muscles in idiopathic inflammatory myopathies results in dysphagia and dystonia. Ulcerations, petechiae, teleangiectasia, and lichenoid lesions are the characteristic symptoms of oral mucosal involvement, but drugs used in systemic treatment can also cause very similar side effects. Salivary gland hypofunction (Sjögren's syndrome) is common, and in addition to the subjective complaints, leads to objective pathologic alterations such as oral mycotic infections, purulent sialadenitis, and increased caries prevalence. The side effects of steroid administration should be taken into account also during dental treatments. Regular dental follow-up and treatment is a basic part of the complex care of these patients in order to diagnose and cure oral abnormalities and salivary gland hypofunction in time. Impairment of hand functions (rheumatoid arthritis, scleroderma) reduces the oral hygienic activity and therefore special devices, local antiseptics and local fluoride preparations are necessary. PMID:12666389

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

    PubMed

    Burness, Celeste B; Duggan, Sean T

    2016-08-01

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

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

    PubMed

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

    2016-05-01

    Autoimmune diseases affect up to 10% of the world's population, and approximately 80% of those affected are female. The majority of autoimmune diseases occur more commonly in females, although some are more frequent in males, while others show no bias by sex. The mechanisms leading to sex biased disease prevalence are not well understood. However, for adult-onset autoimmune disease, at least some of the cause is usually ascribed to sex hormones. This is because levels of sex hormones are one of the most obvious physiological differences between adult males and females, and their impact on immune system function is well recognised. While for paediatric-onset autoimmune diseases a sex bias is not as common, there are several such diseases for which one sex predominates. For example, the oligoarticular subtype of juvenile idiopathic arthritis (JIA) occurs in approximately three times more girls than boys, with a peak age of onset well before the onset of puberty, and at a time when levels of androgen and oestrogen are low and not strikingly different between the sexes. Here, we review potential explanations for autoimmune disease sex bias with a particular focus on paediatric autoimmune disease, and biological mechanisms outside of sex hormone differences. PMID:26970680

  7. Autoimmune disorders

    MedlinePlus

    ... exact cause of autoimmune disorders is unknown. One theory is that some microorganisms (such as bacteria or viruses) or drugs may trigger changes that confuse the immune system. This may happen ...

  8. 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. PMID:27266815

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

    PubMed

    Pellegrino, Paolo; Radice, Sonia; Clementi, Emilio

    2015-07-01

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

  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. 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

  12. A Possible Mechanism behind Autoimmune Disorders Discovered By Genome-Wide Linkage and Association Analysis in Celiac Disease

    PubMed Central

    Östensson, Malin; Montén, Caroline; Bacelis, Jonas; Gudjonsdottir, Audur H.; Adamovic, Svetlana; Ek, Johan; Ascher, Henry; Pollak, Elisabet; Arnell, Henrik; Browaldh, Lars; Agardh, Daniel; Wahlström, Jan; Nilsson, Staffan; Torinsson-Naluai, Åsa

    2013-01-01

    Celiac disease is a common autoimmune disorder characterized by an intestinal inflammation triggered by gluten, a storage protein found in wheat, rye and barley. Similar to other autoimmune diseases such as type 1 diabetes, psoriasis and rheumatoid arthritis, celiac disease is the result of an immune response to self-antigens leading to tissue destruction and production of autoantibodies. Common diseases like celiac disease have a complex pattern of inheritance with inputs from both environmental as well as additive and non-additive genetic factors. In the past few years, Genome Wide Association Studies (GWAS) have been successful in finding genetic risk variants behind many common diseases and traits. To complement and add to the previous findings, we performed a GWAS including 206 trios from 97 nuclear Swedish and Norwegian families affected with celiac disease. By stratifying for HLA-DQ, we identified a new genome-wide significant risk locus covering the DUSP10 gene. To further investigate the associations from the GWAS we performed pathway analyses and two-locus interaction analyses. These analyses showed an over-representation of genes involved in type 2 diabetes and identified a set of candidate mechanisms and genes of which some were selected for mRNA expression analysis using small intestinal biopsies from 98 patients. Several genes were expressed differently in the small intestinal mucosa from patients with celiac autoimmunity compared to intestinal mucosa from control patients. From top-scoring regions we identified susceptibility genes in several categories: 1) polarity and epithelial cell functionality; 2) intestinal smooth muscle; 3) growth and energy homeostasis, including proline and glutamine metabolism; and finally 4) innate and adaptive immune system. These genes and pathways, including specific functions of DUSP10, together reveal a new potential biological mechanism that could influence the genesis of celiac disease, and possibly also other

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

    PubMed Central

    Khan, Deena; Ansar Ahmed, S.

    2015-01-01

    In recent years, IL-17A (IL-17), a pro-inflammatory cytokine, has received intense attention of researchers and clinicians alike with documented effects in inflammation and autoimmune diseases. IL-17 mobilizes, recruits and activates different cells to increase inflammation. Although protective in infections, overproduction of IL-17 promotes inflammation in autoimmune diseases such as multiple sclerosis, rheumatoid arthritis, psoriasis, among others. Regulating IL-17 levels or action by using IL-17-blocking antibodies or IL-17R antagonist has shown to attenuate experimental autoimmune diseases. It is now known that in addition to IL-17-specific transcription factor, RORγt, several other transcription factors and select microRNAs (miRNA) regulate IL-17. Given that miRNAs are dysregulated in autoimmune diseases, a better understanding of transcriptional factors and miRNA regulation of IL-17 expression and function will be essential for devising potential new therapies. In this review, we will overview IL-17 induction and function in relation to autoimmune diseases. In addition, current findings on transcriptional regulation of IL-17 induction and plausible interplay between IL-17 and miRNA in autoimmune diseases are highlighted. PMID:26236331

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2016-07-01

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

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

    PubMed

    Oldstone, Michael B A

    2014-06-01

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

  17. Loss of Myelin Basic Protein Function Triggers Myelin Breakdown in Models of Demyelinating Diseases.

    PubMed

    Weil, Marie-Theres; Möbius, Wiebke; Winkler, Anne; Ruhwedel, Torben; Wrzos, Claudia; Romanelli, Elisa; Bennett, Jeffrey L; Enz, Lukas; Goebels, Norbert; Nave, Klaus-Armin; Kerschensteiner, Martin; Schaeren-Wiemers, Nicole; Stadelmann, Christine; Simons, Mikael

    2016-07-12

    Breakdown of myelin sheaths is a pathological hallmark of several autoimmune diseases of the nervous system. We employed autoantibody-mediated animal models of demyelinating diseases, including a rat model of neuromyelitis optica (NMO), to target myelin and found that myelin lamellae are broken down into vesicular structures at the innermost region of the myelin sheath. We demonstrated that myelin basic proteins (MBP), which form a polymer in between the myelin membrane layers, are targeted in these models. Elevation of intracellular Ca(2+) levels resulted in MBP network disassembly and myelin vesiculation. We propose that the aberrant phase transition of MBP molecules from their cohesive to soluble and non-adhesive state is a mechanism triggering myelin breakdown in NMO and possibly in other demyelinating diseases. PMID:27346352

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

    PubMed Central

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

    2015-01-01

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

  19. Comorbid Latent Adrenal Insufficiency with Autoimmune Thyroid Disease

    PubMed Central

    Yamamoto, Toshihide

    2015-01-01

    Background Autoimmune thyroid disease (ATD) has been occasionally observed in patients with primary adrenal insufficiency (PAI). In contrast, less than 20 cases of comorbid PAI with ATD have been found in the English literature. One conceivable reason is difficulty in detecting latent PAI. Objective Information of clinical presentation and diagnostics is sought to facilitate diagnosis of latent PAI. Methods Latent PAI was pursued in 11 patients among 159 ATD patients. All of them were maintained in a euthyroid state. Except for one patient with nonrheumatic musculoskeletal symptoms, the other patients, who were asymptomatic in their daily lives, presented with recurrent nonspecific gastrointestinal symptoms or fatigue in stress-associated circumstances. Morning cortisol level <303 nmol/l was used as an inclusion criterion. Their basal adrenocorticotropic hormone levels were normal. The adrenal status was examined by a provocation test, either an insulin-induced hypoglycemia test or a 1-μg intravenous corticotrophin test. Eleven patients showed subnormal cortisol response. They were supplemented with hydrocortisone of doses ≤15 mg/day. After a few months of supplementation, PAI was confirmed by another provocation test. Three patients were excluded because of dissociation of two provocation tests. Results Comorbid latent PAI with ATD was pursued from the symptoms stated above and proven by two provocation tests; it was found in 5% (8/159) of the patients. Conclusion When patients with ATD are troubled by recurrent stress-associated gastrointestinal or constitutional symptoms or nonrheumatic musculoskeletal symptoms which have remained unrelieved by adjustment of thyroid medication, these symptoms may be a manifestation of comorbid latent PAI. It is worth investigating such patients for latent PAI. PMID:26558238

  20. Plasticity of Th17 Cells in Autoimmune Kidney Diseases.

    PubMed

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

    2016-07-15

    The ability of CD4(+) T cells to differentiate into pathogenic Th1 and Th17 or protective T regulatory cells plays a pivotal role in the pathogenesis of autoimmune diseases. Recent data suggest that CD4(+) T cell subsets display a considerable plasticity. This plasticity seems to be a critical factor for their pathogenicity, but also for the potential transition of pathogenic effector T cells toward a more tolerogenic phenotype. The aim of the current study was to analyze the plasticity of Th17 cells in a mouse model of acute crescentic glomerulonephritis and in a mouse chronic model of lupus nephritis. By transferring in vitro generated, highly purified Th17 cells and by using IL-17A fate reporter mice, we demonstrate that Th17 cells fail to acquire substantial expression of the Th1 and Th2 signature cytokines IFN-γ and IL-13, respectively, or the T regulatory transcription factor Foxp3 throughout the course of renal inflammation. In an attempt to therapeutically break the stability of the Th17 phenotype in acute glomerulonephritis, we subjected nephritic mice to CD3-specific Ab treatment. Indeed, this treatment induced an immunoregulatory phenotype in Th17 cells, which was marked by high expression of IL-10 and attenuated renal tissue damage in acute glomerulonephritis. In summary, we show that Th17 cells display a minimum of plasticity in acute and chronic experimental glomerulonephritis and introduce anti-CD3 treatment as a tool to induce a regulatory phenotype in Th17 cells in the kidney that may be therapeutically exploited. PMID:27271566

  1. 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

  2. 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

  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. Environmental triggers for inflammatory bowel disease.

    PubMed

    Ananthakrishnan, Ashwin N

    2013-01-01

    Inflammatory bowel diseases [IBD; Crohn's disease (CD), ulcerative colitis (UC)] are chronic immunologically mediated diseases that are due to a dysregulated immune response to intestinal flora in a genetically susceptible host. Despite advances in genetics, the likelihood of occurrence of disease remains incompletely explained and there appears to be a strong role for the environment in mediating risk of disease. Smoking remains the most widely studied and replicated risk factor, contributing to increased risk and severity of CD while conferring protection against UC. Recent data has suggested novel risk factors. Lower plasma vitamin D is associated with an increased risk of Crohn's disease, and vitamin D supplementation may prevent relapse of disease. Several medications including oral contraceptives, post-menopausal hormone replacement, aspirin, NSAIDs, and antibiotics may increase risk of CD or UC with the mechanisms of effect remaining inadequately defined. There is continuing evidence that depression and psychosocial stress may play a role in the pathogenesis of both CD and UC, while at the same time also increasing risk for disease flares. There is also a growing understanding of the role of diet on IBD, in particular through its effect on the microbiome. Animal protein intake and n-6 fatty acids may increase risk of UC while n-3 fatty acids and dietary fiber may confer protection. The effect of diet on established disease remains poorly studied. There is need for routine measurement of a spectrum of environmental exposures in prospective studies to further our understanding. PMID:23250702

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

    PubMed

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

    2016-09-01

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

  6. Shwachman-Diamond syndrome with autoimmune-like liver disease and enteropathy mimicking celiac disease.

    PubMed

    Veropalumbo, Claudio; Campanozzi, Angelo; De Gregorio, Fabiola; Correra, Antonio; Raia, Valeria; Vajro, Pietro

    2015-02-01

    Liver abnormalities that normalize during infancy as well an enteropathy are reported in Shwachman-Diamond syndrome (SDS). The pathogenesis of both conditions is unknown. We report two SDS cases with autoimmune-like (antismooth muscle and/or antinuclear antibody positivity) liver disease and antigliadin antibody positive inflammatory enteropathy. Hypertransaminasemia did not resolve after immunosuppressive therapy and/or a gluten-free diet. These transient autoimmune phenomena and gut-liver axis perturbations may have played a role in transient SDS hepatopathy and enteropathy. Our report may stimulate other studies to define the relationship between the SDS genetic defect and intestinal permeability as the pathogenic mechanism underlying SDS related liver and intestinal inflammation. PMID:25129842

  7. Bioinformatic Screening of Autoimmune Disease Genes and Protein Structure Prediction with FAMS for Drug Discovery

    PubMed Central

    Ishida, Shigeharu; Umeyama, Hideaki; Iwadate, Mitsuo; Y-h, Taguchi

    2014-01-01

    Autoimmune diseases are often intractable because their causes are unknown. Identifying which genes contribute to these diseases may allow us to understand the pathogenesis, but it is difficult to determine which genes contribute to disease. Recently, epigenetic information has been considered to activate/deactivate disease-related genes. Thus, it may also be useful to study epigenetic information that differs between healthy controls and patients with autoimmune disease. Among several types of epigenetic information, promoter methylation is believed to be one of the most important factors. Here, we propose that principal component analysis is useful to identify specific gene promoters that are differently methylated between the normal healthy controls and patients with autoimmune disease. Full Automatic Modeling System (FAMS) was used to predict the three-dimensional structures of selected proteins and successfully inferred relatively confident structures. Several possibilities of the application to the drug discovery based on obtained structures are discussed. PMID:23855671

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

    PubMed

    Hinks, Timothy S C

    2016-05-01

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

  9. 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. PMID:26433772

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

    PubMed

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

    2016-01-01

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

  11. 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

  12. 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…

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

    PubMed Central

    Riedhammer, Christine; Weissert, Robert

    2015-01-01

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

  14. 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

  15. Duration of gluten exposure in adult coeliac disease does not correlate with the risk for autoimmune disorders

    PubMed Central

    Sategna, G; Solerio, E; Scaglione, N; Aimo, G; Mengozzi, G

    2001-01-01

    BACKGROUND AND AIMS—Duration of gluten exposure seems to predispose adolescents with coeliac disease to autoimmune diseases. In a retrospective cohort study, we assessed the relationship between autoimmune disorders and actual gluten exposure in patients in whom coeliac disease was diagnosed in adult life (⩾16 years).
METHODS—We screened for the presence of autoimmunity in 605 controls (16-84 years) and 422 patients (16-84 years), all of whom had been on gluten withdrawal for at least one year (median follow up 9.5 years). A logistic regression analysis, setting the prevalence of autoimmunity as the dependent variable, was employed to control for independent covariates as predictors of the risk of autoimmunity.
RESULTS—The prevalence of autoimmunity was threefold higher (p<0.00001) in patients than in controls. Mean duration of gluten exposure was 31.2 and 32.6 years for patients with or without autoimmunity. Logistic regression showed that increased age at diagnosis of coeliac disease was related to the prevalence of autoimmune disease while "actual gluten exposure" which takes into account diet compliance, follow up, and age at diagnosis of autoimmune disorders were not predictive for the risk of developing autoimmune diseases (odds ratio 0.82 per year).
CONCLUSION—The prevalence of autoimmune diseases in patients with a late coeliac disease diagnosis does not correlate with duration of gluten intake. Early exposure to gluten may modify the immunological response. Gluten withdrawal does not protect patients with a late diagnosis from autoimmune diseases.


Keywords: coeliac disease; autoimmune disorders; prevalence PMID:11559646

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

    PubMed

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

    2016-09-15

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

  17. Cell wall beta-glucan derived from Candida albicans acts as a trigger for autoimmune arthritis in SKG mice.

    PubMed

    Hida, Shunsuke; Miura, Noriko N; Adachi, Yoshiyuki; Ohno, Naohito

    2007-08-01

    SKG mice are a recently established experimental model for rheumatoid arthritis (RA). Although they spontaneously develop chronic autoimmune arthritis under conventional conditions, SKG mice failed to develop chronic arthritis in a strictly controlled specific pathogen-free (SPF) environment. Beta-glucan (BG) from Laminaria digitata, laminarin (LAM), induced arthritis under SPF conditions, thus BG would be a pathogenic factor for arthritis in SKG mice. Therefore, we prepared BG from Candida albicans, a pathogenic fungus and investigated whether BG from C. albicans induced arthritis in SKG mice under SPF conditions. SKG mice were injected intraperitoneally with particulate BG (oxidative-Candida albicans (OX-CA)), soluble BG (Candida soluble beta-glucan (CSBG)) from C. albicans and LAM as a positive control. In addition, schizophyllan (SPG) from Schizophyllum commune or Mycobacterium whole cells were injected into SKG mice to induce arthritis. Mice injected with OX-CA, CSBG and SPG had more severe arthritis than with LAM, and whole Mycobacterium cells. IL-6 concentration in sera from SKG mice injected with OX-CA or CSBG was high, whereas not detected in sera from mice treated with LAM. In histological analysis, infiltration of inflammatory cells was observed in SKG mice injected with BG. These results suggest that fungal infection may be a factor to induce and exacerbate autoimmune diseases such as RA. PMID:17666828

  18. Autoimmune heart disease: role of sex hormones and autoantibodies in disease pathogenesis

    PubMed Central

    Fairweather, DeLisa; Petri, Michelle A; Coronado, Michael J; Cooper, Leslie T

    2012-01-01

    Cardiovascular disease (CVD) and autoimmune diseases (ADs) are the first and third highest causes of death in the USA, respectively. Men have an increased incidence of the majority of CVDs, including atherosclerosis, myocarditis, dilated cardiomyopathy and heart failure. By contrast, nearly 80% of all ADs occur in women. However, in one category of ADs, rheumatic diseases, CVD is the main cause of death. Factors that link rheumatic ADs to CVD are inflammation and the presence of autoantibodies. In this review we will examine recent findings regarding sex differences in the immunopathogenesis of CVD and ADs, explore possible reasons for the increased occurrence of CVD within rheumatic ADs and discuss whether autoantibodies, including rheumatoid factor, could be involved in disease pathogenesis. PMID:22390491

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

    PubMed

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

    2015-08-01

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

  20. 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

  1. 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. PMID:24352680

  2. Immunotherapy of tuberculosis with Mycobacterium leprae Hsp65 as a DNA vaccine triggers cross-reactive antibodies against mammalian Hsp60 but not pathological autoimmunity.

    PubMed

    Doimo, Nayara T S; Zárate-Bladés, Carlos R; Rodrigues, Rodrigo F; Tefé-Silva, Cristiane; Trotte, Marcele N S; Souza, Patrícia R M; Soares, Luana S; Rios, Wendy M; Floriano, Elaine M; Brandão, Izaira T; Masson, Ana P; Coelho, Verônica; Ramos, Simone G; Silva, Celio L

    2014-01-01

    Despite substantial efforts in recent years toward the development of new vaccines and drugs against tuberculosis (TB), success has remained elusive. Immunotherapy of TB with mycobacterial Hsp65 as a DNA vaccine (DNA-hsp65) results in a reduction of systemic bacterial loads and lung tissue damage, but the high homology of Hsp65 with the mammalian protein raises concern that pathological autoimmune responses may also be triggered. We searched for autoimmune responses elicited by DNA-hsp65 immunotherapy in mice chronically infected with TB by evaluating the humoral immune response and comprehensive histopathology using stereology. Cross-reactive antibodies between mycobacterial and mammalian Hsp60/65 were detected; however, no signs of pathological autoimmunity were found up to 60 days after the end of the therapy. PMID:24607935

  3. Immunotherapy of tuberculosis with Mycobacterium leprae Hsp65 as a DNA vaccine triggers cross-reactive antibodies against mammalian Hsp60 but not pathological autoimmunity

    PubMed Central

    Doimo, Nayara TS; Zárate-Bladés, Carlos R; Rodrigues, Rodrigo F; Tefé-Silva, Cristiane; Trotte, Marcele NS; Souza, Patrícia RM; Soares, Luana S; Rios, Wendy M; Floriano, Elaine M; Brandão, Izaira T; Masson, Ana P; Coelho, Verônica; Ramos, Simone G; Silva, Celio L

    2014-01-01

    Despite substantial efforts in recent years toward the development of new vaccines and drugs against tuberculosis (TB), success has remained elusive. Immunotherapy of TB with mycobacterial Hsp65 as a DNA vaccine (DNA-hsp65) results in a reduction of systemic bacterial loads and lung tissue damage, but the high homology of Hsp65 with the mammalian protein raises concern that pathological autoimmune responses may also be triggered. We searched for autoimmune responses elicited by DNA-hsp65 immunotherapy in mice chronically infected with TB by evaluating the humoral immune response and comprehensive histopathology using stereology. Cross-reactive antibodies between mycobacterial and mammalian Hsp60/65 were detected; however, no signs of pathological autoimmunity were found up to 60 days after the end of the therapy. PMID:24607935

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

    PubMed Central

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

    1990-01-01

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

  5. 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

  6. Possible Role of Staphylococcal Enterotoxin B in the Pathogenesis of Autoimmune Diseases.

    PubMed

    Li, Jing; Yang, Jie; Lu, Yu-wei; Wu, Song; Wang, Ming-rui; Zhu, Ji-min

    2015-09-01

    As a member of superantigens (SAgs) produced by Staphylococcus aureus, staphylococcal enterotoxin B (SEB) is a exotoxin superantigen that can regulate the activity of immunomodulatory and pro-inflammatory cell types. In addition, SEB plays a critical role in the pathogenesis of autoimmune disorders either by initiating the autoimmune process or by inducing a relapse in an individual in clinical remission from an autoimmune disorder. SEB can directly activate T lymphocytes, leading to the release of cytokines, superoxides, or other mediators of inflammation either directly or indirectly, because of its unique ability to cross-link human major histocompatibility complex (MHC) class II and T cell receptors (TCR), forming a trimolecular complex. This review discusses the potential effects of SEB in the pathogenesis of autoimmune diseases such as multiple sclerosis, systemic lupus erythematosus, and rheumatoid arthritis, and explores some updated therapeutic medications to neutralize SEB. PMID:26086678

  7. Granuloma annulare: Pathogenesis, disease associations and triggers, and therapeutic options.

    PubMed

    Piette, Evan W; Rosenbach, Misha

    2016-09-01

    Granuloma annulare (GA) represents a cutaneous reaction pattern of unknown cause with a variety of previously described potential disease associations and triggers. This review attempts to synthesize the available data regarding potential etiopathogenesis, reviews the available data on potential GA disease associations and work-up indicated for patients with GA, and discusses potential inciting triggers. In the final part, this article describes the available treatments options and supporting data, and provides a framework for approaching management of patients with GA. The previous accompanying article provided a comprehensive overview of the available information known about the clinical variants, epidemiology, genetics, and histology of GA. PMID:27543210

  8. Subacute Cutaneous Lupus Erythematosus Triggered by Radiotherapy

    PubMed Central

    Kolm, I.; Pawlik, E.; Eggmann, N.; Kamarachev, J.; Kerl, K.; French, L.E.; Hofbauer, G.F.L.

    2013-01-01

    Background The origin of collagen autoimmune diseases is not fully understood. Some studies postulate a mechanism of molecular mimicry or heterologous immunity following viral infections triggering autoimmunity. Apart from infections, other exogenous factors such as visible light or X-rays have been reported to incite autoimmunity. Case Report We report a case of histologically and serologically confirmed subacute lupus erythematosus (SCLE) following radiotherapy for breast cancer. Discussion The close temporal and spatial correlation between radiotherapy and onset of SCLE in this patient suggests that an autoimmune reaction may have been triggered locally by functionally altering the immune system and breaking self-tolerance. PMID:24019776

  9. M. paratuberculosis and Parkinson's disease--is this a trigger.

    PubMed

    Dow, Coad Thomas

    2014-12-01

    Genetic linkage studies and genome wide analysis have provided insights into complex medical diseases. Mycobacterium avium ss. paratuberculosis (MAP) causes Johne's disease, an important enteric inflammatory disease mostly studied in ruminant animals. MAP is also the putative cause of Crohn's disease. Moreover, MAP has been linked to other inflammatory diseases: sarcoidosis, Blau syndrome, autoimmune diabetes, autoimmune thyroiditis and multiple sclerosis. Genetic studies reveal an association between Parkinson's disease (PD), leprosy and Crohn's disease and since discovered, these findings have been considered "surprising". Autophagy and ubiquitin-proteosome systems are cellular systems that both fight intracellular pathogens (xenophagy) and maintain cellular protein quality control. PD is a common neurodegenerative disease that manifests clinically as a profound movement disorder. The recognized genetic defects of PD create disruption of cellular homeostasis that result in protein folding abnormalities of PD called Lewy bodies. Those same genetic defects are associated with susceptibility to intracellular pathogens, including mycobacteria. It is now understood that PD Lewy body pathology starts in the enteric nervous system and "spreads" to the brain in a retrograde fashion via the vagus nerve. This is the same process by which prions affect the brain. Lewy body pathology of the enteric nervous system predates the Lewy body pathology of the central nervous system (CNS) by years or even decades. This article proposes that genetic defects associated with PD also result in a permissive environment for MAP infection--ineffective xenophagy. It postulates that beginning as an enteric infection, MAP--via the vagus nerve--initiates a pathologic process that results in a targeted neuroinvasion of the CNS. The article proposes that MAP infection and resultant PD pathology are due, in the genetically at-risk and age dependant, to the consumptive exhaustion of the protein

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

    PubMed

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

    2009-01-01

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

  11. 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. PMID:25970132

  12. 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

  13. 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

  14. High Prevalence of Systemic Autoimmune Diseases in Patients with Menière's Disease

    PubMed Central

    Gazquez, Irene; Soto-Varela, Andres; Aran, Ismael; Santos, Sofia; Batuecas, Angel; Trinidad, Gabriel; Perez-Garrigues, Herminio; Gonzalez-Oller, Carlos; Acosta, Lourdes; Lopez-Escamez, Jose A.

    2011-01-01

    Background Autoimmunity appears to be associated with the pathophysiology of Meniere's disease (MD), an inner ear disorder characterized by episodes of vertigo associated with hearing loss and tinnitus. However, the prevalence of autoimmune diseases (AD) in patients with MD has not been studied in individuals with uni or bilateral sensorineural hearing loss (SNHL). Methods and Findings We estimated the prevalence of AD in 690 outpatients with MD with uni or bilateral SNHL from otoneurology clinics at six tertiary referral hospitals by using clinica criteria and an immune panel (lymphocyte populations, antinuclear antibodies, C3, C4 and proinflammatory cytokines TNFα, INFγ). The observed prevalence of rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and ankylosing spondylitis (AS) was higher than expected for the general population (1.39 for RA, 0.87 for SLE and 0.70 for AS, respectively). Systemic AD were more frequently observed in patients with MD and diagnostic criteria for migraine than cases with MD and tension-type headache (p = 0.007). There were clinical differences between patients with uni or bilateral SNHL, but no differences were found in the immune profile. Multiple linear regression showed that changes in lymphocytes subpopulations were associated with hearing loss and persistence of vertigo, suggesting a role for the immune response in MD. Conclusions Despite some limitations, MD displays an elevated prevalence of systemic AD such as RA, SLE and AS. This finding, which suggests an autoimmune background in a subset of patients with MD, has important implications for the treatment of MD. PMID:22053211

  15. Toxins Targeting the KV1.3 Channel: Potential Immunomodulators for Autoimmune Diseases

    PubMed Central

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

    2015-01-01

    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. PMID:25996605

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

    PubMed

    Katz, Daphna; Katz, Itay; Golan, Amir

    2016-02-01

    Medical uses of Cannabis sativa have been known for over 6,000 years. Nowadays, cannabis is mostly known for its psychotropic effects and its ability to relieve pain, even though there is evidence of cannabis use for autoimmune diseases like rheumatoid arthritis centuries ago. The pharmacological therapy in autoimmune diseases is mainly based on immunosuppression of diffefent axes of the immune system while many of the drugs have major side effects. In this review we set out to examine the rule of Cannabis sativa as an immunomodulator and its potential as a new treatment option. In order to examine this subject we will focus on some major autoimmune diseases such as diabetes type I and rheumatoid arthritis. PMID:27215114

  17. The emerging relationship between neuromyelitis optica and systemic rheumatologic autoimmune disease.

    PubMed

    Wingerchuk, Dean M; Weinshenker, Brian G

    2012-01-01

    Neuromyelitis optica (NMO) and NMO spectrum disorders (NMOSD) are associated with autoantibodies that target aquaporin-4 and, in many cases, multiple other autoantibodies, including antinuclear antibody and antibodies to extractable nuclear antigens. The clinical syndromes that define NMO and NMOSD, especially longitudinally extensive transverse myelitis and optic neuritis, can also occur in the context of established rheumatologic diseases such as systemic lupus erythematosus and Sjögren syndrome and other organ-specific autoimmune diseases. These observations raise questions fundamental to both clinical practice and etiologic research. For example, they could suggest that NMO is one manifestation of a genetic tendency toward humoral autoimmunity. Alternatively, they might indicate that NMO is a central nervous system complication of a multisystem rheumatologic disease. We describe the historical background of this controversy, summarize the current evidence that addresses NMO-systemic autoimmunity relationships, and discuss the practical implications for clinical management. PMID:22146604

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2015-01-01

    This review summarizes and integrates research on vitamin D and CD4+ T-lymphocyte biology to develop new mechanistic insights into the molecular etiology of autoimmune disease. A deep understanding of molecular mechanisms relevant to gene–environment interactions is needed to deliver etiology-based autoimmune disease prevention and treatment strategies. Evidence linking sunlight, vitamin D, and the risk of multiple sclerosis and type 1 diabetes is summarized to develop the thesis that vitamin D is the environmental factor that most strongly influences autoimmune disease development. Evidence for CD4+ T-cell involvement in autoimmune disease pathogenesis and for paracrine calcitriol signaling to CD4+ T lymphocytes is summarized to support the thesis that calcitriol is sunlight’s main protective signal transducer in autoimmune disease risk. Animal modeling and human mechanistic data are summarized to support the view that vitamin D probably influences thymic negative selection, effector Th1 and Th17 pathogenesis and responsiveness to extrinsic cell death signals, FoxP3+CD4+ T-regulatory cell and CD4+ T-regulatory cell type 1 (Tr1) cell functions, and a Th1–Tr1 switch. The proposed Th1–Tr1 switch appears to bridge two stable, self-reinforcing immune states, pro- and anti-inflammatory, each with a characteristic gene regulatory network. The bi-stable switch would enable T cells to integrate signals from pathogens, hormones, cell–cell interactions, and soluble mediators and respond in a biologically appropriate manner. Finally, unanswered questions and potentially informative future research directions are highlighted to speed delivery of etiology-based strategies to reduce autoimmune disease. PMID:25852682

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

    PubMed

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

    2015-01-01

    This review summarizes and integrates research on vitamin D and CD4(+) T-lymphocyte biology to develop new mechanistic insights into the molecular etiology of autoimmune disease. A deep understanding of molecular mechanisms relevant to gene-environment interactions is needed to deliver etiology-based autoimmune disease prevention and treatment strategies. Evidence linking sunlight, vitamin D, and the risk of multiple sclerosis and type 1 diabetes is summarized to develop the thesis that vitamin D is the environmental factor that most strongly influences autoimmune disease development. Evidence for CD4(+) T-cell involvement in autoimmune disease pathogenesis and for paracrine calcitriol signaling to CD4(+) T lymphocytes is summarized to support the thesis that calcitriol is sunlight's main protective signal transducer in autoimmune disease risk. Animal modeling and human mechanistic data are summarized to support the view that vitamin D probably influences thymic negative selection, effector Th1 and Th17 pathogenesis and responsiveness to extrinsic cell death signals, FoxP3(+)CD4(+) T-regulatory cell and CD4(+) T-regulatory cell type 1 (Tr1) cell functions, and a Th1-Tr1 switch. The proposed Th1-Tr1 switch appears to bridge two stable, self-reinforcing immune states, pro- and anti-inflammatory, each with a characteristic gene regulatory network. The bi-stable switch would enable T cells to integrate signals from pathogens, hormones, cell-cell interactions, and soluble mediators and respond in a biologically appropriate manner. Finally, unanswered questions and potentially informative future research directions are highlighted to speed delivery of etiology-based strategies to reduce autoimmune disease. PMID:25852682

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

    PubMed

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

    2010-03-12

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

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

    PubMed Central

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

    2010-01-01

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

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

    Galipeau, Jacques; Nooka, Ajay K.

    2013-01-01

    The regenerative abilities and the immunosuppressive properties of mesenchymal stromal cells (MSCs) make them potentially the ideal cellular product of choice for treatment of autoimmune and other immune mediated disorders. Although the usefulness of MSCs for therapeutic applications is in early phases, their potential clinical use remains of great interest. Current clinical evidence of use of MSCs from both autologous and allogeneic sources to treat autoimmune disorders confers conflicting clinical benefit outcomes. These varied results may possibly be due to MSC use across wide range of autoimmune disorders with clinical heterogeneity or due to variability of the cellular product. In the light of recent genome wide association studies (GWAS), linking predisposition of autoimmune diseases to single nucleotide polymorphisms (SNPs) in the susceptible genetic loci, the clinical relevance of MSCs possessing SNPs in the critical effector molecules of immunosuppression is largely undiscussed. It is of further interest in the allogeneic setting, where SNPs in the target pathway of MSC's intervention may also modulate clinical outcome. In the present review, we have discussed the known critical SNPs predisposing to disease susceptibility in various autoimmune diseases and their significance in the immunomodulatory properties of MSCs. PMID:24350294

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

    PubMed Central

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

    2006-01-01

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

  6. Alternative strategy for Alzheimer's disease: stress response triggers.

    PubMed

    Smith Sonneborn, Joan

    2012-01-01

    Stress resistance capacity is a hallmark of longevity protection and survival throughout the plant and animal kingdoms. Latent pathway activation of protective cascades, triggered by environmental challenges to tolerate heat, oxygen deprivation, reactive oxygen species (ROS), diet restriction, and exercise provides tolerance to these stresses. Age-related changes and disease vulnerability mark an increase in damage, like damage induced by environmental challenges. An alternative approach to immunotherapy intervention in Alzheimer's Disease is the use of mimetics of stress to upregulate endogenous protective cascades to repair age damage, shift the balance of apoptosis to regeneration to promote delay of onset, and even progression of Alzheimer's disease memory dysfunction. Mimetics of environmental stress, hormetic agents, and triggers, endogenous or engineered, can "trick" activation of expression patterns of repair and rejuvenation. Examples of known candidate triggers of heat response, endogenous antioxidants, DNA repair, exercise, hibernation, and telomeres are available for AD intervention trials. Telomeres and telomerase emerge as major regulators in crossroads of senescence, cancer, and rejuvenation responsive to mimetics of telomeres. Lessons emerge from transgenic rodent models, the long-lived mole rat, clinical studies, and conserved innate pathways of stress resistance. Cross-reaction of benefits of different triggers promises intervention into seemingly otherwise unrelated diseases. PMID:22655213

  7. Autoimmune Liver Disease Post-Liver Transplantation: A Summary and Proposed Areas for Future Research.

    PubMed

    Edmunds, Catherine; Ekong, Udeme D

    2016-03-01

    Autoimmune liver diseases (AILD) are rare diseases with a reported prevalence of less than 50 per 100 000 population. As the research landscape and our understanding of AILDs and liver transplantation evolves, there remain areas of unmet needs. One of these areas of unmet needs is prevention of disease recurrence after liver transplantation. Disease recurrence is not an insignificant event because allograft loss with the need for retransplantation can occur. Patients transplanted for AILD are more likely to experience acute rejection compared to those transplanted for non-AILD, and the reason(s) behind this observation is unclear. Tasks for the future include a better understanding of the pathogenesis of AILD, definition of the precise pathogenetic mechanisms of recurrent AILD, and development of strategies that can identify recipients at risk for disease recurrence. Importantly, the role of crosstalk between alloimmune responses and autoimmune responses in AILD is an important area that needs further study.This article reviews the relevant literature of de novo autoimmune hepatitis, recurrent autoimmune hepatitis, recurrent primary sclerosing cholangitis, and recurrent primary biliary cirrhosis in terms of the clinical entity, the scientific advancements, and future scientific goals to enhance our understanding of these diseases. PMID:26447505

  8. Autoimmune Liver Disease Post-Liver Transplantation: A Summary and Proposed Areas for Future Research

    PubMed Central

    Edmunds, Catherine; Ekong, Udeme D.

    2016-01-01

    Abstract Autoimmune liver diseases (AILD) are rare diseases with a reported prevalence of less than 50 per 100 000 population. As the research landscape and our understanding of AILDs and liver transplantation evolves, there remain areas of unmet needs. One of these areas of unmet needs is prevention of disease recurrence after liver transplantation. Disease recurrence is not an insignificant event because allograft loss with the need for retransplantation can occur. Patients transplanted for AILD are more likely to experience acute rejection compared to those transplanted for non-AILD, and the reason(s) behind this observation is unclear. Tasks for the future include a better understanding of the pathogenesis of AILD, definition of the precise pathogenetic mechanisms of recurrent AILD, and development of strategies that can identify recipients at risk for disease recurrence. Importantly, the role of crosstalk between alloimmune responses and autoimmune responses in AILD is an important area that needs further study. This article reviews the relevant literature of de novo autoimmune hepatitis, recurrent autoimmune hepatitis, recurrent primary sclerosing cholangitis, and recurrent primary biliary cirrhosis in terms of the clinical entity, the scientific advancements, and future scientific goals to enhance our understanding of these diseases. PMID:26447505

  9. The role of neutrophils and NETosis in autoimmune and renal diseases.

    PubMed

    Gupta, Sarthak; Kaplan, Mariana J

    2016-07-01

    Systemic autoimmune diseases are a group of disorders characterized by a failure in self-tolerance to a wide variety of autoantigens. In genetically predisposed individuals, these diseases occur as a multistep process in which environmental factors have key roles in the development of abnormal innate and adaptive immune responses. Experimental evidence collected in the past decade suggests that neutrophils - the most abundant type of white blood cell - might have an important role in the pathogenesis of these diseases by contributing to the initiation and perpetuation of immune dysregulation through the formation of neutrophil extracellular traps (NETs), synthesis of proinflammatory cytokines and direct tissue damage. Many of the molecules externalized through NET formation are considered to be key autoantigens and might be involved in the generation of autoimmune responses in predisposed individuals. In several systemic autoimmune diseases, the imbalance between NET formation and degradation might increase the half-life of these lattices, which could enhance the exposure of the immune system to modified autoantigens and increase the capacity for NET-induced organ damage. This Review details the role of neutrophils and NETs in the pathophysiology of systemic autoimmune diseases, including their effect on renal damage, and discusses neutrophil targets as potential novel therapies for these diseases. PMID:27241241

  10. IL-17/IL-17 receptor system in autoimmune disease: mechanisms and therapeutic potential.

    PubMed

    Zhu, Shu; Qian, Youcun

    2012-06-01

    IL-17 (interleukin-17), a hallmark cytokine of Th17 (T-helper 17) cells, plays critical roles in host defence against bacterial and fungal infections, as well as in the pathogenesis of autoimmune diseases. The present review focuses on current knowledge of the regulation, functional mechanisms and targeting strategies of IL-17 in the context of inflammatory autoimmune diseases. Evidence shows that IL-17 is highly up-regulated at sites of inflammatory tissues of autoimmune diseases and amplifies the inflammation through synergy with other cytokines, such as TNF (tumour necrosis factor) α. Although IL-17 was originally thought to be produced mainly by Th17 cells, a newly defined T-cell subset with a specific differentiation programme and tight regulation, several other cell types (especially innate immune cells) are also found as important sources for IL-17 production. Although IL-17 activates common downstream signalling, including NF-κB (nuclear factor κB), MAPKs (mitogen-activated protein kinases), C/EBPs (CCAAT/enhancer-binding proteins) and mRNA stability, the immediate receptor signalling has been shown to be quite unique and tightly regulated. Mouse genetic studies have demonstrated a critical role for IL-17 in the pathogenesis of variety of inflammatory autoimmune diseases, such as RA (rheumatoid arthritis) and MS (multiple sclerosis). Importantly, promising results have been shown in initial clinical trials of monoclonal antibodies against IL-17 or its receptor (IL-17R) to block IL-17-mediated function in treating autoimmune patients with psoriasis, RA and MS. Therefore targeting IL-17/IL-17R, IL-17-producing pathways or IL-17-mediated signalling pathways can be considered for future therapy in autoimmune diseases. PMID:22324470

  11. Autoimmune hepatitis

    MedlinePlus

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

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

    PubMed

    Rosen, Antony; Casciola-Rosen, Livia

    2016-05-20

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

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

    PubMed

    Li, Xing; Han, Yanping; Sun, Erwei

    2016-05-01

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

  14. A review of the current use of rituximab in autoimmune diseases.

    PubMed

    Gürcan, Hakan M; Keskin, Derin B; Stern, Joel N H; Nitzberg, Matthew A; Shekhani, Haris; Ahmed, A Razzaque

    2009-01-01

    Rituximab is a human/murine chimeric monoclonal antibody primarily used for treating non-Hodgkin's B-cell lymphoma. Recently it has also been used in the treatment of several autoimmune diseases. A literature review was conducted to determine the efficacy of rituximab in the treatment of some of these autoimmune diseases. Multiple mechanisms proposed for the rituximab mediated B cell depletion are also discussed. The efficacy of rituximab is well-established and it is FDA approved for treatment of Rheumatoid arthritis. In this review, data on the use of rituximab is presented from 92 studies involving 1197 patients with the following diseases: systemic lupus erythematosus, idiopathic thrombocytopenic purpura, anti-neutrophil cytoplasmic antibody associated vasculitis, Grave's disease, autoimmune hemolytic anemia, pemphigus vulgaris, hemophilia A, cold agglutinin disease, Sjogren's syndrome, graft vs. host disease, thrombotic thrombocytopenic purpura, cryoglobulinemia, IgM mediated neuropathy, multiple sclerosis, neuromyelitis optica, idiopathic membranous nephropathy, dermatomyositis, and opsoclonus myoclonus. The efficacy varies among different autoimmune diseases. The cumulative data would suggest that in the vast majority of studies in this review, RTX has a beneficial role in their treatment. While rituximab is very effective in the depletion of B cells, current research suggests it may also influence other cells of the immune system by re-establishing immune homeostasis and tolerance. The safety profile of RTX reveals that most reactions are infusion related. In patients with autoimmune diseases the incidence of serious and severe side effects is low. Systemic infection still remains a major concern and may result in death. PMID:19000786

  15. Defining and analyzing geoepidemiology and human autoimmunity.

    PubMed

    Shapira, Yinon; Agmon-Levin, Nancy; Shoenfeld, Yehuda

    2010-05-01

    Autoimmune diseases cumulatively affect 5-10% of the industrial world population and are a significant cause of morbidity and mortality. In recent decades rates are rising worldwide, and autoimmunity can no longer be associated solely with the more developed "Western" countries. Geoepidemiology of autoimmune diseases portrays the burden of these illnesses across various regions and ethnic populations. Furthermore, Geoepidemiology may yield important clues to the genetic and triggering environmental mechanisms of autoimmunity. In this review we compiled and discuss in depth abundant geoepidemiological data pertaining to four major autoimmune conditions, namely type-1 diabetes mellitus, multiple sclerosis, autoimmune thyroid disease, and inflammatory bowel disease. The following key results manifested in this review: 1) Ethno-geographic gradients in autoimmune disease risk are attributable to a complex interplay of genetic and environmental pressures. 2) Industrial regions, particularly Northern Europe and North America, still exhibit the highest rates for most autoimmune diseases. 3) Methods particularly useful in demonstrating the significant influence of genetic and environmental factors include comparative ethnic differences studies, migration studies, and recognition of 'hotspots'. 4) Key environmental determinants of geographical differences include diminished ultraviolet radiation exposure, Western or affluence-related lifestyle, infection exposure, environmental pollutants, nutritional factors and disease-specific precipitants (e.g., iodine exposure). PMID:20034761

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

    PubMed Central

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

    2014-01-01

    Objective Research suggests autoimmune processes to be involved in psychiatric disorders. We aimed to address the prevalence and incidence of autoimmune diseases in a large Finnish patient cohort with anorexia nervosa, bulimia nervosa, and binge eating disorder. Methods Patients (N = 2342) treated at the Eating Disorder Unit of Helsinki University Central Hospital between 1995 and 2010 were compared with general population controls (N = 9368) matched for age, sex, and place of residence. Data of 30 autoimmune diseases from the Hospital Discharge Register from 1969 to 2010 were analyzed using conditional and Poisson regression models. Results Of patients, 8.9% vs. 5.4% of control individuals had been diagnosed with one or more autoimmune disease (OR 1.7, 95% CI 1.5–2.0, P<0.001). The increase in endocrinological diseases (OR 2.4, 95% CI 1.8–3.2, P<0.001) was explained by type 1 diabetes, whereas Crohn's disease contributed most to the risk of gastroenterological diseases (OR 1.8, 95% CI 1.4–2.5, P<0.001). Higher prevalence of autoimmune diseases among patients with eating disorders was not exclusively due to endocrinological and gastroenterological diseases; when the two categories were excluded, the increase in prevalence was seen in the patients both before the onset of the eating disorder treatment (OR 1.5, 95% CI 1.1–2.1, P = 0.02) and at the end of the follow-up (OR 1.4, 95% CI 1.1–1.8, P = 0.01). Conclusions We observed an association between eating disorders and several autoimmune diseases with different genetic backgrounds. Our findings support the link between immune-mediated mechanisms and development of eating disorders. Future studies are needed to further explore the risk of autoimmune diseases and immunological mechanisms in individuals with eating disorders and their family members. PMID:25147950

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

    PubMed

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

    2016-01-01

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

  18. Intrahepatic cholestasis of pregnancy: A risk factor for cancer, autoimmune and cardiovascular diseases?

    PubMed

    Erlinger, Serge

    2016-04-01

    The authors show, in an elegant population-based study, a significant association between intrahepatic cholestasis of pregnancy and liver and biliary cancer. This association is most probably related to the high frequency of hepatitis C and gallstone disease in women with intrahepatic cholestasis of pregnancy, both being risk factors for liver and biliary cancer. In addition, the study clearly shows an increased risk of diabetes mellitus and autoimmune diseases, such as thyroid diseases, psoriasis, autoimmune arthropathies and Crohn's disease, and a small increase in cardiovascular diseases. In practice, a follow-up of liver function tests 6-12 weeks after delivery is strongly recommended to detect a possible associated liver disease. PMID:26500199

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

    PubMed Central

    Simmons, Kimber; Michels, Aaron W.

    2014-01-01

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

  20. Heat shock protein 90: a pathophysiological factor and novel treatment target in autoimmune bullous skin diseases.

    PubMed

    Tukaj, Stefan; Zillikens, Detlef; Kasperkiewicz, Michael

    2015-08-01

    The chaperone heat shock protein 90 (Hsp90), a cell stress-inducible molecule that regulates activity of many client proteins responsible for cellular growth, differentiation and apoptosis, has been proposed as an important therapeutic target in patients with malignancies. More recently, its active participation in (auto)immune processes has been recognized as evidenced by amelioration of inflammatory disease pathways through pharmacological inhibition of Hsp90 in rodent models of autoimmune encephalomyelitis, rheumatoid arthritis and systemic lupus erythematosus. Based on own current research results, this viewpoint essay provides important insights that Hsp90 is also involved as a notable pathophysiological factor in autoimmune blistering dermatoses including epidermolysis bullosa acquisita, bullous pemphigoid and possibly dermatitis herpetiformis. The observed in vitro, ex vivo and in vivo efficacy of anti-Hsp90 treatment in experimental models of autoimmune bullous diseases and its underlying multimodal anti-inflammatory mechanisms of interference with key contributors to autoimmune-mediated blister formation supports the introduction of selective non-toxic Hsp90 inhibitors into the clinical setting for the treatment of patients with these disorders. PMID:25980533

  1. Is obsessive-compulsive disorder an autoimmune disease?

    PubMed

    Arnold, P D; Richter, M A

    2001-11-13

    OBSESSIVE-COMPULSIVE DISORDER (OCD) IS A COMMON and debilitating neuropsychiatric disorder. Although it is widely believed to have a genetic basis, no specific genetic factors have been conclusively identified as yet, leading researchers to look for environmental risk factors that may interact with an underlying genetic susceptibility in affected individuals. Recently, there has been increasing interest in a possible link between streptococcal infections and the development of OCD and tic disorders in children. It has been suggested that OCD in some susceptible individuals may be caused by an autoimmune response to streptococcal infections, that is, a similar biological mechanism to that associated with Sydenham's chorea. The term "pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections" (PANDAS) has been used to describe a subset of children with abrupt onset or exacerbations of OCD or tics, or both, following streptococcal infections. Affected children have relatively early symptom onset, characteristic comorbid symptoms and subtle neurological dysfunction. Neuroimaging studies reveal increased basal ganglia volumes, and the proposed cause involves the cross-reaction of streptococcal antibodies with basal ganglia tissue. Vulnerability to developing PANDAS probably involves genetic factors, and elevated levels of D8/17 antibodies may represent a marker of susceptibility to PANDAS. Prophylactic antibiotic treatments have thus far not been shown to be helpful in preventing symptom exacerbations. Intravenous immunoglobulin therapy may be an effective treatment in selected individuals. Further understanding of the role of streptococcal infections in childhood-onset OCD will be important in determining alternative and effective strategies for treatment, early identification and prevention of this common and debilitating psychiatric disorder. PMID:11760984

  2. Solving the puzzle of autoimmunity: critical questions

    PubMed Central

    Smilek, Dawn E.

    2015-01-01

    Despite recent advances in delineating the pathogenic mechanisms of autoimmune disease, the puzzle that reveals the true picture of these diverse immunological disorders is yet to be solved. We know that the human leukocyte antigen (HLA) loci as well as many different genetic susceptibility loci with relatively small effect sizes predispose to various autoimmune diseases and that environmental factors are involved in triggering disease. Models for mechanisms of disease become increasingly complex as relationships between components of both the adaptive and innate immune systems are untangled at the molecular level. In this article, we pose some of the important questions about autoimmunity where the answers will advance our understanding of disease pathogenesis and improve the rational design of novel therapies. How is autoimmunity triggered, and what components of the immune response drive the clinical manifestations of disease? What determines whether a genetically predisposed individual will develop an autoimmune disease? Is restoring immune tolerance the secret to finding cures for autoimmune disease? Current research efforts seek answers to these big questions. PMID:25750735

  3. Occurrence of Autoimmune Diseases Related to the Vaccine against Yellow Fever

    PubMed Central

    Oliveira, Ana Cristina Vanderley; Maria Henrique da Mota, Licia; dos Santos-Neto, Leopoldo Luiz; De Carvalho, Jozélio Freire; Caldas, Iramaya Rodrigues; Martins Filho, Olindo Assis; Tauil, Pedro Luis

    2014-01-01

    Yellow fever is an infectious disease, endemic in South America and Africa. This is a potentially serious illness, with lethality between 5 and 40% of cases. The most effective preventive vaccine is constituted by the attenuated virus strain 17D, developed in 1937. It is considered safe and effective, conferring protection in more than 90% in 10 years. Adverse effects are known as mild reactions (allergies, transaminases transient elevation, fever, headache) and severe (visceral and neurotropic disease related to vaccine). However, little is known about its potential to induce autoimmune responses. This systematic review aims to identify the occurrence of autoinflammatory diseases related to 17D vaccine administration. Six studies were identified describing 13 possible cases. The diseases were Guillain-Barré syndrome, multiple sclerosis, multiple points evanescent syndrome, acute disseminated encephalomyelitis, autoimmune hepatitis, and Kawasaki disease. The data suggest that 17D vaccination may play a role in the mechanism of loss of self-tolerance. PMID:25405025

  4. Occurrence of Autoimmune Diseases Related to the Vaccine against Yellow Fever.

    PubMed

    Oliveira, Ana Cristina Vanderley; Maria Henrique da Mota, Licia; Dos Santos-Neto, Leopoldo Luiz; De Carvalho, Jozélio Freire; Caldas, Iramaya Rodrigues; Martins Filho, Olindo Assis; Tauil, Pedro Luis

    2014-01-01

    Yellow fever is an infectious disease, endemic in South America and Africa. This is a potentially serious illness, with lethality between 5 and 40% of cases. The most effective preventive vaccine is constituted by the attenuated virus strain 17D, developed in 1937. It is considered safe and effective, conferring protection in more than 90% in 10 years. Adverse effects are known as mild reactions (allergies, transaminases transient elevation, fever, headache) and severe (visceral and neurotropic disease related to vaccine). However, little is known about its potential to induce autoimmune responses. This systematic review aims to identify the occurrence of autoinflammatory diseases related to 17D vaccine administration. Six studies were identified describing 13 possible cases. The diseases were Guillain-Barré syndrome, multiple sclerosis, multiple points evanescent syndrome, acute disseminated encephalomyelitis, autoimmune hepatitis, and Kawasaki disease. The data suggest that 17D vaccination may play a role in the mechanism of loss of self-tolerance. PMID:25405025

  5. Networking in Europe for special centres of excellence for autoimmune diseases.

    PubMed

    Vasconcelos, C; Cervera, R

    2009-09-01

    The studies developed by the European Working Party on Systemic Lupus Erythematosus and the European Forum on Antiphospholipid Antibodies stress the importance of the creation of international networks devoted to the study of autoimmune diseases and the need for centres of excellence in the management of these conditions. This article analyses the importance of such centres and networks in Europe. PMID:19671795

  6. Genetic polymorphisms of CYP2D6 oxidation in patients with autoimmune bullous diseases

    PubMed Central

    Rychlik-Sych, Mariola; Baranska, Małgorzata; Waszczykowska, Elzbieta; Torzecka, Jolanta Dorota; Skretkowicz, Jadwiga

    2013-01-01

    Introduction Bullous skin diseases, which include, among others pemphigoid, pemphigus, and dermatitis herpetiformis are classified as severe autoimmune dermatoses. It has been shown that a pattern of xenobiotic metabolism may play a role in the pathogenesis of autoimmune diseases. Aim To estimate whether the CYP2D6 genotype may be considered a predisposing factor in autoimmune bullous diseases induction. Material and methods The study included 72 patients with autoimmune bullous diseases: 37 with pemphigoid, 21 with pemphigus, and 14 with dermatitis herpetiformis (DH). The CYP2D6 genotypes were analyzed by the polymerase chain reaction fragment length polymorphism (PCR-RFLP) method. Results Relative risk of DH development for particular genotype carriers expressed by odds ratio (OR) was statistically significantly higher for subjects with CYP2D6*1/CYP2D6*4 (OR = 4.2; p = 0.0104) and 2-fold higher for subjects with CYP2D6*4 (OR = 2.3; p = 0.0351). Conclusions The results of the present study show that the CYP2D6 oxidation polymorphism cannot be considered a risk factor for development of pemphigoid and pemphigus, however it might have an impact on dermatitis herpetiformis. PMID:24278077

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

    PubMed

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

    2016-04-01

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

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

    ERIC Educational Resources Information Center

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

    2007-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

    Moustakas, Antonis K; Papadopoulos, George K

    2009-01-01

    The Major Histocompatibility Complex Class II locus is the primary genetic linkage to autoimmune diseases. Susceptibility to each such disease is linked to different alleles, with a few alleles showing also dominant protection. The design of vaccines for autoimmune diseases is a long sought-after goal. As knowledge about the pathogenesis of these diseases has increased, the tools for such an approach have of necessity been refined. We review below the structural essence of MHC II-linked autoimmune diseases which centers on the binding of antigenic peptides to the disease-linked MHC II proteins, and the consequent activation of cognate TCRs from pathogenic CD4+ T cells. The state of affairs in two organ-specific autoimmune diseases, type 1 diabetes, celiac disease are covered, including attempts to treat these via antigen-specific MHC II-guided measures. We offer a couple of testable suggestions as to how this approach could be improved. PMID:19860675

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

    PubMed Central

    Bazsó, Anna; Szodoray, Péter; Szappanos, Ágnes; Korda, Judit; Pálfi, Patrícia; Kiss, Emese; Poór, Gyula

    2015-01-01

    Psoriasis is a systemic immune-inflammatory disease characterized by chronic or recurrent skin symptoms, psoriatic arthritis, enthesopathy, and uveitis. Psoriasis has recently been published to appear with various autoimmune disorders, but the coexistence has been systematically reviewed by only few studies until now. In the present study, charts and electronic database of 4344 patients with various systemic autoimmune disorders, under regular medical control at our department, were reviewed retrospectively searching for association with psoriasis. Hereby, we demonstrate 25 psoriatic patients coinciding with various systemic autoimmune diseases. The coexistence of psoriasis and autoimmune diseases resulted in the worsening of the clinical outcome of the autoimmune diseases as indicated by higher frequency and dosages of glucocorticoid use, need for biologicals, and other comorbidities. These results suggest common environmental and genetic background as well as therapeutic possibilities in the future. PMID:26339139

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

    PubMed

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

    2016-09-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

  16. An evolutionary analysis of RAC2 identifies haplotypes associated with human autoimmune diseases.

    PubMed

    Sironi, Manuela; Guerini, Franca Rosa; Agliardi, Cristina; Biasin, Mara; Cagliani, Rachele; Fumagalli, Matteo; Caputo, Domenico; Cassinotti, Andrea; Ardizzone, Sandro; Zanzottera, Milena; Bolognesi, Elisabetta; Riva, Stefania; Kanari, Yasuyoshi; Miyazawa, Masaaki; Clerici, Mario

    2011-12-01

    The human RAC2 gene encodes a small GTP-binding protein with a pivotal role in immune activation and in the induction of peripheral immune tolerance through restimulation-induced cell death (RICD). Different human pathogens target the protein product of RAC2, suggesting that the gene may be subject to natural selection, and that variants in RAC2 may affect immunological phenotypes in humans. We scanned the genomic region encompassing the entire transcription unit for the presence of putative noncoding regulatory elements conserved across mammals. This information was used to select two RAC2 gene regions and analyze their intraspecific genetic diversity. Results suggest that a region covering the 3' untranslated region has been a target of multiallelic balancing selection (or diversifying selection), and three major RAC2 haplogroups occur in human populations. Haplotypes belonging to one of these clades are associated with increased susceptibility to multiple sclerosis (P = 0.022) and earlier onset of disease symptoms (P = 0.025). This same haplogroup is significantly more common in patients with Crohn's disease compared with healthy controls (P = 0.048). These data reinforce recent evidences that susceptibility alleles/haplotypes are shared among multiple autoimmune disorders and support a causal "role for RAC2" variants in the pathogenesis of autoimmune diseases. Other genes with a role in RICD have previously been associated with autoimmunity in humans, suggesting that this pathway and RAC2 may represent novel therapeutic targets in autoimmune disorders. PMID:21680873

  17. A CD8 T cell transcription signature predicts prognosis in autoimmune disease

    PubMed Central

    McKinney, Eoin F.; Lyons, Paul A.; Carr, Edward J.; Hollis, Jane L.; Jayne, David R. W.; Willcocks, Lisa C.; Koukoulaki, Maria; Brazma, Alvis; Jovanovic, Vojislav; Kemeny, D. Michael; Pollard, Andrew J.; MacAry, Paul A.; Chaudhry, Afzal N.; Smith, Kenneth G. C.

    2010-01-01

    Autoimmune diseases are common and debilitating, but their severe manifestations could be reduced if biomarkers were available to allow individual tailoring of the potentially toxic immunosuppressive therapy required for their control. Gene expression-based biomarkers facilitating individual tailoring of chemotherapy in cancer, but not autoimmunity, have been identified and translated into clinical practice1,2. We show that transcriptional profiling of purified CD8 T cells, which avoids the confounding influences of unseparated cells3,4, identifies two distinct patient subgroups predicting long-term prognosis in two different autoimmune diseases, anti-neutrophil cytoplasmic antibody (ANCA) – associated vasculitis (AAV), a chronic, severe disease characterized by inflammation of medium and small blood vessels5, and systemic lupus erythematosus (SLE), characterized by autoantibodies, immune complex deposition and diverse clinical manifestations ranging from glomerulonephritis to neurological dysfunction6. We show that genes defining the poor prognostic group are enriched for genes of the IL7R pathway, TCR signalling and those expressed by memory T cells. Furthermore, the poor prognostic group is associated with an expanded CD8 T cell memory population. These subgroups, which are also found in the normal population and can be identified by measuring expression of only three genes, raise the prospect of individualized therapy and suggest novel potential therapeutic targets in autoimmunity. PMID:20400961

  18. Neonatal dexamethasone treatment increases susceptibility to experimental autoimmune disease in adult rats.

    PubMed

    Bakker, J M; Kavelaars, A; Kamphuis, P J; Cobelens, P M; van Vugt, H H; van Bel, F; Heijnen, C J

    2000-11-15

    Major concern has emerged about the possible long term adverse effects of glucocorticoid treatment, which is frequently used for the prevention of chronic lung disease in preterm infants. Here we show that neonatal glucocorticoid treatment of rats increases the severity (p< or = 0.01) and incidence (p< or =0.01) of the inflammatory autoimmune disease experimental autoimmune encephalomyelitis in adult life. In search of possible mechanisms responsible for the increased susceptibility to experimental autoimmune encephalomyelitis, we investigated the reactivity of the hypothalamo-pituitary-adrenal axis and of immune cells in adult rats after neonatal glucocorticoid treatment. We observed that neonatal glucocorticoid treatment reduces the corticosterone response after an LPS challenge in adult rats (p< or =0.001). Interestingly, LPS-stimulated macrophages of glucocorticoid-treated rats produce less TNF-alpha and IL-1beta in adult life than control rats (p<0.05). In addition, splenocytes obtained from adult rats express increased mRNA levels of the proinflammatory cytokines IFN-gamma (p<0.01) and TNF-beta (p<0.05) after neonatal glucocorticoid treatment. Apparently, neonatal glucocorticoid treatment has permanent programming effects on endocrine as well as immune functioning in adult life. In view of the frequent clinical application of glucocorticoids to preterm infants, our data demonstrate that neonatal glucocorticoid treatment may be a risk factor for the development of (auto)immune disease in man. PMID:11067955

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

    PubMed Central

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

    2016-01-01

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

  20. A disease-associated PTPN22 variant promotes systemic autoimmunity in murine models

    PubMed Central

    Dai, Xuezhi; James, Richard G.; Habib, Tania; Singh, Swati; Jackson, Shaun; Khim, Socheath; Moon, Randall T.; Liggitt, Denny; Wolf-Yadlin, Alejandro; Buckner, Jane H.; Rawlings, David J.

    2013-01-01

    Multiple autoimmune diseases, including type 1 diabetes, rheumatoid arthritis, Graves disease, and systemic lupus erythematosus, are associated with an allelic variant of protein tyrosine phosphatase nonreceptor 22 (PTPN22), which encodes the protein LYP. To model the human disease-linked variant LYP-R620W, we generated knockin mice expressing the analogous mutation, R619W, in the murine ortholog PEST domain phosphatase (PEP). In contrast with a previous report, we found that this variant exhibits normal protein stability, but significantly alters lymphocyte function. Aged knockin mice exhibited effector T cell expansion and transitional, germinal center, and age-related B cell expansion as well as the development of autoantibodies and systemic autoimmunity. Further, PEP-R619W affected B cell selection and B lineage–restricted variant expression and was sufficient to promote autoimmunity. Consistent with these features, PEP-R619W lymphocytes were hyperresponsive to antigen-receptor engagement with a distinct profile of tyrosine-phosphorylated substrates. Thus, PEP-R619W uniquely modulates T and B cell homeostasis, leading to a loss in tolerance and autoimmunity. PMID:23619366

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

    PubMed

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

    2015-09-01

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

  2. A Systematic Literature Review of the Association of Lipoprotein(a) and Autoimmune Diseases and Atherosclerosis

    PubMed Central

    Missala, I.; Kassner, U.; Steinhagen-Thiessen, E.

    2012-01-01

    Objective. To investigate the association of lipoprotein(a) and atherosclerosis-related autoimmune diseases, to provide information on possible pathophysiologic mechanisms, and to give recommendations for Lp(a) determination and therapeutic options. Methods. We performed a systematic review of English language citations referring to the keywords “Lp(a)” AND “autoimmune disease” AND “atherosclerosis,” “Lp(a)” AND “immune system” OR “antiphospholipid (Hughes) syndrome (APS)” OR “rheumatoid arthritis” OR “Sjögren's syndrome” OR “systemic lupus erythematosus” OR “systemic sclerosis” OR “systemic vasculitis” published between 1991 and 2011 using Medline database. Results. 22 out of 65 found articles were identified as relevant. Lp(a) association was highest in rheumatoid arthritis (RA), followed by systemic lupus erythematosus (SLE), moderate in APS and lowest in systemic sclerosis (SSc). There was no association found between Lp(a) and systemic vasculitis or Sjögren's syndrome. Conclusion. Immune reactions are highly relevant in the pathophysiology of atherosclerosis, and patients with specific autoimmune diseases are at high risk for CVD. Elevated Lp(a) is an important risk factor for premature atherosclerosis and high Lp(a) levels are also associated with autoimmune diseases. Anti-Lp(a)-antibodies might be a possible explanation. Therapeutic approaches thus far include niacin, Lp(a)-apheresis, farnesoid x-receptor-agonists, and CETP-inhibitors being currently under investigation. PMID:23304154

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

    PubMed

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

    2015-12-01

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

  4. Sexual dimorphism of miRNA expression: a new perspective in understanding the sex bias of autoimmune diseases

    PubMed Central

    Dai, Rujuan; Ahmed, S Ansar

    2014-01-01

    Autoimmune diseases encompass a diverse group of diseases which emanate from a dysregulated immune system that launches a damaging attack on its own tissues. Autoimmune attacks on self tissues can occur in any organ or body system. A notable feature of autoimmune disease is that a majority of these disorders occur predominantly in females. The precise basis of sex bias in autoimmune diseases is complex and potentially involves sex chromosomes, sex hormones, and sex-specific gene regulation in response to internal and external stimuli. Epigenetic regulation of genes, especially by microRNAs (miRNAs), is now attracting significant attention. miRNAs are small, non-protein-coding RNAs that are predicted to regulate a majority of human genes, including those involved in immune regulation. Therefore, it is not surprising that dysregulated miRNAs are evident in many diseases, including autoimmune diseases. Because there are marked sex differences in the incidence of autoimmune diseases, this review focuses on the role of sex factors on miRNA expression in the context of autoimmune diseases, an aspect not addressed thus far. Here, we initially review miRNA biogenesis and miRNA regulation of immunity and autoimmunity. We then summarize the recent findings of sexual dimorphism of miRNA expression in diverse tissues, which imply a critical role of miRNA in sex differentiation and in sex-specific regulation of tissue development and/or function. We also discuss the important contribution of the X chromosome and sex hormones to the sexual dimorphism of miRNA expression. Understanding sexually dimorphic miRNA expression in sex-biased autoimmune diseases not only offers us new insight into the mechanism of sex bias of the disease but will also aid us in developing new sex-based therapeutic strategies for the efficient treatment of these diseases with a sex bias. PMID:24623979

  5. LL37-DNA complexes and auto-immune diseases

    NASA Astrophysics Data System (ADS)

    Jin, Fan; Sanders, Lori K.; Xian, Wujing; Gilliet, Michel; Wong, Gerard C. L.; Department of Immunology, University of Texas, Houston Collaboration

    2011-03-01

    LL37 is an alpha-helical host defense peptide in humans. Recent work has shown that Toll-like receptor-9 (TLR9), an intracellular receptor in plasmacytoid dendritic cells (pDCs) of the immune system that normally responds to pathogen nucleic acids, can be pathologically triggered by self DNA in the form of DNA-LL37 complexes. Synchrotron small-angle x-ray scattering (SAXS) measurements reveal an unanticipated form of self-assembly between DNA and this positively charged macroion. We examine the generality of this with other macroions, and propose a new geometric criterion for immune cell activation.

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

    PubMed Central

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

    2009-01-01

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

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

    PubMed

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

    2015-06-01

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

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

    PubMed

    Penberthy, W Todd

    2007-04-01

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

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

    PubMed Central

    Weil, Robert

    2014-01-01

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

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

    PubMed Central

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

    2006-01-01

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

  11. Severe B cell hyperplasia and autoimmune disease in TALL-1 transgenic mice

    PubMed Central

    Khare, Sanjay D.; Sarosi, Ildiko; Xia, Xing-Zhong; McCabe, Susan; Miner, Kent; Solovyev, Irina; Hawkins, Nessa; Kelley, Michael; Chang, David; Van, Gwyneth; Ross, Larry; Delaney, John; Wang, Ling; Lacey, David; Boyle, William J.; Hsu, Hailing

    2000-01-01

    TALL-1/Blys/BAFF is a member of the tumor necrosis factor (TNF) ligand superfamily that is functionally involved in B cell proliferation. Here, we describe B cell hyperplasia and autoimmune lupus-like changes in transgenic mice expressing TALL-1 under the control of a β-actin promoter. The TALL-1 transgenic mice showed severe enlargement of spleen, lymph nodes, and Peyer's patches because of an increased number of B220+ cells. The transgenic mice also had hypergammaglobulinemia contributed by elevations of serum IgM, IgG, IgA, and IgE. In addition, a phenotype similar to autoimmune lupus-like disease was also seen in TALL-1 transgenic mice, characterized by the presence of autoantibodies to nuclear antigens and immune complex deposits in the kidney. Prolonged survival and hyperactivity of transgenic B cells may contribute to the autoimmune lupus-like phenotype in these animals. Our studies further confirm TALL-1 as a stimulator of B cells that affect Ig production. Thus, TALL-1 may be a primary mediator in B cell-associated autoimmune diseases. PMID:10716715

  12. Association scan of 14,500 nonsynonymous SNPs in four diseases identifies autoimmunity variants.

    PubMed

    Burton, Paul R; Clayton, David G; Cardon, Lon R; Craddock, Nick; Deloukas, Panos; Duncanson, Audrey; Kwiatkowski, Dominic P; McCarthy, Mark I; Ouwehand, Willem H; Samani, Nilesh J; Todd, John A; Donnelly, Peter; Barrett, Jeffrey C; Davison, Dan; Easton, Doug; Evans, David M; Leung, Hin-Tak; Marchini, Jonathan L; Morris, Andrew P; Spencer, Chris C A; Tobin, Martin D; Attwood, Antony P; Boorman, James P; Cant, Barbara; Everson, Ursula; Hussey, Judith M; Jolley, Jennifer D; Knight, Alexandra S; Koch, Kerstin; Meech, Elizabeth; Nutland, Sarah; Prowse, Christopher V; Stevens, Helen E; Taylor, Niall C; Walters, Graham R; Walker, Neil M; Watkins, Nicholas A; Winzer, Thilo; Jones, Richard W; McArdle, Wendy L; Ring, Susan M; Strachan, David P; Pembrey, Marcus; Breen, Gerome; St Clair, David; Caesar, Sian; Gordon-Smith, Katharine; Jones, Lisa; Fraser, Christine; Green, Elaine K; Grozeva, Detelina; Hamshere, Marian L; Holmans, Peter A; Jones, Ian R; Kirov, George; Moskivina, Valentina; Nikolov, Ivan; O'Donovan, Michael C; Owen, Michael J; Collier, David A; Elkin, Amanda; Farmer, Anne; Williamson, Richard; McGuffin, Peter; Young, Allan H; Ferrier, I Nicol; Ball, Stephen G; Balmforth, Anthony J; Barrett, Jennifer H; Bishop, Timothy D; Iles, Mark M; Maqbool, Azhar; Yuldasheva, Nadira; Hall, Alistair S; Braund, Peter S; Dixon, Richard J; Mangino, Massimo; Stevens, Suzanne; Thompson, John R; Bredin, Francesca; Tremelling, Mark; Parkes, Miles; Drummond, Hazel; Lees, Charles W; Nimmo, Elaine R; Satsangi, Jack; Fisher, Sheila A; Forbes, Alastair; Lewis, Cathryn M; Onnie, Clive M; Prescott, Natalie J; Sanderson, Jeremy; Matthew, Christopher G; Barbour, Jamie; Mohiuddin, M Khalid; Todhunter, Catherine E; Mansfield, John C; Ahmad, Tariq; Cummings, Fraser R; Jewell, Derek P; Webster, John; Brown, Morris J; Lathrop, Mark G; Connell, John; Dominiczak, Anna; Marcano, Carolina A Braga; Burke, Beverley; Dobson, Richard; Gungadoo, Johannie; Lee, Kate L; Munroe, Patricia B; Newhouse, Stephen J; Onipinla, Abiodun; Wallace, Chris; Xue, Mingzhan; Caulfield, Mark; Farrall, Martin; Barton, Anne; Bruce, Ian N; Donovan, Hannah; Eyre, Steve; Gilbert, Paul D; Hilder, Samantha L; Hinks, Anne M; John, Sally L; Potter, Catherine; Silman, Alan J; Symmons, Deborah P M; Thomson, Wendy; Worthington, Jane; Dunger, David B; Widmer, Barry; Frayling, Timothy M; Freathy, Rachel M; Lango, Hana; Perry, John R B; Shields, Beverley M; Weedon, Michael N; Hattersley, Andrew T; Hitman, Graham A; Walker, Mark; Elliott, Kate S; Groves, Christopher J; Lindgren, Cecilia M; Rayner, Nigel W; Timpson, Nicolas J; Zeggini, Eleftheria; Newport, Melanie; Sirugo, Giorgio; Lyons, Emily; Vannberg, Fredrik; Hill, Adrian V S; Bradbury, Linda A; Farrar, Claire; Pointon, Jennifer J; Wordsworth, Paul; Brown, Matthew A; Franklyn, Jayne A; Heward, Joanne M; Simmonds, Matthew J; Gough, Stephen C L; Seal, Sheila; Stratton, Michael R; Rahman, Nazneen; Ban, Maria; Goris, An; Sawcer, Stephen J; Compston, Alastair; Conway, David; Jallow, Muminatou; Newport, Melanie; Sirugo, Giorgio; Rockett, Kirk A; Bumpstead, Suzannah J; Chaney, Amy; Downes, Kate; Ghori, Mohammed J R; Gwilliam, Rhian; Hunt, Sarah E; Inouye, Michael; Keniry, Andrew; King, Emma; McGinnis, Ralph; Potter, Simon; Ravindrarajah, Rathi; Whittaker, Pamela; Widden, Claire; Withers, David; Cardin, Niall J; Davison, Dan; Ferreira, Teresa; Pereira-Gale, Joanne; Hallgrimsdo'ttir, Ingeleif B; Howie, Bryan N; Su, Zhan; Teo, Yik Ying; Vukcevic, Damjan; Bentley, David; Brown, Matthew A; Compston, Alastair; Farrall, Martin; Hall, Alistair S; Hattersley, Andrew T; Hill, Adrian V S; Parkes, Miles; Pembrey, Marcus; Stratton, Michael R; Mitchell, Sarah L; Newby, Paul R; Brand, Oliver J; Carr-Smith, Jackie; Pearce, Simon H S; McGinnis, R; Keniry, A; Deloukas, P; Reveille, John D; Zhou, Xiaodong; Sims, Anne-Marie; Dowling, Alison; Taylor, Jacqueline; Doan, Tracy; Davis, John C; Savage, Laurie; Ward, Michael M; Learch, Thomas L; Weisman, Michael H; Brown, Mathew

    2007-11-01

    We have genotyped 14,436 nonsynonymous SNPs (nsSNPs) and 897 major histocompatibility complex (MHC) tag SNPs from 1,000 independent cases of ankylosing spondylitis (AS), autoimmune thyroid disease (AITD), multiple sclerosis (MS) and breast cancer (BC). Comparing these data against a common control dataset derived from 1,500 randomly selected healthy British individuals, we report initial association and independent replication in a North American sample of two new loci related to ankylosing spondylitis, ARTS1 and IL23R, and confirmation of the previously reported association of AITD with TSHR and FCRL3. These findings, enabled in part by increased statistical power resulting from the expansion of the control reference group to include individuals from the other disease groups, highlight notable new possibilities for autoimmune regulation and suggest that IL23R may be a common susceptibility factor for the major 'seronegative' diseases. PMID:17952073

  13. Cellular automata simulation of medication-induced autoimmune diseases

    NASA Astrophysics Data System (ADS)

    Stauffer, Dietrich; Proykova, Ana

    2004-01-01

    We implement the cellular automata model proposed by Stauffer and Weisbuch in 1992 to describe the response of the immune system to antigens in the presence of medications. The model contains two thresholds, θ1 and θ2, suggested by de Boer, Segel, and Perelson to present the minimum field needed to stimulate the proliferation of the receptors and to suppress it, respectively. The influence of the drug is mimicked by increasing the second threshold, thus enhancing the immune response. If this increase is too strong, the immune response is triggered in the whole immune repertoire, causing it to attack the own body. This effect is seen in our simulations to depend both on the ratio of the thresholds and on their absolute values.

  14. Requirements for innate immune pathways in environmentally induced autoimmunity.

    PubMed

    Pollard, Kenneth Michael; Kono, Dwight H

    2013-01-01

    There is substantial evidence that environmental triggers in combination with genetic and stochastic factors play an important role in spontaneous autoimmune disease. Although the specific environmental agents and how they promote autoimmunity remain largely unknown, in part because of diverse etiologies, environmentally induced autoimmune models can provide insights into potential mechanisms. Studies of idiopathic and environmentally induced systemic autoimmunity show that they are mediated by common adaptive immune response genes. By contrast, although the innate immune system is indispensable for autoimmunity, there are clear differences in the molecular and cellular innate components that mediate specific systemic autoimmune diseases, suggesting distinct autoimmune-promoting pathways. Some of these differences may be related to the bifurcation of toll-like receptor signaling that distinguishes interferon regulatory factor 7-mediated type I interferon production from nuclear factor-κB-driven proinflammatory cytokine expression. Accordingly, idiopathic and pristane-induced systemic autoimmunity require both type I interferon and proinflammatory cytokines whereas the less aggressive mercury-induced autoimmunity, although dependent on nucleic acid-binding toll-like receptors, does not require type I interferon but needs proinflammatory cytokines. Scavenger receptors and the inflammasome may contribute to silica-induced autoimmunity. Greater understanding of the innate mechanisms responsible for idiopathic and environmentally induced autoimmunity should yield new information into the processes that instigate and drive systemic autoimmunity. PMID:23557436

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

    PubMed Central

    2016-01-01

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

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

    PubMed

    Krzewska, Aleksandra; Ben-Skowronek, Iwona

    2016-01-01

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

  17. Dendritic cells: an important link between antiphospholipid antibodies, endothelial dysfunction, and atherosclerosis in autoimmune and non-autoimmune diseases.

    PubMed

    Broder, Anna; Chan, Jimmy J; Putterman, Chaim

    2013-03-01

    The presence of dendritic cells, antigen-presenting cells that link innate and adaptive immunity, is necessary to generate and maintain the production of antiphospholipid antibodies in response to exposed intracellular phospholipids on the outer surface of apoptotic cells. In turn, antiphospholipid antibodies enhance dendritic cell-induced inflammatory and proatherogenic responses in a number of conditions that are associated with accelerated atherosclerosis, including diabetes, chronic kidney disease, periodontal infections, and aging. While altering dendritic cells by modifying the ubiquitin-proteasome system enhances antiphospholipid antibody production and leads to development of accelerated atherosclerosis and autoimmune features, inducing tolerance by dendritic cell manipulation leads to decreased atherosclerosis and thrombosis. Therefore, further translational studies are needed to understand the interplay between dendritic cells and antiphospholipid antibodies, and to develop potential new therapies for antiphospholipid syndrome and atherosclerosis. Here we review current experimental and translational studies that have examined the role of dendritic cells in antiphospholipid antibody formation and in antiphospholipid-associated atherosclerosis and thrombosis. PMID:23376063

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

    PubMed

    Wu, Dayong; Wang, Junpeng; Pae, Munkyong; Meydani, Simin Nikbin

    2012-02-01

    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 (Th) cells, play a key role in mediating many aspects of autoimmune diseases. Upon antigenic stimulation, naïve CD4(+) T cells proliferate and differentiate into different effector subsets. Th1 and Th17 cells are the pro-inflammatory subsets of Th cells responsible for inducing autoimmunity whereas regulatory T cells (Treg) have an antagonistic effect. Green tea and its active ingredient, epigallocatechin-3-gallate (EGCG), have been shown to improve symptoms and reduce the pathology in some animal models of autoimmune diseases. Whether or not EGCG's effect is mediated through its impact on Th17 and Treg development has not been studied. We conducted a series of studies to investigate EGCG's effect on CD4(+) T cell proliferation and differentiation as well as its impact on the development of autoimmune disease. We first observed that EGCG inhibited CD4(+) T cell expansion in response to either polyclonal or antigen specific stimulation. We then determined how EGCG affects naïve CD4(+) T cell differentiation and found that it impeded Th1 and Th17 differentiation and prevented IL-6-induced inhibition on Treg development. We further demonstrated that EGCG inhibited Th1 and Th17 differentiation by downregulating their corresponding transcription factors (STAT1 and T-bet for Th1, and STAT3 and RORγt for Th17). These effects provide further explanation for previous findings that administration of EGCG by gavage to experimental autoimmune encephalomyelitis (EAE) mice, an animal model for human multiple sclerosis (MS), reduced the clinical symptoms, brain pathology, and proliferation and TNF-α production of encephalitogenic T cells. Upon further investigating the working

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

    PubMed Central

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

    2015-01-01

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

  20. Cell mediated immune regulation in autoimmunity.

    PubMed

    Gillissen, G; Pusztai-Markos, Z

    1979-01-01

    Autoimmunity is the term for the immune conditions characterized by a specific humoral or cell mediated response to the body's own tissues. The termination of the natural state of self tolerance may lead to immunopathological manifestations with clinical consequences, i.e. autoimmune diseases. In a very general sense, one may classify autoimmune diseases into two groups with respect to the underlying mechanism: 1. There are autoimmune diseases which develop in the presence of a normal intact regulation mechanism. 2. Another group whose development must be understood on the basis of a cellular dysfunction. In the first case, dequestered or semi-sequestered autoantigens are liberated as a consequence of exogenic influences inducing the sensitization of immunocompetent cells. The immune system then reacts with these autoantigens in the same way as with foreign substances. This kind of autoimmune disease will, however, not be dealt with here. In the second case, autoantigens are normally, i.e. in healthy individuals, accessible to the immunocompetent cells. To understand the reason for the development of an autoimmune reaction one must first clarify the mechanism of self tolerance. Then one must examine the way in which a break of this physiological state takes place. One of the major unanswered questions is the relative importance of antibody-mediated and cell-mediated immune mechanisms in the onset and further development of autoimmune diseases. Recently it has been suggested that a dysfunction at the cellular level might represent the basic cause which induces the termination of selftolerance. Most of the conceptions about the mechanism by which autoimmune diseases are triggered were gained through experiments with animals. It is, however, difficult to use these experimental results to explain human diseases; in humans many questions are still open. Undoubtedly, the mechanisms of induction and maintenance of self tolerance and also the ways in which autoimmune

  1. Individualized Follow-up of Pregnant Women with Asymptomatic Autoimmune Thyroid Disease

    PubMed Central

    Stoian, Dana; Pantea, Stelian; Margan, Madalin; Timar, Bogdan; Borcan, Florin; Craina, Marius; Craciunescu, Mihaela

    2016-01-01

    Maternal hormones are essential for the normal fetal development during pregnancy. Autoimmune thyroid disease is a frequent pathology in our iodine replete region. The aim of this study is to evaluate the occurrence of subclinical hypothyroidism (SCH) in cases with known autoimmune thyroid disease, which were in a euthyroid state prior to pregnancy, and to assess the association between supplemental treatments administered and the outcome of the pregnancy. The study is a prospective interventional controlled study. The two cohorts comprise the interventional group, consisting of 109 pregnant women with known autoimmune asymptomatic thyroid disease, without any levothyroxine (LT4) treatment and an aged-matched control group, with an unknown thyroid disease. After the pregnancy, a monthly evaluation of TSH, FT3, and FT4 was performed. Offspring evaluation was made at birth time. 88.8% of the women developed SCH in the first four weeks of pregnancy. Average LT4 doses increased as the pregnancy progressed. The monthly adjustment was 12.5 or 25 μg. All SCH cases developed in the first trimester of pregnancy. There was no significant difference regarding the gestational week, weight, or length at birth between the interventional group and controls, when TSH values were in the optimal range, during the whole pregnancy. Premature birth was described in one case in the interventional group. PMID:26771604

  2. Mechanisms of impaired regulation by CD4+CD25+FOXP3+ regulatory T cells in human autoimmune diseases

    PubMed Central

    Buckner, Jane Hoyt

    2011-01-01

    A lack of regulatory T (TReg) cells that express CD4, CD25 and forkhead box P3 (FOXP3) results in severe autoimmunity in both mice and humans. Since the discovery of TReg cells, there has been intense investigation aimed at determining how they protect an organism from autoimmunity and whether defects in their number or function contribute to the development of autoimmunity in model systems. The next phase of investigation — that is, to define the role that defects in TReg cells have in human autoimmunity — is now underway. This Review summarizes our progress so far towards understanding the role of CD4+CD25+FOXP3+ TReg cells in human autoimmune diseases and the impact that this knowledge might have on the diagnosis and treatment of these diseases. PMID:21107346

  3. Methotrexate: an old new drug in autoimmune disease.

    PubMed

    Cipriani, Paola; Ruscitti, Piero; Carubbi, Francesco; Liakouli, Vasiliki; Giacomelli, Roberto

    2014-11-01

    Methotrexate (MTX) is currently considered, among disease-modifying anti-rheumatic drugs (DMARDs), the 'anchor-drug' in the treatment of rheumatoid arthritis. In the last 25 years, there has been a marked expansion in the use of MTX in different inflammatory diseases. Its low cost, associated to a good long-term efficacy and safety profile, justifies the use of MTX as a first-line disease-modifying drug or alternatively, a steroid-sparing medication in this field of medicine. Although new emerging options, including biological treatments, are being established in the therapeutic scenario, the good cost/benefit ratio of MTX supports the choice of this drug in combination with these newer therapies, enhancing the efficacy of these combination therapies and decreasing the risk of potential side effects. PMID:25245537

  4. Myelin-reactive antibodies initiate T cell-mediated CNS autoimmune disease by opsonization of endogenous antigen.

    PubMed

    Kinzel, Silke; Lehmann-Horn, Klaus; Torke, Sebastian; Häusler, Darius; Winkler, Anne; Stadelmann, Christine; Payne, Natalie; Feldmann, Linda; Saiz, Albert; Reindl, Markus; Lalive, Patrice H; Bernard, Claude C; Brück, Wolfgang; Weber, Martin S

    2016-07-01

    In the pathogenesis of central nervous system (CNS) demyelinating disorders, antigen-specific B cells are implicated to act as potent antigen-presenting cells (APC), eliciting waves of inflammatory CNS infiltration. Here, we provide the first evidence that CNS-reactive antibodies (Ab) are similarly capable of initiating an encephalitogenic immune response by targeting endogenous CNS antigen to otherwise inert myeloid APC. In a transgenic mouse model, constitutive production of Ab against myelin oligodendrocyte glycoprotein (MOG) was sufficient to promote spontaneous experimental autoimmune encephalomyelitis (EAE) in the absence of B cells, when mice endogenously contained MOG-recognizing T cells. Adoptive transfer studies corroborated that anti-MOG Ab triggered activation and expansion of peripheral MOG-specific T cells in an Fc-dependent manner, subsequently causing EAE. To evaluate the underlying mechanism, anti-MOG Ab were added to a co-culture of myeloid APC and MOG-specific T cells. At otherwise undetected concentrations, anti-MOG Ab enabled Fc-mediated APC recognition of intact MOG; internalized, processed and presented MOG activated naïve T cells to differentiate in an encephalitogenic manner. In a series of translational experiments, anti-MOG Ab from two patients with an acute flare of CNS inflammation likewise facilitated detection of human MOG. Jointly, these observations highlight Ab-mediated opsonization of endogenous CNS auto-antigen as a novel disease- and/or relapse-triggering mechanism in CNS demyelinating disorders. PMID:27022743

  5. Vitamin D metabolites as clinical markers in autoimmune and chronic disease.

    PubMed

    Blaney, Greg P; Albert, Paul J; Proal, Amy D

    2009-09-01

    Recent research has implicated vitamin D deficiency (serum levels of 25-hydroxyvitamin D <50 nmol/L) with a number of chronic conditions, including autoimmune conditions such as multiple sclerosis, lupus, and psoriasis, and chronic conditions such as osteoporosis, osteoarthritis, metabolic syndrome, fibromyalgia and chronic fatigue syndrome. It has been assumed that low levels of 25-hydroxyvitamin D (25-D) accurately indicate vitamin D storage and vitamin D receptor (VDR)-mediated control of calcium metabolism and innate immunity. To evaluate this assumption, 25-D and 1,25-dihydroxyvitamin D3 (1,25-D) levels were measured in 100 Canadian patients with these conditions. Additionally, other inflammatory markers (CK, CRP) were measured. Results showed a strong positive association between these autoimmune conditions and levels of 1,25-D >110 pmol/L. However, there was little association with vitamin D deficiency or the other inflammatory markers, meaning that the results challenge the assumption that serum levels of 25-D are a sensitive measure of the autoimmune disease state. Rather, these findings support the use of 1,25-D as a clinical marker in autoimmune conditions. High levels of 1,25-D may result when dysregulation of the VDR by bacterial ligands prevents the receptor from expressing enzymes necessary to keep 1,25-D in a normal range. PMID:19758177

  6. The Role of Decay Accelerating Factor in Environmentally Induced and Idiopathic Systemic Autoimmune Disease

    PubMed Central

    Toomey, Christopher B.; Pollard, Kenneth M.

    2014-01-01

    Decay accelerating factor (DAF) plays a complex role in the immune system through complement-dependent and -independent regulation of innate and adaptive immunity. Over the past five years there has been accumulating evidence for a significant role of DAF in negatively regulating adaptive T-cell responses and autoimmunity in both humans and experimental models. This review discusses the relationship between DAF and the complement system and highlights major advances in our understanding of the biology of DAF in human disease, particularly systemic lupus erythematosus. The role of DAF in regulation of idiopathic and environmentally induced systemic autoimmunity is discussed including studies showing that reduction or absence of DAF is associated with autoimmunity. In contrast, DAF-mediated T cell activation leads to cytokine expression consistent with T regulatory cells. This is supported by studies showing that interaction between DAF and its molecular partner, CD97, modifies expression of autoimmunity promoting cytokines. These observations are used to develop a hypothetical model to explain how DAF expression may impact T cell differentiation via interaction with CD97 leading to T regulatory cells, increased production of IL-10, and immune tolerance. PMID:24592327

  7. Safety of high-dose intravenous immunoglobulin in systemic autoimmune diseases.

    PubMed

    Tufan, Fatih; Kamali, Sevil; Erer, Burak; Gul, Ahmet; Inanc, Murat; Ocal, Lale; Konice, Meral; Aral, Orhan

    2007-11-01

    It is reported that the usage of high-dose intravenous immunoglobulin (HD-IVIG) in systemic autoimmune diseases is associated with various adverse events in a wide range of severity. We aimed to investigate the frequency and profile of adverse events in a group of patients with diffuse connective tissue diseases and Wegener's granulomatosis (WG) who were administrated HD-IVIG for different indications. We recorded the data of 38 patients (25 females and 13 males) aged 38 +/- 15 (12-75) years who were followed up with the diagnosis of systemic autoimmune diseases between 1994 and 2006 according to a predefined protocol. Patients with active disease were treated with HD-IVIG and standard immunosuppressives concomitantly. We evaluated the occurrence of allergy, acute renal failure, thromboembolic events, neutropenia, hemolytic anemia, aseptic meningitis, and vasculitis during infusion therapy of HD-IVIG and in the following 3 weeks. We commenced a total of 130 infusions of HD-IVIG. Patients were administrated 1-12 (3.4 +/- 2.6) infusions of HD-IVIG as needed. Indications for HD-IVIG were unresponsiveness or partial response to standard treatment, severe infections along with disease activity, and severe thrombocytopenia in the preoperative period in 97, 23, and 5% of patients, respectively. Minor adverse events were seen in two patients during HD-IVIG infusions. One patient with WG developed rapidly progressive renal failure during severe disease flare between HD-IVIG infusions. Another patient with WG developed recurrence of deep-vein thrombosis during severe disease flare 3 months after HD-IVIG. Both events were attributed to severe disease activity. Adverse events like allergy, acute renal failure, thromboembolic events, hematological problems, aseptic meningitis, and vasculitis are reported in different frequencies (1-81%) in patients who were administered HD-IVIG for systemic autoimmune diseases. HD-IVIG is considered a safe treatment in selected patients

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

    PubMed

    Pers, Yves Marie; Jorgensen, Christian

    2016-09-01

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

  9. Anti-Hsp90 therapy in autoimmune and inflammatory diseases: a review of preclinical studies.

    PubMed

    Tukaj, Stefan; Węgrzyn, Grzegorz

    2016-03-01

    Heat shock protein 90 (Hsp90), a 90-kDa molecular chaperone, is responsible for biological activities of key signaling molecules (clients) such as protein kinases, ubiquitin ligases, steroid receptors, cell cycle regulators, and transcription factors regulating various cellular processes, including growth, survival, differentiation, and apoptosis. Because Hsp90 is also involved in stabilization of oncogenic 'client' proteins, its specific chaperone activity blockers are currently being tested as anticancer agents in advanced clinical trials. Recent in vitro and in vivo studies have shown that Hsp90 is also involved in activation of innate and adaptive cells of the immune system. For these reasons, pharmacological inhibition of Hsp90 has been evaluated in murine models of autoimmune and inflammatory diseases. This mini-review summarizes current knowledge of the effects of Hsp90 inhibitors on autoimmune and inflammatory diseases' features and is based solely on preclinical studies. PMID:26786410

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

    PubMed

    Harifi, Ghita; Sibilia, Jean

    2016-04-01

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

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

    PubMed Central

    Harifi, Ghita; Sibilia, Jean

    2016-01-01

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

  12. Autoimmune Pancreatitis and IgG4 Related Disease in Three Children

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-07-01

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

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

    PubMed

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

    2014-04-01

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

  15. PROGESTERONE TREATMENT REDUCES DISEASE SEVERITY AND INCREASES IL-10 IN EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS

    PubMed Central

    Yates, M.A; Li, Y.; Chlebeck, P.; Proctor, T.; Vandenbark, A.A.; Offner, H.

    2010-01-01

    Ovarian hormones, including progesterone, are known to have immunomodulatory and neuroprotective effects which may alter the disease course of experimental autoimmune encephalomyelitis (EAE). In the current study, we examined the treatment potential of progesterone beginning at the onset of EAE symptoms. Progesterone treated animals showed reduced peak disease scores and cumulative disease indices, and decreased inflammatory cytokine secretion (IL-2 and IL-17). In addition, increased production of IL-10 was accompanied by increased numbers of CD19+ cells and an increase in CD8+ cells. Decreased chemokine and chemokine receptor expression in the spinal cord also contributed to decreased lesions in the spinal cord. PMID:20153059

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

    PubMed Central

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

    2013-01-01

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

  17. Diagnostic procedures for autoimmune vesiculobullous diseases: A review

    PubMed Central

    Rastogi, Varun; Sharma, Rachna; Misra, Satya Ranjan; Yadav, Lalita

    2014-01-01

    Oral soft tissues are affected by numerous pathologic conditions of variable etiology and hence their appropriate management relies on their accurate diagnosis. Clinical identification of intact vesicle and bulla in the oral cavity is really a challenge due to the regular irritation and the friable nature of oral mucosa. Rupture of these lesions leads to erosions or ulcerations on the surface, hence making the diagnosis of vesiculobullous (VB) lesions is even more difficult due to the fact that the differential diagnosis along with VB lesions will also include ulcerative, immunological-mediated diseases, and neoplasms and systemic diseases. Hence, knowledge of the clinical presentation of these disorders and the relevant diagnostic procedures is important not just for dermatologists, but also for general practitioners and dentists. In this article, the various procedures have been explained that can be used for the diagnostic purpose of VB lesions. PMID:25948994

  18. Auto-antibodies to vascular endothelial cadherin in humans: association with autoimmune diseases.

    PubMed

    Bouillet, L; Baudet, A E; Deroux, A; Sidibé, A; Dumestre-Perard, C; Mannic, T; Treillard, B; Arboleas, M A; Chiquet, C A; Gulino-Debrac, D G; Vilgrain, I Y

    2013-11-01

    To identify patients with autoimmune diseases who are at high risk of developing vascular cell dysfunction, early biomarkers must be identified. This study was designed to detect and characterize circulating autoantibodies to VE-cadherin (AAVEs) in patients with early-stage autoimmune diseases. An enzyme-linked immunosorbent assay (ELISA) was developed to capture autoantibodies, using a recombinant human VE-cadherin fragment covering the extracellular domains as a target antigen. AAVEs specificity for the target antigen was confirmed by western blotting. Basal AAVEs levels were determined for healthy donors (n=75). Sera from patients (n=100) with various autoimmune diseases, including rheumatoid arthritis (n=23), systemic lupus erythematosus (SLE, n=31), systemic sclerosis (n=30), and Behçet's disease (BD, n=16) were also tested. Levels of AAVEs were significantly higher in rheumatoid arthritis (P<0.0001), SLE (P<0.05), and BD (P<0.05) populations than in healthy subjects. Purified immunoglobulin G (IgG) from a BD patient with exceptionally high AAVEs levels recognized the EC1-4 fragment in western blots. Further characterization of the epitopes recognized by AAVEs showed that BD patients had antibodies specific for the EC3 and EC4 domains, whereas SLE patients preferentially recognized the EC1 fragment. This suggests that distinct epitopes of human VE-cadherin might be recognized in different immune diseases. Purified IgG from BD patients was found to induce endothelial cell retraction, redistribution of VE-cadherin, and cause the formation of numerous intercellular gaps. Altogether, these data demonstrate a potential pathogenic effect of AAVEs isolated from patients with dysimmune disease. This is the first description of AAVEs in humans. Because regions EC1 and EC3-4 have been shown to be involved in homophilic VE-cadherin interactions, AAVEs produced in the course of dysimmune diseases might be specific biomarkers for endothelial injury, which is part of the

  19. Peripheral blood and intrathyroidal T cell clones from patients with thyroid autoimmune diseases.

    PubMed

    Massart, C; Caroff, G; Maugendre, D; Genetet, N; Gibassier, J

    1999-01-01

    For a better understanding of the pathogenesis of thyroid autoimmune diseases, we have studied morphological and functional properties of T clones from peripheral blood lymphocytes (PBL) and from intrathyroidal lymphocytes (ITL) obtained from 3 patients with Graves' disease or 1 Hashimoto's thyroiditis. Investigations were carried out on clones cultured alone or cocultured with autologous thyrocytes. Clonage efficiency ranged from 30% to 33% for PBL and 10% to 36% for ITL. A predominance of CD4-positive clones was observed whatever the origin of the lymphocytes or the autoimmune pathology. Gamma interferon (IFN-gamma) was detected in the majority (17/19) of the clones tested. Intracytoplasmic interleukin (IL-4) was secreted in 7/19 clones and both cytokines were produced in 5/19 clones. In coculture a proliferative response and tumour necrosis factor (TNF-alpha) production were observed with 6 clones (4 from Graves thyrocytes and 2 from thyroiditis). No cytotoxic clone was derived from Graves or thyroiditis tissues. These data demonstrate that the large majority of T clones are principally CD4-T cells; all the clones secreted TNF-alpha and a large majority produced IFN-gamma. Only a few clones produced IL-4 alone or associated with IFN-gamma. Six T clones induced proliferative response and of TNF-alpha secretion in coculture. Further investigations must be performed on these antigen-reactive T clones to analyse their role in the pathogenesis of the human thyroid autoimmune diseases. PMID:10739333

  20. Spinster 2, a sphingosine-1-phosphate transporter, plays a critical role in inflammatory and autoimmune diseases.

    PubMed

    Donoviel, Michael S; Hait, Nitai C; Ramachandran, Subramaniam; Maceyka, Michael; Takabe, Kazuaki; Milstien, Sheldon; Oravecz, Tamas; Spiegel, Sarah

    2015-12-01

    Sphingosine 1-phosphate (S1P) is a pleiotropic bioactive sphingolipid metabolite that regulates numerous processes important for immune responses. S1P is made within cells and must be transported out of cells to exert its effects through activation of 5 specific cell surface GPCRs in an autocrine or paracrine fashion. Spinster 2 (Spns2) transports S1P out of cells, and its deletion in mice reduces circulating levels of S1P, alters immune cell trafficking, and induces lymphopenia. Here we examined the effects of Spns2 deletion on adaptive immune responses and in autoimmune disease models. Airway inflammation and hypersensitivity as well as delayed-type contact hypersensitivity were attenuated in Spns2(-/-) mice. Similarly, Spns2 deletion reduced dextran sodium sulfate- and oxazolone-induced colitis. Intriguingly, Spns2(-/-) mice were protected from the development of experimental autoimmune encephalopathy, a model of the autoimmune disease multiple sclerosis. Deletion of Spns2 also strongly alleviated disease development in collagen-induced arthritis. These results point to a broad role for Spns2-mediated S1P transport in the initiation and development of adaptive immune related disorders. PMID:26324848

  1. Implication of human endogenous retroviruses in the development of autoimmune diseases.

    PubMed

    Balada, Eva; Vilardell-Tarrés, Miquel; Ordi-Ros, Josep

    2010-08-01

    Retroviruses can exist in an endogenous form, in which viral sequences are integrated into the human germ line and are vertically transmitted in a Mendelian fashion. Human endogenous retroviruses (HERVs), probably representing footprints of ancient germ-cell retroviral infections, occupy about 1% of the human genome. Some HERVs emerged in the genome over 25 million years ago, while others have appeared rather recently, at about the time of hominid and ape lineages divergence. Although some of these elements show mutations and deletions, some HERVs are transcriptionally active and produce functional proteins. Some medical conditions, such as cancer and autoimmune diseases, are linked to the transcription of some of the HERVs genes, to the expression of HERVs proteins (that may act as superantigens, for example), and/or to the development of antibodies against them that might cross-react with our own proteins. Their genetic sequences may also be, totally or partially, integrated into genes that regulate the immune response. These mechanisms could give rise to autoimmune diseases, such as lupus erythematosus, insulin-dependent diabetes mellitus, multiple sclerosis, Sjögren's syndrome, and rheumatoid arthritis, among others. This review is aimed at discussing evidence for a possible role of HERVs in the etiopathogenesis of different autoimmune diseases. PMID:20635879

  2. Insulin-like growth factor-1 stimulates regulatory T cells and suppresses autoimmune disease

    PubMed Central

    Bilbao, Daniel; Luciani, Luisa; Johannesson, Bjarki; Piszczek, Agnieszka; Rosenthal, Nadia

    2014-01-01

    The recent precipitous rise in autoimmune diseases is placing an increasing clinical and economic burden on health systems worldwide. Current therapies are only moderately efficacious, often coupled with adverse side effects. Here, we show that recombinant human insulin-like growth factor-1 (rhIGF-1) stimulates proliferation of both human and mouse regulatory T (Treg) cells in vitro and when delivered systemically via continuous minipump, it halts autoimmune disease progression in mouse models of type 1 diabetes (STZ and NOD) and multiple sclerosis (EAE) in vivo. rhIGF-1 administration increased Treg cells in affected tissues, maintaining their suppressive properties. Genetically, ablation of the IGF-1 receptor specifically on Treg cell populations abrogated the beneficial effects of rhIGF-1 administration on the progression of multiple sclerotic symptoms in the EAE model, establishing a direct effect of IGF-1 on Treg cell proliferation. These results establish systemically delivered rhIGF-1 as a specific, effective stimulator of Treg cell action, underscoring the clinical feasibility of manipulating natural tolerance mechanisms to suppress autoimmune disease. PMID:25339185

  3. Rare variants in the TREX1 gene and susceptibility to autoimmune diseases.

    PubMed

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

    2013-01-01

    TREX1 (DNase III) is an exonuclease involved in response to oxidative stress and apoptosis. Heterozygous mutations in TREX1 were previously observed in patients with systemic lupus erythematosus (SLE) and Sjögren's syndrome (SS). We performed a mutational analysis of the TREX1 gene on three autoimmune diseases: SLE (210 patients) and SS (58 patients), to confirm a TREX1 involvement in the Italian population, and systemic sclerosis (SSc, 150 patients) because it shares similarities with SLE (presence of antinuclear antibodies and connective tissue damage). We observed 7 variations; two of these are novel nonsynonymous variants (p.Glu198Lys and p.Met232Val). They were detected in one SS and in one SSc patient, respectively, and in none of the 200 healthy controls typed in this study and of the 1712 published controls. In silico analysis predicts a possibly damaging role on protein function for both variants. The other 5 variations are synonymous and only one of them is novel (p.Pro48Pro). This study contributes to the demonstration that TREX1 is involved in autoimmune diseases and proposes that the spectrum of involved autoimmune diseases can be broader and includes SSc. We do not confirm a role of TREX1 variants in SLE. PMID:24224166

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

    PubMed Central

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

    2013-01-01

    TREX1 (DNase III) is an exonuclease involved in response to oxidative stress and apoptosis. Heterozygous mutations in TREX1 were previously observed in patients with systemic lupus erythematosus (SLE) and Sjögren's syndrome (SS). We performed a mutational analysis of the TREX1 gene on three autoimmune diseases: SLE (210 patients) and SS (58 patients), to confirm a TREX1 involvement in the Italian population, and systemic sclerosis (SSc, 150 patients) because it shares similarities with SLE (presence of antinuclear antibodies and connective tissue damage). We observed 7 variations; two of these are novel nonsynonymous variants (p.Glu198Lys and p.Met232Val). They were detected in one SS and in one SSc patient, respectively, and in none of the 200 healthy controls typed in this study and of the 1712 published controls. In silico analysis predicts a possibly damaging role on protein function for both variants. The other 5 variations are synonymous and only one of them is novel (p.Pro48Pro). This study contributes to the demonstration that TREX1 is involved in autoimmune diseases and proposes that the spectrum of involved autoimmune diseases can be broader and includes SSc. We do not confirm a role of TREX1 variants in SLE. PMID:24224166

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

    PubMed Central

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

    2014-01-01

    The global effort to prevent iodine deficiency disorders through iodine supplementation, such as universal salt iodization, has achieved impressive progress during the last few decades. However, iodine excess, due to extensive environmental iodine exposure in addition to poor monitoring, is currently a more frequent occurrence than iodine deficiency. Iodine excess is a precipitating environmental factor in the development of autoimmune thyroid disease. Excessive amounts of iodide have been linked to the development of autoimmune thyroiditis in humans and animals, while intrathyroidal depletion of iodine prevents disease in animal strains susceptible to severe thyroiditis. Although the mechanisms by which iodide induces thyroiditis are still unclear, several mechanisms have been proposed: (1) excess iodine induces the production of cytokines and chemokines that can recruit immunocompetent cells to the thyroid; (2) processing excess iodine in thyroid epithelial cells may result in elevated levels of oxidative stress, leading to harmful lipid oxidation and thyroid tissue injuries; and (3) iodine incorporation in the protein chain of thyroglobulin may augment the antigenicity of this molecule. This review will summarize the current knowledge regarding excess iodide as an environmental toxicant and relate it to the development of autoimmune thyroid disease. PMID:25050783

  6. Computational Modelling Approaches on Epigenetic Factors in Neurodegenerative and Autoimmune Diseases and Their Mechanistic Analysis

    PubMed Central

    Khanam Irin, Afroza; Tom Kodamullil, Alpha; Gündel, Michaela; Hofmann-Apitius, Martin

    2015-01-01

    Neurodegenerative as well as autoimmune diseases have unclear aetiologies, but an increasing number of evidences report for a combination of genetic and epigenetic alterations that predispose for the development of disease. This review examines the major milestones in epigenetics research in the context of diseases and various computational approaches developed in the last decades to unravel new epigenetic modifications. However, there are limited studies that systematically link genetic and epigenetic alterations of DNA to the aetiology of diseases. In this work, we demonstrate how disease-related epigenetic knowledge can be systematically captured and integrated with heterogeneous information into a functional context using Biological Expression Language (BEL). This novel methodology, based on BEL, enables us to integrate epigenetic modifications such as DNA methylation or acetylation of histones into a specific disease network. As an example, we depict the integration of epigenetic and genetic factors in a functional context specific to Parkinson's disease (PD) and Multiple Sclerosis (MS). PMID:26636108

  7. Clinical pharmacokinetics and pharmacodynamics of mycophenolate in patients with autoimmune disease.

    PubMed

    Abd Rahman, Azrin N; Tett, Susan E; Staatz, Christine E

    2013-05-01

    Mycophenolic acid (MPA), the active drug moiety of mycophenolate, is a potent immunosuppressant agent, which is increasingly being used in the treatment of patients with various autoimmune diseases. An understanding of the pharmacokinetics and pharmacodynamics of mycophenolate in this population should assist the clinician with rational dosage decisions. This review aims to provide an overview of the published literature on the clinical pharmacokinetics of mycophenolate in autoimmune disease and a briefer summary of current pharmacodynamic knowledge, and to identify areas of potential future research in this field. A literature search was conducted using PubMed and EMBASE databases as well as bibliographies of relevant articles and 'on-line early' pages of key journals. Twenty-six pharmacokinetic/pharmacodynamic studies of mycophenolate in people with autoimmune disease were identified and appraised. Twenty-two of these studies used non-compartmental analysis techniques and four used population modelling methods to estimate mycophenolate pharmacokinetic parameters. Seven studies linked mycophenolate exposure to treatment outcomes. Only four studies measured free (unbound) as well as total mycophenolate exposure and only two studies characterised MPA disposition following enteric-coated mycophenolate sodium (EC-MPS) administration. Across all studies MPA displayed erratic and complex pharmacokinetics with substantial between-subject variability. Based on total drug measurement, the dose-normalised MPA area under the plasma concentration-time curve (AUC) from 0 to 12 h post-dose (AUC12) varied at least five- to ten-fold between subjects. Typical values for apparent oral clearance (CL/F) of MPA during nonlinear mixed-effects modelling ranged from 8.3 to 25.3 L/h. Patient renal function, serum albumin levels, sex, ethnicity, food intake, concurrent administration of interacting drugs such as antacids, metal-containing medications and proton pump inhibitors and

  8. Intense immunosuppressive therapy followed by autologous peripheral blood selected progenitor cell reinfusion for severe autoimmune disease.

    PubMed

    Musso, M; Porretto, F; Crescimanno, A; Bondi, F; Polizzi, V; Scalone, R

    2001-02-01

    Autologous stem cell transplantation (HSCT) has been shown to be effective in curing a large spectrum of autoimmune disorders. Case reports are being collected in the EBMT/EULAR Autoimmune Disease Stem Cell Project registry, which reports transplant-related mortality (TRM) of 6%. In order to reduce TRM and preserve the anti-autoimmune effect we evaluated a more immunoablative as opposed to myeloablative conditioning regimen for the autotransplant of severe immunomediated diseases. We enrolled patients affected by systemic lupus erythematosus (SLE: 3 patients), by autoimmune thrombocytopenic purpura (AITP: one patient), by thrombotic thrombocytopenic purpura (TTP: one patient), by pure red cell aplasia (PRCA: one patient), and by a severe cryoglobulinemia (one patient). All patients were mobilized with cyclophosphamide (Cy) 4 g/m2 + G-csf. Conditioning regimen consisted of Cy 50 mg/kg/day (days -6 and -5); anti-T-globulin (ATG) 10 mg/kg/day and 6-methylprednisolone (PDN) 1 g/day (days -4, -3, and -2). Immunomagnetically selected CD34+ cells were re-infused on day 0. In three patients neutrophil count fell below 0.5 x 10(9)/l, while a PLT count below 20 x 10(9)/l was registered in two patients. Extrahematological toxicity was very low. Four patients (2 SLE, 1 TTP, 1 cryoglobulinemia) are in complete corticosteroid-free remission with a median follow up of 335 days. The third SLE patient improved considerably; however, he still needs low-dose corticosteroid maintenance. The AITP and PRCA patients achieved a CR but soon relapsed; nevertheless, the procedure restored a steroid-sensitive status. The use of this immunoablative conditioning regimen in auto-HSCT transplant was shown to be effective in controlling disease progression and could be a valuable strategy in reducing TRM. PMID:11421302

  9. Autoimmune Manifestations in the 3xTg-AD Model of Alzheimer's Disease

    PubMed Central

    Marchese, Monica; Cowan, David; Head, Elizabeth; Ma, Donglai; Karimi, Khalil; Ashthorpe, Vanessa; Kapadia, Minesh; Zhao, Hui; Davis, Paulina; Sakic, Boris

    2015-01-01

    Background Immune system activation is frequently reported in patients with Alzheimer's disease (AD). However, it remains unknown whether this is a cause, a consequence, or an epiphenomenon of brain degeneration. Objective The present study examines whether immunological abnormalities occur in a well-established murine AD model and if so, how they relate temporally to behavioral deficits and neuropathology. Methods A broad battery of tests was employed to assess behavioral performance and autoimmune/inflammatory markers in 3xTg-AD (AD) mice and wild type controls from 1.5 to 12 months of age. Results Aged AD mice displayed severe manifestations of systemic autoimmune/inflammatory disease, as evidenced by splenomegaly, hepatomegaly, elevated serum levels of anti-nuclear/anti-dsDNA antibodies, low hematocrit, and increased number of double-negative T splenocytes. However, anxiety-related behavior and altered spleen function were evident as early as 2 months of age, thus preceding typical AD-like brain pathology. Moreover, AD mice showed altered olfaction and impaired “cognitive” flexibility in the first 6 months of life, suggesting mild cognitive impairment-like manifestations before general learning/memory impairments emerged at an older age. Interestingly, all of these features were present in 3xTg-AD mice prior to significant amyloid-β or tau pathology. Conclusion The results indicate that behavioral deficits in AD mice develop in parallel with systemic autoimmune/inflammatory disease. These changes antedate AD-like neuropathology, thus supporting a causal link between autoimmunity and aberrant behavior. Consequently, 3xTg-AD mice may be a useful model in elucidating the role of immune system in the etiology of AD. PMID:24150111

  10. Epigenetic Modulation as a Therapeutic Prospect for Treatment of Autoimmune Rheumatic Diseases

    PubMed Central

    O'Reilly, Steven

    2016-01-01

    Systemic inflammatory rheumatic diseases are considered as autoimmune diseases, meaning that the balance between recognition of pathogens and avoidance of self-attack is impaired and the immune system attacks and destroys its own healthy tissue. Treatment with conventional Disease Modifying Antirheumatic Drugs (DMARDs) and/or Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) is often associated with various adverse reactions due to unspecific and toxic properties of those drugs. Although biologic drugs have largely improved the outcome in many patients, such drugs still pose significant problems and fail to provide a solution to all patients. Therefore, development of more effective treatments and improvements in early diagnosis of rheumatic diseases are badly needed in order to increase patient's functioning and quality of life. The reversible nature of epigenetic mechanisms offers a new class of drugs that modulate the immune system and inflammation. In fact, epigenetic drugs are already in use in some types of cancer or cardiovascular diseases. Therefore, epigenetic-based therapeutics that control autoimmunity and chronic inflammatory process have broad implications for the pathogenesis, diagnosis, and management of rheumatic diseases. This review summarises the latest information about potential therapeutic application of epigenetic modification in targeting immune abnormalities and inflammation of rheumatic diseases. PMID:27594771

  11. Epigenetic Modulation as a Therapeutic Prospect for Treatment of Autoimmune Rheumatic Diseases.

    PubMed

    Ciechomska, Marzena; O'Reilly, Steven

    2016-01-01

    Systemic inflammatory rheumatic diseases are considered as autoimmune diseases, meaning that the balance between recognition of pathogens and avoidance of self-attack is impaired and the immune system attacks and destroys its own healthy tissue. Treatment with conventional Disease Modifying Antirheumatic Drugs (DMARDs) and/or Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) is often associated with various adverse reactions due to unspecific and toxic properties of those drugs. Although biologic drugs have largely improved the outcome in many patients, such drugs still pose significant problems and fail to provide a solution to all patients. Therefore, development of more effective treatments and improvements in early diagnosis of rheumatic diseases are badly needed in order to increase patient's functioning and quality of life. The reversible nature of epigenetic mechanisms offers a new class of drugs that modulate the immune system and inflammation. In fact, epigenetic drugs are already in use in some types of cancer or cardiovascular diseases. Therefore, epigenetic-based therapeutics that control autoimmunity and chronic inflammatory process have broad implications for the pathogenesis, diagnosis, and management of rheumatic diseases. This review summarises the latest information about potential therapeutic application of epigenetic modification in targeting immune abnormalities and inflammation of rheumatic diseases. PMID:27594771

  12. Expert Panel Workshop Consensus Statement on the Role of the Environment in the Development of Autoimmune Disease

    PubMed Central

    Parks, Christine G.; Miller, Frederick W.; Pollard, Kenneth Michael; Selmi, Carlo; Germolec, Dori; Joyce, Kelly; Rose, Noel R.; Humble, Michael C.

    2014-01-01

    Autoimmune diseases include 80 or more complex disorders characterized by self-reactive, pathologic immune responses in which genetic susceptibility is largely insufficient to determine disease onset. In September 2010, the National Institute of Environmental Health Sciences (NIEHS) organized an expert panel workshop to evaluate the role of environmental factors in autoimmune diseases, and the state of the science regarding relevant mechanisms, animal models, and human studies. The objective of the workshop was to analyze the existing data to identify conclusions that could be drawn regarding environmental exposures and autoimmunity and to identify critical knowledge gaps and areas of uncertainty for future study. This consensus document summarizes key findings from published workshop monographs on areas in which “confident” and “likely” assessments were made, with recommendations for further research. Transcribed notes and slides were reviewed to synthesize an overview on exposure assessment and questions addressed by interdisciplinary panels. Critical advances in the field of autoimmune disease research have been made in the past decade. Collaborative translational and interdisciplinary research is needed to elucidate the role of environmental factors in autoimmune diseases. A focus on exposure assessment methodology is needed to improve the effectiveness of human studies, and more experimental studies are needed to focus on causal mechanisms underlying observed associations of environmental factors with autoimmune disease in humans. PMID:25196523

  13. Vogt-Koyanagi-Harada disease: review of a rare autoimmune disease targeting antigens of melanocytes.

    PubMed

    Lavezzo, Marcelo Mendes; Sakata, Viviane Mayumi; Morita, Celso; Rodriguez, Ever Ernesto Caso; Abdallah, Smairah Frutuoso; da Silva, Felipe T G; Hirata, Carlos Eduardo; Yamamoto, Joyce Hisae

    2016-01-01

    Vogt-Koyanagi-Harada disease (VKHD) is a rare granulomatous inflammatory disease that affects pigmented structures, such as eye, inner ear, meninges, skin and hair. This disease is mainly a Th1 lymphocyte mediated aggression to melanocytes after a viral trigger in the presence of HLA-DRB1*0405 allele. The absence of ocular trauma or previous intraocular surgery sets VKHD appart from sympathetic ophthalmia, its main differential diagnosis. The disease has an acute onset of bilateral blurred vision with hyperemia preceded by flu-like symptoms. The acute uveitic stage is characterized by a diffuse choroiditis with serous retinal detachment and optic disc hyperemia and edema. Fluorescein angiography in this phase demonstrates multiple early hyperfluorescent points. After the acute uveitic stage, ocular and integumentary system pigmentary changes may appear. Ocular findings may be accompanied by lymphocytic meningitis, hearing impairment and/or tinnitus in a variable proportion of patients. Prompt diagnosis followed by early, aggressive and long-term treatment with high-dose corticosteroids is most often ensued by good visual outcomes. However, some patients may experience chronic uveal inflammation with functional eye deterioration. The current review discusses the general features of VKHD, including epidemiology, classification into categories, differential diagnosis and current therapeutic approaches. PMID:27008848

  14. Statistical Colocalization of Genetic Risk Variants for Related Autoimmune Diseases in the Context of Common Controls

    PubMed Central

    Fortune, Mary D.; Guo, Hui; Burren, Oliver; Schofield, Ellen; Walker, Neil M.; Ban, Maria; Sawcer, Stephen J.; Bowes, John; Worthington, Jane; Barton, Ann; Eyre, Steve; Todd, John A.; Wallace, Chris

    2015-01-01

    Identifying whether potential causal variants for related diseases are shared can identify overlapping etiologies of multifactorial disorders. Colocalization methods disentangle shared and distinct causal variants. However, existing approaches require independent datasets. Here we extend two colocalization methods to allow for the shared control design commonly used in comparison of genome-wide association study results across diseases. Our analysis of four autoimmune diseases, type 1 diabetes (T1D), rheumatoid arthritis, celiac disease and multiple sclerosis, revealed 90 regions that were associated with at least one disease, 33 (37%) of which with two or more disorders. Nevertheless, for 14 of these 33 shared regions there was evidence that causal variants differed. We identified novel disease associations in 11 regions previously associated with one or more of the other three disorders. Four of eight T1D-specific regions contained known type 2 diabetes candidate genes: COBL, GLIS3, RNLS and BCAR1, suggesting a shared cellular etiology. PMID:26053495

  15. Caffeic acid phenethyl ester lessens disease symptoms in an experimental autoimmune uveoretinitis mouse model.

    PubMed

    Choi, Jae-Hyeog; Roh, Kug-Hwan; Oh, Hana; Park, Sol-Ji; Ha, Sung-Min; Kang, Mi Seon; Lee, Ji-Hyun; Jung, So Young; Song, Hyunkeun; Yang, Jae Wook; Park, SaeGwang

    2015-05-01

    Experimental autoimmune uveoretinitis (EAU) is an autoimmune disease that models human uveitis. Caffeic acid phenethyl ester (CAPE), a phenolic compound isolated from propolis, possesses anti-inflammatory and immunomodulatory properties. CAPE demonstrates therapeutic potential in several animal disease models through its ability to inhibit NF-κB activity. To evaluate these therapeutic effects in EAU, we administered CAPE in a model of EAU that develops after immunization with interphotoreceptor retinal-binding protein (IRBP) in B10.RIII and C57BL/6 mice. Importantly, we found that CAPE lessened the severity of EAU symptoms in both mouse strains. Notably, treated mice exhibited a decrease in the ocular infiltration of immune cell populations into the retina; reduced TNF-α, IL-6, and IFN-γ serum levels: and inhibited TNF-α mRNA expression in retinal tissues. Although CAPE failed to inhibit IRBP-specific T cell proliferation, it was sufficient to suppress cytokine, chemokine, and IRBP-specific antibody production. In addition, retinal tissues isolated from CAPE-treated EAU mice revealed a decrease in NF-κB p65 and phospho-IκBα. The data identify CAPE as a potential therapeutic agent for autoimmune uveitis that acts by inhibiting cellular infiltration into the retina, reducing the levels of pro-inflammatory cytokines, chemokine, and IRBP-specific antibody and blocking NF-κB pathway activation. PMID:25795054

  16. Autoimmune hepatitis, one disease with many faces: Etiopathogenetic, clinico-laboratory and histological characteristics

    PubMed Central

    Gatselis, Nikolaos K; Zachou, Kalliopi; Koukoulis, George K; Dalekos, George N

    2015-01-01

    Autoimmune hepatitis (AIH) is an unresolving progressive liver disease of unknown etiology characterized by hypergammaglobulinemia, autoantibodies detection and interface hepatitis. Due to the absence of specific diagnostic markers and the large heterogeneity of its clinical, laboratory and histological features, AIH diagnosis may be potentially difficult. Therefore, in this in-depth review we summarize the substantial progress on etiopathogenesis, clinical, serological and histological phenotypes of AIH. AIH has a global distribution affecting any age, both sexes and all ethnic groups. Clinical manifestations vary from asymptomatic to severe or rarely fulminant hepatitis. Hypergammaglobulinemia with selective elevation of IgG is found in most cases. Autoimmune attack is perpetuated, possibly via molecular mimicry, and favored by the impaired control of T-regulatory cells. Histology (interface hepatitis, emperipolesis and hepatic rosette formation) and autoantibodies detection although not pathognomonic, are still the hallmark for a timely diagnosis. AIH remains a major diagnostic challenge. AIH should be considered in every case in the absence of viral, metabolic, genetic and toxic etiology of chronic or acute hepatitis. Laboratory personnel, hepato-pathologists and clinicians need to become more familiar with disease expressions and the interpretation of liver histology and autoimmune serology to derive maximum benefit for the patient. PMID:25574080

  17. Induction of autoimmune disease by deletion of CTLA-4 in mice in adulthood.

    PubMed

    Klocke, Katrin; Sakaguchi, Shimon; Holmdahl, Rikard; Wing, Kajsa

    2016-04-26

    Cytotoxic T lymphocyte antigen-4 (CTLA-4) is essential for immunological (self-) tolerance, but due to the early fatality of CTLA-4 KO mice, its specific function in central and peripheral tolerance and in different systemic diseases remains to be determined. Here, we further examined the role of CTLA-4 by abrogating CTLA-4 expression in adult mice and compared the resulting autoimmunity that follows with that produced by congenital CTLA-4 deficiency. We found that conditional deletion of CTLA-4 in adult mice resulted in spontaneous lymphoproliferation, hypergammaglobulinemia, and histologically evident pneumonitis, gastritis, insulitis, and sialadenitis, accompanied by organ-specific autoantibodies. However, in contrast to congenital deficiency, this was not fatal. CTLA-4 deletion induced preferential expansion of CD4(+)Foxp3(+) Treg cells. However, T cells from CTLA-4-deficient inducible KO mice were able to adoptively transfer the diseases into T cell-deficient mice. Notably, cell transfer of thymocytes de novo produced myocarditis, otherwise not observed in donor mice depleted in adulthood. Moreover, CTLA-4 deletion in adult mice had opposing impacts on induced autoimmune models. Thus, although CTLA-4-deficient mice had more severe collagen-induced arthritis (CIA), they were protected against peptide-induced experimental autoimmune encephalomyelitis (EAE); however, onset of protein-induced EAE was only delayed. Collectively, this indicates that CTLA-4 deficiency affects both central and peripheral tolerance and Treg cell-mediated suppression. PMID:27071130

  18. Early-Onset Autoimmune Disease as a Manifestation of Primary Immunodeficiency

    PubMed Central

    Carneiro-Sampaio, Magda; Coutinho, Antonio

    2015-01-01

    Autoimmune disorders (AID) have been increasingly observed in association with primary immunodeficiencies (PIDs). Here, we discuss the interface between PID and AID, focusing on autoimmune manifestations early in life, which can be diagnostic clues for underlying PIDs. Inflammatory bowel disease in infants and children has been associated with IL-10 and IL-10R deficiencies, chronic granulomatous disease, immunedysregulation-polyendocrinopathy-enteropathy-X-linked syndrome (IPEX), autoinflammatory disorders, and others. Some PIDs have been identified as underlying defects in juvenile systemic lupus erythematosus: C1q-, IgA-, IgM deficiencies, alterations of the IFN-α pathway (in Aicardi–Goutières syndrome due to TREX1 mutation). IPEX (due to FOXP3 mutation leading to Treg cell deficiency), usually appearing in the first months of life, was recently observed in miscarried fetuses with hydrops who presented with CD3+ infiltrating lymphocytes in the pancreas. Hemophagocytic lymphohistiocytosis due to perforin deficiency was also identified as a cause of fetal hydrops. In conclusion, PID should be suspected in any infant with signs of autoimmunity after excluding transferred maternal effects, or in children with multiple and/or severe AID. PMID:25999944

  19. Induction of autoimmune disease by adoptive transfer of an atypical NK cell subset

    PubMed Central

    Voynova, Elisaveta; Qi, Chen-Feng; Scott, Bethany; Bolland, Silvia

    2015-01-01

    Several mouse models of SLE, including FcγRIIB-KO and TLR7tg mice, develop an expansion of an atypical NK cell subset with functional similarity to cells referred as IKDCs or pre-mNKs in other systems. Here we show that atypical NKs purified from spleens of SLE-prone mice, and identified as NK1.1+CD11c+CD122+MHC-II+, induce persistent autoimmune disease in an IFN-I and CD40L-dependent manner when transferred to WT mice. A single transfer of 4x106 NK1.1+ cells from TLR7tg into WT induces a 2-week-long wave of inflammatory cytokines in the serum, a sustained increase in T cell activation and follicular helper cells for the following months, and a progressive expansion of dendritic cells, monocytes and granulocytes. Furthermore IL15 deficiency, which impedes development of NK cells, ameliorates the autoimmune pathology of TLR7tg mice. These results suggest that cells of the NK lineage can develop into cytokine producing/antigen-presenting cells that affect the priming and progression of systemic autoimmune disease. PMID:26109646

  20. T cell subsets and their signature cytokines in autoimmune and inflammatory diseases.

    PubMed

    Raphael, Itay; Nalawade, Saisha; Eagar, Todd N; Forsthuber, Thomas G

    2015-07-01

    CD4(+) T helper (Th) cells are critical for proper immune cell homeostasis and host defense, but are also major contributors to pathology of autoimmune and inflammatory diseases. Since the discovery of the Th1/Th2 dichotomy, many additional Th subsets were discovered, each with a unique cytokine profile, functional properties, and presumed role in autoimmune tissue pathology. This includes Th1, Th2, Th17, Th22, Th9, and Treg cells which are characterized by specific cytokine profiles. Cytokines produced by these Th subsets play a critical role in immune cell differentiation, effector subset commitment, and in directing the effector response. Cytokines are often categorized into proinflammatory and anti-inflammatory cytokines and linked to Th subsets expressing them. This article reviews the different Th subsets in terms of cytokine profiles, how these cytokines influence and shape the immune response, and their relative roles in promoting pathology in autoimmune and inflammatory diseases. Furthermore, we will discuss whether Th cell pathogenicity can be defined solely based on their cytokine profiles and whether rigid definition of a Th cell subset by its cytokine profile is helpful. PMID:25458968