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Sample records for non-endocrine autoimmune disorders

  1. Autoimmune disorders

    MedlinePlus

    ... tissue and antigens. As a result, the body sets off a reaction that destroys normal tissues. The exact cause of autoimmune disorders is unknown. One theory is that some microorganisms (such as bacteria or ...

  2. Autoimmune basal ganglia disorders.

    PubMed

    Dale, Russell C; Brilot, Fabienne

    2012-11-01

    The basal ganglia are deep nuclei in the brain that include the caudate, putamen, globus pallidus, and substantia nigra. Pathological processes involving the basal ganglia often result in disorders of movement and behavior. A number of different autoimmune disorders predominantly involve the basal ganglia and can result in movement and psychiatric disorders. The classic basal ganglia autoimmune disorder is Sydenham chorea, a poststreptococcal neuropsychiatric disorder. Resurgence in the interest in Sydenham chorea is the result of the descriptions of other poststreptococcal neuropsychiatric disorders including tics and obsessive-compulsive disorder, broadly termed pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection. Encephalitic processes affecting the basal ganglia are also described including the syndromes basal ganglia encephalitis, encephalitis lethargica, and bilateral striatal necrosis. Last, systemic autoimmune disorders such as systemic lupus erythematosus and antiphospholipid syndrome can result in chorea or parkinsonism. Using paradigms learned from other autoantibody associated disorders, the authors discuss the autoantibody hypothesis and the role of systemic inflammation in autoimmune basal ganglia disorders. Identification of these entities is important as the clinician has an increasing therapeutic repertoire to modulate or suppress the aberrant immune system. PMID:22832771

  3. Autoimmune movement disorders.

    PubMed

    Mckeon, Andrew; Vincent, Angela

    2016-01-01

    Autoimmune movement disorders encapsulate a large and diverse group of neurologic disorders occurring either in isolation or accompanying more diffuse autoimmune encephalitic illnesses. The full range of movement phenomena has been described and, as they often occur in adults, many of the presentations can mimic neurodegenerative disorders, such as Huntington disease. Disorders may be ataxic, hypokinetic (parkinsonism), or hyperkinetic (myoclonus, chorea, tics, and other dyskinetic disorders). The autoantibody targets are diverse and include neuronal surface proteins such as leucine-rich, glioma-inactivated 1 (LGI1) and glycine receptors, as well as antibodies (such as intracellular antigens) that are markers of a central nervous system process mediated by CD8+ cytotoxic T cells. However, there are two conditions, stiff-person syndrome (also known as stiff-man syndrome) and progressive encephalomyelitis with rigidity and myoclonus (PERM), that are always autoimmune movement disorders. In some instances (such as Purkinje cell cytoplasmic antibody-1 (PCA-1) autoimmunity), antibodies detected in serum and cerebrospinal fluid can be indicative of a paraneoplastic cause, and may direct the cancer search. In other instances (such as 65kDa isoform of glutamic acid decarboxylase (GAD65) autoimmunity), a paraneoplastic cause is very unlikely, and early treatment with immunotherapy may promote improvement or recovery. Here we describe the different types of movement disorder and the clinical features and antibodies associated with them, and discuss treatment. PMID:27112684

  4. Autoimmune thyroid disorders.

    PubMed

    Antonelli, Alessandro; Ferrari, Silvia Martina; Corrado, Alda; Di Domenicantonio, Andrea; Fallahi, Poupak

    2015-02-01

    Autoimmune thyroid diseases (AITD) result from a dysregulation of the immune system leading to an immune attack on the thyroid. AITD are T cell-mediated organ-specific autoimmune disorders. The prevalence of AITD is estimated to be 5%; however, the prevalence of antithyroid antibodies may be even higher. The AITD comprise two main clinical presentations: Graves' disease (GD) and Hashimoto's thyroiditis (HT), both characterized by lymphocytic infiltration of the thyroid parenchyma. The clinical hallmarks of GD and HT are thyrotoxicosis and hypothyroidism, respectively. The mechanisms that trigger the autoimmune attack to the thyroid are still under investigation. Epidemiological data suggest an interaction among genetic susceptibility and environmental triggers as the key factor leading to the breakdown of tolerance and the development of disease. Recent studies have shown the importance of cytokines and chemokines in the pathogenesis of AT and GD. In thyroid tissue, recruited T helper 1 (Th1) lymphocytes may be responsible for enhanced IFN-γ and TNF-α production, which in turn stimulates CXCL10 (the prototype of the IFN-γ-inducible Th1 chemokines) secretion from the thyroid cells, therefore creating an amplification feedback loop, initiating and perpetuating the autoimmune process. Associations exist between AITD and other organ specific (polyglandular autoimmune syndromes), or systemic autoimmune disorders (Sjögren's syndrome, rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, cryoglobulinemia, sarcoidosis, psoriatic arthritis). Moreover, several studies have shown an association of AITD and papillary thyroid cancer. These data suggest that AITD patients should be accurately monitored for thyroid dysfunctions, the appearance of thyroid nodules, and other autoimmune disorders. PMID:25461470

  5. Autoimmune Neuromuscular Disorders

    PubMed Central

    Kraker, Jessica; Živković, Saša A

    2011-01-01

    Autoimmune neuromuscular disorders affecting peripheral nerves, neuromuscular junction or muscle have a wide clinical spectrum with diverse pathogenetic mechanisms. Peripheral nervous system may be targeted in the context of complex immune reactions involving different cytokines, antigen-presenting cells, B cells and different types of T cells. Various immunomodulating and cytotoxic treatments block proliferation or activation of immune cells by different mechanisms attempting to control the response of the immune system and limit target organ injury. Most treatment protocols for autoimmune neuromuscular disorders are based on the use of corticosteroids, intravenous immunoglobulins and plasmapheresis, with cytotoxic agents mostly used as steroid-sparing medications. More recently, development of specific monoclonal antibodies targeting individual cell types allowed a different approach targeting specific immune pathways, but these new treatments are also associated with various adverse effects and their long-term efficacy is still unknown. PMID:22379454

  6. Autoimmune sleep disorders.

    PubMed

    Silber, Michael H

    2016-01-01

    A number of autoantibodies, some paraneoplastic, are associated with sleep disorders. Morvan syndrome and limbic encephalitis, associated with voltage-gated potassium channel-complex antibodies, principally against CASPR2 and LGI1, can result in profound insomnia and rapid eye movement sleep behavior disorder (RBD). Patients with aquaporin-4 antibodies and neuromyelitis optica may develop narcolepsy in association with other evidence of hypothalamic dysfunction, sometimes as the initial presentation. Central sleep apnea and central neurogenic hypoventilation are found in patients with anti-N-methyl-d-aspartate receptor antibody encephalitis, and obstructive sleep apnea, stridor, and hypoventilation are prominent features of a novel tauopathy associated with IgLON5 antibodies. In addition, paraneoplastic diseases may involve the hypothalamus and cause sleep disorders, particularly narcolepsy and RBD in those with Ma1 and Ma2 antibodies. Patients with antineuronal nuclear autoantibodies type 2 may develop stridor. Several lines of evidence suggest that narcolepsy is an autoimmune disorder. There is a strong relationship with the human leukocyte antigen (HLA) DQB1*06:02 haplotype and polymorphisms in the T-cell receptor alpha locus and purinergic receptor P2Y11 genes. Patients with recent-onset narcolepsy may have high titers of antistreptococcal or other antibodies, although none has yet been shown to be disease-specific but, supporting an immune basis, recent evidence indicates that narcolepsy in children can be precipitated by one type of vaccination against the 2009-2010 H1N1 influenza pandemic. PMID:27112685

  7. Autoimmune disorders in diabetes.

    PubMed

    Boitard, C; Debray-Sachs, M; Bach, J F

    1986-01-01

    The development of IDDM correlates with the presence of biologic markers pointing to the involvement of the immune system in the disease process. In addition to clinical observations of association of IDDM with other autoimmune disease and morphologic evidence of a mononuclear cell infiltration of the islets of Langerhans at the onset of the disease, anti-islet cell antibodies are detected in the serum of IDDM patients. Moreover, a strong genetic association with HL-A DR3 and DR4 identifies a genetic background compatible with autoimmune phenomena. Whether autoimmune phenomena are primary or secondary to an initial damage of the islets by infectious agents or other environmental factors is unknown. Whether or not the autoimmune response participates in the selective destruction of insulin-secreting cells has been a major issue in the past five years. The presence of T lymphocytes and anti-islet cell antibodies, which selectively inhibit or lyse insulin-secreting cells in vitro, strongly suggests that it may be the case. A definitive demonstration is difficult to provide in human IDDM. The development of animal models for IDDM has allowed useful insight into the pathogenetic mechanisms responsible for IDDM. In both the BB rat and the low-dose streptozotocin mouse model, the role of the immune system in the destruction of the islets of Langerhans is supported by the prevention of the disease by treatments interfering with the immune system. The BB rat develops a spontaneous autoimmune disease on a genetic background defined by the association with a major histocompatibility complex allele without any evidence for a role in initial damage of islets of a triggering infectious or chemical process. The low-dose streptozotocin model is an autoimmune IDDM secondary to the selective damage of islet cells by a toxin. The present scheme of an islet cell target and specific autoreactive T and B lymphocyte clones raises two major issues: what is the target antigen on islet cells and what is the role at the molecular level of class II major histocompatibility complex genes in susceptibility for IDDM? The first issue is presently being addressed in several laboratories using the hybridoma technology. The second issue is addressed at the biochemical level by studying restriction site polymorphism of major histocompatibility genes in susceptible individuals and IDDM patients, and at the functional level by studying the action of monoclonal antibodies to class II antigen on the development of IDDM in animal models. These steps are likely to be a prerequisite to antigen-specific immunotherapy in IDDM. PMID:3082114

  8. Celiac sprue: a unique autoimmune disorder

    PubMed Central

    Rashtak, Shadi; Marietta, Eric V; Murray, Joseph A

    2011-01-01

    Celiac sprue (CS) is a gluten-sensitive enteropathy with many autoimmune features. CS involves multiple organs through immune and nonimmune processes, and is frequently associated with other autoimmune disorders. This article reviews the co-occurrence of CS with autoimmune disorders of the cutaneous, nervous, endocrine, musculoskeletal, gastrointestinal and cardiovascular systems. The types of autoimmune disorders associated with CS and the prevalence of CS in other autoimmune disorders are also discussed. A brief review of the literature on the potential mechanisms behind these associations and the therapeutic effects of a gluten-free diet for autoimmune comorbidities in CS is also provided. PMID:20477645

  9. Emerging therapies for autoimmune disorders.

    PubMed

    Zack, Eric

    2014-01-01

    Several monoclonal antibodies and other biologic drugs are used to treat a variety of common autoimmune disorders that are progressive in nature or resistant to standard therapies. Although monoclonal antibodies were recently removed from the hazardous drugs list, most of these drugs are considered high-risk substances that require specialized knowledge regarding care before, during, and after administration. Yet no national standards exist for nurses working with autoimmune patients, nor have minimum nursing practice competency guidelines been identified. Expert practitioners must continue to educate other health care professionals about the drugs, their intended and off-label uses, their potential side effects, and proactive measures that need to be taken to ensure patient safety during the entire drug administration process. PMID:24583941

  10. Pediatric autoimmune neuropsychiatric disorders after streptococcus infection.

    PubMed

    Maini, Baljeet; Bathla, Manish; Dhanjal, Gurdeep S; Sharma, Prem D

    2012-10-01

    Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infection (PANDAS) is a group of disorders recently recognized as a clinical entity. A case of PANDAS is described here, which remitted after 1 month of treatment. Recent Group A beta-hemolytic streptococcus infection should be considered in a child who presents with a sudden explosive onset of tics or obsessive compulsive symptoms. PMID:23372243

  11. Natural killer cells in human autoimmune disorders.

    PubMed

    Fogel, Leslie A; Yokoyama, Wayne M; French, Anthony R

    2013-01-01

    Natural killer (NK) cells are innate lymphocytes that play a critical role in early host defense against viruses. Through their cytolytic capacity and generation of cytokines and chemokines, NK cells modulate the activity of other components of the innate and adaptive immune systems and have been implicated in the initiation or maintenance of autoimmune responses. This review focuses on recent research elucidating a potential immunoregulatory role for NK cells in T-cell and B-cell-mediated autoimmune disorders in humans, with a particular focus on multiple sclerosis, rheumatoid arthritis, and systemic lupus erythematous. A better understanding of the contributions of NK cells to the development of autoimmunity may lead to novel therapeutic targets in these diseases. PMID:23856014

  12. Tic disorders and obsessive-compulsive disorder: is autoimmunity involved?

    PubMed

    Hoekstra, Pieter J; Minderaa, Ruud B

    2005-12-01

    The precise cause of tic disorders and paediatric obsessive-compulsive disorder (OCD) is unknown. In addition to genetic factors, autoimmunity may play a role, possibly as a sequela of preceding streptococcal throat infections in susceptible children. Here we review the most recent findings, from July 2003 onwards, with regard to a possible relationship between tics/OCD and autoimmunity. Evidence about an intriguing correlation between streptococcal infections and tic disorders and OCD is accumulating. Specific criteria have been outlined for paediatric autoimmune disorders associated with streptococcal infections (PANDAS), but autoimmunity may also be involved in tic disorders and/or OCD in general. Anti-basal ganglia auto-antibodies are an important potential indicator of autoimmunity. Although the lack of a standardized methodology makes comparisons of findings difficult, new data has emerged pointing to the possible involvement of specific auto-antigens. Earlier findings of increased D8/17 B cell expression as a putative susceptibility marker could not be replicated, possibly due to instability of the D8/17-binding antibody. Although PANDAS patients have been reported to improve after therapeutic plasma exchange, and antibiotics may prevent symptom exacerbations, immune-based treatments should not be routinely given. In future studies, demonstrating the pathogenetic significance of anti-basal ganglia antibodies in animals is a major challenge to draw any firm conclusions about a role for autoimmunity. Future longitudinal studies should be aimed at assessing the precise relationship between symptom exacerbations, infections, and immune parameters, possibly along with gene expression profiles. PMID:16401548

  13. Autoimmune thyroid disorders and coeliac disease.

    PubMed

    Collin, P; Salmi, J; Hällström, O; Reunala, T; Pasternack, A

    1994-02-01

    Eighty-three patients with autoimmune thyroid disorders were screened for coeliac disease. The screening was performed with IgA-class reticulin and endomysium antibody, IgA- and IgG-class gliadin antibody tests, and various biochemical tests for malabsorption. None of the tested subjects had selective IgA deficiency, which excludes the possibility of not detecting positives by an IgA-class test. Of the 83 patients, three asymptomatic coeliac patients were found, and one patient with coeliac disease previously diagnosed, an overall frequency of 4.8%. In addition, 25 patients with a solitary nodule of the thyroid gland were examined and one of them (4%) was found to have coeliac disease. By contrast, one (0.4%) out of 249 age- and sex-matched blood donors was found to have coeliac disease. All newly detected coeliac patients had IgA-class gliadin, reticulin and endomysium antibodies, but none of the patients had any gastrointestinal symptoms or abnormal biochemical findings suggesting coeliac disease. Treatment of thyroid disorders and coeliac disease was successful in these patients. The present results confirm that the frequency of subclinical coeliac disease is increased among patients with autoimmune thyroid disorders. IgA-class reticulin, endomysium or gliadin antibody tests are suitable screening methods for detecting these patients, as far as selective IgA-deficiency is excluded. PMID:8130887

  14. 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

  15. Steroid receptor antibodies in autoimmune disorders.

    PubMed

    Feldman, M

    1987-06-30

    Sera from patients with autoimmune disorders have been analyzed for the presence of antibodies against the estrogen receptor. About 42% of the male and 34% of the female patients had measureable levels of antibody under our assay conditions. However, whereas the male patient population had significantly higher levels of anti-estrogen receptor than normal males, there was no significant difference between female patients and controls. Separation of the estrogen receptor by sucrose gradient centrifugation into the large (9-10S) and small (4S) molecular weight forms demonstrated that only the large form was antigenic, suggesting that the antibodies are not interacting with the steroid binding subunit. The clinical significance of increased levels of antibodies against the estrogen receptor in a percentage of male patients remains to be established. PMID:3606605

  16. [Polyglandular autoimmune syndromes : An overview].

    PubMed

    Komminoth, P

    2016-05-01

    Polyglandular autoimmune syndromes (PGAS), also known as autoimmune polyendocrinopathy syndromes (APS), are a heterogeneous group of rare, genetically caused diseases of the immune system which lead to inflammatory damage of various endocrine glands resulting in malfunctions. In addition, autoimmune diseases of non-endocrine organs may also be found. Early diagnosis of PGAS is often overlooked because of heterogeneous symptoms and the progressive occurrence of the individual diseases. The two most important forms of PGAS are the juvenile and adult types. The juvenile type (PGAS type 1) is caused by mutations in the autoimmune regulator (AIRE) gene on chromosome 21, exhibits geographic variations in incidence and is defined by the combination of mucocutaneous candidiasis, Addison's disease and hypoparathyroidism. In addition, autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) syndrome and other autoimmune diseases can also occur. The adult form of PGAS (PGAS type 2) is a multigenetic disorder associated with some HLA haplotypes, is more common than the juvenile type, shows female predominance and exhibits the combination of type 1 diabetes, autoimmune thyroid disease, Addison's disease and other autoimmune disorders. The histological alterations in affected organs of PGAS patients are similar to findings in sporadically occurring autoimmune diseases of these organs but there are no pathognomic fine tissue findings. If patients exhibit autoimmune changes in two different endocrine glands or if there are indications of several autoimmune disorders from the patient history, it is important to consider PGAS and inform the clinicians of this suspicion. PMID:27099223

  17. Cytokines and HCV-related autoimmune disorders.

    PubMed

    Antonelli, Alessandro; Ferrari, Silvia Martina; Ruffilli, Ilaria; Fallahi, Poupak

    2014-12-01

    Cytokines are intercellular mediators involved in viral control and liver damage being induced by infection with hepatitis C virus (HCV). The complex cytokine network operating during initial infection allows a coordinated, effective development of both innate and adaptive immune responses. However, HCV interferes with cytokines at various levels and escapes immune response by inducing a T-helper (Th)2/T cytotoxic 2 cytokine profile. Inability to control infection leads to the recruitment of inflammatory infiltrates into the liver parenchyma by interferon (IFN)-γ-inducible CXC chemokine ligand (CXCL)9, -10, and -11 chemokines, which results in sustained liver damage and eventually in liver cirrhosis. The most important systemic HCV-related extrahepatic diseases-mixed cryoglobulinemia, lymphoproliferative disorders, thyroid autoimmune disorders, and type 2 diabetes-are associated with a complex dysregulation of the cytokine/chemokine network, involving proinflammatory and Th1 chemokines. The therapeutical administration of cytokines such as IFN-α may result in viral clearance during persistent infection and revert this process. Theoretically agents that selectively neutralize CXCL10 could increase patient responsiveness to traditional IFN-based HCV therapy. Several studies have reported IL-28B polymorphisms and circulating CXCL10 may be a prognostic markers for HCV treatment efficacy in HCV genotype 1 infection. PMID:25381483

  18. B-cell survival factors in autoimmune rheumatic disorders

    PubMed Central

    Morais, Sandra A.; Vilas-Boas, Andreia

    2015-01-01

    Autoimmune rheumatic disorders have complex etiopathogenetic mechanisms in which B cells play a central role. The importance of factors stimulating B cells, notably the B-cell activating factor (BAFF) and A proliferation inducing ligand (APRIL) axis is now recognized. BAFF and APRIL are cytokines essential for B-cell proliferation and survival from the immature stages to the development of plasma cells. Their levels are increased in some subsets of patients with autoimmune disorders. Several recent biologic drugs have been developed to block this axis, namely belimumab [already licensed for systemic lupus erythematosus (SLE) treatment], tabalumab, atacicept and blisibimod. Many clinical trials to evaluate the safety and efficacy of these drugs in several autoimmune disorders are ongoing, or have been completed recently. This review updates the information on the use of biologic agents blocking BAFF/APRIL for patients with SLE, rheumatoid arthritis, Sjögren’s syndrome and myositis. PMID:26288664

  19. Rheumatic and autoimmune thyroid disorders: a causal or casual relationship?

    PubMed

    Bourji, Khalil; Gatto, Mariele; Cozzi, Franco; Doria, Andrea; Punzi, Leonardo

    2015-01-01

    A number of dysfunctions may affect the thyroid gland leading either to hyper- or hypothyroidism which are mediated by autoimmune mechanisms. Thyroid abnormalities may represent an isolated alteration or they may be the harbinger of forthcoming disorders as is the case of well-characterized polyendocrine syndromes. Also, they may precede or follow the appearance of rheumatic manifestations in patients affected with connective tissue diseases or rheumatoid arthritis. The mechanisms by which autoimmune thyroid disorders may be linked to systemic autoimmune diseases have not been fully unraveled yet, however alterations of common pathways are suggested by shared genetic variants affecting autoantigen presentation and regulation of the immune response. On the other hand, the higher prevalence of autoimmune thyroid disorders over rheumatic diseases compels the chance of a mere causal concomitancy in the same patient. The aim of our paper is to provide an overview of available data on thyroid involvement in different rheumatic diseases and to go over the main rheumatic manifestations in the context of autoimmune thyroid diseases. PMID:25315745

  20. [SPECIFIC CLINICAL FEATURES OF TYPE 1 AUTOIMMUNE POLYGLANDULAR SYNDROME].

    PubMed

    Mikhina, M S; Molashenko, N V; Troshina, E A; Orlova, E M; Sozaeva, L S; Eystein, S H; Breivik, S

    2015-01-01

    Autoimmune polyglandular syndrome is a primary autoimmune disorder affecting two or more peripheral endocrine glands and responsible for their incompetence. It is frequently combined with various organ-specific non-endocrine diseases. Patients with this pathology need life-long replacement therapy and dynamic observation by endocrinologists and other specialists to monitor the effectiveness of the treatment and detect new components of the disease. We report a variant of type 1 autoimmune polyglandular syndrome. Special emphasis is laid on the importance of succession of actions of endocrinologists and specialists in related medical disciplines dealing with children and adult patients. PMID:26669033

  1. PSYCHOTIC DISORDERS GENERATED BY AUTOIMMUNE ENCEPHALITIS (CLINICAL CASE).

    PubMed

    Craciun, Georgiana; Cucoş, Liliana; Ungureanu, Elena; Pendefunda, L; Petrariu, F D; Nechita, Petronela

    2015-01-01

    Encephalitis is a brain inflammation, which could involve also the meninges. The etiology of encephalitis could be: viral, bacterial, fungal or autoimmune. Anti-NMDAR encephalitis is an immune disorder, easy to diagnose and is a treatable condition. Most patients with anti-NMDAR encephalitis develop a multistage illness that progresses from psychosis, memory deficits, seizures, to catatonic state and breathing instability. We present a case report of a 20-year old woman, who presented: amnesia, visual hallucination, illusions, seizures after that occurred following autoimmune encephalitis. The exact incidence of anti-NMDAR encephalitis is unknown, but it seems to be more frequent than any other known paraneoplastic encephalitis. The present case is important considering that autoimmune encephalitis is a rare frequency disorder in Romania, with patients presenting resounding psychiatric and neurological manifestations. PMID:26793848

  2. Evaluation of autoimmune phenomena in patients with pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS).

    PubMed

    Stagi, Stefano; Rigante, Donato; Lepri, Gemma; Bertini, Federico; Matucci-Cerinic, Marco; Falcini, Fernanda

    2014-12-01

    The pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) are basically characterized by obsessive-compulsive symptoms and/or tics triggered by group-A beta-hemolytic Streptococcus infections. Poor data are available about the clear definition of PANDAS's autoimmune origin. The aim of our study was to evaluate the prevalence of autoimmune phenomena, including thyroid function abnormalities, specific celiac disease antibodies, and positivity of organ- or nonorgan-specific autoantibodies in a large cohort of Caucasian children and adolescents with PANDAS. Seventy-seven consecutive patients (59 males, 18 females; mean age 6.3±2.5 years, range 2.0-14.5 years) strictly fulfilling the clinical criteria for PANDAS diagnosis were recruited. In all subjects we evaluated serum concentrations of free-T3, free-T4, thyrotropin, and the following auto-antibodies: anti-thyroperoxidase, anti-thyroglobulin, anti-thyrotropin receptor, anti-gliadin, anti-endomysium, anti-tissue transglutaminase, anti-nuclear, anti-smooth muscle, anti-extractable nuclear antigens, anti-phospholipid, plus lupus-like anticoagulant. The results were compared with those obtained from 197 age- and sex-matched healthy controls (130 males, 67 females; mean age 6.8±2.9 years, range 2.3-14.8 years). The frequencies of subclinical (3.8% vs 3.6%) and overt hypothyroidism (1.2% vs 0%), autoimmune thyroiditis (2.46% vs 1.14%), celiac disease (1.2% vs 0.05%), and positivity of organ- and nonorgan-specific autoantibodies (5.1% vs 4.8%) were not statistically significant between patients with PANDAS and controls. Evaluating the overall disease duration, we did not observe any significant difference between patients with (3.4±2.15 years) and without (3.4±2.89 years) autoimmune abnormalities. However, PANDAS patients with autoimmune diseases or positivity for any organ- and nonorgan-specific antibodies showed significantly higher anti-streptolysin O and anti-DNAse B titers, as well as a history of more frequent throat infections than controls (p<0.0001). Abnormalities of thyroid function and thyroid autoimmune diseases, as well as the association with celiac disease or organ- and nonorgan-specific autoimmunity seem not more frequent in children and adolescents with PANDAS than in healthy controls. A potential relationship between autoimmunity and PANDAS should be assessed further in larger studies. Children and adolescents with PANDAS should not be actually screened for thyroid function, celiac disease and/or autoimmune diseases. PMID:25151976

  3. [Complex family association in autoimmune polyendocrine syndrome].

    PubMed

    Femiano, P; Castaldo, V; Iossa, C

    2003-04-01

    Autoimmune polyglandular syndromes (APS) are conditions characterized by the association of two or more endocrine and non-endocrine autoimmune disorders. Diabetes mellitus type 1 (T1DM) is one of the most frequent components of APS and is often its first symptom. The frequency of autoimmune pathologies in patients affected by T1DM is proportional to the persistance of ICA. Even in first relatives of these patients, an increase in incidence of latent or manifest autoimmune pathology is noticed. The association of T1DM with autoimmune thyroiditis and celiac disease in a girl from a family affected by high incidence of autoimmune pathology is described. The role of gluten in the pathogenesis of T1DM and some other autoimmune conditions in genetically predisposed subjects. Infact studies are still inadequate for demostrating how a gluten-free diet could delay or mitigate the course of T1DM and of other autoimmune pathologies in genetically predisposed subjects. Nevertheless, it is suggested that gluten could represent a starting or a maintenance factor of autoimmune processes and the risk of autoimmune pathologies is proportional to the duration of the exposure to gluten. A screening for a quick singling out of autoimmune pathologies is suggested for T1DM patients, their first relatives and for subjects affected by other autoimmune diseases or celiac disease. PMID:12754461

  4. Carpal tunnel syndrome as a herald of autoimmune rheumatic disorders.

    PubMed Central

    Pal, B

    1997-01-01

    In six patients aged 59-71 years carpal tunnel syndrome, seemingly idiopathic, was followed by connective tissue disorders, in most cases autoimmune in nature. Patients with idiopathic carpal tunnel syndrome may therefore require long-term follow-up, if inflammatory rheumatic conditions are not to be missed. PMID:9155757

  5. [A review on thyroid autoimmune disorders and HCV chronic infection].

    PubMed

    Di Domenicantonio, A; Politti, U; Marchi, S; De Bortoli, N; Giuggioli, D; Antonelli, A; Ferri, C

    2014-01-01

    Frequently, patients with hepatitis C virus (HCV) chronic infection have high levels of serum anti-thyroperoxidase and/or anti-thyroglobulin autoantibodies, ultrasonographical signs of chronic autoimmune thyroiditis, and subclinical hypothyroidism, in female gender, vs healthy controls, or hepatitis B virus infected patients. In patients with "HCV-associated mixed cryoglobulinemia" (MC+HCV), a higher prevalence of autoimmune thyroid disorders was shown not only compared to controls, but also compared to HCV patients without cryoglobulinemia. Patients with MC+HCV or with HCV chronic infection, show an higher prevalence of papillary thyroid cancer than in controls, in particular in patients with autoimmune thyroiditis. Patients with HCV chronic infection, or with MC+HCV, in presence of autoimmune thyroiditis, show higher serum levels of T-helper (Th)1 (C-X-C motif) ligand 10 (CXCL10) chemokine than patients without thyroiditis. Probably, HCV thyroid infection acts by upregulating CXCL10 gene expression and secretion in thyrocytes recruiting Th1 lymphocytes, that secrete interferon-gamma and tumor necrosis factor-alpha. These cytokines might induce a further CXCL10 secretion by thyrocytes, thus perpetuating the immune cascade, that may lead into the appearance of autoimmune thyroid disorders in genetically predisposed subjects. A careful monitoring of thyroid function and nodules are recommanded in HCV patients. PMID:25366958

  6. Post-streptococcal autoimmune disorders of the central nervous system.

    PubMed

    Dale, Russell C

    2005-11-01

    Group A Streptococcus can induce autoimmune disease in humans with particular involvement of the heart, joints, and brain. The spectrum of post-streptococcal disease of the central nervous system (CNS) has been widened recently and includes movement disorders (chorea, tics, dystonia, and Parkinsonism), psychiatric disorders (particularly emotional disorders), and associated sleep disorders. Neuroimaging and pathological studies indicate that the most vulnerable brain region is the basal ganglia. The immunopathogenesis of the disease is incompletely defined, and although there is some support for autoantibody-mediated disease, several conflicting studies cast doubt on the autoantibody hypothesis. It has been speculated that post-streptococcal autoimmunity has a role in common neuropsychiatric disease but the evidence is conflicting and routine screening of patients with Tourette syndrome and obsessive-compulsive disorder for post-streptococcal autoimmune abnormalities is not be recommended at present. However, post-streptococcal disorders of the CNS remain a useful model of neuropsychiatric disease, which may improve our understanding of abnormal movements and behaviours in children. PMID:16225745

  7. Movement disorders in paraneoplastic and autoimmune disease

    PubMed Central

    Panzer, Jessica; Dalmau, Josep

    2013-01-01

    Purpose of review The most relevant advances in immune-mediated movement disorders are described, with emphasis on the clinical–immunological associations, novel antigens, and treatment. Recent findings Many movement disorders previously considered idiopathic or degenerative are now recognized as immune-mediated. Some disorders are paraneoplastic, such as anti-CRMP5-associated chorea, anti-Ma2 hypokinesis and rigidity, anti-Yo cerebellar ataxia and tremor, and anti-Hu ataxia and pesudoathetosis. Other disorders such as Sydenham's chorea, or chorea related to systemic lupus erythematosus and antiphospholipid syndrome occur in association with multiple antibodies, are not paraneoplastic, and are triggered by molecular mimicry or unknown mechanisms. Recent studies have revealed a new category of disorders that can be paraneoplastic or not, and associate with antibodies against cell-surface or synaptic proteins. They include anti-N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis, which may cause dyskinesias, chorea, ballismus or dystonia (NMDAR antibodies), the spectrum of Stiff-person syndrome/muscle rigidity (glutamic acid decarboxylase, amphiphysin, GABAA-receptor-associated protein, or glycine receptor antibodies), neuromyotonia (Caspr2 antibodies), and opsoclonus–myoclonus–ataxia (unknown antigens). Summary Neurologists should be aware that many movement disorders are immune-mediated. Recognition of these disorders is important because it may lead to the diagnosis of an occult cancer, and a substantial number of patients, mainly those with antibodies to cell-surface or synaptic proteins, respond to immunotherapy. PMID:21577108

  8. Neutrophil extracellular traps (Nets) impact upon autoimmune disorders.

    PubMed

    Pruchniak, Micha? Przemys?aw; Kotu?a, Iwona; Manda-Handzlik, Aneta

    2015-01-01

    Friend or foe? This is often asked question when it comes to neutrophil extracellular traps studies. There is no simple answer to that. At the time of their discovery they were considered to be protectors of our well-being. Excellent pathogen fighting skills were described as purely beneficial. But it was not long before those guardians of immunity reveal their dark side. What seemed to be profitable could also take its toll. They are perfectly constructed, made from nucleic deoxyribonucleic acid ornamented with cytoplasmic and granular proteins, to fight invaders. But this unique build is prone to become considered by our body as a threat. Since there is a thin line which when crossed turns a savior into enemy, it was postulated that Nets can play a significant role in autoimmune disorders pathogenesis and disease exacerbation. Recent years have brought a new insight into autoimmune disorders trying to connect the old knowledge and suspicions with modern discoveries. PMID:26557037

  9. Neutrophil extracellular traps (Nets) impact upon autoimmune disorders

    PubMed Central

    Kotuła, Iwona; Manda-Handzlik, Aneta

    2015-01-01

    Friend or foe? This is often asked question when it comes to neutrophil extracellular traps studies. There is no simple answer to that. At the time of their discovery they were considered to be protectors of our well-being. Excellent pathogen fighting skills were described as purely beneficial. But it was not long before those guardians of immunity reveal their dark side. What seemed to be profitable could also take its toll. They are perfectly constructed, made from nucleic deoxyribonucleic acid ornamented with cytoplasmic and granular proteins, to fight invaders. But this unique build is prone to become considered by our body as a threat. Since there is a thin line which when crossed turns a savior into enemy, it was postulated that Nets can play a significant role in autoimmune disorders pathogenesis and disease exacerbation. Recent years have brought a new insight into autoimmune disorders trying to connect the old knowledge and suspicions with modern discoveries. PMID:26557037

  10. Clinical implications of copy number variations in autoimmune disorders

    PubMed Central

    Yim, Seon-Hee; Jung, Seung-Hyun; Chung, Boram

    2015-01-01

    Human genetic variation is represented by the genetic differences both within and among populations, and most genetic variants do not cause overt diseases but contribute to disease susceptibility and influence drug response. During the last century, various genetic variants, such as copy number variations (CNVs), have been associated with diverse human disorders. Here, we review studies on the associations between CNVs and autoimmune diseases to gain some insight. First, some CNV loci are commonly implicated in various autoimmune diseases, such as Fc? receptors in patients with systemic lupus erythemoatosus or idiopathic thrombocytopenic purpura and ?-defensin genes in patients with psoriasis or Crohn's disease. This means that when a CNV locus is associated with a particular autoimmune disease, we should examine its potential associations with other diseases. Second, interpopulation or interethnic differences in the effects of CNVs on phenotypes exist, including disease susceptibility, and evidence suggests that CNVs are important to understand susceptibility to and pathogenesis of autoimmune diseases. However, many findings need to be replicated in independent populations and different ethnic groups. The validity and reliability of detecting CNVs will improve quickly as genotyping technology advances, which will support the required replication. PMID:25995659

  11. ELEVATED RISK FOR AUTOIMMUNE DISORDERS IN IRAQ AND AFGHANISTAN VETERANS WITH POSTTRAUMATIC STRESS DISORDER

    PubMed Central

    O’Donovan, Aoife; Cohen, Beth E.; Seal, Karen; Bertenthal, Dan; Margaretten, Mary; Nishimi, Kristen; Neylan, Thomas C.

    2014-01-01

    BACKGROUND Posttraumatic stress disorder (PTSD) is associated with endocrine and immune abnormalities that could increase risk for autoimmune disorders. However, little is known about the risk for autoimmune disorders among individuals with PTSD. METHODS We conducted a retrospective cohort study of 666,269 Iraq and Afghanistan veterans under age 55 who were enrolled in the Department of Veterans Affairs (VA) healthcare system between October 7, 2001 and March 31, 2011. Generalized linear models were used to examine if PTSD, other psychiatric disorders, and military sexual trauma exposure (MST) increase risk for autoimmune disorders, including thyroiditis, inflammatory bowel disease, rheumatoid arthritis, multiple sclerosis, and lupus erythematosus, adjusting for age, gender, race, and primary care visits. RESULTS PTSD was diagnosed in 203,766 (30.6%) veterans, and psychiatric disorders other than PTSD were diagnosed in an additional 129,704 (19.5%) veterans. Veterans diagnosed with PTSD had significantly higher adjusted relative risk (ARR) for diagnosis with any of the autoimmune disorders alone or in combination compared to veterans with no psychiatric diagnoses (ARR = 2.00, 95% CI, 1.91, 2.09), and compared to veterans diagnosed with psychiatric disorders other than PTSD (ARR = 1.51, 95% CI, 1.43, 1.59, p < .001). The magnitude of the PTSD-related increase in risk for autoimmune disorders was similar in women and men, and MST was independently associated with increased risk in both women and men. CONCLUSIONS Trauma exposure and PTSD may increase risk for autoimmune disorders. Altered immune function, lifestyle factors, or shared etiology may underlie this association. PMID:25104173

  12. Audiovestibular disorders as autoimmune reaction in patients with melanoma.

    PubMed

    Barozzi, S; Ginocchio, D; Socci, M; Alpini, D; Cesarani, A

    2015-09-01

    Melanoma is an aggressive form of cancer derived from neuroectodermal melanocytes. Melanocytes are present in the skin and hair follicles, as well as in the eye (iris and choroids), the leptomeninges, the anal canal and the inner ear. In the inner ear melanocytes are found both in the intermediate layer of the stria vascularis of the cochlea and in the dark cells of the vestibular organs. They are believed to play an important role in the production of endolymphatic potentials and in the maintenance of normal volumes of the inner ear fluids. Recently, audiovestibular dysfunctions have been demonstrated in patients treated with immunotherapy for metastatic melanoma and have been related to an autoimmune attack on the normal melanocytes of the inner ear. Melanoma is an immunogenic tumor type frequently associated with spontaneous autoimmune manifestations which seem to be associated with better prognosis. The melanoma-associated antigens are also expressed in normal melanocytes in the skin, eye and ear. We hypothesize that inner ear melanocytes could be a target of an autoimmune process in patients affected by melanoma. The immune system could produce antibodies that cross-react with both the melanoma cells and the labyrinth melanocytes causing an altered homeostasis of endolymphatic liquids and provoking some labyrinthic disorders such as vertigo, hearing loss, aural fullness and tinnitus resembling or influencing Ménière's disease. In this perspective, audiovestibular disorders could be interpreted as an attempt by the individual immune system to develop anti-tumor response. In patients affected by melanoma an autoimmune genesis has already been advocated for ocular symptoms in melanoma-associated retinopathy, where the cross-reaction happens against retinal cells. A possible role of inner ear melanocytes should be considered as a potential cause of audiovestibular disorders. Further research is needed to demonstrate a connection between melanoma and labyrinth dysfunctions such as in melanoma-associated retinopathy. PMID:26115944

  13. Pediatric autoimmune neuropsychiatric disorders associated with Streptococcus in identical siblings.

    PubMed

    Lewin, Adam B; Storch, Eric A; Murphy, Tanya K

    2011-04-01

    Termed pediatric autoimmune neuropsychiatric disorders associated with Streptococcus (PANDAS), these cases of childhood-onset obsessive compulsive disorder and tic disorders resemble the presentation of Sydenham chorea, in that they have an acute onset following a group A beta-hemolytic streptococcal infection (group A Streptococcus), with accompanying neurological signs, and an episodic or sawtooth course. Familial associations of this subgroup of patients remain understudied. This report provides phenotypic descriptions of three youth with PANDAS as well as their genetically identical siblings (in two cases of twins and one case of triplets). These cases highlight the potential for environmental influences for discordant presentations in genetically identical siblings. Despite identical genetics, presentations showed marked variation across siblings (from a full PANDAS presentation to asymptomatic). Further research into environmentally driven influences such as postinfectious molecular mimicry and epigenetic factors that may influence the manifestation of these pediatric neuropsychiatric disorders will promote our understanding of their prevention and treatment. PMID:21486169

  14. Association between autoimmune thyroiditis and depressive disorder in psychiatric outpatients.

    PubMed

    Degner, Detlef; Haust, Merle; Meller, Johannes; Rüther, Eckart; Reulbach, Udo

    2015-02-01

    Thyroid diseases are often associated with psychiatric disorders. The prevalence of autoimmune thyroiditis in the general population is estimated to be at about 5-14 %. A clinical study was conducted to evaluate the association between autoimmune thyroiditis and depression in psychiatric outpatients. Fifty-two patients with depression and nineteen patients with schizophrenia (serving as control group), attending a psychiatric outpatient unit, were included. In addition to the measurement of thyroid-stimulating hormone (TSH), free triiodothyronine, free thyroxine, antithyroid peroxidase (anti-TPO) antibodies, and anti-thyroglobulin antibodies, ultrasound examination of the thyroid gland was performed. The proportion of pathologically increased anti-TPO levels in patients with depression was high. Furthermore, the distribution of pathologically increased anti-TPO levels was significantly (χ (2) = 5.5; p = 0.019) different between patients with depression (32.7 %) and patients with schizophrenia (5.3 %). In a gender- and age-adjusted logistic regression, the odds ratio of uni- or bipolar patients with depression for an autoimmune thyroiditis was ten times higher (95 % CI = 1.2-85.3) when compared with schizophrenia patients. TSH basal level did not differ between patients with depression and patients with schizophrenia. Our study demonstrates a strong association between anti-TPO levels, which are considered to be of diagnostic value for autoimmune thyroiditis (in combination with a hypoechoic thyroid in ultrasonography) with uni- or bipolar depression. It should be noted that the routinely measured TSH level is not sufficient in itself to diagnose this relevant autoimmune comorbidity. PMID:25193677

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

    PubMed

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

    2015-01-01

    In recent years, the authors of epidemiological studies have documented that autoimmune diseases are a major problem of modern society and are classified as diseases of civilization. Autoimmune thyroid diseases (ATDs) are caused by an abnormal immune response to autoantigens present in the thyroid gland - they often coexist with other autoimmune diseases. The most common dysfunctions of the thyroid gland are hypothyroidism, Graves-Basedow disease and Hashimoto's disease. Hashimoto's thyroiditis can be the main cause of primary hypothyroidism of the thyroid gland. Anthropometric, biochemical and physicochemical parameters are used to assess the nutritional status during the diagnosis and treatment of thyroid diseases. Patients with hypothyroidism are often obese, whereas patients with hyperthyroidism are often afflicted with rapid weight loss. The consequence of obesity is a change of the thyroid hormones' activity; however, weight reduction leads to their normalization. The activity and metabolic rate of thyroid hormones are modifiable. ATDs are associated with abnormalities of glucose metabolism and thus increased risk of developing diabetes mellitus type 1 and type 2. Celiac disease (CD) also increases the risk of developing other autoimmune diseases. Malnutrition or the presence of numerous nutritional deficiencies in a patient's body can be the cause of thyroid disorders. Coexisting deficiencies of such elements as iodine, iron, selenium and zinc may impair the function of the thyroid gland. Other nutrient deficiencies usually observed in patients suffering from ATD are: protein deficiencies, vitamin deficiencies (A, C, B6, B5, B1) and mineral deficiencies (phosphorus, magnesium, potassium, sodium, chromium). Proper diet helps to reduce the symptoms of the disease, maintains a healthy weight and prevents the occurrence of malnutrition. This article presents an overview of selected documented studies and scientific reports on the relationship of metabolic disorders and nutritional status with the occurrence of ATD. PMID:25614676

  16. Paedatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal Infection in an Indian Adolescent--A Case Report

    ERIC Educational Resources Information Center

    Sharma, Sachin; Vaish, Supriya; Chopra, Saurabh; Singh, Vindyaprakash; Sharma, Priyanka

    2012-01-01

    Pediatric Autoimmune Neuropsychiatric Disorders associated with Streptococcal infection (PANDAS) is a unique constellation of signs and symptoms that exist in a subset of children with rapid onset or exacerbation of obsessive-compulsive disorder (OCD) and/or tic disorders due to an initial autoimmune reaction to a Group A Beta Hemolytic…

  17. The impact of autoimmune disorders and adverse pregnancy outcome.

    PubMed

    Mecacci, Federico; Pieralli, Annalisa; Bianchi, Barbara; Paidas, Michael J

    2007-08-01

    Autoimmune diseases are a group of heterogeneous disorders equally characterized by the same pathogenetic mechanism: an immunological reaction against self antigens promoted by antibodies, immuno-complex formation, and self-reactive T lymphocytes. Autoimmune diseases may be separated into organ-restricted diseases and systemic ones. The damage of single organs produced by antibodies focused against specific cellular antigens characterizes the first group of diseases, whereas the latter are produced by a systemic inflammatory process initiated by inappropriate and excess immune activation that leads to immuno-complex formation and deposition onto sensitive tissues. Since connective and vascular tissue are principally damaged in these disorders, systemic autoimmune diseases are more commonly known as "connective tissue diseases" (CTD) and include: systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis, Sjogren syndrome, and others. Although they are considered as different from a pathogenetic point of view, they overlap in many aspects, such as general symptoms as fever and fatigue, chronical ongoing, steroid therapy. As patients suffering from CTD are predominantly young women between the ages of 20 and 40 years, which is the period of the highest childbearing potential, particular interest must be regarded to the impact that these diseases and their therapies have on pregnancy and, conversely, the effect of pregnancy on these disorders, which may have long-lasting implications for mothers and neonates. Adverse fetal outcomes, maternal disease flares, and drug potential teratogenic risk are the main reasons why women suffering from CTD and who are pregnant or intend to become pregnant are considered a high-risk population. These patients require integrated, interdisciplinary care, addressing every aspect of rheumatology, obstetrics, and neonatology to reduce maternal, fetal, and neonatal complications. PMID:17825677

  18. SLE: Another Autoimmune Disorder Influenced by Microbes and Diet?

    PubMed Central

    Mu, Qinghui; Zhang, Husen; Luo, Xin M.

    2015-01-01

    Systemic lupus erythematosus (SLE) is a multi-system autoimmune disease. Despite years of study, the etiology of SLE is still unclear. Both genetic and environmental factors have been implicated in the disease mechanisms. In the past decade, a growing body of evidence has indicated an important role of gut microbes in the development of autoimmune diseases, including type 1 diabetes, rheumatoid arthritis, and multiple sclerosis. However, such knowledge on SLE is little, though we have already known that environmental factors can trigger the development of lupus. Several recent studies have suggested that alterations of the gut microbial composition may be correlated with SLE disease manifestations, while the exact roles of either symbiotic or pathogenic microbes in this disease remain to be explored. Elucidation of the roles of gut microbes – as well as the roles of diet that can modulate the composition of gut microbes – in SLE will shed light on how this autoimmune disorder develops, and provide opportunities for improved biomarkers of the disease and the potential to probe new therapies. In this review, we aim to compile the available evidence on the contributions of diet and gut microbes to SLE occurrence and pathogenesis. PMID:26648937

  19. 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

  20. Approaches to Managing Autoimmune Cytopenias in Novel Immunological Disorders with Genetic Underpinnings Like Autoimmune Lymphoproliferative Syndrome

    PubMed Central

    Rao, V. Koneti

    2015-01-01

    Autoimmune lymphoproliferative syndrome (ALPS) is a rare disorder of apoptosis. It is frequently caused by mutations in FAS (TNFRSF6) gene. Unlike most of the self-limiting autoimmune cytopenias sporadically seen in childhood, multi lineage cytopenias due to ALPS are often refractory, as their inherited genetic defect is not going to go away. Historically, more ALPS patients have died due to overwhelming sepsis following splenectomy to manage their chronic cytopenias than due to any other cause, including malignancies. Hence, current recommendations underscore the importance of avoiding splenectomy in ALPS, by long-term use of corticosteroid-sparing immunosuppressive agents like mycophenolate mofetil and sirolimus. Paradigms learnt from managing ALPS patients in recent years is highlighted here and can be extrapolated to manage refractory cytopenias in patients with as yet undetermined genetic bases for their ailments. It is also desirable to develop international registries for children with rare and complex immune problems associated with chronic multilineage cytopenias in order to elucidate their natural history and long-term comorbidities due to the disease and its treatments. PMID:26258116

  1. PANDAS (Paediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal Infection).

    PubMed

    Lynch, N E; Deiratany, S; Webb, D W; McMenamin, J B

    2006-05-01

    PANDAS (Paediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal Infection) is a rare condition first described in 1998. It describes the presence of obsessive-compulsive disorder (OCD) or tics with an episodic course, and a temporal relationship to Group A beta haemolytic streptococcal infection (GABHS). Recurrent episodes can be disruptive and upsetting for a child, but the best way to treat the condition has yet to be established. Penicillin prophylaxis has not proved effective, and other therapies are experimental. There is some evidence in the literature to support the role of tonsillectomy in improving the condition. We report a case of a 6-year-old boy who presented with tic and hemi-chorea associated with GABHS throat infection. He had a recurrence of his symptoms associated with a further GABHS infection, but has had no further symptoms following tonsillectomy. This case report lends further evidence to the role of tonsillectomy in the management of PANDAS. PMID:16892924

  2. Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections: an overview.

    PubMed

    Esposito, S; Bianchini, S; Baggi, E; Fattizzo, M; Rigante, D

    2014-12-01

    The acronym PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections) has been used to describe a syndrome characterized by various obsessions, compulsions, tics, hyperactivity, motor stereotypies, and paroxysmal movement disorders that are correlated with prior infection by group A beta-hemolytic Streptococcus pyogenes (GABHS) infections. Five clinical criteria can be used to diagnose PANDAS: (1) the presence of obsessive-compulsive disorder (OCD) and/or any other tic disorders; (2) prepuberal onset (between 3 years of age and the start of puberty); (3) abrupt onset and relapsing-remitting symptom course; (4) a distinct association with GABHS infection; and (5) association with neurological abnormalities during exacerbations (adventitious movements or motoric hyperactivity). The exact pathogenesis of PANDAS remains unclear, and several theories that focus on multiple etiologic or contributive factors have emerged. PANDAS appears to be a neurobiological disorder that potentially complicates GABHS infections in genetically susceptible individuals. The current standard of care for PANDAS patients remains symptomatic, and cognitive behavioral therapy, such as exposure and response prevention, combined with family counseling and psychoeducation, should be the first approach for treating PANDAS. This review examines current theories of PANDAS pathogenesis, identifies possible treatments for managing this complex condition, and highlights areas for future research. Moving forward, developing more standardized diagnostic criteria and identifying specific laboratory markers to facilitate PANDAS diagnoses are crucial. PMID:24953744

  3. Paraneoplastic and Other Autoimmune Disorders of the Central Nervous System

    PubMed Central

    McKeon, Andrew

    2013-01-01

    As a result of the burgeoning growth of disease-specific neural autoantibody markers available for diagnostic patient evaluation, there has been increasing awareness of autoimmune central nervous system (CNS) disorders in hospital practice. Hospital-based neurologists have also taken great interest in these disorders since many occur in the setting of an occult systemic cancer which can be detected and treated at an early stage, and many affected patients are responsive to immunotherapy. Associated neurological disorders are typically subacute in onset, some are common or classic (eg, limbic encephalitis, cerebellar degeneration), but others have atypical or multifocal presentations. For patients with a suspected paraneoplastic disorder, many and costly oncological evaluations may be required for diagnosis. Comprehensive serological and cerebrospinal fluid (CSF) evaluation for neural autoantibodies may permit a focused cancer evaluation (eg, antineuronal nuclear antibody type 1 [ANNA-1] is associated with small cell lung carcinoma), and in some circumstances may indicate the likelihood of a good response to therapy (eg, voltage-gated potassium channel complex antibody) or poor neurological prognosis (eg, purkinje cell cytoplasmic antibody type 1 [antiYo]). Positron-emission tomography–computed tomography (PET-CT) imaging of trunk may increase the diagnostic yield for certain cancers where other modalities have been negative. For some patients, rapid treatment with immunotherapy may facilitate marked improvement, or full recovery; multiple sequential trials of one or more of steroids, intravenous immunoglobulin or plasma exchange, or combination therapy are often required. For patients with N-methyl-d-aspartate receptor antibody encephalitis, early treatment with immunosuppressants and weeks or months of supportive intensive care may additionally be required. One or more of clinical examination, electroencephalogram (including video telemetry), and imaging provide objective parameters to which posttreatment outcomes can be compared. PMID:23983888

  4. The role of epigenetic mechanisms and processes in autoimmune disorders

    PubMed Central

    Greer, Judith M; McCombe, Pamela A

    2012-01-01

    The lack of complete concordance of autoimmune disease in identical twins suggests that nongenetic factors play a major role in determining disease susceptibility. In this review, we consider how epigenetic mechanisms could affect the immune system and effector mechanisms in autoimmunity and/or the target organ of autoimmunity and thus affect the development of autoimmune diseases. We also consider the types of stimuli that lead to epigenetic modifications and how these relate to the epidemiology of autoimmune diseases and the biological pathways operative in different autoimmune diseases. Increasing our knowledge of these epigenetic mechanisms and processes will increase the prospects for controlling or preventing autoimmune diseases in the future through the use of drugs that target the epigenetic pathways. PMID:23055689

  5. Hair disorders associated with autoimmune connective tissue diseases.

    PubMed

    Cassano, N; Amerio, P; D'Ovidio, R; Vena, G A

    2014-10-01

    Hair disorders are frequently observed in various systemic diseases, including autoimmune connective tissue diseases (CTDs), with predilection of lupus erythematosus (LE), followed by dermatomyositis (DM) and scleroderma. Hair disorders in CTDs may manifest as various clinical patterns, such as telogen hair loss, diffuse thinning or fragility of hair, and scarring alopecia. Less common hair disorders include anagen effluvium, alopecia areata, and trichomegaly. Some drugs used to treat CTDs may cause hair loss in a drug-related manner or hyperthrichosis. In the assessment of common hair loss patterns, such as telogen effluvium, the possible association with CTDs must be borne in mind and should not be overlooked. Alopecia appears to be a significant sign in the course of LE and especially systemic LE. In DM, the involvement of the scalp is common, and is often characterized by a diffuse, violaceous, scaly, non-scarring and symptomatic hair loss. Linear scleroderma en coup de sabre is an uncommon localized form of morphea with involvement of the paramedian forehead and frontal scalp, where it is associated with cicatricial alopecia. The most important variant of scarring alopecia in the context of CTDs is that associated with discoid lupus erythematosus (DLE). In the diagnostic work-up of DLE-related cicatrical alopecia, histopathological and immunopathological studies are useful, and a relevant role has been attributed to dermatoscopy (trichoscopy) over the last years. Hair loss has been reported in several other CTDs, including mixed and undifferentiated CTDs, and primary Sjögren's syndrome, although it is likely to be underestimated in such diseases. PMID:24975949

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

    PubMed Central

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

    2015-01-01

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

  7. Autoimmune Complications after Hematopoietic Stem Cell Transplantation in Children with Nonmalignant Disorders

    PubMed Central

    Khalil, Abdalla; Zaidman, Irena; Bergman, Reuven; Elhasid, Ronit; Ben-Arush, Myriam Weyl

    2014-01-01

    Background. Hematopoietic stem cell transplantation (HSCT) remains the only curative treatment for many nonmalignant disorders, such as autoimmune disorders, inborn metabolic disorders, hemoglobinopathies, and immunodeficiency disorders. Autoimmune complications (AICs) after HSCT, such as autoimmune cytopenias, autoimmune hepatitis, primary biliary cirrhosis, and autoimmune cutaneous manifestations, are still neither well defined nor characterized. Patients. Between 2000 and 2012, 92 patients (47 males, 45 females) were treated with HSCT in our hospital, 51 with congenital hemoglobinopathies, 19 with primary immunodeficiency disease, 10 with metabolic disorders, five with Fanconi anemia, three with aplastic anemia, and four with familial hemophagocytic lymphohistiocytosis. Results. Mean age at HSCT was 6.4 years (range, 0.232 years) and mean duration of followup after HSCT was 6.81 years (range, 111 years). Sixteen (17.4%) patients developed chronic GVHD and five (5.4%) showed sclerodermatous features. Five (5.4%) patients were diagnosed with scleroderma manifestations, six (6.5%) with vitiligo, six (6.5%) with autoimmune hemolytic anemia (AIHA), six (6.5%) with idiopathic thrombocytopenia, three (3.3%) with mild leucopenia, two (2.2%) with aplastic anemia, two (2.2%) (one boy, one girl) with autoimmune thyroid disease, and one (1.1%) with autoimmune hepatitis. Conclusions. It was concluded that AICs are clinically significant complications after HSCT that contribute to morbidity but not to mortality. AICs are more frequent after HSCT for metabolic disorders, and sclerodermatous GVHD is more significant in children who underwent allogeneic HSCT for hemoglobinopathies. The potential to identify risk factors for AICs could lead to less morbidity and mortality and to maintain the patient's quality of life. PMID:24574898

  8. Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infection (PANDAS): a Controversial Diagnosis.

    PubMed

    de Oliveira, Sheila Knupp Feitosa; Pelajo, Christina Feitosa

    2010-03-01

    Despite more than a decade of studying pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS), it is still not possible to confirm its existence and whether it is a poststreptococcal autoimmune disorder. Many controversies remain: the diagnostic criteria have not been validated, evidence of autoimmunity remains inconclusive, evidence of a genetic predisposition is weak, and streptococcal infections are common in childhood and could represent only a trigger of exacerbations of tics and obsessive-compulsive disorder. Patients who fit the PANDAS criteria appear to represent a subgroup of children with chronic tic disorder and/or obsessive-compulsive disorder who may experience symptom exacerbations after group A β-hemolytic streptococci infections; however, those infections are not the sole or even the most common antecedent of exacerbations. There is not enough evidence to support PANDAS as a unique clinical entity. PMID:21308506

  9. Clinical and Pathological Implications of Concurrent Autoimmune Thyroid Disorders and Papillary Thyroid Cancer

    PubMed Central

    Cunha, L. L.; Ferreira, R. C.; Marcello, M. A.; Vassallo, J.; Ward, L. S.

    2011-01-01

    Cooccurrences of chronic lymphocytic thyroiditis (CLT) and thyroid cancer (DTC) have been repeatedly reported. Both CLT and DTC, mainly papillary thyroid carcinoma (PTC), share some epidemiological and molecular features. In fact, thyroid lymphocytic inflammatory reaction has been observed in association with PTC at variable frequency, although the precise relationship between the two diseases is still debated. It also remains a matter of debate whether the association with a CLT or even an autoimmune disorder could influence the prognosis of PTC. A better understanding about clinical implications of autoimmunity in concurrent thyroid cancer could raise new insights of thyroid cancer immunotherapy. In addition, elucidating the molecular mechanisms involved in autoimmune disease and concurrent cancer allowed us to identify new therapeutic strategies against thyroid cancer. The objective of this article was to review recent literature on the association of these disorders and its potential significance. PMID:21403889

  10. 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

  11. Human T lymphotropic virus type I in arthropathy and autoimmune disorders.

    PubMed

    Nishioka, K; Sumida, T; Hasunuma, T

    1996-08-01

    The progressive nature of the disease and the persistent inflammation affecting various organs are common features of idiopathic autoimmune disorders of unknown etiology. Therefore, the HTLV-I-associated disorders described in the present review are outstandingly important models for our understanding of the pathologic mechanisms of organ-specific immune disorders. HTLV-I arthropathy is characterized by chronic inflammatory and proliferative synovitis with lymphoid follicles and pannus formation in the affected joints, indistinguishable from the findings in idiopathic RA. The presence of the tax gene in HTLV-I-negative SS patients suggests that it is responsible for the exocrine gland abnormality, characterized by extensive lymphoproliferative epithelial lesions. Furthermore, the pulmonary lesions of HTLV-I bronchopneumonopathy are similar to those of idiopathic interstitial pneumonitis. Based on these observations, the clinical findings associated with the immunologic abnormalities in HTLV-I-infected patients provide us with valuable information for understanding the pathogenetic mechanisms of chronic inflammatory conditions associated with immune regulatory disorders. Although the clinical and pathologic features of the 2 common HTLV-I-associated disorders, ATL and HAM/TSP, have been well characterized and are clearly distinguishable from those of the idiopathic forms of these disorders, other HTLV-I-related autoimmune diseases, e.g., arthropathy, SS, or bronchopneumonopathy, are clinically indistinguishable from the idiopathic forms of the diseases. Such similarity may serve as a clue to the pathogenetic mechanisms of idiopathic autoimmune disorders. PMID:8702452

  12. Gastrointestinal Disorder Associated with Olmesartan Mimics Autoimmune Enteropathy

    PubMed Central

    Meresse, Bertrand; Guegan, Nicolas; Brousse, Nicole; Verkarre, Virginie; Derrieux, Coralie; Macintyre, Elizabeth; Seksik, Philippe; Savoye, Guillaume; Cadiot, Guillaume; Vuitton, Lucine; Marthey, Lysiane; Carbonnel, Franck; Cerf-Bensussan, Nadine; Cellier, Christophe

    2015-01-01

    Background and Objectives Anti-hypertensive treatment with the angiotensin II receptor antagonist olmesartan is a rare cause of severe Sprue-like enteropathy. To substantiate the hypothesis that olmesartan interferes with gut immune homeostasis, clinical, histopathological and immune features were compared in olmesartan-induced-enteropathy (OIE) and in autoimmune enteropathy (AIE). Methods Medical files of seven patients with OIE and 4 patients with AIE enrolled during the same period were retrospectively reviewed. Intestinal biopsies were collected for central histopathological review, T cell Receptor clonality and flow cytometric analysis of isolated intestinal lymphocytes. Results Among seven olmesartan-treated patients who developed villous atrophy refractory to a gluten free diet, three had extra-intestinal autoimmune diseases, two had antibodies reacting with the 75 kilodalton antigen characteristic of AIE and one had serum anti-goblet cell antibodies. Small intestinal lesions and signs of intestinal lymphocyte activation were thus reminiscent of the four cases of AIE diagnosed during the same period. Before olmesartan discontinuation, remission was induced in all patients (7/7) by immunosuppressive drugs. After interruption of both olmesartan and immunosuppressive drugs in six patients, remission was maintained in 4 but anti-TNF-α therapy was needed in two. Conclusion This case-series shows that olmesartan can induce intestinal damage mimicking AIE. OIE usually resolved after olmesartan interruption but immunosuppressive drugs may be necessary to achieve remission. Our data sustain the hypothesis that olmesartan interferes with intestinal immuno regulation in predisposed individuals. PMID:26101883

  13. Acquired Hemophilia A: A Frequently Overlooked Autoimmune Hemorrhagic Disorder

    PubMed Central

    Takeda, Tomohiro

    2014-01-01

    Acquired hemophilia A (AHA) is a rare hemorrhagic disease in which autoantibodies against coagulation factor VIII- (FVIII-) neutralizing antibodies (inhibitors) impair the intrinsic coagulation system. As the inhibitors developed in AHA are autoantibodies, the disease may have an autoimmune cause and is often associated with autoimmune disease. Although acute hemorrhage associated with AHA may be fatal and is costly to treat, AHA is often unrecognized or misdiagnosed. AHA should thus be considered in the differential diagnosis particularly in postpartum women and the elderly with bleeding tendency or prolonged activated partial thromboplastin time. Cross-mixing tests and measurement of FVIII-binding antibodies are useful to confirm AHA diagnosis. For treatment of acute hemorrhage, hemostatic therapy with bypassing agents should be provided. Unlike in congenital hemophilia A with inhibitors, in which immune tolerance induction therapy using repetitive infusions of high-dose FVIII concentrates is effective for inhibitor eradication, immune tolerance induction therapy has shown poor efficacy in treating AHA. Immunosuppressive treatment should thus be initiated to eradicate inhibitors as soon as the diagnosis of AHA is confirmed. PMID:24741588

  14. Common Genetic Determinants of Uveitis Shared with Other Autoimmune Disorders1

    PubMed Central

    Mattapallil, Mary J.; Sahin, Azize; Silver, Phyllis B.; Sun, Shu-Hui; Chan, Chi-Chao; Remmers, Elaine F.; Hejtmancik, J. Fielding; Caspi, Rachel R.

    2008-01-01

    Uveitis is a complex multifactorial autoimmune disease of the eye characterized by inflammation of the uvea and retina, degeneration of the retina, and blindness in genetically predisposed patients. Using the rat model of experimental autoimmune uveitis (EAU), we previously identified three quantitative trait loci (QTL) associated with EAU on rat chromosomes 4, 12, and 10 (Eau1, Eau2, and Eau3). The primary goal of the current study is to delineate additional non-MHC chromosomal regions that control susceptibility to EAU, and to identify any QTLs that overlap with the QTLs of other autoimmune diseases. Using a set of informative microsatellite markers and F2 generations of resistant and susceptible MHC class II-matched rat strains (F344 and LEW), we have identified several new significant or suggestive QTLs on rat chromosomes 2, 3, 7, 10, and 19 that control susceptibility to EAU. A protective allele was identified in the susceptible LEW strain in the Eau5 locus at D7Wox18, and epistatic interactions between QTLs were found to influence the severity of disease. The newly identified regions (Eau4 through Eau9) colocalize with the genetic determinants of other autoimmune disease models, and to disease-regulating syntenic regions identified in autoimmune patients on human chromosomes 4q21-31, 5q31-33, 16q22-24, 17p11-q12, 20q11-13, and 22q12-13. Our results suggest that uveitis shares some of the pathogenic mechanisms associated with other autoimmune diseases, and lends support to the “common gene, common pathway” hypothesis for autoimmune disorders. PMID:18453595

  15. Genome-wide Association Study of Dermatomyositis Reveals Genetic Overlap with other Autoimmune Disorders

    PubMed Central

    Miller, Frederick W.; Cooper, Robert G.; Vencovsky, Jiri; Rider, Lisa G.; Danko, Katalin; Wedderburn, Lucy R.; Lundberg, Ingrid E.; Pachman, Lauren M.; Reed, Ann M.; Ytterberg, Steven R.; Padyukov, Leonid; Selva-O’Callaghan, Albert; Radstake, Timothy; Isenberg, David A.; Chinoy, Hector; Ollier, William E. R.; O’Hanlon, Terrance P.; Peng, Bo; Lee, Annette; Lamb, Janine A.; Chen, Wei; Amos, Christopher I.; Gregersen, Peter K.

    2014-01-01

    Objective To identify new genetic associations with juvenile and adult dermatomyositis (DM). Methods We performed a genome-wide association study (GWAS) of adult and juvenile DM patients of European ancestry (n = 1178) and controls (n = 4724). To assess genetic overlap with other autoimmune disorders, we examined whether 141 single nucleotide polymorphisms (SNPs) outside the major histocompatibility complex (MHC) locus, and previously associated with autoimmune diseases, predispose to DM. Results Compared to controls, patients with DM had a strong signal in the MHC region consisting of GWAS-level significance (P < 5x10−8) at 80 genotyped SNPs. An analysis of 141 non-MHC SNPs previously associated with autoimmune diseases showed that three SNPs linked with three genes were associated with DM, with a false discovery rate (FDR) < 0.05. These genes were phospholipase C like 1 (PLCL1, rs6738825, FDR=0.00089), B lymphoid tyrosine kinase (BLK, rs2736340, FDR=0.00031), and chemokine (C-C motif) ligand 21 (CCL21, rs951005, FDR=0.0076). None of these genes was previously reported to be associated with DM. Conclusion Our findings confirm the MHC as the major genetic region associated with DM and indicate that DM shares non-MHC genetic features with other autoimmune diseases, suggesting the presence of additional novel risk loci. This first identification of autoimmune disease genetic predispositions shared with DM may lead to enhanced understanding of pathogenesis and novel diagnostic and therapeutic approaches. PMID:23983088

  16. The immunobiology of Tourette's disorder, pediatric autoimmune neuropsychiatric disorders associated with Streptococcus, and related disorders: a way forward.

    PubMed

    Murphy, Tanya K; Kurlan, Roger; Leckman, James

    2010-08-01

    Obsessive-compulsive disorder (OCD) and related conditions including Tourette's disorder (TD) are chronic, relapsing disorders of unknown etiology associated with marked impairment and disability. Associated immune dysfunction has been reported and debated in the literature since the late 80s. The immunologic culprit receiving the most interest has been Group A Streptococcus (GAS), which began to receive attention as a potential cause of neuropsychiatric symptoms, following the investigation of the symptoms reported in Sydenham's chorea (SC) and rheumatic fever, such as motor tics, vocal tics, and both obsessive-compulsive and attention deficit/hyperactivity symptoms. Young children have been described as having a sudden onset of these neuropsychiatric symptoms temporally associated with GAS, but without supporting evidence of rheumatic fever. This presentation of OCD and tics has been termed pediatric autoimmune neuropsychiatric disorders associated with Streptococcus (PANDAS). Of note, SC, OCD, and TD often begin in early childhood and share common anatomic areas--the basal ganglia of the brain and the related cortical and thalamic sites--adding support to the possibility that these disorders might share a common immunologic and/or genetic vulnerability. Relevant manuscripts were identified through searches of the PsycINFO and MedLine databases using the following keywords: OCD, immune, PANDAS, Sydenham chorea, Tourette's disorder Group A Streptococcus. Articles were also identified through reference lists from research articles and other materials on childhood OCD, PANDAS, and TD between 1966 and December 2010. Considering the overlap of clinical and neuroanatomic findings among these disorders, this review explores evidence regarding the immunobiology as well as the relevant clinical and therapeutic aspects of TD, OCD, and PANDAS. PMID:20807070

  17. The Immunobiology of Tourette's Disorder, Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus, and Related Disorders: A Way Forward

    PubMed Central

    Kurlan, Roger; Leckman, James

    2010-01-01

    Abstract Obsessive-compulsive disorder (OCD) and related conditions including Tourette's disorder (TD) are chronic, relapsing disorders of unknown etiology associated with marked impairment and disability. Associated immune dysfunction has been reported and debated in the literature since the late 80s. The immunologic culprit receiving the most interest has been Group A Streptococcus (GAS), which began to receive attention as a potential cause of neuropsychiatric symptoms, following the investigation of the symptoms reported in Sydenham's chorea (SC) and rheumatic fever, such as motor tics, vocal tics, and both obsessive-compulsive and attention deficit/hyperactivity symptoms. Young children have been described as having a sudden onset of these neuropsychiatric symptoms temporally associated with GAS, but without supporting evidence of rheumatic fever. This presentation of OCD and tics has been termed pediatric autoimmune neuropsychiatric disorders associated with Streptococcus (PANDAS). Of note, SC, OCD, and TD often begin in early childhood and share common anatomic areas—the basal ganglia of the brain and the related cortical and thalamic sites—adding support to the possibility that these disorders might share a common immunologic and/or genetic vulnerability. Relevant manuscripts were identified through searches of the PsycINFO and MedLine databases using the following keywords: OCD, immune, PANDAS, Sydenham chorea, Tourette's disorder Group A Streptococcus. Articles were also identified through reference lists from research articles and other materials on childhood OCD, PANDAS, and TD between 1966 and December 2010. Considering the overlap of clinical and neuroanatomic findings among these disorders, this review explores evidence regarding the immunobiology as well as the relevant clinical and therapeutic aspects of TD, OCD, and PANDAS. PMID:20807070

  18. Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcus: Comparison of Diagnosis and Treatment in the Community and at a Specialty Clinic

    PubMed Central

    Gabbay, Vilma; Coffey, Barbara J.; Babb, James S.; Meyer, Laura; Wachtel, Carly; Anam, Seeba; Rabinovitz, Beth

    2009-01-01

    OBJECTIVES This study aimed to examine whether pediatric autoimmune neuropsychiatric disorders associated with streptococcus were appropriately diagnosed in the community and to determine subsequent rates of unwarranted use of antibiotic treatment for tics and obsessive-compulsive symptoms without the identification of an infection. METHODS The design was a retrospective, cross-sectional, observational study of 176 children and adolescents who were evaluated in a specialty program for tics, Tourette's disorder, and related problems. Previously published diagnostic criteria were used to establish the diagnosis of pediatric autoimmune neuropsychiatric disorders associated with streptococcus in our clinic. RESULTS Subjects were significantly less likely to receive a diagnosis of pediatric autoimmune neuropsychiatric disorders associated with streptococcus at the specialty clinic than in the community. In the community, subjects were significantly more likely to be treated with antibiotics or immunosuppressant medication if they received a diagnosis of pediatric autoimmune neuropsychiatric disorders associated with streptococcus. Of the 27 subjects with a community diagnosis of pediatric autoimmune neuropsychiatric disorders associated with streptococcus who were treated with antibiotics, 22 (82%) were treated without laboratory evidence of an infection; 2 were treated with immunomodulatory medications. CONCLUSIONS Our results support our hypothesis that pediatric autoimmune neuropsychiatric disorders associated with streptococcus are frequently diagnosed in the community without the application of all working diagnostic criteria. This phenomenon has resulted in unwarranted use of antibiotic treatment for tics/obsessive-compulsive disorder without evidence of laboratory infection. PMID:18676543

  19. Autoimmune neurological disorders associated with group-A beta-hemolytic streptococcal infection.

    PubMed

    Hachiya, Yasuo; Miyata, Rie; Tanuma, Naoyuki; Hongou, Kazuhisa; Tanaka, Keiko; Shimoda, Konomi; Kanda, Sachiko; Hoshino, Ai; Hanafusa, Yukiko; Kumada, Satoko; Kurihara, Eiji; Hayashi, Masaharu

    2013-08-01

    Although central nervous system (CNS) disorders associated with group-A beta-hemolytic streptococcal (GABHS) infection occur only rarely, Sydenham's chorea is a well-recognized disease that can arise following infection. Children may develop a tic, obsessive compulsive disorder (OCD), and extrapyramidal movement subsequent to GABHS infection. These disorders have been termed pediatric autoimmune neuropsychiatric disorders associated with streptococci (PANDAS). Herein we report one case each of acute disseminated encephalomyelitis (ADEM), PANDAS and subacute encephalitis associated with GABHS infection. To evaluate the pathogenesis of the CNS disorders associated with GABHS infection, we measured levels of neurotransmitters, cytokines, anti-neuronal autoantibodies, and performed immunohistochemistry using patient sera to stain human brain sections. All three cases showed psychiatric behavioral disorders. Immunotherapy was effective, and homovanillic acid levels in the cerebrospinal fluid (CSF) were elevated at the acute stage in all three cases. In each case of ADEM and PANDAS, immunohistochemistry demonstrated neuronal impairment in the basal ganglia during the acute stage. Neuronal immunoreactivity was visualized in the cerebral cortex at the acute stage in the case of subacute encephalitis. There was no direct correlation between immunoreactivity of patient sera on the brain sections and positivity of anti-neuronal autoantibodies or CSF biomarkers. The results suggest that autoimmune responses may modulate neurotransmission, and the use of patient serum for immunohistochemistry is a sensitive screening method for the detection of anti-neuronal autoantibodies in CNS disorders associated with GABHS infection. PMID:23142103

  20. BAFF: B cell survival factor and emerging therapeutic target for autoimmune disorders.

    PubMed

    Kalled, Susan L; Ambrose, Christine; Hsu, Yen-Ming

    2003-02-01

    The prevailing treatment strategies for autoimmune disorders employ global immunosuppressants that have harmful side effects with long-term use. A new vision for drug development relies on the generation of therapeutics that have specific and narrow targets, such as pathogenic cell populations. The cellular processes that initiate and maintain B cell dysregulation are not well understood and autoimmune disease results, in part, from the survival and activation of self-reactive B cells. Such B cells produce tissue-damaging pathogenic autoantibodies. BAFF (B cell-activating factor belonging to the TNF family), a member of the TNF family of ligands, may play a role in B cell-mediated diseases. BAFF is a survival factor for peripheral B cells. When BAFF is overexpressed in mice, B cell number and immunoglobulin production is increased and an autoimmune-like phenotype is observed. Mouse models of lupus-nephritis have been shown to exhibit increased serum BAFF levels correlating with disease severity, and many autoimmune patients were found to have higher levels of circulating BAFF than healthy volunteers. Thus, modulating the level and activity of BAFF in these patients may alleviate symptoms associated with their disease. Several potential therapeutic inhibitors targeting BAFF are under investigation, including an anti-BAFF antibody and receptor-Fc fusion proteins. PMID:12556207

  1. Spasmodic dysphonia in an adolescent patient with an autoimmune neurologic disorder.

    PubMed

    Boseley, Mark E; Gherson, Shirley; Hartnick, Christopher J

    2007-01-01

    Pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections (PANDAS) has been primarily described in the neurology and psychiatry literature. The symptoms of this syndrome typically are a range of obsessive compulsive disorders and neuromuscular tics. The otolaryngologist occasionally becomes involved with these children when it is deemed that chronic tonsil infections are the source. We report here on a child diagnosed with PANDAS who presented with severe ventricular hyperfunction and adductor spasmodic dysphonia. She was treated with botulinum toxin, which resulted in a significant improvement in subjective voice as well as reduced jitter and shimmer on objective voice measurements. PMID:17362824

  2. Antibodies and neuronal autoimmune disorders of the CNS.

    PubMed

    Graus, Francesc; Saiz, Albert; Dalmau, Josep

    2010-04-01

    We review the neuronal antibodies described in CNS disorders in order to clarify their diagnostic value, emphasize potentials pitfalls and limitations in the diagnosis of paraneoplastic neurological syndromes (PNS), and examine the current evidence for a possible pathogenic role. We propose to classify the neuronal antibodies associated with syndromes resulting from CNS neuronal dysfunction into two groups according to the location of the antigen: inside the neuron or in the cell membrane. Group I includes antibodies which target intracellular antigens and probably are not pathogenic. They are further subdivided into three groups. Group Ia comprises well-characterized onconeural antibodies (Hu (ANNA1), Yo (PCA1), Ri (ANNA2), CV2 (CRMP5), amphiphysin, Ma2) that are useful for the diagnosis of PNS. Group Ib antibodies (SOX and ZIC) are cancer-specific but there is no evidence that the immune response is in any way pathogenically related to the PNS. Antibodies in group Ic (glutamic acid decarboxylase (GAD), adenylate kinase 5 and Homer 3) identify non-PNS: stiff-person syndrome (SPS), cerebellar ataxia, and limbic encephalitis (LE). Group II antibodies recognize neuronal surface antigens. Antibodies in group IIa associate with characteristic CNS syndromes but their detection does not indicate that the disorder is paraneoplastic. Antibodies to potassium channels, AMPA and GABA(B) receptors are associated with LE, NMDA receptor antibodies identify a well-defined encephalitis, and antibodies against glycine receptors associate with SPS with encephalitis. A pathogenic role of the antibodies is suggested by the response of symptoms to immunotherapy and the correlation between antibody titers and neurological outcome. Lastly, Group IIb includes antibodies that are found in patients with paraneoplastic cerebellar ataxia associated with lung cancer (P/Q type calcium channels antibodies) or Hodgkin disease (metabotropic glutamate receptor type 1 antibodies). PMID:20035430

  3. Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal Infections (PANDAS): Experience at a Tertiary Referral Center

    PubMed Central

    Helm, Caitlin E.; Blackwood, R. Alexander

    2015-01-01

    Background Pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections (PANDAS) is an autoimmune disorder presenting with obsessive compulsive disorder and/or tics. Like Sydenham’s chorea, its presumed pathogenesis consists of autoantibodies cross-reacting with neurons in response to a group A beta-hemolytic streptococcal infection (GASI). There are currently no diagnostic laboratory findings and management ranges from antibiotic prophylaxis to intravenous immunoglobulin to plasmapheresis. The diagnosis remains controversial, resulting in inconsistent referrals and significant patient anxiety. Methods A retrospective study was performed on all patients referred to the Pediatric Infectious Disease Division with a pre-referral diagnosis of PANDAS. Patients were analyzed by demographics, medical history, co-morbidities, symptoms, prior treatment, laboratory tests, management strategies, and treatment outcomes. Results From 2003 to 2013, there were 21 patients with a pre-referral diagnosis of PANDAS. Only five met the diagnostic criteria. No patient at referral had an objective scale to monitor symptoms. Eight referrals had a major psychiatric disorder, and none fulfilled diagnostic criteria (p<0.01). Discussion The majority of the patients referred with a pre-diagnosis of PANDAS do not fulfill diagnostic criteria nor do they have objective criteria for symptom monitoring. Major psychiatric disorders do not seem to be associated with PANDAS, and better physician education may prevent misdiagnoses. Multidisciplinary management is recommended. PMID:26196024

  4. Autoimmune epilepsy.

    PubMed

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

    2016-03-01

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

  5. Ibrutinib-A double-edge sword in cancer and autoimmune disorders.

    PubMed

    Kokhaei, Parviz; Jadidi-Niaragh, Farhad; Sotoodeh Jahromi, Abdolreza; Osterborg, Anders; Mellstedt, Håkan; Hojjat-Farsangi, Mohammad

    2016-06-01

    Targeted therapies have appeared as new treatment options for several disease types, including cancer and autoimmune disorders. Of several targets, tyrosine kinases (TKs) are among the most promising. Overexpression of TKs provides a target for novel therapeutic agents, including small molecule inhibitors of tyrosine kinases (TKI). Ibrutinib (PCI-32765) is a TKI of Bruton's tyrosine kinase (Btk), a key kinase of the B-cell receptor signaling pathway that plays a significant role in the proliferation, differentiation and survival of B cells. In addition to inhibitory effects, recent studies have shown that ibrutinib has multiple immunomodulatory effects. It binds covalently to IL-2 inducible tyrosine kinase (Itk) in T lymphocytes and suppresses the survival of T-helper (Th) 2 cells. This changes the balance of Th1/Th2 cells toward Th1 subset, which are the main immune cells targeting tumor cells. The dual activity of ibrutinib has paid a great attention and several studies are evaluating the anti-tumor and immunomodulatory effects in cancer, autoimmune disorders and infectious diseases. In this article we review the inhibitory and immunomodulatory effects of ibrutinib in B-cell malignancies, autoimmune diseases and infections, as well as the communication between the Ror1 receptor tyrosine kinase and BCR and effects of ibrutinib on this crosstalk. PMID:26362595

  6. JMML and RALD (Ras-associated autoimmune leukoproliferative disorder): common genetic etiology yet clinically distinct entities

    PubMed Central

    Calvo, Katherine R.; Price, Susan; Braylan, Raul C.; Oliveira, Joao Bosco; Lenardo, Michael; Fleisher, Thomas A.

    2015-01-01

    Ras-associated autoimmune leukoproliferative disorder (RALD) is a chronic, nonmalignant condition that presents with persistent monocytosis and is often associated with leukocytosis, lymphoproliferation, and autoimmune phenomena. RALD has clinical and laboratory features that overlap with those of juvenile myelomonocytic leukemia (JMML) and chronic myelomonocytic leukemia (CMML), including identical somatic mutations in KRAS or NRAS genes noted in peripheral blood mononuclear cells. Long-term follow-up of these patients suggests that RALD has an indolent clinical course whereas JMML is fatal if left untreated. Immunophenotyping peripheral blood from RALD patients shows characteristic circulating activated monocytes and polyclonal CD10+ B cells. Distinguishing RALD from JMML and CMML has implications for clinical care and prognosis. PMID:25691160

  7. Celiac disease and transglutaminase 2: Model for posttranslational modification of antigens and HLA association in the pathogenesis of autoimmune disorders

    PubMed Central

    Sollid, Ludvig M.; Jabri, Bana

    2011-01-01

    Posttranslational modification (PTM) of antigen is a way to break T-cell tolerance to self-antigens and promote autoimmunity. However, the precise mechanisms by which modifications would facilitate autoimmune T-cell responses and how they relate to particular autoimmune-associated MHC molecules remain elusive. Celiac disease is a T-cell mediated enteropathy with a strong HLA association where the immune response is directed mainly against deamidated cereal gluten peptides that have been modified by the enzyme transglutaminase 2. The disease is further characterized by autoantibodies to transglutaminase 2 that have extraordinary high disease specificity and sensitivity. There have been important advances in the knowledge of celiac disease pathogenesis, and these insights may be applicable to other autoimmune disorders where posttranslational modification plays a role. This insight gives clues for understanding the involvement of PTMs in other autoimmune diseases. PMID:21917438

  8. Lyme disease and pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS): an overview

    PubMed Central

    Rhee, Hanna; Cameron, Daniel J

    2012-01-01

    Lyme disease (LD) is a complex, multisystemic illness. As the most common vector- borne disease in the United States, LD is caused by bacterial spirochete Borrelia burgdorferi sensu stricto, with potential coinfections from agents of anaplasmosis, babesiosis, and ehrlichiosis. Persistent symptoms and clinical signs reflect multiorgan involvement with episodes of active disease and periods of remission, not sparing the coveted central nervous system. The capability of microorganisms to cause and exacerbate various neuropsychiatric pathology is also seen in pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS), a recently described disorder attributed to bacterium Streptococcus pyogenes of group A beta-hemolytic streptococcus in which neurologic tics and obsessive-compulsive disorders are sequelae of the infection. In the current overview, LD and PANDAS are juxtaposed through a review of their respective infectious etiologies, clinical presentations, mechanisms of disease development, courses of illness, and treatment options. Future directions related to immunoneuropsychiatry are also discussed. PMID:22393303

  9. Lyme disease and pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS): an overview.

    PubMed

    Rhee, Hanna; Cameron, Daniel J

    2012-01-01

    Lyme disease (LD) is a complex, multisystemic illness. As the most common vector- borne disease in the United States, LD is caused by bacterial spirochete Borrelia burgdorferi sensu stricto, with potential coinfections from agents of anaplasmosis, babesiosis, and ehrlichiosis. Persistent symptoms and clinical signs reflect multiorgan involvement with episodes of active disease and periods of remission, not sparing the coveted central nervous system. The capability of microorganisms to cause and exacerbate various neuropsychiatric pathology is also seen in pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS), a recently described disorder attributed to bacterium Streptococcus pyogenes of group A beta-hemolytic streptococcus in which neurologic tics and obsessive-compulsive disorders are sequelae of the infection. In the current overview, LD and PANDAS are juxtaposed through a review of their respective infectious etiologies, clinical presentations, mechanisms of disease development, courses of illness, and treatment options. Future directions related to immunoneuropsychiatry are also discussed. PMID:22393303

  10. Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS): an indication for tonsillectomy.

    PubMed

    Alexander, Alan A Z; Patel, Nitin J; Southammakosane, Cathy A; Mortensen, Melissa M

    2011-06-01

    Children with obsessive compulsive disorder or tic disorders that are associated with streptococcal infections (Group A beta-hemolytic) in the oro-pharyngeal region are given the diagnosis of pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS). Tonsillectomy has been reported to resolve the neuro-psychiatric symptoms in these children. We have a case of a 9-year-old boy who was seen in our clinic with multiple recurrent streptococcal infections of the oro-pharyngeal cavity. He also exhibited neuro-psychiatric symptoms including agitation, hyperactivity, and tics. These symptoms followed his recurrent infections. Tonsillectomy was performed and in one year follow-up the patient did not have any recurrent streptococcal infections, and his neuro-psychiatric symptoms resolved completely. Guidelines for medical and surgical management of recurrent strep infections in the face of PANDAS are reviewed. PMID:21466900

  11. Tic disorder probably associated with steroid responsive encephalopathy with autoimmune thyroiditis (SREAT).

    PubMed

    Saygi, Semra; Ozkale, Yasemin; Erol, Ilknur

    2014-10-01

    Steroid responsive encephalopathy with autoimmune thyroiditis (SREAT), a rare disorder in individuals of all age groups, including children, is characterized by high titers of anti-thyroid peroxidase antibodies. The present report concerns a previously healthy 12-y-old boy who presented with motor tics. The patient underwent an extensive work-up to identify the underlying etiologies and risk factors predisposing him to tic disorder. Based on the clinical and laboratory results, a diagnosis of SREAT was made. Although some studies have reported associated behavioral and cognitive changes, myoclonus, seizures, pyramidal tract dysfunction, psychosis, and coma. The authors describe a case of tic disorder, probably due to SREAT, as well as its course of treatment. PMID:24633901

  12. Familial Autoimmune Thyroid Disease as a Risk Factor for Regression in Children with Autism Spectrum Disorder: A CPEA Study

    ERIC Educational Resources Information Center

    Molloy, Cynthia A.; Morrow, Ardythe L.; Meinzen-Derr, Jareen; Dawson, Geraldine; Bernier, Raphael; Dunn, Michelle; Hyman, Susan L.; McMahon, William M.; Goudie-Nice, Julie; Hepburn, Susan; Minshew, Nancy; Rogers, Sally; Sigman, Marian; Spence, M. Anne; Tager-Flusberg, Helen; Volkmar, Fred R.; Lord, Catherine

    2006-01-01

    A multicenter study of 308 children with Autism Spectrum Disorder (ASD) was conducted through the Collaborative Programs of Excellence in Autism (CPEA), sponsored by the National Institute of Child Health and Human Development, to compare the family history of autoimmune disorders in children with ASD with and without a history of regression. A…

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

    PubMed

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

    2014-07-14

    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

  14. 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

  15. Interaction between psychiatric and autoimmune disorders in celiac disease patients in the Northeastern United States

    PubMed Central

    GARUD, S.; LEFFLER, D.; DENNIS, M.; EDWARDS-GEORGE, J.; SARYAN, D.; SHETH, S.; SCHUPPAN, D.; JAMMA, S.; KELLY, C. P.

    2009-01-01

    Summary Background Previous studies yielded conflicting results regarding the presence of an association between celiac disease (CD) and psychiatric disorders including depression. This association has not been studied in the United States. Aim To determine the prevalence of psychiatric and autoimmune disorders in patients with CD in the US compared to control groups. Methods In a case control study, the prevalence of psychiatric and autoimmune disorders was compared in 600 CD patients, 200 irritable bowel syndrome (IBS) patients and 200 healthy controls. Results The prevalence of depression in CD was 17.2% and was similar to that in IBS (18.5%, P = 0.74) and controls (16.0%, P = 0.79). Among CD patients, type I DM was identified as a significant risk factor for depression (P < 0.01) with 37% of patients with both CD and type I DM having clinical depression. Conclusion The prevalence of depression in CD is similar to that in other chronic gastrointestinal diseases and healthy controls. However, there is a markedly elevated risk of depression in patients with both type I DM and CD. Differing rates of type 1 DM among celiac populations may account for disparity in published rates of depression in patients with CD. PMID:19183153

  16. A link between perianal strep and pediatric autoimmune neuropsychiatric disorder associated with streptococcal infection (PANDAS).

    PubMed

    Toufexis, Megan; Deoleo, Caroline; Elia, Josephine; Murphy, Tanya K

    2014-04-01

    Perianal streptococcal dermatitis is an infection caused by group A streptococcus (GAS). Children with a pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections (PANDAS) phenotype may have tics or obsessive compulsive symptoms secondary to a systemic immune activation by GAS infecting perianal areas. In this retrospective case series, the authors describe three children with symptoms consistent with PANDAS and a confirmed perianal streptococcal dermatitis as the likely infectious trigger. Concomitant perianal dermatitis and new-onset obsessive-compulsive symptoms and/or tics are strong indications for perianal culture and rapid antigen detection test in young children. PMID:24763762

  17. Autoimmune epilepsy.

    PubMed

    Britton, Jeffrey

    2016-01-01

    Seizures are a common manifestation of autoimmune limbic encephalitis and multifocal paraneoplastic disorders. Accumulating evidence supports an autoimmune basis for seizures in the absence of syndromic manifestations of encephalitis. The autoimmune epilepsies are immunologically mediated disorders in which recurrent seizures are a primary and persistent clinical feature. When other etiologies have been excluded, an autoimmune etiology is suggested in a patient with epilepsy upon detection of neural autoantibodies and/or the presence of inflammatory changes on cerebrospinal fluid (CSF) or magnetic resonance imaging. In such patients, immunotherapy may be highly effective, depending on the particular autoimmune epilepsy syndrome present. In this chapter, several autoimmune epilepsy syndromes are discussed. First, epilepsies secondary to other primary autoimmune disorders will be discussed, and then those associated with antibodies that are likely to be pathogenic, such as voltage-gated potassium channel-complex and N-methyl-d-aspartate receptor, gamma-aminobutyric acid A and B receptor antibodies. For each syndrome, the typical clinical, imaging, electroencephaloram, CSF, and serologic features, and pathophysiology and treatment are described. Finally, suggested guidelines for the recognition, evaluation, and treatment of autoimmune epilepsy syndromes are provided. PMID:27112680

  18. Interleukin-1 as a Common Denominator from Autoinflammatory to Autoimmune Disorders: Premises, Perils, and Perspectives

    PubMed Central

    Lopalco, Giuseppe; Cantarini, Luca; Vitale, Antonio; Iannone, Florenzo; Anelli, Maria Grazia; Andreozzi, Laura; Lapadula, Giovanni; Galeazzi, Mauro; Rigante, Donato

    2015-01-01

    A complex web of dynamic relationships between innate and adaptive immunity is now evident for many autoinflammatory and autoimmune disorders, the first deriving from abnormal activation of innate immune system without any conventional danger triggers and the latter from self-/non-self-discrimination loss of tolerance, and systemic inflammation. Due to clinical and pathophysiologic similarities giving a crucial role to the multifunctional cytokine interleukin-1, the concept of autoinflammation has been expanded to include nonhereditary collagen-like diseases, idiopathic inflammatory diseases, and metabolic diseases. As more patients are reported to have clinical features of autoinflammation and autoimmunity, the boundary between these two pathologic ends is becoming blurred. An overview of monogenic autoinflammatory disorders, PFAPA syndrome, rheumatoid arthritis, type 2 diabetes mellitus, uveitis, pericarditis, Behçet's disease, gout, Sjögren's syndrome, interstitial lung diseases, and Still's disease is presented to highlight the fundamental points that interleukin-1 displays in the cryptic interplay between innate and adaptive immune systems. PMID:25784780

  19. Demographic and clinical features of autoimmune thyroid disorder in Japanese patients with systemic sclerosis.

    PubMed

    Toki, Sayaka; Motegi, Sei-ichiro; Yamada, Kazuya; Uchiyama, Akihiko; Ishikawa, Osamu

    2014-12-01

    Autoimmune thyroid disorders (AITD) are characterized by the impairment of the thyroid gland as a result of systemic or organ-specific autoimmune disorders, and the presence of antithyroid autoantibodies, such as antithyroglobulin antibody (AbTg) and antithyroid peroxidase antibody (AbTPO). Several studies have reported the association of AITD with systemic sclerosis (SSc). However, none of those studies analyzed the association between AITD and skin sclerosis in SSc patients. The aim of this study was to examine the demographic and clinical features of SSc patients with AITD treated in our department. Of a total of 210 SSc patients, we identified 30 with AITD (14.3%), including 29 with Hashimoto's disease (13.8%) and one patient with Graves' disease (0.5%), indicating that hypothyroidism was more common among SSc patients with AITD. All patients with AITD were female, and anticentromere antibody positivity, the complication of Sjögren's syndrome, severe facial skin sclerosis and atrophy of the thyroid gland were significantly prevalent in SSc patients with AITD. SSc patients with such clinical features may be at high risk of AITD and require regular follow up of thyroid function including ultrasonography and the examination of serum hormone levels to start an early treatment. PMID:25387898

  20. GWAS implicates a role for quantitative immune traits and threshold effects in risk for human autoimmune disorders

    PubMed Central

    Gregersen, Peter K.; Diamond, Betty; Plenge, Robert M.

    2016-01-01

    Genome wide association studies in human autoimmune disorders has provided a long list of alleles with rather modest degrees of risk. A large fraction of these associations are likely due to either quantitative differences in gene expression or amino acid changes that regulate quantitative aspects of the immune response. While functional studies are still lacking for most of these associations, we present examples of autoimmune disease risk alleles that influence quantitative changes in lymphocyte activation, cytokine signaling and dendritic cell function. The analysis of immune quantitative traits associated with autoimmune loci is clearly going to be an important component of understanding the pathogenesis of autoimmunity. This will require both new and more efficient ways of characterizing the normal immune system, as well as large population resources with which genotype-phenotype correlations can be convincingly demonstrated. Future development of new therapies will depend on understanding the mechanistic underpinnings of immune regulation by these new risk loci. PMID:23026397

  1. Autoimmunity against dopamine receptors in neuropsychiatric and movement disorders: a review of Sydenham chorea and beyond.

    PubMed

    Cunningham, M W; Cox, C J

    2016-01-01

    Antineuronal autoantibodies are associated with the involuntary movement disorder Sydenham chorea (SC) and paediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) which are characterized by the acute onset of tics and/or obsessive compulsive disorder (OCD). In SC and PANDAS, autoantibodies signal human neuronal cells and activate calcium calmodulin-dependent protein kinase II (CaMKII). Animal models immunized with group A streptococcal antigens demonstrate autoantibodies against dopamine receptors and concomitantly altered behaviours. Human monoclonal antibodies (mAbs) derived from SC target and signal the dopamine D2L (long) receptor (D2R). Antibodies against D2R were elevated over normal levels in SC and acute-onset PANDAS with small choreiform movements, but were not elevated over normal levels in PANDAS-like chronic tics and OCD. The expression of human SC-derived anti-D2R autoantibody V gene in B cells and serum of transgenic mice demonstrated that the human autoantibody targets dopaminergic neurones in the basal ganglia and other types of neurones in the cortex. Here, we review current evidence supporting the hypothesis that antineuronal antibodies, specifically against dopamine receptors, follow streptococcal exposures and may target dopamine receptors and alter central dopamine pathways leading to movement and neuropsychiatric disorders. PMID:26454143

  2. Autoimmune Bullous Skin Disorders with Immune Checkpoint Inhibitors Targeting PD-1 and PD-L1.

    PubMed

    Naidoo, Jarushka; Schindler, Katja; Querfeld, Christiane; Busam, Klaus; Cunningham, Jane; Page, David B; Postow, Michael A; Weinstein, Alyona; Lucas, Anna Skripnik; Ciccolini, Kathryn T; Quigley, Elizabeth A; Lesokhin, Alexander M; Paik, Paul K; Chaft, Jamie E; Segal, Neil H; D'Angelo, Sandra P; Dickson, Mark A; Wolchok, Jedd D; Lacouture, Mario E

    2016-05-01

    Monoclonal antibodies (mAb) targeting immune checkpoint pathways such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed death 1 (PD-1) may confer durable disease control in several malignancies. In some patients, immune checkpoint mAbs cause cutaneous immune-related adverse events. Although the most commonly reported cutaneous toxicities are mild, a subset may persist despite therapy and can lead to severe or life-threatening toxicity. Autoimmune blistering disorders are not commonly associated with immune checkpoint mAb therapy. We report a case series of patients who developed bullous pemphigoid (BP), an autoimmune process classically attributed to pathologic autoantibody formation and complement deposition. Three patients were identified. Two patients developed BP while receiving the anti-PD-1 mAb nivolumab, and one while receiving the anti-PD-L1 mAb durvalumab. The clinicopathologic features of each patient and rash, and corresponding radiologic findings at the development of the rash and after its treatment, are described. Patients receiving an anti-PD-1/PD-L1 mAb may develop immune-related BP. This may be related to both T-cell- and B-cell-mediated responses. Referral to a dermatologist for accurate diagnosis and management is recommended. Cancer Immunol Res; 4(5); 383-9. ©2016 AACR. PMID:26928461

  3. Adult hemophagocytic lymphohistiocytosis causing multi organ dysfunction in a patient with multiple autoimmune disorders: when the immune system runs amok.

    PubMed

    Fleischmann, Robert; Böhmerle, Wolfgang; von Laffert, Maximilian; Jöhrens, Korinna; Mengel, Annerose; Hotter, Benjamin; Lindenberg, Robert; Scheibe, Franziska; Köhnlein, Martin; von Bahr Greenwood, Tatiana; Henter, Jan Inge; Meisel, Andreas

    2016-02-01

    We report a case of several autoimmune disorders eventually presenting as severe multi organ dysfunction syndrome caused by adult hemophagocytic lymphohistiocytosis (HLH). Clinical and laboratory tests might lead to fatal misinterpretation without awareness of its diagnostic evaluation, as HLH shares common features with sepsis and immune-mediated systemic inflammatory response syndromes. PMID:26862416

  4. Use of Intravenous Immunoglobulin in the Treatment of Twelve Youths with Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections

    PubMed Central

    Kovacevic, Miro; Grant, Paul

    2015-01-01

    Abstract This is a case series describing 12 youths treated with intravenous immunoglobulin (IVIG) for pediatric autoimmune neuropsychiatric disorder associated with streptococcal infection (PANDAS). Although it is a clinically based series, the case reports provide new information about the short-term benefits of IVIG therapy, and are the first descriptions of long-term outcome for PANDAS patients. PMID:25658609

  5. [Autoimmune thyroiditis].

    PubMed

    Cardot-Bauters, Catherine; Wémeau, Jean-Louis

    2014-06-01

    Autoimmune thyroiditis are common and benign disorders, affecting preferentially women, at any age of life. They may occur singly or integrated as a part of familial predisposition to autoimmune thyroid disease or autoimmune polyendocrinopathies. Clinical presentation is variable: goiter or thyroid atrophy, euthyroid or temporary or permanent hypothyroidism, rarely transient thyrotoxicosis. Commune features are the presence of antithyroperoxydase antibodies and lymphoplasmocytic infiltrate of the thyroid parenchyma. It is important to distinguish the cases in which thyroid dysfunction is transient and requires only monitoring and those in which hypothyroidism is permanent and justifies thyroid hormone replacement. In the forms with goiter, clinical and ultrasonic control of the thyroid is justified. PMID:25090773

  6. Efficacy of Azacitidine in autoimmune and inflammatory disorders associated with myelodysplastic syndromes and chronic myelomonocytic leukemia.

    PubMed

    Fraison, Jean-Baptiste; Mekinian, Arsène; Grignano, Eric; Kahn, Jean-Emmanuel; Arlet, Jean-Benoit; Decaux, Olivier; Denis, Guillaume; Buchdahl, Anne-Laure; Omouri, Mohamed; Maigne, Gwenola; Aouba, Achille; Leon, Nathalie; Berthier, Sabine; Liozon, Eric; Park, Sophie; Gardin, Claude; Lortholary, Olivier; Rossignol, Julien; Fenaux, Pierre; Fain, Olivier; Braun, Thorsten

    2016-04-01

    This retrospective study describes efficacy of Azacitidine on autoimmune disorders (AID) associated with MDS/CMML in 22 patients. Response of AID to Azacitidine was observed in 19 patients (86%). Reduction or discontinuation of steroids and/or immunosuppressive therapy (IST) was possible in 16 cases (73%). Hematologic response was seen in 55% of the patients. MDS/CMML and AID evolution was concordant in 13 cases (59%): both favorable (n=11), both unfavorable (n=2), but AID improved while MDS/CMML worsened (n=8) and vice versa (n=1). Azacitidine frequently seems effective in controlling steroid-dependent AID associated with MDS/CMML, but prospective studies are necessary to confirm those findings. PMID:26922775

  7. Maternal autoimmune diseases and the risk of autism spectrum disorders in offspring: A systematic review and meta-analysis.

    PubMed

    Chen, Shao-Wei; Zhong, Xue-Shan; Jiang, Li-Na; Zheng, Xue-Yan; Xiong, Yi-Quan; Ma, Shu-Juan; Qiu, Min; Huo, Shu-Ting; Ge, Jing; Chen, Qing

    2016-01-01

    Although inherited and immune disorder factors are known to be involved in autism spectrum disorders (ASD), controversy still exists as to whether maternal autoimmune disease is an independent risk of ASD in offspring. We aimed to quantitatively summarize the risk of ASD in offspring in relation to maternal autoimmune diseases. A literature search in Pubmed, Web of science, Embase, and China national knowledge internet was conducted to identify relevant studies. Pooled odd ratio (OR) and its 95% confidence interval (CI) were computed by STATA version 12.0. Nine case-control studies and one cohort studies comprising 9775 cases and 952,211 controls were included in this study. A positive association between maternal autoimmune diseases and the risk of ASD in offspring was identified assuming a fixed effect model (pooled OR, 1.34; 95% CI, 1.23-1.46; I(2), 27.9%). There were statistically significant associations between maternal autoimmune diseases developed during pregnancy or maternal thyroid disease and the risk of ASD in offspring (pooled OR, 1.30, 1.29, respectively). Maternal autoimmune disease is likely to be an independent risk factor of ASD in offspring. PMID:26327239

  8. Autoimmune neuropsychiatric disorders associated with streptococcal infection: Sydenham chorea, PANDAS, and PANDAS variants.

    PubMed

    Pavone, Piero; Parano, Enrico; Rizzo, Renata; Trifiletti, Rosario R

    2006-09-01

    Streptococcal infection in children is usually benign and self-limited. In a small percentage of children, prominent neurologic and/or psychiatric sequelae can occur. Sydenham chorea is the best defined and best recognized. PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection) is a well-defined syndrome in which tics (motor and/or vocal) and/or obsessive-compulsive disorder consistently exacerbate in temporal correlation to a group A beta-hemolytic streptococcal infection. PANDAS constitutes a subset of children with tics, Tourette syndrome, and obsessive-compulsive disorder. In addition to strictly defined PANDAS, we and others have recognized several PANDAS variants, including adult-onset variant, a dystonic variant, a myoclonic variant, and a "chronic" PANDAS variant. The nosology and classification of these entities are rapidly evolving. The recognition that some pediatric neurobehavioral syndromes have infectious and/or immunologic triggers points to important new avenues of disease treatment. In this review, we summarize this complex and rapidly evolving area of clinical research. PMID:16970875

  9. Pediatric autoimmune neuropsychiatric disorder associated with group a streptococcal infection: the role of surgical treatment.

    PubMed

    Pavone, P; Rapisarda, V; Serra, A; Nicita, F; Spalice, A; Parano, E; Rizzo, R; Maiolino, L; Di Mauro, P; Vitaliti, G; Coco, A; Falsaperla, A; Trifiletti, R R; Cocuzza, S

    2014-01-01

    Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus (PANDAS) is a well-defined syndrome in which tics (motor and/or vocal) and/or obsessive compulsive disorders (OCD) consistently exacerbate in temporal correlation to a Group A beta-haemolytic streptococcal infection. In children with PANDAS, there is speculation about whether tonsillectomy or adenotonsillectomy might improve the neuropsychiatric course. Our objective was to examine whether such surgery impacted remission or, in patients without remission, modified clinical course of the disease, streptococcal antibody titers, neuronal antibodies or clinical severity of Obsessive-Compulsive Disorder (OCD) and/or tics. Study participants (n = 120) with positive PANDAS criteria were recruited, examined, and divided into surgical or non-surgery groups. The surgical group consisted of children with tonsillectomy or adenotonsillectomy (n=56). The remaining children were categorized as non-surgery (n=64). Clinical follow-up was made every 2 months for more than 2 years. Surgery did not affect symptomatology progression, streptococcal and neuronal antibodies, or the clinical severity of neuropsychiatric symptoms in these children. In conclusion, in our series clinical progression, antibody production, and neuropsychiatric symptom severity did not differ on the basis of surgical status. We cannot uphold surgical management as likely to impact positive remission rates, course of OCD/tics, or antibody concentrations in children with PANDAS. PMID:25280028

  10. 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

  11. Movement disorders in children with anti-NMDAR encephalitis and other autoimmune encephalopathies.

    PubMed

    Mohammad, Shekeeb S; Fung, Victor S C; Grattan-Smith, Padraic; Gill, Deepak; Pillai, Sekhar; Ramanathan, Sudarshini; Brilot, Fabienne; Dale, Russell C

    2014-10-01

    Accurate recognition of movement disorder phenomenology may differentiate children with anti-N-methyl D-aspartate receptor (NMDAR) encephalitis, autoimmune basal ganglia encephalitis (BGE), and Sydenham's chorea (SC). Three neurologists blinded to the diagnoses recorded dominant and associated movement disorders seen on videos of 31 patients with anti-NMDAR encephalitis (n = 10), BGE (n = 12), and SC (n = 9). Stereotypy was only seen in anti-NMDAR encephalitis (8/10) and not in BGE and SC (P < 0.001). Perseveration was only seen in anti-NMDAR encephalitis (5/10) and not in BGE and SC (P < 0.001). Akinesia was more commonly seen in BGE (5/12) than in anti-NMDAR encephalitis (1/10, P = 0.097). Tremor was more commonly seen in BGE (5/12) than in anti-NMDAR encephalitis (1/10, P = 0.097). Chorea was seen in all groups: anti-NMDAR encephalitis (4/10), BGE (3/12), and SC (9/9). Likewise, dystonia was seen in all groups: anti-NMDAR encephalitis (6/10), BGE (7/12), and SC (2/9). Stereotypies or perseveration are suggestive of anti-NMDAR encephalitis, whereas their absence and the presence of akinesia and tremor is more suggestive of BGE. Chorea and dystonia are least discriminating. PMID:25154478

  12. Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS): An Evolving Concept.

    PubMed

    Macerollo, Antonella; Martino, Davide

    2013-01-01

    Pediatric autoimmune neuropsychiatric disorders associated with streptococcus infections (PANDAS) originated from the observational work of Swedo and collaborators, who formalized their definition in 1998 in a set of operational criteria. The application of these criteria, which focuses on tics and obsessive-compulsive symptoms as core symptoms, has encountered difficulties, eventually leading to a high rate of misdiagnosis. In particular, the core feature represented by the association between newly diagnosed infections and neuropsychiatric symptom relapses in youths with this diagnosis could not be demonstrated by longitudinal studies. Exploratory studies aiming to identify clinical or cognitive features that could discriminate PANDAS from other pediatric obsessive-compulsive and tic disorders present methodological limitations, and therefore are not conclusive. Other behavioral features, in addition to obsessive-compulsive symptoms and tics, have been included in pediatric acute-onset neuropsychiatric syndromes (PANS) and childhood acute neuropsychiatric syndromes (CANS), two new concepts recently proposed in order to define a much broader clinical spectrum encompassing etiologically diverse entities. Given the uncertainties on the clinical definition of PANDAS, it is not surprising that evidence in support of a post-infectious, immune-mediated pathophysiology is also insufficient. Anti-dopamine receptor antibodies might be relevant to both Sydenham's chorea (SC)-the prototypical post-streptococcal neuropsychiatric disorder-and some rare forms of encephalitis targeting the basal ganglia specifically, but studies exploring their association with children fulfilling Swedo's criteria for PANDAS have been inconclusive. Moreover, we lack evidence in favor of the efficacy of antibiotic prophylaxis or tonsillectomy in patients fulfilling Swedo's criteria for PANDAS, whereas a response to immune-mediated treatments like intravenous immunoglobulins has been documented by one study, but needs replication in larger trials. Overall, the available evidence does not convincingly support the concept that PANDAS are a well-defined, isolated clinical entity subdued by definite pathophysiological mechanisms; larger, prospective studies are necessary to reshape the nosography and disease mechanisms of post-streptococcal acute neuropsychiatric disorders other than SC. Research is also under way to shed further light on a possible relationship between streptococcal infections, other biological and psychosocial stressors, and the complex pathobiology of chronic tic disorders. PMID:24106651

  13. Nucleolar proteins identified in human cells as antigens by sera from dogs with autoimmune disorders.

    PubMed

    Soulard, M; Lagaye, S; Della Valle, V; Danon, F; Larsen, C J; Barque, J P

    1989-06-01

    In the course of a systematic screening of sera from dogs suffering from autoimmune disorders, three sera were shown by indirect immunofluorescence to characteristically label the nucleoli and nucleoplasm of human cell lines (Hep-2 and HeLa). This pattern of staining persisted throughout the cell cycle, except for mitosis when the fluorescence was localized in extrachromosomal areas. By immunoblotting nuclear and subnuclear fractions, three polypeptides of 110,000, 95,000, and 45,000 Da apparent molecular weight were identified, which reacted with all three sera. By means of affinity purification, it was shown that an antibody specific for any one of the three proteins also reacts with the two others. This antigenic cross-reactivity suggested regions of structural homology shared by the three proteins. Indeed, treatment of nucleoli with high concentrations of DNase I containing residual proteolytic activity resulted in the disappearance of the 110- and 95-kDa proteins and the concomitant appearance of a doublet of 45-kDa proteins. Subnuclear localization studies indicated that all three polypeptides were located in both nucleoli and nucleoplasm. Significantly, the 110-kDa protein differs from the major nucleolar protein, nucleolin, by its electrophoretic mobility in two-dimensional gels, its location in nucleoli and in nucleoplasm, its absence in nucleolar organizer regions of chromosomes, and its differential solubility of DNase I. Therefore, the three antigenically related species reported in this study constitute a new class of nucleolar proteins. PMID:2656278

  14. Autoimmune hepatitis.

    PubMed

    Mieli-Vergani, Giorgina; Heller, Solange; Jara, Paloma; Vergani, Diego; Chang, Mei-Hwei; Fujisawa, Tomoo; González-Peralta, Regino P; Kelly, Deirdre; Mohan, Neelam; Shah, Uzma; Murray, Karen F

    2009-08-01

    Autoimmune hepatitis is characterized by inflammatory liver histology, circulating nonorgan-specific autoantibodies, and increased levels of immunoglobulin G, in the absence of a known etiology. Two types of juvenile autoimmune hepatitis (AIH) are recognized according to seropositivity for smooth muscle and/or anti-nuclear antibody (AIH type 1) or liver kidney microsomal antibody (AIH type 2). There is a female predominance in both. AIH type 2 presents more acutely, at a younger age and commonly with immunoglobulin A deficiency, whereas duration of symptoms before diagnosis, clinical signs, family history of autoimmunity, presence of associated autoimmune disorders, response to treatment, and long-term prognosis are similar in the 2 groups. Immunosuppressive treatment with steroids and azathioprine, which should be instituted promptly to avoid progression to cirrhosis, induces remission in 80% of cases. Relapses are common, often due to nonadherence. Drugs effective in refractory cases include cyclosporine and mycophenolate mofetil. Long-term treatment is usually required, with only some 20% of AIH type 1 patients able to discontinue therapy successfully. In childhood, sclerosing cholangitis with strong autoimmune features, including interface hepatitis and serological features identical to AIH type 1, is as prevalent as AIH, but it affects boys and girls equally. Differential diagnosis relies on cholangiographic studies. In autoimmune sclerosing cholangitis liver parenchymal damage responds satisfactorily to immunosuppressive treatment, whereas bile duct disease tends to progress. In this article we review the state of the art of diagnosis, monitoring, and treatment for children with AIH. PMID:19561543

  15. Autoimmune disorders and risk of non-Hodgkin lymphoma subtypes: a pooled analysis within the InterLymph Consortium

    PubMed Central

    Vajdic, Claire M.; Falster, Michael; Engels, Eric A.; Martínez-Maza, Otoniel; Turner, Jennifer; Hjalgrim, Henrik; Vineis, Paolo; Seniori Costantini, Adele; Bracci, Paige M.; Holly, Elizabeth A.; Willett, Eleanor; Spinelli, John J.; La Vecchia, Carlo; Zheng, Tongzhang; Becker, Nikolaus; De Sanjosé, Silvia; Chiu, Brian C.-H.; Dal Maso, Luigino; Cocco, Pierluigi; Maynadié, Marc; Foretova, Lenka; Staines, Anthony; Brennan, Paul; Davis, Scott; Severson, Richard; Cerhan, James R.; Breen, Elizabeth C.; Birmann, Brenda; Grulich, Andrew E.; Cozen, Wendy

    2008-01-01

    Some autoimmune disorders are increasingly recognized as risk factors for non-Hodgkin lymphoma (NHL) overall, but large-scale systematic assessments of risk of NHL subtypes are lacking. We performed a pooled analysis of self-reported autoimmune conditions and risk of NHL and subtypes, including 29 423 participants in 12 case-control studies. We computed pooled odds ratios (OR) and 95% confidence intervals (CI) in a joint fixed-effects model. Sjögren syndrome was associated with a 6.5-fold increased risk of NHL, a 1000-fold increased risk of parotid gland marginal zone lymphoma (OR = 996; 95% CI, 216-4596), and with diffuse large B-cell and follicular lymphomas. Systemic lupus erythematosus was associated with a 2.7-fold increased risk of NHL and with diffuse large B-cell and marginal zone lymphomas. Hemolytic anemia was associated with diffuse large B-cell NHL. T-cell NHL risk was increased for patients with celiac disease and psoriasis. Results for rheumatoid arthritis were heterogeneous between studies. Inflammatory bowel disorders, type 1 diabetes, sarcoidosis, pernicious anemia, and multiple sclerosis were not associated with risk of NHL or subtypes. Thus, specific autoimmune disorders are associated with NHL risk beyond the development of rare NHL subtypes in affected organs. The pattern of associations with NHL subtypes may harbor clues to lymphomagenesis. PMID:18263783

  16. Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS): An Evolving Concept

    PubMed Central

    Macerollo, Antonella; Martino, Davide

    2013-01-01

    Pediatric autoimmune neuropsychiatric disorders associated with streptococcus infections (PANDAS) originated from the observational work of Swedo and collaborators, who formalized their definition in 1998 in a set of operational criteria. The application of these criteria, which focuses on tics and obsessive-compulsive symptoms as core symptoms, has encountered difficulties, eventually leading to a high rate of misdiagnosis. In particular, the core feature represented by the association between newly diagnosed infections and neuropsychiatric symptom relapses in youths with this diagnosis could not be demonstrated by longitudinal studies. Exploratory studies aiming to identify clinical or cognitive features that could discriminate PANDAS from other pediatric obsessive-compulsive and tic disorders present methodological limitations, and therefore are not conclusive. Other behavioral features, in addition to obsessive-compulsive symptoms and tics, have been included in pediatric acute-onset neuropsychiatric syndromes (PANS) and childhood acute neuropsychiatric syndromes (CANS), two new concepts recently proposed in order to define a much broader clinical spectrum encompassing etiologically diverse entities. Given the uncertainties on the clinical definition of PANDAS, it is not surprising that evidence in support of a post-infectious, immune-mediated pathophysiology is also insufficient. Anti-dopamine receptor antibodies might be relevant to both Sydenham’s chorea (SC)—the prototypical post-streptococcal neuropsychiatric disorder—and some rare forms of encephalitis targeting the basal ganglia specifically, but studies exploring their association with children fulfilling Swedo’s criteria for PANDAS have been inconclusive. Moreover, we lack evidence in favor of the efficacy of antibiotic prophylaxis or tonsillectomy in patients fulfilling Swedo’s criteria for PANDAS, whereas a response to immune-mediated treatments like intravenous immunoglobulins has been documented by one study, but needs replication in larger trials. Overall, the available evidence does not convincingly support the concept that PANDAS are a well-defined, isolated clinical entity subdued by definite pathophysiological mechanisms; larger, prospective studies are necessary to reshape the nosography and disease mechanisms of post-streptococcal acute neuropsychiatric disorders other than SC. Research is also under way to shed further light on a possible relationship between streptococcal infections, other biological and psychosocial stressors, and the complex pathobiology of chronic tic disorders. PMID:24106651

  17. Opportunistic Autoimmune Disorders Potentiated by Immune-Checkpoint Inhibitors Anti-CTLA-4 and Anti-PD-1

    PubMed Central

    Kong, Yi-chi M.; Flynn, Jeffrey C.

    2014-01-01

    To improve the efficacy of immunotherapy for cancer and autoimmune diseases, recent ongoing and completed clinical trials have focused on specific targets to redirect the immune network toward eradicating a variety of tumors and ameliorating the self-destructive process. In a previous review, both systemic immunomodulators and monoclonal antibodies (mAbs), anti-CTLA-4, and anti-CD52, were discussed regarding therapeutics and autoimmune sequelae, as well as predisposing factors known to exacerbate immune-related adverse events (irAEs). This review will focus on immune-checkpoint inhibitors, and the data from most clinical trials involve blockade with anti-CTLA-4 such as ipilimumab. However, despite the mild to severe irAEs observed with ipilimumab in ~60% of patients, overall survival (OS) averaged ~22–25% at 3–5 years. To boost OS, other mAbs targeting programed death-1 and its ligand are undergoing clinical trials as monotherapy or dual therapy with anti-CTLA-4. Therapeutic combinations may generate different spectrum of opportunistic autoimmune disorders. To simulate clinical scenarios, we have applied regulatory T cell perturbation to murine models combined to examine the balance between thyroid autoimmunity and tumor-specific immunity. PMID:24904570

  18. PANDAS: Frequently Asked Questions about Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal ....

    MedlinePlus

    ... Disorder (OCD) (2 items) Panic Disorder (1 item) Post-Traumatic Stress Disorder (4 items) Schizophrenia (2 items) Social Phobia ( ... Disorder (OCD) (2 items) Panic Disorder (1 item) Post-Traumatic Stress Disorder (4 items) Schizophrenia (2 items) Social Phobia ( ...

  19. Brain-reactive IgG correlates with autoimmunity in mothers of a child with an autism spectrum disorder.

    PubMed

    Brimberg, L; Sadiq, A; Gregersen, P K; Diamond, B

    2013-11-01

    It is believed that in utero environmental factors contribute to autism spectrum disorder (ASD). The goal of this study was to demonstrate, using the largest cohort reported so far, that mothers of an ASD child have an elevated frequency of anti-brain antibodies and to assess whether brain reactivity is associated with an autoimmune diathesis of the mother. We screened plasma of 2431 mothers of an ASD child from Simon Simplex Collection and plasma of 653 unselected women of child-bearing age for anti-brain antibodies using immunohistology on mouse brain. Positive and negative plasma from mothers with an ASD child were analyzed for anti-nuclear antibodies and for autoimmune disorders. Mothers of an ASD child were four times more likely to harbor anti-brain antibodies than unselected women of child-bearing age (10.5 vs 2.6%). A second cohort from The Autism Genetic Resource Exchange with multiplex families displayed an 8.8% prevalence of anti-brain antibodies in the mothers of these families. Fifty-three percent of these mothers with anti-brain antibodies also exhibited anti-nuclear autoantibodies compared with 13.4% of mothers of an ASD child without anti-brain antibodies and 15% of control women of child-bearing age. The analysis of ASD mothers with brain-reactive antibodies also revealed an increased prevalence of autoimmune diseases, especially rheumatoid arthritis and systemic lupus erythematosus. This study provides robust evidence that brain-reactive antibodies are increased in mothers of an ASD child and may be associated with autoimmunity. The current study serves as a benchmark and justification for studying the potential pathogenicity of these antibodies on the developing brain. The detailed characterization of the specificity of these antibodies will provide practical benefits for the management and prevention of this disorder. PMID:23958959

  20. Clinical Presentation of Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections in Research and Community Settings

    PubMed Central

    Seidlitz, Jakob; Kovacevic, Miro; Latimer, M. Elizabeth; Hommer, Rebecca; Lougee, Lorraine; Grant, Paul

    2015-01-01

    Abstract Background: The first cases of pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) were described>15 years ago. Since that time, the literature has been divided between studies that successfully demonstrate an etiologic relationship between Group A streptococcal (GAS) infections and childhood-onset obsessive-compulsive disorder (OCD), and those that fail to find an association. One possible explanation for the conflicting reports is that the diagnostic criteria proposed for PANDAS are not specific enough to describe a unique and homogeneous cohort of patients. To evaluate the validity of the PANDAS criteria, we compared clinical characteristics of PANDAS patients identified in two community practices with a sample of children meeting full research criteria for PANDAS. Methods: A systematic review of clinical records was used to identify the presence or absence of selected symptoms in children evaluated for PANDAS by physicians in Hinsdale, Illinois (n=52) and Bethesda, Maryland (n=40). Results were compared against data from participants in National Institute of Mental Health (NIMH) research investigations of PANDAS (n=48). Results: As described in the original PANDAS cohort, males outnumbered females (95:45) by ∼ 2:1, and symptoms began in early childhood (7.3±2.7 years). Clinical presentations were remarkably similar across sites, with all children reporting acute onset of OCD symptoms and multiple comorbidities, including separation anxiety (86–92%), school issues (75–81%), sleep disruptions (71%), tics (60–65%), urinary symptoms (42–81%), and others. Twenty of the community cases (22%) failed to meet PANDAS criteria because of an absence of documentation of GAS infections. Conclusions: The diagnostic criteria for PANDAS can be used by clinicians to accurately identify patients with common clinical features and shared etiology of symptoms. Although difficulties in documenting an association between GAS infection and symptom onset/exacerbations may preclude a diagnosis of PANDAS in some children with acute-onset OCD, they do appear to meet criteria for pediatric acute-onset neuropsychiatric syndrome (PANS). PMID:25695941

  1. Upregulation of lymphocyte apoptosis as a strategy for preventing and treating autoimmune disorders: a role for whole-food vegan diets, fish oil and dopamine agonists.

    PubMed

    McCarty, M F

    2001-08-01

    Induced apoptosis of autoreactive T-lymphocyte precursors in the thymus is crucial for the prevention of autoimmune disorders. IGF-I and prolactin, which are lymphocyte growth factors, may have the potential to suppress apoptosis in thymocytes and thus encourage autoimmunity; conversely, dietary fish oil rich in omega-3 fats appears to upregulate apoptosis in lymphocytes. Since whole-food vegan diets may downregulate systemic IGF-I activity, it is proposed that such a diet, in conjunction with fish oil supplementation and treatment with dopamine agonists capable of suppressing prolactin secretion, may have utility for treating and preventing autoimmune disorders. This prediction is consistent with the extreme rarity of autoimmune disorders among sub-Saharan black Africans as long as they followed their traditional quasi-vegan lifestyles, and with recent ecologic studies correlating risks for IDDM and for multiple sclerosis mortality with animal product and/or saturated fat consumption. Moreover, there is evidence that vegan or quasi-vegan diets are useful in the management of rheumatoid arthritis, multiple sclerosis, and possibly SLE. The dopamine agonist bromocryptine exerts anti-inflammatory effects in rodent models of autoimmunity, and there is preliminary evidence that this drug may be clinically useful in several human autoimmune diseases; better tolerated D2-specific agonists such as cabergoline may prove to be more practical for use in therapy. The moderate clinical utility of supplemental fish oil in rheumatoid arthritis and certain other autoimmune disorders is documented. It is not unlikely that extra-thymic anti-inflammatory effects contribute importantly to the clinical utility of vegan diets, bromocryptine, and fish oil in autoimmunity. The favorable impact of low latitude or high altitude on autoimmune risk may be mediated by superior vitamin D status, which is associated with decreased secretion of parathyroid hormone; there are theoretical grounds for suspecting that parathyroid hormone may inhibit apoptosis in thymocytes. Androgens appear to up-regulate thymocyte apoptosis, may be largely responsible for the relative protection from autoimmunity enjoyed by men, and merit further evaluation for the management of autoimmunity in women. It will probably prove more practical to prevent autoimmune disorders than to reverse them once established; a whole-food vegan diet, coupled with fish oil and vitamin D supplementation, may represent a practical strategy for achieving this prevention, while concurrently lowering risk for many other life-threatening 'Western' diseases. PMID:11461185

  2. Autoimmune encephalopathies.

    PubMed

    Lim, Ming; Hacohen, Yael; Vincent, Angela

    2015-06-01

    Antibody-mediated diseases of the central nervous system are a relatively new and challenging field in autoimmune neurologic disease and of major clinical importance in children and adults. The antibodies bind to cell-surface epitopes on neuronal or glial proteins, and the patients demonstrate either focal or more generalized clinical signs depending on the extent of brain regions targeted by the antibodies. The presence of seizures, movement disorders, autonomic dysfunction and sleep disorders, alongside neuroimaging and electrophysiological features may indicate a specific antibody-mediated disorder. However, phenotypic variation may be observed in children with the same antibody. Regardless, many patients benefit from immunotherapy with substantial improvement. PMID:26022169

  3. Sjögren syndrome and neuromyelitis optica spectrum disorder co-exist in a common autoimmune milieu.

    PubMed

    Carvalho, Diogo C; Tironi, Tauana S; Freitas, Denise S; Kleinpaul, Rodrigo; Talim, Natalia C; Lana-Peixoto, Marco A

    2014-08-01

    The relationship between Sjögren's syndrome (SS) and neuromyelitis optica spectrum disorder (NMOSD) is not completely understood. We report two patients with both conditions and review 47 other previously reported cases meeting currently accepted diagnostic criteria, from 17 articles extracted from PubMed. Out of 44 patients whose gender was informed, 42 were females. Mean age at onset of neurological manifestation was 36.2 years (10-74). Serum anti-AQP4-IgG was positive in 32 patients, borderline in 1, and negative in 4. Our Case 1 was seronegative for AQP4-IgG and had no non-organ-specific autoantibodies other than anti-SSB antibodies. Our Case 2 had serum anti-AQP4, anti-SSA/SSB, anti-thyreoglobulin and anti-acethylcholine-receptor antibodies, as well as clinical hypothyreoidism, but no evidence of myasthenia gravis. Our Cases and others, as previously reported in literature, with similar heterogeneous autoimmune response to aquaporin-4, suggest that SS and NMO co-exist in a common autoimmune milieu which is not dependent on aquaporin-4 autoimmunity. PMID:25098478

  4. Fenofibrate treatment of rats with experimental autoimmune myocarditis by alleviating Treg/Th17 disorder

    PubMed Central

    Cheng, Huilei; Xi, Yanqin; Chi, Xianna; Wu, Yanxia

    2016-01-01

    Objective To investigate the curative effect of fenofibrate on rats with experimental autoimmune myocarditis (EAM) and its immunological mechanism. Material and methods Twenty-four rats were equally randomised into three groups: an EAM group, fenofibrate group, and control group, then a subcutaneous injection of purified pig cardiac myosin was given to the EAM group rats and the fenofibrate group, while equivalent normal saline (NS) was given to the control group. After that, the fenofibrate group received fenofibrate by gavage (100 mg/kg/d) and equivalent NS was given to the other groups, lasting for 17 days. Then the rats were sacrificed in order to take heart tissues; HE staining and qRT-PCR method was used to assess the severity of heart failure and mRNA level of cytokines; NK-κB protein content was analyzed by Western-blot. Healthy rat spleen tissue was prepared for splenocyte suspension. Subsequently, splenocytes were administrated similarly to the test in vivo for detecting cytokine mRNA levels. Results Compared with the control group, heart weight in EAM group was heavier than in the other groups (p < 0.05), and there was severe inflammatory cell infiltration in heart tissue of the EAM group. Th17 cell-related cytokines mRNA levels in the EAM group/induction group were evidently higher than in other groups (p < 0.05); FOX-p3 mRNA level in the EAM group/induction group was lower than other groups, mRNA levels of IL-10 and FOX-p3 in the fenofibrate group were higher than in the EAM group/induction group (p < 0.05). Fenofibrate could significantly inhibit the up-regulation of NF-κB protein in EAM rats (p < 0.05). Conclusions By inhibiting the development of Th17 cells and promoting the differentiation of Tregs, fenofibrate alleviated Treg/Th17 disorder and inhibited inflammation in rats with EAM, thus improving the prognosis. PMID:27095924

  5. Increased Serum Type I Interferon Activity in Organ-Specific Autoimmune Disorders: Clinical, Imaging, and Serological Associations

    PubMed Central

    Mavragani, Clio P.; Niewold, Timothy B.; Chatzigeorgiou, Antonis; Danielides, Stamatina; Thomas, Dimitrios; Kirou, Kyriakos A.; Kamper, Elli; Kaltsas, Grigorios; Crow, Mary K.

    2013-01-01

    Background: Activation of the type I interferon (IFN) pathway has been implicated in the pathogenesis of systemic autoimmune disorders but its role in the pathogenesis of organ-specific autoimmunity is limited. We tested the hypothesis that endogenous expression of type I IFN functional activity contributes to the pathogenesis of autoimmune thyroid disease (ATD) and type I diabetes (T1DM). Methods: We studied 39 patients with ATD and 39 age and sex matched controls along with 88 T1DM patients and 46 healthy matched controls respectively. Available clinical and serological parameters were recorded by chart review, and thyroid ultrasound was performed in 17 ATD patients. Type I IFN serum activity was determined in all subjects using a reporter cell assay. The rs1990760 SNP of the interferon-induced helicase 1 gene was genotyped in ATD patients. Results: Serum type I IFN activity was increased in patients with ATD and T1DM compared to controls (p-values: 0.002 and 0.04, respectively). ATD patients with high type I IFN serum activity had increased prevalence of antibodies against thyroglobulin (anti-Tg) and cardiopulmonary manifestations compared to those with low IFN activity. Additionally, the presence of micronodules on thyroid ultrasound was associated with higher type I IFN levels. In patients with T1DM, high IFN levels were associated with increased apolipoprotein-B levels. Conclusion: Serum type I IFN activity is increased in ATD and T1DM and is associated with specific clinical, serological, and imaging features. These findings may implicate type I IFN pathway in the pathogenesis of specific features of organ-specific autoimmunity. PMID:23966997

  6. Epigenetics in autoimmune disorders: highlights of the 10th Sjögren's syndrome symposium.

    PubMed

    Lu, Qianjin; Renaudineau, Yves; Cha, Seunghee; Ilei, Gabor; Brooks, Wesley H; Selmi, Carlo; Tzioufas, Athanasios; Pers, Jacques-Olivier; Bombardieri, Stefano; Gershwin, M Eric; Gay, Steffen; Youinou, Pierre

    2010-07-01

    During the 10th International Symposium on Sjögren's Syndrome held in Brest, France, from October 1-3, 2009 (http://www.sjogrensymposium-brest2009.org), the creation of an international epigenetic autoimmune group has been proposed to establish gold standards and to launch collaborative studies. During this "epigenetics session", leading experts in the field presented and discussed the most recent developments of this topic in Sjögren's Syndrome research. The "Brest epigenetic task force" was born and has scheduled a meeting in Ljubljana, Slovenia during the 7th Autoimmunity congress in May 2010.The following is a report of that session. PMID:20452464

  7. 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 chronic disorders with an inflammatory component. PMID:23936387

  8. Pearls in autoimmunity.

    PubMed

    de Carvalho, Jozélio Freire; Pereira, Rosa Maria Rodrigues; Shoenfeld, Yehuda

    2011-05-01

    This manuscript does a review of the more frequent issues published at Autoimmunity Reviews, Journal of Autoimmunity and Autoimmunity in the period of January-December 2009. The following topics were commented: (1) multiple sclerosis (MS) and its relationships with Epstein Barr infection, with vitamin D polymorphism and the new modalities of MS treatment. (2) Type 1 diabetes and genetic discovers, studies with GAD 65 and IA-2 autoantigen and the association T1D and autoimmune organ-specific diseases. (3) Autoimmune thyroid disorders and its association with susceptibility genes and polymorphisms. (4) Multiplex autoantibody profiling approaches in MS and rheumatoid arthritis. (5) Th17 cytokine in primary biliary cirrhosis, experimental autoimmune encephalomyelitis and celiac disease. (6) Vitamin D and experimental autoimmune prostatitis and pulmonary alveolar proteinosis. PMID:26000114

  9. The role of autologous haemopoietic stem cell transplantation in the treatment of autoimmune disorders.

    PubMed

    Rebeiro, P; Moore, J

    2016-01-01

    Autologous haemopoietic stem cell transplantation (HSCT) has been used for over 30?years for malignant haematological diseases, such as myeloma and lymphoma, with considerable success. More recently this procedure has been adopted as a form of high dose immunosuppression in selected patients with autoimmune diseases that are resistant to conventional therapies. Animal models have previously outlined the rationale and validity of HSCT in patients with these non-malignant, but in many cases, life-threatening conditions. Recent data have that deletion of putative autoreactive immune clones with reconstitution of a thymic driven, tolerant immune system occurs in HSCT for auto-immune patients. Two randomised control trials have confirmed that HSCT is superior to monthly cyclophosphamide in systemic sclerosis with a highly significant disease free and overall survival benefit demonstrated in the Autologous Stem cell Transplantation International Scleroderma trial. Over 2000 patients worldwide with autoimmune conditions have been treated with HSCT - the commonest indications being multiple sclerosis (MS) and systemic sclerosis. Encouraging relapse free survival of 70-80% at 4?years, in heavily pre-treated MS patients, has been demonstrated in Phase II trials. A Phase III trial in MS patients who have failed interferon is currently accruing patients. Future challenges include improvements in safety of HSCT, particularly in cardiac assessment of systemic sclerosis patients, cost-benefit analyses of HSCT compared to standard therapy and establishment of centres of excellence to continue to enhance the safety and benefit of this exciting new therapy. PMID:26524106

  10. Autoimmune Autonomic Ganglionopathy

    MedlinePlus

    ... organizations outside of the National Institutes of Health. Overview Listen Autoimmune autonomic ganglionopathy (AAG) is rare autoimmune disorder in which the body's immune system mistakenly attacks and damages certain parts of the autonomic nervous system . Signs and symptoms of the condition vary ...

  11. Selective interleukin-1 receptor-associated kinase 4 inhibitors for the treatment of autoimmune disorders and lymphoid malignancy.

    PubMed

    Kelly, Priscilla N; Romero, Donna L; Yang, Yibin; Shaffer, Arthur L; Chaudhary, Divya; Robinson, Shaughnessy; Miao, Wenyan; Rui, Lixin; Westlin, William F; Kapeller, Rosana; Staudt, Louis M

    2015-12-14

    Pathological activation of the Toll-like receptor signaling adaptor protein MYD88 underlies many autoimmune and inflammatory disease states. In the activated B cell-like (ABC) subtype of diffuse large B cell lymphoma (DLBCL), the oncogenic MYD88 L265P mutation occurs in 29% of cases, making it the most prevalent activating mutation in this malignancy. IRAK4 kinase accounts for almost all of the biological functions of MYD88, highlighting IRAK4 as a therapeutic target for diseases driven by aberrant MYD88 signaling. Using innovative structure-based drug design methodologies, we report the development of highly selective and bioavailable small molecule IRAK4 inhibitors, ND-2158 and ND-2110. These small molecules suppressed LPS-induced TNF production, alleviated collagen-induced arthritis, and blocked gout formation in mouse models. IRAK4 inhibition promoted killing of ABC DLBCL lines harboring MYD88 L265P, by down-modulating survival signals, including NF-κB and autocrine IL-6/IL-10 engagement of the JAK-STAT3 pathway. In ABC DLBCL xenograft models, IRAK4 inhibition suppressed tumor growth as a single agent, and in combination with the Bruton's tyrosine kinase (BTK) inhibitor ibrutinib or the Bcl-2 inhibitor ABT-199. Our findings support pharmacological inhibition of IRAK4 as a therapeutic strategy in autoimmune disorders, in a genetically defined population of ABC DLBCL, and possibly other malignancies dependent on aberrant MYD88 signaling. PMID:26621451

  12. There might be a role for CD200 in the pathogenesis of autoimmune and inflammatory skin disorders

    PubMed Central

    Akman-Karakaş, Ayşe; Yalcin, Arzu Didem; Koç, Saliha; Gumuslu, Saadet; Şenol, Yeşim Yiğiter; Özkesici, Birgül; Genc, Gizem Esra; Ergun, Erkan; Ongut, Gozde; Yilmaz, Ertan; Uzun, Soner; Alpsoy, Erkan

    2013-01-01

    Background Soluble CD200 (sCD200) is a novel immuno-effective molecule, which acts to regulate inflammatory and acquired immune responses. Recently, our study group showed that sCD200 was present in serum and blister fluid in a patient with bullous pemphigoid and a patient with toxic epidermal necrolysis. We therefore planned this study to evaluate the sCD200 levels of autoimmune and inflammatory skin disorder patients and to compare them with that of healthy controls. Maleral/Methods Our study included 30 consecutive patients with psoriasis vulgaris, 15 with pemphigus vulgaris, and 15 healthy controls. Clinical examination and laboratory tests were performed on the same day. Psoriasis patients were also assessed with the Psoriasis Area and Severity Index (PASI) and pemphigus patients were assessed using the Pemphigus Disease Area Index (PDAI). Levels of sCD200 in the serum samples were quantified using ELISA kits. Results The serum sCD200 level was observed to be statistically significantly higher in patients with psoriasis vulgaris (96.7±15.8) compared to patients with pemphigus vulgaris (76.2±14.6), (p<0.001) and healthy controls (26.8±7.0) (p<0.001). The serum sCD200 levels were observed to be statistically significantly higher in patients with pemphigus vulgaris compared with that in healthy controls (p<0.001). In addition, there was a statistically significant correlation between serum sCD200 levels and PDAI (r=0.987, p=0.001). Nevertheless, there was no statistically significant correlation between serum sCD200 levels and PASI (r=0.154, p=0.407). Conclusions sCD200 might play a role in immune response in the pathogenesis of autoimmune and inflammatory skin disorders. However, it remains to be fully elucidated how sCD200 can orchestrate inflammatory response in psoriasis and pemphigus. PMID:24157657

  13. Nonsegmental vitiligo and autoimmune mechanism.

    PubMed

    Oiso, Naoki; Suzuki, Tamio; Fukai, Kazuyoshi; Katayama, Ichiro; Kawada, Akira

    2011-01-01

    Nonsegmental vitiligo is a depigmented skin disorder showing acquired, progressive, and depigmented lesions of the skin, mucosa, and hair. It is believed to be caused mainly by the autoimmune loss of melanocytes from the involved areas. It is frequently associated with other autoimmune diseases, particularly autoimmune thyroid diseases including Hashimoto's thyroiditis and Graves' disease, rheumatoid arthritis, type 1 diabetes, psoriasis, pernicious anemia, systemic lupus erythematosus, Addison's disease, and alopecia areata. This indicates the presence of genetically determined susceptibility to not only vitiligo but also to other autoimmune disorders. Here, we summarize current understanding of autoimmune pathogenesis in non-segmental vitiligo. PMID:21804820

  14. Nonsegmental Vitiligo and Autoimmune Mechanism

    PubMed Central

    Oiso, Naoki; Suzuki, Tamio; Fukai, Kazuyoshi; Katayama, Ichiro; Kawada, Akira

    2011-01-01

    Nonsegmental vitiligo is a depigmented skin disorder showing acquired, progressive, and depigmented lesions of the skin, mucosa, and hair. It is believed to be caused mainly by the autoimmune loss of melanocytes from the involved areas. It is frequently associated with other autoimmune diseases, particularly autoimmune thyroid diseases including Hashimoto's thyroiditis and Graves' disease, rheumatoid arthritis, type 1 diabetes, psoriasis, pernicious anemia, systemic lupus erythematosus, Addison's disease, and alopecia areata. This indicates the presence of genetically determined susceptibility to not only vitiligo but also to other autoimmune disorders. Here, we summarize current understanding of autoimmune pathogenesis in non-segmental vitiligo. PMID:21804820

  15. Translational Mini-Review Series on B Cell-Directed Therapies: Recent advances in B cell-directed biological therapies for autoimmune disorders

    PubMed Central

    Levesque, M C

    2009-01-01

    B cell-directed therapies are promising treatments for autoimmune disorders. Besides targeting CD20, newer B cell-directed therapies are in development that target other B cell surface molecules and differentiation factors. An increasing number of B cell-directed therapies are in development for the treatment of autoimmune disorders. Like rituximab, which is approved as a treatment for rheumatoid arthritis (RA), many of these newer agents deplete B cells or target pathways essential for B cell development and function; however, many questions remain about their optimal use in the clinic and about the role of B cells in disease pathogenesis. Other therapies besides rituximab that target CD20 are the furthest along in development. Besides targeting CD20, the newer B cell-directed therapies target CD22, CD19, CD40–CD40L, B cell activating factor belonging to the TNF family (BAFF) and A proliferation-inducing ligand (APRIL). Rituximab is being tested in an ever-increasing number of autoimmune disorders and clinical studies of rituximab combined with other biological therapies are being pursued for the treatment of rheumatoid arthritis (RA). B cell-directed therapies are being tested in clinical trials for a variety of autoimmune disorders including RA, systemic lupus erythematosus (SLE), Sjögren's syndrome, vasculitis, multiple sclerosis (MS), Graves' disease, idiopathic thrombocytopenia (ITP), the inflammatory myopathies (dermatomyositis and polymyositis) and the blistering skin diseases pemphigus and bullous pemphigoid. Despite the plethora of clinical studies related to B cell-directed therapies and wealth of new information from these trials, much still remains to be discovered about the pathophysiological role of B cells in autoimmune disorders. PMID:19604259

  16. Risk of multiple myeloma and monoclonal gammopathy of undetermined significance among white and black male United States veterans with prior autoimmune, infectious, inflammatory, and allergic disorders

    PubMed Central

    Gridley, Gloria; Check, David; Landgren, Ola

    2008-01-01

    In a retrospective cohort of more than 4 million white and black male United States (US) veterans, we explored the role of specific prior autoimmune, infectious, inflammatory, and allergic disorders in the etiology of multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS). Patients were selected from computerized inpatient discharge records at US Veterans Affairs hospitals. The analysis included 4641 patients (3040 white, 1601 black) and 2046 patients (1312 white; 734 black) with a discharge diagnosis of MM and MGUS, respectively. Using Poisson regression, we calculated age-adjusted relative risks (RRs) and 95% confidence intervals (CIs) for the relationship between MM, MGUS, and specific prior medical conditions. Significantly elevated risks of MM were associated with broad categories of autoimmune (RR, 1.15; 95% CI, 1.02-1.28), infectious (RR, 1.29; 95% CI, 1.20-1.38), and inflammatory disorders (RR, 1.18; 95% CI, 1.10-1.27) and specific prior autoimmune (polymyositis/dermatomyositis, systemic sclerosis, autoimmune hemolytic anemia, pernicious anemia, and ankylosing spondylitis), infectious (pneumonia, hepatitis, meningitis, septicemia, herpes zoster, and poliomyelitis), and inflammatory (glomerulonephritis, nephrotic syndrome, and osteoarthritis) disorders. Risks for MGUS were generally of similar magnitude. Our results indicate that various types of immune-mediated conditions might act as triggers for MM/MGUS development. PMID:18239085

  17. Low vitamin D levels in healthy controls and patients with autoimmune neuromuscular disorders in Greece.

    PubMed

    Chroni, Elisabeth; Dimisianos, Nikolaos; Punga, Anna Rostedt

    2016-03-01

    Normal autoimmune function is dependent on adequate levels of activated vitamin D, 25 hydroxy vitamin D [25(OH)D]. A recent study presented deficiency of 25(OH)D levels in Swedish MG patients. We aimed to study 25(OH)D levels in patients with MG and autoimmune polyneuropathies (PNP) at a southern latitude in Greece. Plasma levels of 25(OH)D were analyzed in Greek patients with MG (n = 19), immune-mediated PNP (N = 11) and in 30 Greek healthy age- and sex-matched controls. Ten MG patients received supplementation with vitamin D3. The MG Composite Score (MGC) and MG quality of life assessed disease severity in MG patients, whereas the INCAT Disability Scale assessed clinical features in the PNP patients. MG patients with and without vitamin D3 supplementation had higher 25(OH)D levels (mean 58.8 ± 16.3 and 62.0 ± 22.4 nmol/L, respectively) than PNP patients (mean 42.1 ± 11.5 nmol/L, p = 0.01) and healthy controls (mean 45.7 ± 13.8 nmol/L, p = 0.01). Plasma 25(OH)D levels was lower with age in all groups. There were no correlations between 25(OH)D and disease duration, MGC score, or INCAT score. Vitamin D deficiency was found in all Greek patient groups and healthy controls. Levels of 25(OH)D were higher in MG patients with as well as without vitamin D supplementation compared to healthy controls, whereas CIDP/GBS patients had levels similar to controls. PMID:26183131

  18. Association of type 1 diabetes mellitus and autoimmune disorders in Brazilian children and adolescents

    PubMed Central

    Alves, Crésio; Santos, Larissa Siqueira; Toralles, Maria Betânia P.

    2016-01-01

    Context: Type 1 diabetes mellitus (T1DM) is caused by an immune-mediated destruction of pancreatic beta cells. Other autoimmune diseases can be observed in association with T1DM. The screening for celiac disease (CD) and Hashimoto's thyroiditis is necessary due to the increased prevalence of these pathologies in T1DM patients. Aims: This study aimed to investigate the prevalence of autoimmune markers for pancreatitis, thyroiditis, and CD in racially admixtured children and adolescents with T1DM. Settings and Design: Cross-sectional clinic-based study. Methods: Seventy-one patients with T1DM (average: 11.6 ± 5.1 years). In all patients, the following antibodies were surveyed: Anti-glutamic acid decarboxylase (anti-GAD), immunoglobulin A (IgA) anti-transglutaminase (anti-tTG), Antithyroglobulin (AAT), anti-thyroid peroxidase (anti-TPO), and IgA. Statistical Analysis Used: The quantitative variables were expressed as a mean and standard deviation and the qualitative variables in contingency tables. Student's t-test and χ2 tests were used to assess the differences between the groups. The level of significance was established as P < 0.05. Results: The prevalence of anti-GAD antibodies was 5.9%; anti-tTG IgA, 7.4%; anti-TPO, 11.8%; and AAT, 11.8%. Conclusions: Children and adolescents with T1DM have increased the prevalence of antithyroid and CD-related antibodies. The positivity for anti-GAD and antithyroid antibodies was less frequent than in other studies. The prevalence of anti-tTG antibodies was similar to the literature.

  19. Complement and membrane-bound complement regulatory proteins as biomarkers and therapeutic targets for autoimmune inflammatory disorders, RA and SLE.

    PubMed

    Das, Nibhriti

    2015-11-01

    Complement system is a major effecter system of the innate immunity that bridges with adaptive immunity. The system consists of about 40 humoral and cell surface proteins that include zymogens, receptors and regulators. The zymogens get activated in a cascade fashion by antigen-antibody complex, antigen alone or by polymannans, respectively, by the classical, alternative and mannose binding lectin (MBL) pathways. The ongoing research on complement regulators and complement receptors suggest key role of these proteins in the initiation, regulation and effecter mechanisms of the innate and adaptive immunity. Although, the complement system provides the first line of defence against the invading pathogens, its aberrant uncontrolled activation causes extensive self tissue injury. A large number of humoral and cell surface complement regulatory protein keep the system well-regulated in healthy individuals. Complement profiling had brought important information on the pathophysiology of several infectious and chronic inflammatory disorders. In view of the diversity of the clinical disorders involving abnormal complement activity or regulation, which include both acute and chronic diseases that affect a wide range of organs, diverse yet specifically tailored therapeutic approaches may be needed to shift complement back into balance. This brief review discusses on the complement system, its functions and its importance as biomarkers and therapeutic targets for autoimmune diseases with focus on SLE and RA. PMID:26669012

  20. Autoimmune Hepatitis

    MedlinePlus

    ... Organizations ​​ (PDF, 341 KB)​​​​​ Alternate Language URL Autoimmune Hepatitis Page Content On this page: What is autoimmune ... Points to Remember Clinical Trials What is autoimmune hepatitis? Autoimmune hepatitis is a chronic—or long lasting— ...

  1. Autoimmunity in visual loss.

    PubMed

    Petzold, Axel; Wong, Sui; Plant, Gordon T

    2016-01-01

    There are a number of autoimmune disorders which can affect visual function. There are a very large number of mechanisms in the visual pathway which could potentially be the targets of autoimmune attack. In practice it is the retina and the anterior visual pathway (optic nerve and chiasm) that are recognised as being affected in autoimmune disorders. Multiple Sclerosis is one of the commonest causes of visual loss in young adults because of the frequency of attacks of optic neuritis in that condition, however the basis of the inflammation in Multiple Sclerosis and the confirmation of autoimmunity is lacking. The immune process is known to be highly unusual in that it is not systemic and confined to the CNS compartment. Previously an enigmatic partner to Multiple Sclerosis, Neuromyelitis Optica is now established to be autoimmune and two antibodies - to Aquaporin4 and to Myelin Oligodendrocyte Glycoprotein - have been implicated in the pathogenesis. The term Chronic Relapsing Inflammatory Optic Neuropathy is applied to those cases of optic neuritis which require long term immunosuppression and hence are presumed to be autoimmune but where no autoimmune pathogenesis has been confirmed. Optic neuritis occurring post-infection and post vaccination and conditions such as Systemic Lupus Erythematosus and various vasculitides may cause direct autoimmune attack to visual structures or indirect damage through occlusive vasculopathy. Chronic granulomatous disorders such as Sarcoidosis affect vision commonly by a variety of mechanisms, whether and how these are placed in the autoimmune panoply is unknown. As far as the retina is concerned Cancer Associated Retinopathy and Melanoma Associated Retinopathy are well characterised clinically but a candidate autoantibody (recoverin) is only described in the former disorder. Other, usually monophasic, focal retinal inflammatory disorders (Idiopathic Big Blind Spot Syndrome, Acute Zonal Occult Outer Retinopathy and Acute Macular Neuroretinitis) are of obscure pathogenesis but an autoimmune disorder of the post-infectious type is plausible. Visual loss in autoimmunity is an expanding field: the most significant advances in research have resulted from taking a well characterised phenotype and making educated guesses at the possible molecular targets of autoimmune attack. PMID:27112687

  2. Autoimmune encephalitis update

    PubMed Central

    Dalmau, Josep; Rosenfeld, Myrna R.

    2014-01-01

    Cancer-associated immune-mediated disorders of the central nervous system are a heterogeneous group. These disorders include the classic paraneoplastic neurologic disorders and the more recently described autoimmune encephalitis associated with antibodies to neuronal cell-surface or synaptic receptors that occur with and without a cancer association. Autoimmune encephalitis is increasingly recognized as the cause of a variety of neuropsychiatric syndromes that can be severe and prolonged. In contrast to the classic paraneoplastic disorders that are poorly responsive to tumor treatment and immunotherapy, autoimmune encephalitis often responds to these treatments, and patients can have full or marked recoveries. As early treatment speeds recovery, reduces disability, and decreases relapses that can occur in about 20% of cases, it is important that the immune pathogenesis of these disorders is recognized. PMID:24637228

  3. Retroperitoneal disorders associated with IgG4-related autoimmune pancreatitis.

    PubMed

    Hara, Noboru; Kawaguchi, Makoto; Takeda, Keisuke; Zen, Yoh

    2014-11-28

    IgG4-related autoimmune pancreatitis is frequently accompanied by relevant lesions in the genitourinary tract and retroperitoneal organs, which cause various clinical problems, ranging from non-specific back pain or bladder outlet obstruction to renal failure. The diagnosis of IgG4-related retroperitoneal fibrosis requires a multidisciplinary approach, including serological tests, histological examination, imaging analysis, and susceptibility to steroid therapy. Radiological examinations are helpful to diagnose this condition, but surgical resection is occasionally unavoidable to exclude malignancy, particularly for patients with isolated retroperitoneal involvement. Steroid therapy is the treatment of choice for this condition, the same as for other manifestations of IgG4-related disease. For patients with severe ureteral obstruction, additional ureteral stenting needs to be considered prior to steroid therapy to preserve the renal function. Some papers have suggested that IgG4-related disease can affect male reproductive organs including the prostate and testis. IgG4-related prostatitis usually causes lower urinary tract symptoms, such as dysuria and pollakisuria. Patients sometimes state that corticosteroids given for IgG4-related disease at other sites relieve their lower urinary tract symptoms, which leads us to suspect prostatic involvement in this condition. Because of the limited number of publications available, further studies are warranted to better characterize IgG4-related disease in male reproductive organs. PMID:25469023

  4. 99th Dahlem conference on infection, inflammation and chronic inflammatory disorders: triggering of autoimmune diseases by infections.

    PubMed

    Getts, M T; Miller, S D

    2010-04-01

    Human autoimmune diseases, such as multiple sclerosis, type 1 diabetes, rheumatoid arthritis and systemic lupus erythematosus (SLE), are linked genetically to distinct major histocompatibility complex (MHC) class II molecules and other immune modulators. However, genetic predisposition is only one risk factor for the development of these diseases, and low concordance rates in monozygotic twins as well as geographical distribution of disease risk suggest a critical role for environmental factors in the triggering of these autoimmune diseases. Among potential environmental factors, infections have been implicated in the onset and/or promotion of autoimmunity. This review will discuss human autoimmune diseases with a potential viral cause, and outline potential mechanisms by which pathogens can trigger autoimmune disease as discerned from various animal models of infection-induced autoimmune disease. PMID:20415846

  5. Autoimmunity, Seizures, and Status Epilepticus

    PubMed Central

    Davis, Rebecca; Dalmau, Josep

    2013-01-01

    Summary The recent discovery of a category of autoimmune encephalitis associated with antibodies against neuronal cell-surface and synaptic proteins has renewed interest for autoimmune causes of epilepsy. The identification of autoimmune encephalitis has changed paradigms in the diagnosis and management of several novel and treatable syndromes that occur with seizures and status epilepticus previously attributed to viral or idiopathic etiologies. This review focuses on the novel group of autoimmune encephalitis and also discusses some classical paraneoplastic syndromes that constitute another group of autoimmune disorders that may result in seizures. PMID:24001072

  6. Hashimoto thyroiditis, distal renal tubular acidosis, pernicious anaemia and encephalopathy: a rare combination of auto-immune disorders in a 12-year-old girl.

    PubMed

    Suzuki, N; Mitamura, R; Ohmi, H; Itoh, Y; Yano, K; Okuno, A; Tateno, M; Itoh, T

    1994-02-01

    A case of a 12-year-old girl with a multiple auto-immune disorder is reported. She showed Hashimoto thyroiditis which subsequently developed to hashitoxicosis and distal renal tubular acidosis at 5 years of age, pernicious anaemia at the age of 9 and severe encephalopathy at the age of 12. Laboratory studies revealed very high titres of anti-microsomal and anti-thyroglobulin antibodies and positive gastric parietal cell antibody. As to the encephalopathy, positive oligoclonal IgG bands and high values of IgG index and IgG synthesis ratio in CSF were observed with aggravation of her neurological symptoms. High-dose steroid therapy was effective toward the encephalopathy. Paediatricians should pay careful attention to patients with Hashimoto thyroiditis for association with other autoimmune disorders. PMID:8157029

  7. The Autoimmune Ecology

    PubMed Central

    Anaya, Juan-Manuel; Ramirez-Santana, Carolina; Alzate, Maria A.; Molano-Gonzalez, Nicolas; Rojas-Villarraga, Adriana

    2016-01-01

    Autoimmune diseases (ADs) represent a heterogeneous group of disorders that affect specific target organs or multiple organ systems. These conditions share common immunopathogenic mechanisms (i.e., the autoimmune tautology), which explain the clinical similarities they have among them as well as their familial clustering (i.e., coaggregation). As part of the autoimmune tautology, the influence of environmental exposure on the risk of developing ADs is paramount (i.e., the autoimmune ecology). In fact, environment, more than genetics, shapes immune system. Autoimmune ecology is akin to exposome, that is all the exposures – internal and external – across the lifespan, interacting with hereditary factors (both genetics and epigenetics) to favor or protect against autoimmunity and its outcomes. Herein, we provide an overview of the autoimmune ecology, focusing on the immune response to environmental agents in general, and microbiota, cigarette smoking, alcohol and coffee consumption, socioeconomic status (SES), gender and sex hormones, vitamin D, organic solvents, and vaccines in particular. Inclusion of the autoimmune ecology in disease etiology and health will improve the way personalized medicine is currently conceived and applied. PMID:27199979

  8. Complete Genome Sequence of emm4 Streptococcus pyogenes MEW427, a Throat Isolate from a Child Meeting Clinical Criteria for Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus (PANDAS)

    PubMed Central

    Jacob, Kristin M.; Spilker, Theodore; LiPuma, John J.; Dawid, Suzanne R.

    2016-01-01

    We report the complete genome assembly of the Streptococcus pyogenes type emm4 strain MEW427 (also referred to as strain UM001 in the Pediatric Acute-Onset Neuropsychiatric Syndrome [PANS] Research Consortium), a throat isolate from a child with acute-onset neuropsychiatric symptoms meeting clinical criteria for PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcus). The genome length is 1,814,455 bp with 38.51% G+C%. PMID:26988046

  9. Complete Genome Sequence of emm4 Streptococcus pyogenes MEW427, a Throat Isolate from a Child Meeting Clinical Criteria for Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus (PANDAS).

    PubMed

    Jacob, Kristin M; Spilker, Theodore; LiPuma, John J; Dawid, Suzanne R; Watson, Michael E

    2016-01-01

    We report the complete genome assembly of the Streptococcus pyogenes type emm4 strain MEW427 (also referred to as strain UM001 in the Pediatric Acute-Onset Neuropsychiatric Syndrome [PANS] Research Consortium), a throat isolate from a child with acute-onset neuropsychiatric symptoms meeting clinical criteria for PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcus). The genome length is 1,814,455 bp with 38.51% G+C%. PMID:26988046

  10. Tonsillectomies and Adenoidectomies Do Not Prevent the Onset of Pediatric Autoimmune Neuropsychiatric Disorder Associated with Group A Streptococcus

    PubMed Central

    Murphy, Tanya K.; Lewin, Adam B.; Parker-Athill, E. Carla; Storch, Eric A.; Mutch, P. Jane

    2013-01-01

    Background In children presenting with obsessive compulsive disorder (OCD) and/or tics, especially those with a temporal association with streptococcal pharyngitis (e.g., PANDAS; Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus), there is speculation about whether tonsillectomy/adenoidectomy might improve the child’s neuropsychiatric course. Our objective was to examine whether removal of tonsils and/or adenoids impacted streptococcal antibody titers, the timing of onset of OCD and/or tics, and the clinical severity of these symptoms. Methods Study participants (n=112; average age=9.2 ± 2.4; 44 female) were recruited as part of a prospective investigation of neuropsychiatric phenomena with temporal association to streptococcal pharyngitis and examined by family history, diagnostic interview, physical examination, medical record review, psychological testing, and streptococcal antibodies and divided into surgical or non-surgery groups. The surgical group consisted of children having previously had a tonsillectomy and/or adenoidectomy (n=32). The remaining children were categorized as non-surgery (N=76). Measures of OCD and tic severity, streptococcal antibody titers, and PANDAS classification were compared between both groups. Results There were no significant differences as determined by streptococcal antibody titers, PANDAS classification, and OCD or tic severity between the surgical and non-surgery groups. Most participants had surgery before onset of neuropsychiatric symptoms and surgery did not affect symptomology. Conclusions Streptococcal antibodies and neuropsychiatric symptom severity did not differ on the basis of surgical status. From these data we cannot support that tonsillectomy and adenoidectomy are likely to impact positively the course of OCD/tics or streptococcal antibody concentrations. PMID:23518825

  11. 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 process is not clear. In this manuscript, we review novel findings about disease processes and mechanisms that lead to autoimmunity in the liver and their possible involvement in the immune response vs. the graft after LT. PMID:24084655

  12. The pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS) etiology for tics and obsessive-compulsive symptoms: hypothesis or entity? Practical considerations for the clinician.

    PubMed

    Kurlan, Roger; Kaplan, Edward L

    2004-04-01

    Clinicians have been faced with much publicity and contradictory scientific evidence regarding a recently described condition termed pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS). It has been proposed that children with PANDAS experience tics, obsessive-compulsive behavior, and perhaps other neuropsychiatric symptoms as an autoimmune response to streptococcal infection. We review current scientific information and conclude that PANDAS remains a yet-unproven hypothesis. Until more definitive scientific proof is forthcoming, there seems to be insufficient evidence to support 1) routine microbiologic or serologic testing for group A streptococcus in children who present with neuropsychiatric symptoms or 2) the clinical use of antibiotic or immune-modifying therapies in such patients. The optimum diagnostic and therapeutic approach awaits the results of additional research studies. PMID:15060240

  13. Inflammasomes and autoimmunity

    PubMed Central

    Shaw, Patrick J.; McDermott, Michael F.; Kanneganti, Thirumala-Devi

    2010-01-01

    The NOD-like receptor (NLR) family members are cytosolic sensors of microbial components and danger signals. A subset of NLRs control inflammasome assembly that results in caspase-1 activation and, in turn, IL-1β and IL-18 production. Excessive inflammasome activation can cause autoinflammatory disorders, including the hereditary periodic fevers. Autoinflammatory and autoimmune diseases form a disease spectrum of aberrant, immune-mediated inflammation against self, through innate and adaptive immunity. However, the role of inflammasomes in autoimmune disease is less clear than in autoinflammation, despite the numerous effects IL-1β and IL-18 can have on shaping adaptive immunity. We summarize the role of inflammasomes in autoimmune disorders, highlight the need for a better understanding of inflammasomes in these conditions and offer suggestions for future research directions. PMID:21163704

  14. Latent autoimmune diabetes in adults (LADA) and autoimmune thyroiditis.

    PubMed

    Matejkova-Behanova, M

    2001-09-01

    Latent autoimmune diabetes in adults (LADA) is characterized by clinical presentation as type 2 diabetes after 25 years of age, initial control achieved with diet or oral hypoglycaemic agents during at least 6 months, presence of autoantibodies (first of all GADA) and some immunogenetic features of diabetes mellitus type 1. In patients with an autoimmune endocrine disease, which could be also autoimmune diabetes, there is a high risk of development of another autoimmune endocrine disorder. The coexistence of two or more autoimmune endocrine diseases is pathognomonic for autoimmune polyglandular syndrome. Autoimmune thyroiditis and type 1 diabetes mellitus are the most common combination of autoimmune endocrine diseases reported. Most studies reported the prevalence of autoimmune thyroiditis in "typical" type 1 adult diabetic subjects about 20 - 40%. Little is known about the prevalence of autoimmune thyroiditis in subjects with LADA. Only a few studies confirmed a high prevalence of thyroid autoantibodies in type 2 diabetic subjects with GADA compared to type 2 diabetic subjects without GADA and compared to non-diabetic population too. PMID:11674844

  15. [A rare case of juvenile diabetes mellitus associated with APECED (autoimmune poly-endocrinopathy, candidiasis and ectodermal dystrophy) with strong X-linked familial inheritance].

    PubMed

    Iannello, S; Campanile, E; Cipolli, D; Gallina, M; Merola, A; Puglisi, S; Tabita, V; Belfiore, F

    1997-06-01

    The polyglandular autoimmune syndromes (PGA) are well known and are distinguished into type I, type II and type III. PGAI, also called APECED (autoimmune polyendocrinopathy, candidiasis and ectodermal dystrophy), is an autosomal recessive disorder, appearing in childhood and typically characterized by hypoparathyroidism (unusual in PGAII and PGAIII) and adrenal insufficiency. In APECED, autoimmune destruction of the pancreatic beta cells with development of insulin-dependent type 1 diabetes is possible, but less frequent than in the other PGAs, especially PGAII. The pathogenesis of this unique autoimmune disease is unknown. No HLA association seems to exist and genetic studies have assigned the autosomal APECED locus to chromosome 21. The case of a 28-years-old female suggesting the diagnosis of APECED, is presented, characterized by psycho-somatic abnormal development, teeth alterations, post-puberal gonadal failure with dystrophic hypoplasia of external genitalia, previous vaginal candidiasis, a slowly developing juvenile brittle diabetes. Intestinal malabsorption induced by Giardia lamblia occurred (probably resulting, like candidiasis, from immunological anergy). A strong familiarity linked to female sex was noticed (the mother, a sister, the little nice and some maternal female cousins being affected) while the father and a brother were healthy. Diabetes seems to be characterized by early onset and severe complications. In this patient no organo-specific antibodies were detected and the only immunologic disorder was a small decrease of CD3 and CD4/CD8 ratio, both CD4 and CD8 being at the lower normal range. This patient (and her female maternal relatives) needs a long-term follow-up in order to evaluate the function of endocrine glands and to initiate early treatment for hormonal deficits, as well as to detect the non-endocrine components of disease. PMID:9304048

  16. Heat-solubilized curry spice curcumin inhibits antibody-antigen interaction in in vitro studies: a possible therapy to alleviate autoimmune disorders.

    PubMed

    Kurien, Biji T; D'Souza, Anil; Scofield, R Hal

    2010-08-01

    Chronic and complex autoimmune diseases, currently treated palliatively with immunosuppressives, require multi-targeted therapy for greater effectiveness. The naturally occurring polyphenol curcumin has emerged as a powerful "nutraceutical" that interacts with multiple targets to regress diseases safely and inexpensively. Up to 8 g/day of curcumin for 18 months was non-toxic to humans. However, curcumin's utility is limited by its aqueous insolubility. We have demonstrated a heat-mediated 12-fold increase in curcumin's aqueous solubility. Here, we show by SDS-PAGE and surface plasmon resonance that heat-solubilized curcumin binds to proteins. Based on this binding we hypothesized that heat-solubilized curcumin or turmeric would prevent autoantibody targeting of cognate autoantigens. Heat-solubilized curcumin/turmeric significantly decreased binding of autoantibodies from Sjögren's syndrome (up to 43/70%, respectively) and systemic lupus erythematosus (up to 52/70%, respectively) patients as well as an animal model of Sjögren's syndrome (up to 50/60%, respectively) to their cognate antigens. However, inhibition was not specific to autoimmunity. Heat-solubilized curcumin/turmeric also inhibited binding of commercial polyclonal anti-spectrin to spectrin (50/56%, respectively). Thus, we suggest that the multifaceted heat-solubilized curcumin can ameliorate autoimmune disorders. In addition, the non-toxic curcumin could serve as a new protein stain in SDS-PAGE even though it is less sensitive than the Coomassie system which involves toxic chemicals. PMID:20146265

  17. The Role of AhR in Autoimmune Regulation and Its Potential as a Therapeutic Target against CD4 T Cell Mediated Inflammatory Disorder

    PubMed Central

    Zhu, Conghui; Xie, Qunhui; Zhao, Bin

    2014-01-01

    AhR has recently emerged as a critical physiological regulator of immune responses affecting both innate and adaptive systems. Since the AhR signaling pathway represents an important link between environmental stimulators and immune-mediated inflammatory disorder, it has become the object of great interest among researchers recently. The current review discusses new insights into the mechanisms of action of a select group of inflammatory autoimmune diseases and the ligand-activated AhR signaling pathway. Representative ligands of AhR, both exogenous and endogenous, are also reviewed relative to their potential use as tools for understanding the role of AhR and as potential therapeutics for the treatment of various inflammatory autoimmune diseases, with a focus on CD4 helper T cells, which play important roles both in self-immune tolerance and in inflammatory autoimmune diseases. Evidence indicating the potential use of these ligands in regulating inflammation in various diseases is highlighted, and potential mechanisms of action causing immune system effects mediated by AhR signaling are also discussed. The current review will contribute to a better understanding of the role of AhR and its signaling pathway in CD4 helper T cell mediated inflammatory disorder. Considering the established importance of AhR in immune regulation and its potential as a therapeutic target, we also think that both further investigation into the molecular mechanisms of immune regulation that are mediated by the ligand-specific AhR signaling pathway, and integrated research and development of new therapeutic drug candidates targeting the AhR signaling pathway should be pursued urgently. PMID:24905409

  18. Hepatitis C virus syndrome: A constellation of organ- and non-organ specific autoimmune disorders, B-cell non-Hodgkin’s lymphoma, and cancer

    PubMed Central

    Ferri, Clodoveo; Sebastiani, Marco; Giuggioli, Dilia; Colaci, Michele; Fallahi, Poupak; Piluso, Alessia; Antonelli, Alessandro; Zignego, Anna Linda

    2015-01-01

    The clinical course of chronic hepatitis C virus (HCV) infection is characterized by possible development of both liver and extrahepatic disorders. The tropism of HCV for the lymphoid tissue is responsible for several immune-mediated disorders; a poly-oligoclonal B-lymphocyte expansion, commonly observed in a high proportion of patients with HCV infection, are responsible for the production of different autoantibodies and immune-complexes, such as mixed cryoglobulins. These serological alterations may characterize a variety of autoimmune or neoplastic diseases. Cryoglobulinemic vasculitis due to small-vessel deposition of circulating mixed cryoglobulins is the prototype of HCV-driven immune-mediated and lymphoproliferative disorders; interestingly, in some cases the disease may evolve to frank malignant lymphoma. In addition, HCV shows an oncogenic potential as suggested by several clinico-epidemiological and laboratory studies; in addition to hepatocellular carcinoma that represents the most frequent HCV-related malignancy, a causative role of HCV has been largely demonstrated in a significant percentage of patients with isolated B-cells non-Hodgkin’s lymphomas. The same virus may be also involved in the pathogenesis of papillary thyroid cancer, a rare neoplastic condition that may complicate HCV-related thyroid involvement. Patients with HCV infection are frequently asymptomatic or may develop only hepatic alteration, while a limited but clinically relevant number can develop one or more autoimmune and/or neoplastic disorders. Given the large variability of their prevalence among patients’ populations from different countries, it is possible to hypothesize a potential role of other co-factors, i.e., genetic and/or environmental, in the pathogenesis of HCV-related extra-hepatic diseases. PMID:25848462

  19. Hepatitis C virus syndrome: A constellation of organ- and non-organ specific autoimmune disorders, B-cell non-Hodgkin's lymphoma, and cancer.

    PubMed

    Ferri, Clodoveo; Sebastiani, Marco; Giuggioli, Dilia; Colaci, Michele; Fallahi, Poupak; Piluso, Alessia; Antonelli, Alessandro; Zignego, Anna Linda

    2015-03-27

    The clinical course of chronic hepatitis C virus (HCV) infection is characterized by possible development of both liver and extrahepatic disorders. The tropism of HCV for the lymphoid tissue is responsible for several immune-mediated disorders; a poly-oligoclonal B-lymphocyte expansion, commonly observed in a high proportion of patients with HCV infection, are responsible for the production of different autoantibodies and immune-complexes, such as mixed cryoglobulins. These serological alterations may characterize a variety of autoimmune or neoplastic diseases. Cryoglobulinemic vasculitis due to small-vessel deposition of circulating mixed cryoglobulins is the prototype of HCV-driven immune-mediated and lymphoproliferative disorders; interestingly, in some cases the disease may evolve to frank malignant lymphoma. In addition, HCV shows an oncogenic potential as suggested by several clinico-epidemiological and laboratory studies; in addition to hepatocellular carcinoma that represents the most frequent HCV-related malignancy, a causative role of HCV has been largely demonstrated in a significant percentage of patients with isolated B-cells non-Hodgkin's lymphomas. The same virus may be also involved in the pathogenesis of papillary thyroid cancer, a rare neoplastic condition that may complicate HCV-related thyroid involvement. Patients with HCV infection are frequently asymptomatic or may develop only hepatic alteration, while a limited but clinically relevant number can develop one or more autoimmune and/or neoplastic disorders. Given the large variability of their prevalence among patients' populations from different countries, it is possible to hypothesize a potential role of other co-factors, i.e., genetic and/or environmental, in the pathogenesis of HCV-related extra-hepatic diseases. PMID:25848462

  20. Cellular Targeting in Autoimmunity

    PubMed Central

    Rogers, Jennifer L.; Serafin, Donald S.; Timoshchenko, Roman G.; Tarrant, Teresa K.

    2012-01-01

    Many biologic agents that were first approved for the treatment of malignancies are now being actively investigated and used in a variety of autoimmune diseases such as rheumatoid arthritis (RA), antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, systemic lupus erythematosus (SLE), and Sjogren’s syndrome. The relatively recent advance of selective immune targeting has significantly changed the management of autoimmune disorders, and in part, can be attributed to the progress made in understanding effector cell function and their signaling pathways. In this review, we will discuss the recent FDA approved biologic therapies that directly target immune cells as well as the most promising investigational drugs affecting immune cell function and signaling for the treatment of autoimmune disease. PMID:23054625

  1. 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

  2. Hepatitis C virus infection and thyroid autoimmune disorders: A model of interactions between the host and the environment

    PubMed Central

    Pastore, Francesca; Martocchia, Antonio; Stefanelli, Manuela; Prunas, Pietro; Giordano, Stefania; Toussan, Lavinia; Devito, Antonio; Falaschi, Paolo

    2016-01-01

    The hepatitis C virus (HCV) infection is an important public health problem and it is associated with hepatic and extrahepatic manifestations. Autoimmune thyroid diseases are common in HCV infected patients and the standard interferon-based treatment is associated with an increase of the immune-mediated thyroid damage. Recent evidence in the literature analyzed critical points of the mechanisms of thyroid damage, focusing on the balance between the two sides of the interaction: The environment (virus infection with potential cross-reaction) and the host (susceptibility genes with consistent immune response). The spectrum of antiviral treatment for chronic HCV infection is rapidly expanding for the development of dual o triple therapy. The availability of interferon-free combined treatment with direct antiviral agents for HCV is very promising, in order to ameliorate the patient compliance and to reduce the development of thyroid autoimmunity. PMID:26807204

  3. Autoimmune encephalitis.

    PubMed

    Newman, M P; Blum, S; Wong, R C W; Scott, J G; Prain, K; Wilson, R J; Gillis, D

    2016-02-01

    Over the past decade, the clinical spectrum of autoimmune encephalitis has expanded with the emergence of several new clinicopathological entities. In particular, autoimmune encephalitis has recently been described in association with antibodies to surface receptors and ion channels on neurological tissues. Greater clinician awareness has resulted in autoimmune encephalitis being increasingly recognised in patients with unexplained neurological and psychiatric symptoms and signs. The clinical spectrum of presentations, as well as our understanding of disease mechanisms and treatment regimens, is rapidly developing. An understanding of these conditions is important to all subspecialties of Internal Medicine, including neurology and clinical immunology, psychiatry, intensive care and rehabilitation medicine. This review provides a contemporary overview of the aetiology, investigations and treatment of the most recently described autoimmune encephalitides. PMID:26899887

  4. Autoimmune hepatitis

    MedlinePlus

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

  5. [Autoimmune encephalitis].

    PubMed

    Davydovskaya, M V; Boyko, A N; Beliaeva, I A; Martynov, M Yu; Gusev, E I

    2015-01-01

    The authors consider the issues related to pathogenesis, clinical features, diagnosis and treatment of autoimmune encephalitis. It has been demonstrated that the development of autoimmune encephalitis can be associated with the oncologic process or be of idiopathic character. The pathogenesis of autoimmune encephalitis is caused by the production of antibodies that directly or indirectly (via T-cell mechanism) damage exo-and/or endocellular structures of the nerve cells. The presence of antobodies to endocellular structures of neurons in the cerebrospinal fluid of patients with autoimmune encephalitis in the vast majority of cases (> 95%) indicates the concomitant oncologic process, the presence of antibodies to membranes or neuronal synapses can be not associated with the oncologic process. Along with complex examination, including neuroimaging, EEG, cerebrospinal fluid and antibodies, the diagnostic algorithm in autoimmune encephalitis should include the search for the nidus of cancer. The treatment algorithm in autoimmune encephalitis included the combined immunosupressive therapy, plasmapheresis, immunoglobulines, cytostatics as well as treatment of the oncologic process. PMID:26322363

  6. Celiac disease associated with autoimmune hepatitis and autoimmune hyperthyroidism.

    PubMed

    Milić, Sandra; Mikolašević, Ivana; Mijandrušić-Sinčić, Brankica; Bulić, Zlatko; Giljača, Vanja; Štimac, Davor

    2013-08-01

    Although celiac disease (CD) may occur in patients with other immune-mediated disorders, its coexistence with multiple autoimmune diseases is not frequently described. We report the case of a 23-year-old woman referred to our centre because of jaundice and diarrhoea, who was diagnosed with CD in childhood. She complied with a gluten-free diet until puberty. Laboratory tests and liver biopsy were performed to establish the diagnosis of autoimmune hepatitis. Her thyroid- specific peroxides levels and thyroid gland function tests were altered as well, indicating the presence of an autoimmune disorder of the thyroid gland. Immunosuppressive treatment led to normalization of transaminases levels and bilirubin. In conclusion, other autoimmune diseases should be ruled out in patients with CD. PMID:23892869

  7. Shaping the spectrum - From autoinflammation to autoimmunity.

    PubMed

    Hedrich, Christian M

    2016-04-01

    Historically, autoimmune-inflammatory disorders were subdivided into autoinflammatory vs. autoimmune diseases. About a decade ago, an immunological continuum was proposed, placing "classical" autoinflammatory disorders, characterized by systemic inflammation in the absence of high-titer autoantibodies or autoreactive T lymphocytes, at the one end, and autoimmune disorders at the other end. We provide an overview of recent developments and observations, filling in some of the gaps and showing strong interconnections between innate and adaptive immune mechanisms, indicating that disorders from both ends of the immunological spectrum indeed share key pathomechanisms. We focus on three exemplary disorders: i) systemic juvenile idiopathic arthritis representing "classical" autoinflammatory disorders; ii) psoriasis, a mixed pattern disease; and iii) systemic lupus erythematosus, a prototypical autoimmune disease. We summarize scientific observations suggesting that, depending on disease stages and/or duration, individualized treatment targeting innate or adaptive immune mechanisms in disorders from either end of the immunological spectrum may control disease activity. PMID:26948930

  8. Serum levels of adhesion molecules ICAM-1 and VCAM-1 and tissue inhibitor of metalloproteinases, TIMP-1, are elevated in patients with autoimmune thyroid disorders: relevance to vascular inflammation.

    PubMed

    Jublanc, C; Beaudeux, J L; Aubart, F; Raphael, M; Chadarevian, R; Chapman, M J; Bonnefont-Rousselot, D; Bruckert, E

    2011-10-01

    Serum levels of ICAM-1 (Inter Cellular Adhesion Molecule-1), VCAM-1 (Vascular cell Adhesion Molecule-1-I), TIMP-1 (tissue inhibitor of metalloproteinases 1) and MMP-9 (Metalloproteinase 9) are well established markers of inflammation. The physiopathological link between inflammation, atherosclerosis and autoimmunity is well demonstrated. However, serum levels of these biomarkers in patients with autoimmune-mediated dysthyroidism, including their evolution after improvement of the thyroid disorder have not been assessed. So, we evaluated the circulating levels of these markers in autoimmune and in non-autoimmune-mediated dysthyroid patients, and their evolution after treatment of thyroid disease. We conducted a prospective study to evaluate these markers before and after treatment in hyperthyroid patients (n = 33; 28 patients with autoimmune disease), hypothyroid patients (n = 38; 33 patients with autoimmune disease) and euthyroid subjects (n = 33). At baseline, serum levels of ICAM-1, VCAM-1 and TIMP-1 were significantly elevated in patients with hyperthyroidism as compared to euthyroid and hypothyroid patients (respectively p = 0.0005 and p < 0.0001). In multivariate analysis, the differences remained significant for VCAM-1 and TIMP-1. Median levels of ICAM-1, VCAM-1 and TIMP-1 were significantly higher in patients with autoimmune-mediated dysthyroidism compared to euthyroid patients (respectively p < 0.0001 and p = 0.002). In hyperthyroid patients, ICAM-1, VCAM-1 and TIMP-1 concentrations fell significantly after they had become euthyroid (respectively p = 0.0006; p < 0.0001 and p = 0.0009), although VCAM-1 values remained higher than those observed in the control group (p = 0.005). We found that autoimmune-mediated dysthyroidism were associated with increased peripheral blood concentrations of VCAM-1, ICAM-1 and TIMP-1. Whether these biological abnormalities translate into increase intima remodelling and atherosclerosis remains to be studied. PMID:20685094

  9. 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.

  10. Endocrine autoimmunity in Turner syndrome

    PubMed Central

    2013-01-01

    Background Turner syndrome is caused by numeric and structural abnormalities of the X chromosome. An increased frequency of autoimmunity as well as an elevated incidence of autoantibodies was observed in Turner patients. The aim of this study was to conduct a retrospective analysis of the incidence of autoimmunity in 66 Italian patients affected by Turner syndrome. Methods Sixty-six unselected and consecutive Italian Turner patients were recruited. The association between age, karyotype and the presence of clinical/pre-clinical autoimmune disorders and of autoantibodies was examined. Results Out of the 66 Turner patients, 26 had thyroid autoimmune disorders (39.4%), 14 patients had Hashimoto’s thyroiditis with clinical or subclinical hypothyroidism (21.2%) and 12 patients had circulating anti-thyroid antibodies, echographic pattern of diffuse hypoechogenicity and normal thyroid hormone levels (18.2%). None were affected by Graves’ disease. We analyzed the overall incidence of thyroid autoimmunity within the 3 different age groups 0–9.9, 10–19.9 and 20–29.9 years. No statistically significant difference was observed in the incidence of thyroid autoimmunity within the age-groups (χ2-test p > 0.05). Out of the 66 patients, 31 patients had the 45,X karyotype; within this first group 14 out of 31 patients were affected by autoimmune thyroid disease. A second group of 29 patients included 19 patients with mosaicism, 5 patients with deletions and 5 patients with ring chromosome; out of these 29 patients 7 were affected by autoimmune thyroid disease. A third group included 6 patients with X isochromosome; 5 out of 6 were affected by autoimmune thyroid disease. A statistically significant difference in the frequency of thyroid autoimmunity within the different karyotype groups was observed (χ2-test p = 0.0173). When comparing the X isochromosome group with the pooled group of other karyotypes, of note, the frequency of thyroid autoimmunity was statistically higher in the X isochromosome group (Fisher exact test p = 0.0315). Conclusions Our data confirm a high frequency of thyroid autoimmunity in Italian Turner patients. Patients with X isochromosome are more prone to develop thyroid autoimmunity. Further, an early assay of autoantibodies and monitoring thyroid hormones is fundamental for detecting hypothyroidism earlier and start adequate replacement therapy. PMID:24355069

  11. Associated autoimmune diseases in children and adolescents with type 1 diabetes mellitus (T1DM).

    PubMed

    Kakleas, Kostas; Soldatou, Alexandra; Karachaliou, Feneli; Karavanaki, Kyriaki

    2015-09-01

    Type 1 diabetes (T1DM) is an autoimmune disease with aberrant immune responses to specific ?-cell autoantigens, resulting in insulin deficiency. Children and adolescents with T1DM may also develop organ-specific multiple autoimmunity in the context of APS (autoimmune polyendocrine syndrome) type 1, 2 or 3. The most frequently encountered associated autoimmune disorders in T1DM are autoimmune thyroid, followed by celiac, autoimmune gastric disease and other rare autoimmune conditions. There are limited previous studies on the prevalence of associated autoimmunity, especially multiple, in children with T1DM. The present review reports on the classification of autoimmune diabetes, and on the prevalence, pathogenesis, predictive factors and clinical presentation of pancreatic autoimmunity and of all associated autoimmune disorders in children with T1DM. The impact of associated autoimmunity on diabetes control and general health is also discussed, along with suggestions regarding screening strategies and follow-up for early detection and management of the autoimmunity. PMID:26001590

  12. Type 1 diabetes associated autoimmunity.

    PubMed

    Kahaly, George J; Hansen, Martin P

    2016-07-01

    Diabetes mellitus is increasing in prevalence worldwide. The economic costs are considerable given the cardiovascular complications and co-morbidities that it may entail. Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by the loss of insulin-producing pancreatic β-cells. The pathogenesis of T1D is complex and multifactorial and involves a genetic susceptibility that predisposes to abnormal immune responses in the presence of ill-defined environmental insults to the pancreatic islets. Genetic background may affect the risk for autoimmune disease and patients with T1D exhibit an increased risk of other autoimmune disorders such as autoimmune thyroid disease, Addison's disease, autoimmune gastritis, coeliac disease and vitiligo. Approximately 20%-25% of patients with T1D have thyroid antibodies, and up to 50% of such patients progress to clinical autoimmune thyroid disease. Approximately 0.5% of diabetic patients have concomitant Addison's disease and 4% have coeliac disease. The prevalence of autoimmune gastritis and pernicious anemia is 5% to 10% and 2.6% to 4%, respectively. Early detection of antibodies and latent organ-specific dysfunction is advocated to alert physicians to take appropriate action in order to prevent full-blown disease. Patients and family members should be educated to be able to recognize signs and symptoms of underlying disease. PMID:26903475

  13. Predisposing factors to autoimmune disease.

    PubMed

    Lahita, R G

    1997-01-01

    There are many factors that predispose women to autoimmune disease. The protective effect of testosterone during development prevents most males from getting autoimmune disease, although in some instances this protective effect can be bypassed by either genetic anomalies or endocrinopathies. Autoimmunity is defined as the development of symptoms and antibodies referable to one or another autoimmune disease. Some of the factors that predispose young women to autoimmunity also directly involve the endocrine system and indirectly, disorders of gonadal development. Altered sex steroid metabolism is one endogenous factor that predisposes a young woman to autoimmunity. The metabolism of estrone which can be directed to either the 16-or the 2-metabolites by diet, thyroid function, or certain drugs has a major influence on immune function and possibly gonadal pathology. Attempts to shift the metabolism of estrone to the 2-compounds with a variety of agents actually decreases the predisposition to autoimmunity. Other pre-disposing factors are all related to hormone metabolism and include hyperprolactinemia, the use of exogenous estrogenic agents, or compounds that change basic steroid metabolism. Most of these conditions are reversible. PMID:9160222

  14. Levels of regulatory T cells CD69(+)NKG2D(+)IL-10(+) are increased in patients with autoimmune thyroid disorders.

    PubMed

    Rodríguez-Muñoz, Ana; Vitales-Noyola, Marlen; Ramos-Levi, Ana; Serrano-Somavilla, Ana; González-Amaro, Roberto; Marazuela, Mónica

    2016-03-01

    Regulatory T (Treg) cells play an important role in the pathogenesis of autoimmune thyroid disorders (AITD). New subsets of CD4(+)CD69(+) and CD4(+)NKG2D(+) T lymphocytes that behave as regulatory cells have been recently reported. The role of these immunoregulatory lymphocytes has not been previously explored in AITD. We analyzed by multi-parametric flow cytometry different Treg cell subsets in peripheral blood from 32 patients with AITD and 19 controls, and in thyroid tissue from seven patients. The suppressive activity was measured by an assay of inhibition of lymphocyte activation. We found a significant increased percentage of CD4(+)CD69(+)IL-10(+), CD4(+)CD69(+)NKG2D(+), and CD4(+)CD69(+)IL-10(+)NKG2D(+) cells, in peripheral blood from GD patients compared to controls. The increase in CD4(+)CD69(+)IL-10(+) and CD4(+)CD69(+)IL-10(+)NKG2D(+) T cells was especially remarkable in patients with active Graves' ophthalmopathy (GO), and a significant positive correlation between GO activity and CD4(+)CD69(+)IL-10(+) or CD4(+)CD69(+)IL-10(+)NKG2D(+) cells was also found. In addition, these cells were increased in patients with a more severe and/or prolonged disease. Thyroid from AITD patients showed an increased proportion of CD69(+) regulatory T cells subpopulations compared to autologous peripheral blood. The presence of CD69(+), NKG2D(+), and IL-10(+) cells was confirmed by immunofluorescence microscopy. In vitro functional assays showed that CD69(+) Treg cells exerted an important suppressive effect on the activation of T effector cells in controls, but not in AITD patients. Our findings suggest that the levels of CD69(+) regulatory lymphocytes are increased in AITD patients, but they are apparently unable to down-modulate the autoimmune response and tissue damage. PMID:26100786

  15. LADA type diabetes, celiac diasease, cerebellar ataxia and stiff person syndrome. A rare association of autoimmune disorders.

    PubMed

    Soós, Zsuzsanna; Salamon, Mónika; Erdei, Katalin; Kaszás, Nóra; Folyovich, András; Szücs, Anna; Barcs, Gábor; Arányi, Zsuzsanna; Skaliczkis, József; Vadasdi, Károly; Winkler, Gábor

    2014-05-30

    Celiac disease--in its typical form--is a chronic immune-mediated enteropathy with typical clinical symptoms that develops against gliadin content of cereal grains, and is often associated with other autoimmune diseases. In cases of atypical manifestation classic symptoms may be absent or mild, and extra-intestinal symptoms or associated syndromes dominate clinical picture. The authors present a longitudinal follow-up of such a case. A 63-years old woman was diagnosed with epilepsy at the age of 19, and with progressive limb ataxia at the age of 36, which was initially thought to be caused by cerebellar atrophy, later probably by stiff person syndrome. At the age 59, her diabetes mellitus manifested with type 2 diabetic phenotype, but based on GAD positivity later was reclassified as type 1 diabetes. Only the last check-up discovered the celiac disease, retrospectively explaining the entire disease course and neurological symptoms. By presenting this case, the authors would like to draw attention to the fact that one should think of the possibility of celiac disease when cerebellar ataxia, progressive neurological symptoms and diabetes are present at the same time. An early diagnosis may help to delay the progression of disease and help better treatment. PMID:25087381

  16. Autoimmune dementia and encephalopathy.

    PubMed

    Flanagan, Eoin P; Drubach, Daniel A; Boeve, Bradley F

    2016-01-01

    Autoimmune dementia and encephalopathies (ADE) are complex disorders that can cause immune-mediated cognitive deficits and have confusing nomenclature. Presentation varies from acute limbic encephalitis to subacute or chronic disorders of cognition mimicking neurodegenerative dementia. It may occur as a paraneoplastic phenomenon or an idiopathic autoimmune phenomenon. The presence of a personal/family history of autoimmunity, inflammatory spinal fluid, serologic evidence of autoimmunity (neural or nonorgan-specific), or mesial temporal magnetic resonance imaging abnormalities are clues to diagnosis. Bedside cognitive assessment and/or detailed neuropsychologic testing are useful. Neural-specific autoantibodies, mostly discovered in the past two decades, may bind antigens on the cell surface (e.g., N-methyl-d-aspartate receptor autoantibodies) and are likely to be pathogenic, with treatment aimed at antibody-depleting agents often with success, while antibodies binding intracellular antigens (e.g., antineuronal nuclear autoantibody type 1 (ANNA1 or anti-Hu)) are a marker of a T-cell-mediated process and treated with T-cell-depleting immunotherapies, with variable responses. Detection and treatment of cancer (when present) are essential. High-dose corticosteroids are the initial treatment in most patients and may serve as a diagnostic test when the diagnosis is uncertain. Repeat cognitive testing after immunotherapy helps document objective improvements. Maintenance immunotherapy is recommended in those at risk for relapse. Prognosis is variable, but paraneoplastic ADE with antibodies to intracellular antigens have a worse prognosis. The field is still developing and future studies should provide guidelines for diagnosis and treatments. PMID:27112681

  17. Autoimmune thyroid disease: an expanding spectrum.

    PubMed

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

    1987-08-01

    Autoimmune thyroid disease classically has included Hashimoto's thyroiditis and Graves' disease. Hashimoto's thyroiditis probably also includes focal thyroiditis, fibrous thyroiditis, primary myxedema, and Hashitoxicosis as variants. Graves' disease is associated with ophthalmopathy and dermopathy, and recent evidence suggests that these manifestations are autoimmune phenomena as well. Other associated autoimmune disorders include idiopathic thrombocytopenic purpura and antigen-antibody complex nephritis. Nonthyroid endocrine autoimmune deficiency disorders also have been classified as part of the spectrum of thyroid autoimmune disease. With the recent recognition of the spectrum of autoimmune mechanisms and antibody types and methods to distinguish antibody functions or types, our understanding of postpartum and neonatal thyroid disorders has been advanced considerably. The spectrum of neonatal thyroid disorders in the infants of women with autoimmune disease relates to the levels and types of antithyroid antibodies acquired from the mother. Finally, there is suggestive evidence that nonspecific goiter, including simple adolescent goiter and multinodular goiter as well as some cases of sporadic cretinism, may be part of an even more expanded spectrum of autoimmune thyroid disease. PMID:3302899

  18. Gangliosides and autoimmune diabetes.

    PubMed

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

    1997-09-01

    Gangliosides are sialic acid-containing glycolipids which are formed by a hydrophobic portion, the ceramide, and a hydrophilic part, i.e. the oligosaccharide chain. First described in neural tissue, several studies have shown that gangliosides are almost ubiquitous molecules expressed in all vertebrate tissues. Within cells, gangliosides are usually associated with plasma membranes, where they can act as receptors for a variety of molecules and have been shown to take part in cell-to-cell interaction and in signal transduction. In addition, gangliosides are expressed in cytosol membranes like those of secretory granules of some endocrine cells (adrenal medulla, pancreatic islets). As far as the role of gangliosides in diseases is concerned, there are some cases in which an aberrant ganglioside expression plays a crucial role in the disease pathogenetic process. These diseases include two major forms of ganglioside storage, namely GM2-gangliosidosis (Tay-Sachs and its beta-hexosaminidase deficiency) and GM1-gangliosidosis (beta-galactosidase deficiency), where the most prominent pathological characteristic is the lysosomal ganglioside accumulation in neurons. Other inflammatory or degenerative diseases both within and outside the nervous system have been shown to be associated with an altered pattern of ganglioside expression in the target organ. Since monoclonal antibodies have been discovered and used in immunology, a large variety of ganglioside antigens has been described both as blood group antigens and as tumour-related antigens. Several studies have also indicated that gangliosides can act not only as antigens, but also as autoantigens. As a matter of fact, auto-antibodies to gangliosides, detected by immunostaining methods performed directly on TLC plates or by ELISA, have been described in several autoimmune disorders such as Guillain-Barré syndrome, multiple sclerosis, lupus erythematosus, Hashimoto's thyroiditis and, last but not least, insulin-dependent (type 1) diabetes mellitus. This last disease is caused by the autoimmune destruction of insulin-producing pancreatic islet cells in genetically predisposed individuals. Autoantibodies and T lymphocytes directed towards multiple islet autoantigens have been detected in the circulation, well before the clinical onset of the disease, in a prodromal phase during which pancreatic islet beta-cells are presumably destroyed. Among the target autoantigens, some are of protein nature but others are acidic glycolipids such as sulphatides158 and the gangliosides GT3, GD3 and especially GM2-1. This last component is specifically expressed in pancreatic islets and has been shown to represent a target of IgG autoantibodies highly associated with diabetes development in first-degree relatives of type 1 diabetic individuals. In addition, the GM2-1 ganglioside appears to be one of the antigens recognized by cytoplasmic ICA, a heterogeneous group of antibodies which specifically react with islets on pancreatic frozen sections. In conclusion, studies performed in the last decade have clearly indicated that gangliosides represent a heterogeneous class of molecules that are involved in several cellular processes that are of crucial importance in physiological as well as in pathological conditions. Interestingly, these molecules, despite their small size, have been shown to represent not only important antigens in tumour immunology but are also able to elicit a specific autoimmune response, thus representing important autoantigens in some autoimmune disorders. It is of interest that, in addition to neurological autoimmune disorders where autoimmunity to gangliosides is frequent and usually of considerable magnitude, an autoimmune response to this class of molecules has been observed in autoimmune diabetes. (ABSTRACT TRUNCATED) PMID:9307889

  19. Comorbidity of Allergic and Autoimmune Diseases in Patients with Autism Spectrum Disorder: A Nationwide Population-Based Study

    ERIC Educational Resources Information Center

    Chen, Mu-Hong; Su, Tung-Ping; Chen, Ying-Sheue; Hsu, Ju-Wei; Huang, Kai-Lin; Chang, Wen-Han; Chen, Tzeng-Ji; Bai, Ya-Mei

    2013-01-01

    Previous clinical and genetic studies have suggested autism spectrum disorders (ASDs) is associated with immunological abnormalities involving cytokines, immunoglobulins, inflammation, and cellular immunity, but epidemiological reports are still limited. Patients with ASDs were identified in the National Health Insurance Database from 1996 to…

  20. Comorbidity of Allergic and Autoimmune Diseases in Patients with Autism Spectrum Disorder: A Nationwide Population-Based Study

    ERIC Educational Resources Information Center

    Chen, Mu-Hong; Su, Tung-Ping; Chen, Ying-Sheue; Hsu, Ju-Wei; Huang, Kai-Lin; Chang, Wen-Han; Chen, Tzeng-Ji; Bai, Ya-Mei

    2013-01-01

    Previous clinical and genetic studies have suggested autism spectrum disorders (ASDs) is associated with immunological abnormalities involving cytokines, immunoglobulins, inflammation, and cellular immunity, but epidemiological reports are still limited. Patients with ASDs were identified in the National Health Insurance Database from 1996 to

  1. Autoimmune Encephalitis in Children

    PubMed Central

    Armangue, Thaís; Petit-Pedrol, Mar; Dalmau, Josep

    2013-01-01

    The causes of encephalitis are numerous, and extensive investigations for infectious agents and other etiologies are often negative. The discovery that many of these encephalitis are immune mediated has changed the approach to the diagnosis and treatment of these disorders. Moreover, the broad spectrum of symptoms including, psychosis, catatonia, alterations of behavior and memory, seizures, abnormal movements, and autonomic dysregulation usually requires a multidisciplinary treatment approach. This review focuses in several forms of encephalitis that occur in children, and for which an autoimmune etiology has been demonstrated (eg, anti-N-methyl-D-aspartate receptor encephalitis) or is strongly suspected (eg, Rasmussen encephalitis, limbic encephalitis, opsoclonus-myoclonus). The authors also review several disorders that may be immune mediated, such as the rapid onset obesity with hypothalamic dysfunction, hypoventilation and autonomic dysregulation (ROHHAD) syndrome and some encephalopathies with fever and status epilepticus. Recognition of novel immune-mediated encephalitis is important because some of these disorders are highly responsive to immunotherapy. PMID:22935553

  2. 4. Autoimmunity, vasculitis, and autoantibodies.

    PubMed

    Lee, Susan J; Kavanaugh, Arthur

    2006-02-01

    Autoimmune diseases are distinct clinical syndromes characterized by various alterations in normal immune responsiveness, such that there is a loss of tolerance to particular host constituents. In most cases, despite years of intense investigation, the etiopathogenic antigens initiating these systemic inflammatory conditions remain undefined. However, a great deal has been learned about the changes in components of the immune response relevant to the propagation and sustenance of these often chronic disorders. In addition, various hormonal, environmental, physiologic, and other influences that affect their expression have been identified. The expression and ultimate clinical outcome of autoimmune diseases usually relate to inflammation-related damage to the target organ with subsequent dysfunction. Certain immune conditions, such as autoimmune thyroid disease, largely affect a single organ, whereas others, such as systemic lupus erythematosus, heterogeneously affect sundry organ systems. Autoantibodies directed against normal host antigens are a common feature of many autoimmune diseases. In some cases they are pathogenic, whereas in others they serve as markers for organ involvement or outcomes. Clinical descriptions of autoimmune diseases date back many decades in some cases. Recent efforts at formulating classification criteria have allowed clearer distinctions and more accurate stratification. Greater understanding of the immunopathogenesis of autoimmune conditions has led to the development and introduction into the clinic of novel immunomodulatory therapies and treatment paradigms that have substantially improved the outcomes for patients affected by these serious conditions. PMID:16455344

  3. [Pathogenesis of autoimmune thyroid diseases].

    PubMed

    Sgarbi, José Augusto; Maciel, Rui M B

    2009-02-01

    Autoimmune thyroid disease (AITD) is the most common organ-specific autoimmune disorder affecting 2% to 5% of the population in Western countries. Clinical presentation varies from hyperthyroidism in Graves' Disease to hypothyroidism in Hashimoto's thyroiditis. While the exact etiology of thyroid autoimmunity is not known, interaction between genetic susceptibility and environmental factors appears to be of fundamental importance to initiate the process of thyroid autoimmunity. It has been postulated that 79% of the susceptibility to develop AITD is attributed to genetic factors, while environmental factors contribute to 21%. The identified AITD susceptibility genes include immune-modulating genes, such as the major histocompatibility complex (MHC), cytotoxic T lymphocyte antigen-4 (CTLA-4), CD40 molecule, and protein tyrosine phosphatase-22 (PTPN22), and thyroid-specific genes, including TSH receptor (TSHR) and thyroglobulin (TG). The exact nature of the role environmental factors play in AITD is still not well known, but the involvement of several factors such as iodine diet content, stress, drugs and infections has been reported. However, there is no clear evidence of causality and the mechanisms by which environmental factors trigger thyroid autoimmunity in genetically predisposed individuals remain not fully understood. Knowledge of the precise mechanisms of interaction between environmental factors and genes in inducing thyroid autoimmunity could result in the development of new strategies for prevention and treatment. PMID:19347180

  4. Could ehrlichial infection cause some of the changes associated with leukemia, myelodysplastic diseases and autoimmune disorders, and offer antibiotic treatment options?

    PubMed

    Kallick, Charles A; Friedman, Daniel A; Nyindo, Mramba B A

    2015-12-01

    We hypothesize that a large group of medical conditions of unknown etiology including leukemia, multiple myeloma, myelodysplastic and autoimmune disorders, may be associated with or caused by an obscure group of intracellular obligate parasitic bacteria named Ehrlichia/Anaplasma (EA). Ensconced in the stem cells of the bone marrow, EA may disrupt the normal development and function of many of the cells of immunity, manifesting itself as different syndromes. Recent studies of the activity of EA suggest direct effects on the immune system consistent with the manifestations of leukemia. We reference here three leukemia patients with direct or indirect evidence of EA infection. Moreover, EA have been shown to be most sensitive to rifamycins. Two moribund leukemia patients with levels of platelets and white cells incompatible with life were treated with therapeutic doses of Rifampin. Though they did not survive, their condition improved dramatically for a time, suggesting Rifampin provided some therapeutic benefit. We assert that these results warrant more extensive study. PMID:26394545

  5. Leptin in autoimmune diseases.

    PubMed

    Procaccini, Claudio; Pucino, Valentina; Mantzoros, Christos S; Matarese, Giuseppe

    2015-01-01

    The past twenty years of research on leptin has provided crucial information on the link between metabolic state and immune system function. Adipocytes influence not only the endocrine system but also the immune response, through several cytokine-like mediators known as adipokines, which include leptin. Initially described as an antiobesity hormone, leptin has subsequently been shown also to influence hematopoiesis, thermogenesis, reproduction, angiogenesis, and more importantly immune homeostasis. As a cytokine, leptin can affect thymic homeostasis and the secretion of acute-phase reactants such as interleukin-1 (IL-1) and tumor-necrosis factor-alpha (TNF-α). Leptin links nutritional status and proinflammatory T helper 1 (Th1) immune responses and the decrease in leptin plasma concentration during food deprivation leads to impaired immune function. Conversely, elevated circulating leptin levels in obesity appear to contribute to the low-grade inflammatory background which makes obese individuals more susceptible to increased risk of developing cardiovascular diseases, diabetes, or degenerative disease including autoimmunity and cancer. In this review, we provide an overview of recent advances on the role of leptin in the pathogenesis of several autoimmune disorders that may be of particular relevance in the modulation of the autoimmune attack through metabolic-based therapeutic approaches. PMID:25467840

  6. Associated Autoimmune Diseases

    MedlinePlus

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

  7. Achalasia in a Patient with Polyglandular Autoimmune Syndrome Type II

    PubMed Central

    Amr, Bashar S.; Mamillapalli, Chaitanya

    2015-01-01

    Achalasia is a rare disease characterized by aperistalsis of the esophageal body and failure of the lower esophageal sphincter to relax. The etiology of this disease remains unknown. Polyglandular autoimmune syndrome type II is a well-identified disease characterized by the occurrence of autoimmune Addison's disease in combination with autoimmune thyroid disease and/or type 1 diabetes mellitus. We report a case that suggests autoimmunity and immunogenicity as a probable contributing factor for association of these two rare disorders. PMID:26078736

  8. Mechanisms underlying autoimmune synaptic encephalitis leading to disorders of memory, behavior and cognition: insights from molecular, cellular and synaptic studies

    PubMed Central

    Moscato, Emilia H.; Jain, Ankit; Peng, Xiaoyu; Hughes, Ethan G.; Dalmau, Josep; Balice-Gordon, Rita J.

    2010-01-01

    Recently, several novel, potentially lethal, and treatment-responsive syndromes that affect hippocampal and cortical function have been shown to be associated with auto-antibodies against synaptic antigens, notably glutamate or GABA-B receptors. Patients with these auto-antibodies, sometimes associated with teratomas and other neoplasms, present with psychiatric symptoms, seizures, memory deficits, and decreased level of consciousness. These symptoms often improve dramatically after immunotherapy or tumor resection. Here we discuss studies of the cellular and synaptic effects of these antibodies in hippocampal neurons in vitro and preliminary work in rodent models. Our work suggests that patient antibodies lead to rapid and reversible removal of neurotransmitter receptors from synaptic sites, leading to changes in synaptic and circuit function that in turn are likely to lead to behavioral deficits. We also discuss several of the many questions raised by these and related disorders. Determining the mechanisms underlying these novel anti-neurotransmitter receptor encephalopathies will provide insights into the cellular and synaptic bases of the memory and cognitive deficits that are hallmarks of these disorders, and potentially suggest avenues for therapeutic intervention. PMID:20646055

  9. Aquaporin-4 autoimmunity

    PubMed Central

    Zekeridou, Anastasia

    2015-01-01

    Neuromyelitis optica (NMO) and a related spectrum of inflammatory CNS disorders are unified by detection of a serum autoantibody specific for the aquaporin-4 (AQP4) water channel, which is abundant in astrocytic foot processes. The classic clinical manifestations of NMO are optic neuritis and longitudinally extensive transverse myelitis. Newly recognized manifestations of AQP4 autoimmunity include lesions of circumventricular organs and skeletal muscle. NMO is commonly relapsing, is frequently accompanied by other autoimmune disorders, and sometimes occurs in a paraneoplastic context. The goals of treatment are to minimize neurologic disability in the acute attack and thereafter to prevent relapses and cumulative disability. The disease specificity of AQP4 immunoglobulin (Ig) G approaches 100% using optimized molecular-based detection assays. Clinical, immunohistopathologic, and in vitro evidence support this antibody being central to NMO pathogenesis. Current animal models yield limited histopathologic characteristics of NMO, with no clinical deficits to date. Recent descriptions of a myelin oligodendrocyte glycoprotein autoantibody in a minority of patients with NMO spectrum phenotype who lack AQP4-IgG predict serologic delineation of additional distinctive disease entities. PMID:26185772

  10. Free radical theory of autoimmunity

    PubMed Central

    Kannan, Subburaj

    2006-01-01

    Background Despite great advances in clinical oncology, the molecular mechanisms underlying the failure of chemotherapeutic intervention in treating lymphoproliferative and related disorders are not well understood. Hypothesis A hypothetical scheme to explain the damage induced by chemotherapy and associated chronic oxidative stress is proposed on the basis of published literature, experimental data and anecdotal observations. Brief accounts of multidrug resistance, lymphoid malignancy, the cellular and molecular basis of autoimmunity and chronic oxidative stress are assembled to form a basis for the hypothesis and to indicate the likelihood that it is valid in vivo. Conclusion The argument set forward in this article suggests a possible mechanism for the development of autoimmunity. According to this view, the various sorts of damage induced by chemotherapy have a role in the pattern of drug resistance, which is associated with the initiation of autoimmunity. PMID:16759382

  11. Autoimmune pancreatitis mimicking pancreatic cancer

    PubMed Central

    Hammami, Mohamed; Noomen, Faouzi; Toumi, Omar; Harzallah, Olfa; Mahmoudi, Ammar; Kallel, Wassim; Zouari, Khadija; Hamdi, Abdelaziz

    2011-01-01

    Context: Autoimmune pancreatitis is a particular type of pancreatitis of presumed autoimmune etiology, it is an entity distinct from all others forms of chronic pancreatitis, characterized by clinical, histopathological, radiographic, serologic and therapeutic features. This benign disease resembles pancreatic carcinoma both clinically and radiographically. Case Report: A 27-year-old man presented with obstructive jaundice and evocative image of pancreatic tumor. A pancreaticoduodenectomy (Whipple operation) was performed and pathological examination of the specimen diagnosed AIP. Patient responded well to a course of corticosteroids with resolution of clinical and biological disorders. Conclusion: Accurate and timely diagnosis of autoimmune pancreatitis is particularly important because steroid therapy is effective and pancreatic resection is not necessary. PMID:22361500

  12. Thyroid dysfunction: an autoimmune aspect.

    PubMed

    Khan, Farah Aziz; Al-Jameil, Noura; Khan, Mohammad Fareed; Al-Rashid, May; Tabassum, Hajera

    2015-01-01

    Auto immune thyroid disease (AITD) is the common organ specific autoimmune disorder, Hashimoto thyroiditis (HT) and Grave's disease (GD) are its well-known sequelae. It occurs due to loss of tolerance to autoantigens thyroid peroxidase (TPO), thyroglobulin (Tg), thyroid stimulating hormone receptor (TSH-R) which leads to the infiltration of the gland. T cells in chronic autoimmune thyroiditis (cAIT) induce apoptosis in thyroid follicular cells and cause destruction of the gland. Presences of TPO antibodies are common in HT and GD, while Tg has been reported as an independent predictor of thyroid malignancy. Cytokines are small proteins play an important role in autoimmunity, by stimulating B and T cells. Various cytokines IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-13, IL-14, TNF-α and IFN-γ are found in thyroid follicular cells which enhance inflammatory response with nitric oxide (NO) and prostaglandins. PMID:26221205

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

    PubMed

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

    2015-10-01

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

  14. 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

  15. Skin involvement in systemic autoimmune diseases.

    PubMed

    Rashtak, Shadi; Pittelkow, Mark R

    2008-01-01

    Autoimmune diseases present with varied and broad-ranging cutaneous manifestations. Connective tissue disorders have a plethora of skin manifestations such as rheumatoid nodules in rheumatoid arthritis, psoriatic plaques in psoriatic arthritis, acne and pustulosis in SAPHO syndrome, livedo reticularis and ulceration in antiphospholipid antibody syndrome and xerosis in Sjgren syndrome. Cutaneous manifestations of autoimmune vasculitides such as polyarteritis nodosa, Kawasaki disease, Henoch-Schnlein purpura, cryoglobulinemic vasculitis, Behcet disease, Wegener granulomatosis, microscopic polyangiitis and Churg-Strauss syndrome range from papules, subcutaneous nodules and livedo reticularis, to palpable purpura, hemorrhagic bulla and ulcerating lesions. Pathological skin manifestations in autoimmune endocrinopathies include pretibial myxedema/dermopathy in Graves' disease, diabetic dermopathy and necrobiosis lipoidica in type I autoimmune diabetes mellitus, candidiasis, ectodermal dysplasia, vitiligo and alopecia areata in APECED and uniform hyperpigmentation of the skin in Addison's disease. Autoimmune gastrointestinal disorders such as inflammatory bowel disease (with erythema nodosum), gluten-sensitive enteropathy (with dermatitis herpetiformis), autoimmune hepatitis and primary biliary cirrhosis (with jaundice and pruritus), hematologic/oncologic disorders such as acute and chronic graft-versus-host disease (with skin manifestations ranging from pruritic maculopapular eruptions and lichen planus-like lesions to generalized scleroderma), and paraneoplastic autoimmune dermatoses are discussed as well. PMID:18460895

  16. Criteria for Environmentally Associated Autoimmune Diseases

    PubMed Central

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

    2012-01-01

    Increasing evidence supports a role for the environment in the development of autoimmune diseases, as reviewed in the accompanying three papers from the National Institute of Environmental Health Sciences Expert Panel Workshop. An important unresolved issue, however, is the development of criteria for identifying autoimmune disease phenotypes for which the environment plays a causative role, herein referred to as environmentally associated autoimmune diseases. There are several different areas in which such criteria need to be developed, including: 1) identifying the necessary and sufficient data to define environmental risk factors for autoimmune diseases meeting current classification criteria; 2) establishing the existence of and criteria for new environmentally associated autoimmune disorders that do not meet current disease classification criteria; and 3) identifying in clinical practice specific environmental agents that induce autoimmune disease in individual patients. Here we discuss approaches that could be useful for developing criteria in these three areas, as well as factors that should be considered in evaluating the evidence for criteria that can distinguish individuals with such disorders from individuals without such disorders with high sensitivity and specificity. Current studies suggest that multiple lines of complementary evidence will be important and that in many cases there will be clinical, serologic, genetic, epigenetic, and/or other laboratory features that could be incorporated as criteria for environmentally associated autoimmune diseases to improve diagnosis and treatment and possibly allow for preventative strategies in the future. PMID:22771005

  17. Therapeutic Plasma Apheresis as a Treatment for 35 Severely Ill Children and Adolescents with Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections

    PubMed Central

    Latimer, M. Elizabeth; L'Etoile, Nathan; Seidlitz, Jakob

    2015-01-01

    Abstract Background: Because of its reported similarities to Sydenham chorea, therapeutic plasma apheresis (TPA) has been proposed as a potential treatment of pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS). To date, support for the use of TPA has been limited to a few anecdotal reports and a small placebo-controlled trial demonstrating dramatic symptom improvements at 1 month and 1 year follow-up. To evaluate the safety and efficacy of TPA further, we undertook a retrospective review of all PANDAS patients treated with TPA at Georgetown University Hospital between August 2009 and October 2013. Methods: Forty patients were identified, and sufficient information was available from medical records and telephone interview for 35 cases (88%). All 35 (23 boys; 12 girls) met diagnostic criteria for PANDAS (Swedo et al. 1998) and had severe symptoms. The TPA procedures were performed at Georgetown University Hospital using a protocol that processes a total of 4.5 blood volumes over 3–5 days (three treatments of 1.5 volumes each). Overall symptom improvements at 6 months post-TPA and long-term follow-up were estimated by parents, who also rated changes in individual symptoms to provide information about patterns of improvement. Results: All patients were reported to have received at least some benefit from TPA, with average improvement of 65% at 6 months post-TPA and 78% at longer-term follow-up. A decrease in the number of reported symptoms also occurred, with particular improvements in obsessive-compulsive disorder (OCD), anxiety, tics, and somatic symptoms, including dysgraphia, sleep difficulties, and urinary urgency or frequency. Contrary to expectations, preceding duration of illness was not correlated with degree of improvement following TPA, suggesting that acuity of illness is not a factor affecting response. Only two adverse events were reported: both involved reopening of the site where the central line had been placed and resolved immediately following application of pressure and re-dressing of the puncture site. Conclusions: Therapeutic plasma apheresis is an invasive medical intervention that should be reserved for treatment of children and adolescents who are severely affected by PANDAS. In such patients, it appears to be a safe, well-tolerated, and beneficial treatment option. PMID:25658452

  18. 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

  19. 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 probably does not change the natural history of associated autoimmune disorders. PMID:18056028

  20. Autoimmune Thyroiditis in Childhood

    PubMed Central

    Brown, Rosalind S.

    2013-01-01

    Autoimmune thyroiditis (AIT) is the most common thyroid disorder in the pediatric age range. The disease results from an as yet poorly characterized defect or defects in immunoregulation and a cascade of events progressing from lymphocyte infiltration of the thyroid, to T-cell- and cytokine-mediated thyroid follicular cell injury, and apoptotic cell death. Approximately 70% of disease risk has been attributed to genetic background with environmental factors being important in triggering disease in susceptible individuals. The contribution of individual genes is small and probably polymorphisms in multiple genes play a role. Some immunosusceptibility genes affect immune recognition or response in general, while others are thyroid-specific. Environmental agents may act through an epigenetic mechanism. Antibodies (Abs) to a variety of thyroid-specific antigens are detectable in a majority of patients, but the role of Abs in mediating cell injury and death is unclear and only thyrotropin (TSH) receptor Abs significantly affect thyroid function by interfering with (or stimulating) the action of TSH. Nonetheless, thyroid peroxidase (TPO) Abs and thyroglobulin (Tg) Abs, present in a majority of patients, are valuable diagnostically as markers of underlying autoimmune thyroid destruction. TSH receptor blocking Abs are found in ˜18% of children and adolescents with severe hypothyroidism and, when persistent, may identify an adolescent likely to have a baby with TSH receptor blocking Ab-induced congenital hypothyroidism. AIT may coexist with other organ-specific autoimmune diseases. Although the most common age at presentation is adolescence, the disease may occur rarely in children <1 year of life. Conflict of interest:None declared. PMID:23154164

  1. Introduction: mechanisms of tissue injury in autoimmune diseases.

    PubMed

    Eilat, Dan

    2014-09-01

    This issue of Seminars in Immunopathology is devoted to the most recent developments in our understanding of the mechanisms leading to tissue injury in autoimmune diseases. These include rheumatoid arthritis, systemic lupus erythematosus, type I diabetes, autoimmune liver diseases, inflammatory bowel diseases, autoimmune skin diseases, autoimmune uveitis, and autoinflammatory diseases. This impressive account of basic and clinical research in a wide spectrum of immunological disorders provides the reader with a comprehensive view of the common and unique features of these diverse conditions. It may also provide one with many new ideas for therapeutic intervention in the natural course of these autoimmune syndromes. PMID:25168400

  2. Autoimmune cytopenias in common variable immunodeficiency.

    PubMed

    Podjasek, Jenna C; Abraham, Roshini S

    2012-01-01

    Common variable immunodeficiency (CVID) is a humoral immunodeficiency whose primary diagnostic features include hypogammaglobulinemia involving two or more immunoglobulin isotypes and impaired functional antibody responses in the majority of patients. While increased susceptibility to respiratory and other infections is a common thread that binds a large cross-section of CVID patients, the presence of autoimmune complications in this immunologically and clinically heterogeneous disorder is recognized in up to two-thirds of patients. Among the autoimmune manifestations reported in CVID (20-50%; Chapel et al., 2008; Cunningham-Rundles, 2008), autoimmune cytopenias are by far the most common occurring variably in 4-20% (Michel et al., 2004; Chapel et al., 2008) of these patients who have some form of autoimmunity. Association of autoimmune cytopenias with granulomatous disease and splenomegaly has been reported. The spectrum of autoimmune cytopenias includes thrombocytopenia, anemia, and neutropenia. While it may seem paradoxical "prima facie" that autoimmunity is present in patients with primary immune deficiencies, in reality, it could be considered two sides of the same coin, each reflecting a different but inter-connected facet of immune dysregulation. The expansion of CD21 low B cells in CVID patients with autoimmune cytopenias and other autoimmune features has also been previously reported. It has been demonstrated that this unique subset of B cells is enriched for autoreactive germline antibodies. Further, a correlation has been observed between various B cell subsets, such as class-switched memory B cells and plasmablasts, and autoimmunity in CVID. This review attempts to explore the most recent concepts and highlights, along with treatment of autoimmune hematological manifestations of CVID. PMID:22837758

  3. Autoimmune diseases and Sjogren's syndrome: an autoimmune exocrinopathy.

    PubMed

    Fox, Philip C

    2007-03-01

    Autoimmune diseases include a diverse group of over 80 conditions. Sjögren's syndrome is the second most common autoimmune rheumatic disease, with an estimated prevalence in the United States of 2-4 million persons. There are prominent and consistent oral and dental findings in Sjögren's syndrome related to the autoimmune-mediated loss of normal salivary function. Additionally, nonoral clinical manifestations of Sjögren's syndrome include: dry eyes (with specific ocular surface changes termed keratoconjunctivitis sicca); other xeroses, such as dryness of the nose, throat, skin, and vagina; peripheral (and less frequently central) neuropathies; myalgias and arthralgias; thyroid disorders (particularly autoimmune thyroiditis); pulmonary disorders; renal disorders; and lymphoma. There is a significant (20- to 40-fold) increase in the incidence of malignant lymphoma, particularly in primary Sjögren's syndrome. Establishing the diagnosis of Sjögren's syndrome has been difficult in the light of its nonspecific symptoms (dry eyes and mouth), disagreement on diagnostic criteria, and a lack of both sensitive and specific laboratory markers. Many serum and salivary biomarkers for Sjögren's syndrome have been proposed although, to date, none has proven to be sufficiently specific for diagnostic purposes or has been well correlated with disease activity measures. Investigators have recently begun to apply modern genomic and proteomic approaches to identify candidate biomarkers in Sjögren's syndrome. The results of these investigations promise to provide a wealth of information on candidate biomarkers and possible etiopathological mechanisms underlying this disorder. Further, this information will improve clinical outcomes by fostering the design of new rational therapeutics and assisting in the monitoring of clinical disease. PMID:17332090

  4. Cytokines in Autoimmune Uveitis

    PubMed Central

    Horai, Reiko

    2011-01-01

    Autoimmune uveitis is a complex group of sight-threatening diseases that arise without a known infectious trigger. The disorder is often associated with immunological responses to retinal proteins. Experimental models of autoimmune uveitis targeting retinal proteins have led to a better understanding of the basic immunological mechanisms involved in the pathogenesis of uveitis and have provided a template for the development of novel therapies. The disease in humans is believed to be T cell-dependent, as clinical uveitis is ameliorated by T cell-targeting therapies. The roles of T helper 1 (Th1) and Th17 cells have been major topics of interest in the past decade. Studies in uveitis patients and experiments in animal models have revealed that Th1 and Th17 cells can both be pathogenic effectors, although, paradoxically, some cytokines produced by these subsets can also be protective, depending on when and where they are produced. The major proinflammatory as well as regulatory cytokines in uveitis, the therapeutic approaches, and benefits of targeting these cytokines will be discussed in this review. PMID:21787221

  5. Outer causes inner conflicts: environment and autoimmunity.

    PubMed Central

    Heimer, H

    1999-01-01

    Autoimmune diseases are some of the most common yet least understood maladies in medicine today. Some estimates place the number of sufferers of such diseases as high as 20% of the U.S. population, most of them women. The disorders involved range from the familiar to the relatively uncommon to the obscure. What these disorders have in common is that they cause the immune system to attack the body's own tissues. Uncertainty in the field of autoimmune disease extends even to the fundamental questions of what an autoimmune disease is and how many people are affected; identifying specific environmental risk factors for autoimmune diseases is still highly speculative. To gain some sense of direction, scientists are looking at a few documented environmental exposures that have led to autoimmune syndromes, as well as some animal models that exhibit autoimmune syndromes similar to those seen in humans. At a September 1998 NIEHS workshop on environmental links to autoimmune diseases, participants prioritized research needs in five main categories, a step that should help scientists develop strategies for investigating this family of diseases. PMID:10504165

  6. Autoimmune Hemolysis: A Journey through Time

    PubMed Central

    Freedman, John

    2015-01-01

    Summary The existence of autoimmune diseases in humans has been known for almost 100 years. Currently, autoimmune pathogenesis has been attributed to more than 40 human diseases; yet it is still not clear what immune abnormalities conclusively prove underlying autoimmune pathogenesis. Hence, although much has been learned, research is still needed for complete elucidation of the mechanisms of the immune dysregulation in AIHA. Better understanding of the underlying mechanism(s) may allow for development of more specific therapies of these not uncommon and often difficult-to-treat disorders. PMID:26696795

  7. [Autoimmune diseases in type 1 diabetes].

    PubMed

    Lechleitner, Monika; Hoppichler, Friedrich; Kaser, Susanne

    2016-04-01

    According to literature about 30 % of the patients with type 1 diabetes develop further autoimmune diseases. Thyroid dysfunction represents with 15‒30 % the most common disorder, followed by gastritis with 5‒10 %, celiac disease with 4‒9 % and vitiligo with 2‒10 %. Addison's disease seems to be less prevalent. Diagnostic procedures in the course of the comprehensive care for diabetic patients should therefore include screening for further autoimmune diseases. PMID:27052247

  8. Association between pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections disease and tumor necrosis factor-α gene−308 g/a, −850 c/t polymorphisms in 4-12-year-old children in Adana/Turkey

    PubMed Central

    Luleyap, H. Umit; Onatoglu, Dilge; Yilmaz, M. Bertan; Alptekin, Davut; Tahiroglu, Aysegul Y.; Cetiner, Salih; Pazarbasi, Ayfer; Unal, Ilker; Avci, Ayse; Comertpay, Gamze

    2013-01-01

    OBJECTIVES: Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) is a newly defined disease in neuropsychiatry and occurs with an autoimmune mechanism after Group A Beta Hemolytic Streptococcus (GABHS) infection. Tumor necrosis factor (TNF), encoded by TNF-α gene has an important role in the apoptotic mechanisms of autoimmune diseases. Recently, TNF-α polymorphisms and autoimmune/psychiatric disorders have been reported to be related. In this regard, we focused on to investigate a possible relation between the TNF-α gene promoter region−308 G/A and − 850 C/T polymorphisms and PANDAS. MATERIALS AND METHODS: In this study, ages of PANDAS patient and control groups were ranging from 4 years to 12-year-old. Patient group includes childhood onset PANDAS patients (n = 42) and control group includes healthy children (n = 58). Diagnoses have been carried out according to Diagnostic and Statistical Manual of Mental Disorder (DSM-IV) criteria with Affective Disorders and Schizophrenia-Present and Lifetime (KSAD-S-PL) and Children Yale-Brown Obsessive Compulsive Scale Moreover, PANDAS criteria established by the American National Psychiatry Institute have been employed for diagnoses. For identifying polymorphisms; Polymerase Chain Reaction, Restriction Fragment Length Polymorphism and Polyacrylamid Gel Electrophoresis were used. RESULTS AND DISCUSSION: For −308 polymorphism, 37 of 42 PANDAS patients’ results and for −850 C/T polymorphism, 38 of 42 PANDAS patients’ results were obtained. According to our statistical analysis there is a positive relationship between PANDAS patients for −308 G/A polymorphism but not for −850 C/T polymorphism. There is no positive relationship between −308 G/A polymorphism and antistrep-tolysin O (ASO) titers and no relationship between −850 C/T polymorphism and ASO titers. We found, however, positive relationship between genders of patients (boys) and the disease. According to our results, we propose that the AA polymorphism of −308 G/A polymorphism can be used as a molecular indicator for PANDAS. PMID:24019622

  9. Epstein-Barr virus-associated posttransplantation lymphoproliferative disorder after high-dose immunosuppressive therapy and autologous CD34-selected hematopoietic stem cell transplantation for severe autoimmune diseases.

    PubMed

    Nash, Richard A; Dansey, Roger; Storek, Jan; Georges, George E; Bowen, James D; Holmberg, Leona A; Kraft, George H; Mayes, Maureen D; McDonagh, Kevin T; Chen, Chien-Shing; Dipersio, John; Lemaistre, C Fred; Pavletic, Steven; Sullivan, Keith M; Sunderhaus, Julie; Furst, Daniel E; McSweeney, Peter A

    2003-09-01

    High-dose immunosuppressive therapy followed by autologous hematopoietic stem cell transplantation (HSCT) is currently being evaluated for the control of severe autoimmune diseases. The addition of antithymocyte globulin (ATG) to high-dose chemoradiotherapy in the high-dose immunosuppressive therapy regimen and CD34 selection of the autologous graft may induce a higher degree of immunosuppression compared with conventional autologous HSCT for malignant diseases. Patients may be at higher risk of transplant-related complications secondary to the immunosuppressed state, including Epstein-Barr virus (EBV)-associated posttransplantation lymphoproliferative disorder (PTLD), but this is an unusual complication after autologous HSCT. Fifty-six patients (median age, 42 years; range, 23-61 years) with either multiple sclerosis (n = 26) or systemic sclerosis (n = 30) have been treated. The median follow-up has been 24 months (range, 2-60 months). Two patients (multiple sclerosis, n = 1; systemic sclerosis, n = 1) had significant reactivations of herpesvirus infections early after HSCT and then developed aggressive EBV-PTLD and died on days +53 and +64. Multiorgan clonal B-cell infiltrates that were EBV positive by molecular studies or immunohistology were identified at both autopsies. Both patients had positive screening skin tests for equine ATG (Atgam) and had been converted to rabbit ATG (Thymoglobulin) from the first dose. Of the other 54 patients, 2 of whom had partial courses of rabbit ATG because of a reaction to the intravenous infusion of equine ATG, only 1 patient had a significant clinical reactivation of a herpesvirus infection (herpes simplex virus 2) early after HSCT, and none developed EBV-PTLD. The T-cell count in the peripheral blood on day 28 was 0/microL in all 4 patients who received rabbit ATG; this was significantly less than in patients who received equine ATG (median, 174/microL; P =.001; Mann-Whitney ranked sum test). Although the numbers are limited, the time course and similarity of the 2 cases of EBV-PTLD and the effect on day 28 T-cell counts support a relationship between the development of EBV-PTLD and the administration of rabbit ATG. The differences between equine and rabbit ATG are not yet clearly defined, and they should not be considered interchangeable in this regimen without further study. PMID:14506660

  10. Thyroid autoimmunity and environment.

    PubMed

    Tanda, M L; Piantanida, E; Lai, A; Lombardi, V; Dalle Mule, I; Liparulo, L; Pariani, N; Bartalena, L

    2009-06-01

    Autoimmune thyroid disorders (AITDs) are the result of a complex interplay between genetic and environmental factors, the former account for about 70-80% of liability to develop AITDs. However, at least 20-30% is contributed by environmental factors, which include certainly smoking (at least for Graves' disease and orbitopathy), probably stress, iodine and selenium intake, several drugs, irradiation, pollutants, viral and bacterial infections, allergy, pregnancy, and post-partum. Evidence for the intervention of these factors is often limited, and the mechanisms whereby environmental factors may concur to the onset of AITDs are in many instances unclear. Nevertheless, gene-environment interaction seems a fundamental process for the occurrence of AITDs. PMID:19343619

  11. Thyroid autoimmunity as a window to autoimmunity: An explanation for sex differences in the prevalence of thyroid autoimmunity.

    PubMed

    Merrill, Stephen J; Mu, Ying

    2015-06-21

    Autoimmune thyroid diseases (AITDs), predominately Graves׳ disease and Hashimoto׳s thyroiditis, comprise the most common autoimmune diseases in humans. Both have the production of anti-thyroid antibody as an important aspect and both are much more prevalent in females, being at least 10 times more common than in males. Using these two clues, a hypothesis for the initiation of thyroid autoimmunity is proposed that helps to make the case that the thyroid is one of the most sensitive sites for autoimmunity and helps account for the prevalence and the observed sex differences in AITDs and associated diseases, such as type 1 diabetes and Latent Autoimmune Diabetes in Adults (LADA). The primary mechanisms proposed involve the underlying state of inflammation as a result of the adipokines, especially leptin, TNF-α, and IL-6, and the receptors able to recognize pathogen-associated molecular patterns (PAMP׳s) and damage-associated molecular patterns (DAMP׳s) through Toll-like receptors (TLR) and others receptors present on thyrocytes. The adipokines are produced by adipose tissue, but have hormone-like and immune modulating properties. As the levels of leptin are significantly higher in females, an explanation for the sex difference in thyroid autoimmunity emerges. The ability of the thyrocytes to participate in innate immunity through the TLR provides an adjuvant-like signal and allows for the action of other agents, such as environmental factors, viruses, bacteria, and even stress to provide the initiation step to break tolerance to thyroid self-antigens. Seeing the thyroid as one of the most sensitive sites for autoimmunity, means that for many autoimmune disorders, if autoimmunity is present, it is likely to also be present in the thyroid - and that that condition in the thyroid was probably earlier. The evidence is seen in multiple autoimmune syndrome. PMID:25576242

  12. Toxicology of Autoimmune Diseases

    PubMed Central

    Hultman, Per; Kono, Dwight H.

    2010-01-01

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

  13. Associated Autoimmune Diseases

    MedlinePlus

    ... Education Bulletin Associated Autoimmune Diseases Updated June 2014 Celiac Disease and Associated Autoimmune Diseases: The Connection People who have celiac disease or dermatitis herpetiformis (celiac disease that manifests as ...

  14. Perspectives on autoimmunity

    SciTech Connect

    Cohen, I.R.

    1987-01-01

    The contents of this book are: HLA and Autoimmunity; Self-Recognition and Symmetry in the Immune System; Immunology of Insulin Dependent Diabetes Mellitus; Multiple Sclerosis; Autoimmunity and Immune Pathological Aspects of Virus Disease; Analyses of the Idiotypes and Ligand Binding Characteristics of Human Monoclonal Autoantibodies to DNA: Do We Understand Better Systemic Lupus Erythematosus. Autoimmunity and Rheumatic Fever; Autoimmune Arthritis Induced by Immunization to Mycobacterial Antigens; and The Interaction Between Genetic Factors and Micro-Organisms in Ankylosing Spondylitis: Facts and Fiction.

  15. Cholestatic phenotypes of autoimmune hepatitis.

    PubMed

    Czaja, Albert J

    2014-09-01

    Autoimmune hepatitis can have cholestatic features that are outside the codified diagnostic criteria. These features have uncertain effects on the clinical presentation and progression of disease. Patients with autoimmune hepatitis can have antimitochondrial antibodies and coincidental bile duct injury or loss (2%-13% of patients), focal biliary strictures and dilations based on cholangiography (2%-11%), or histologic changes of bile duct injury or loss in the absence of other features (5%-11%). These findings probably represent atypical manifestations of autoimmune hepatitis or variants of primary biliary cirrhosis or primary sclerosing cholangitis, depending on the predominant findings. Serum levels of alkaline phosphatase and γ-glutamyl transferase, histologic features of bile duct injury, and findings from cholangiography are associated with responsiveness to corticosteroid therapy and individualized alternative treatments. Corticosteroid therapy, in combination with low-dose ursodeoxycholic acid, has been promulgated by international societies, but these recommendations are not based on strong evidence. The frequency, variable outcomes, and uncertainties in diagnosis and management of the cholestatic phenotypes must be addressed by a collaborative investigational network. This network should define the genetic and pathologic features of these disorders, standardize their nomenclature, and establish a treatment algorithm. In this review, the different cholestatic phenotypes of autoimmune hepatitis, mechanisms of pathogenesis, current management strategies and outcomes, and opportunities for improving understanding and therapy are presented. PMID:24013108

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

    PubMed

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

    2015-12-01

    Autoimmune diseases are characterized by the impaired function and the destruction of tissues that are caused by an immune response in which aberrant antibodies are generated and attack the body's own cells and tissues. Interleukin (IL) -37, a new member of the IL-1 family, broadly reduces innate inflammation as well as acquired immune responses. Recently, studies have shown that expression of IL-37 was abnormal in autoimmune diseases, such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), inflammatory bowel disease (IBD), ankylosing spondylitis (AS), psoriasis, Graves' disease (GD). In addition, functional analysis indicated that IL-37 is negatively involved in the development and pathogenesis of these autoimmune disorders. The strong association of this cytokine with autoimmune diseases promotes us to systematically review what had been published recently on the crucial nature of IL-37 in relation to autoimmune diseases gaining attention for its regulatory capability in these autoimmune disorders. PMID:26264940

  17.  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

  18. The Diagnosis and Treatment of Autoimmune Encephalitis.

    PubMed

    Lancaster, Eric

    2016-01-01

    Autoimmune encephalitis causes subacute deficits of memory and cognition, often followed by suppressed level of consciousness or coma. A careful history and examination may show early clues to particular autoimmune causes, such as neuromyotonia, hyperekplexia, psychosis, dystonia, or the presence of particular tumors. Ancillary testing with MRI and EEG may be helpful for excluding other causes, managing seizures, and, rarely, for identifying characteristic findings. Appropriate autoantibody testing can confirm specific diagnoses, although this is often done in parallel with exclusion of infectious and other causes. Autoimmune encephalitis may be divided into several groups of diseases: those with pathogenic antibodies to cell surface proteins, those with antibodies to intracellular synaptic proteins, T-cell diseases associated with antibodies to intracellular antigens, and those associated with other autoimmune disorders. Many forms of autoimmune encephalitis are paraneoplastic, and each of these conveys a distinct risk profile for various tumors. Tumor screening and, if necessary, treatment is essential to proper management. Most forms of autoimmune encephalitis respond to immune therapies, although powerful immune suppression for weeks or months may be needed in difficult cases. Autoimmune encephalitis may relapse, so follow-up care is important. PMID:26754777

  19. The Diagnosis and Treatment of Autoimmune Encephalitis

    PubMed Central

    2016-01-01

    Autoimmune encephalitis causes subacute deficits of memory and cognition, often followed by suppressed level of consciousness or coma. A careful history and examination may show early clues to particular autoimmune causes, such as neuromyotonia, hyperekplexia, psychosis, dystonia, or the presence of particular tumors. Ancillary testing with MRI and EEG may be helpful for excluding other causes, managing seizures, and, rarely, for identifying characteristic findings. Appropriate autoantibody testing can confirm specific diagnoses, although this is often done in parallel with exclusion of infectious and other causes. Autoimmune encephalitis may be divided into several groups of diseases: those with pathogenic antibodies to cell surface proteins, those with antibodies to intracellular synaptic proteins, T-cell diseases associated with antibodies to intracellular antigens, and those associated with other autoimmune disorders. Many forms of autoimmune encephalitis are paraneoplastic, and each of these conveys a distinct risk profile for various tumors. Tumor screening and, if necessary, treatment is essential to proper management. Most forms of autoimmune encephalitis respond to immune therapies, although powerful immune suppression for weeks or months may be needed in difficult cases. Autoimmune encephalitis may relapse, so follow-up care is important. PMID:26754777

  20. Virus infection, antiviral immunity, and autoimmunity

    PubMed Central

    Getts, Daniel R.; Chastain, Emily M. L.; Terry, Rachael L.; Miller, Stephen D.

    2014-01-01

    Summary As a group of disorders, autoimmunity ranks as the third most prevalent cause of morbidity and mortality in the Western World. However, the etiology of most autoimmune diseases remains unknown. Although genetic linkage studies support a critical underlying role for genetics, the geographic distribution of these disorders as well as the low concordance rates in monozygotic twins suggest that a combination of other factors including environmental ones are involved. Virus infection is a primary factor that has been implicated in the initiation of autoimmune disease. Infection triggers a robust and usually well-coordinated immune response that is critical for viral clearance. However, in some instances, immune regulatory mechanisms may falter, culminating in the breakdown of self-tolerance, resulting in immune-mediated attack directed against both viral and self-antigens. Traditionally, cross-reactive T-cell recognition, known as molecular mimicry, as well as bystander T-cell activation, culminating in epitope spreading, have been the predominant mechanisms elucidated through which infection may culminate in an T-cell-mediated autoimmune response. However, other hypotheses including virus-induced decoy of the immune system also warrant discussion in regard to their potential for triggering autoimmunity. In this review, we discuss the mechanisms by which virus infection and antiviral immunity contribute to the development of autoimmunity. PMID:23947356

  1. Sexual dimorphism in autoimmunity.

    PubMed

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

    2015-06-01

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

  2. Role of Complement in Autoimmune Hemolytic Anemia

    PubMed Central

    Berentsen, Sigbjørn

    2015-01-01

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

  3. Bitter correlationship between autoimmune hepatitis and smoking.

    PubMed

    Bose, Tanima

    2015-02-01

    Cigarette smoke contains numerous toxic, carcinogenic and mutagenic chemicals, stable and unstable free radicals and reactive oxygen species (ROS) which cause biological oxidative damage. Continuous exposure to those chemicals leads to immense amount of damage to the human health either directly or indirectly. A hypothesis is advanced here that a possible explanation for developing autoimmune hepatitis (AIH) is due to regular smoking for long years of time. To examine this hypothesis, I relied on an experience of a case of a patient, as well as critical reading of the literature on smoking and different autoimmune disorders. Among the autoimmune diseases, rheumatoid arthritis (RA), multiple sclerosis (MS), thyroid disease, primary biliary cirrhosis (PBC) are reported mostly among tobacco-exposed animals. The observational and theoretical knowledge strengthen the hypothesis that smoking can be one of the causes of generating autoimmune hepatitis. This hypothesis could lead to a new diagnostic category, as well as therapeutic approaches for changing the regular smoking behavior. PMID:25543266

  4. Autoimmune Cytopenias in Chronic Lymphocytic Leukemia

    PubMed Central

    D'Arena, Giovanni; Guariglia, Roberto; La Rocca, Francesco; Trino, Stefania; Condelli, Valentina; De Martino, Laura; Musto, Pellegrino

    2013-01-01

    The clinical course of chronic lymphocytic leukemia (CLL) may be complicated at any time by autoimmune phenomena.The most common ones are hematologic disorders, such as autoimmune hemolytic anemia (AIHA) and immune thrombocytopenia (ITP). Pure red cell aplasia (PRCA) and autoimmune agranulocytosis (AG) are, indeed, more rarely seen. However, they are probably underestimated due to the possible misleading presence of cytopenias secondary to leukemic bone marrow involvement or to chemotherapy cytotoxicity. The source of autoantibodies is still uncertain, despite the most convincing data are in favor of the involvement of resting normal B-cells. In general, excluding the specific treatment of underlying CLL, the managementof these complications is not different from that of idiopathic autoimmune cytopenias or of those associated to other causes. Among different therapeutic approaches, monoclonal antibody rituximab, given alone or in combination, has shown to be very effective. PMID:23690826

  5. Rethinking Mechanisms of Autoimmune Pathogenesis

    PubMed Central

    Pillai, Shiv

    2016-01-01

    Why exactly some individuals develop autoimmune disorders remains unclear. The broadly accepted paradigm is that genetic susceptibility results in some break in immunological tolerance, may enhance the availability of autoantigens, and may enhance inflammatory responses. Some environmental insults that occur on this background of susceptibility may then contribute to autoimmunity. In this review we discuss some aspects related to inhibitory signaling and rare genetic variants, as well as additional factors that might contribute to autoimmunity including the possible role of clonal somatic mutations, the role of epigenetic events and the contribution of the intestinal microbiome. Genetic susceptibility alleles generally contribute to the loss of immunological tolerance, the increased availability of asutoantigens, or an increase in inflammation. Apart from common genetic variants, rare loss-of-function genetic variants may also contribute to the pathogenesis of autoimmunity. Studies of an inhibitory signaling pathway in B cells helped identify a negative regulatory enzyme called sialic acid acetyl esterase. The study of rare genetic variants of this enzyme provides an illustrative example showing the importance of detailed functional analyses of variant alleles and the need to exclude functionally normal common or rare genetic variants from analysis. It has also become clear that pathways that are functionally impacted by either common or rare defective variants can also be more significantly compromised by gene expression changes that may result from epigenetic alterations. Another important and evolving area that has been discussed relates to the role of the intestinal microbiome in influencing helper T cell polarization and the development of autoimmunity. PMID:23809879

  6. 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

  7. Update on Autoimmune Hepatitis

    PubMed Central

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

    2015-01-01

    Autoimmune hepatitis (AIH), a liver disorder affecting both children and adults, is characterized by inflammatory liver histology, elevated transaminase levels, circulating nonorganspecific autoantibodies, and increased levels of immunoglobulin G, in the absence of a known etiology. Two types of AIH are recognized according to seropositivity: smooth muscle antibody and/or antinuclear antibody define AIH type 1 and antibodies to liver-kidney microsome type 1 and/or liver cytosol type 1 define AIH type 2. AIH type 1 affects both adults and children, while AIH type 2 is mainly a paediatric disease, though it does occasionally affects young adults. AIH should be considered during the diagnostic workup of any patient with increased liver enzyme levels. AIH is exquisitely responsive to immunosuppressive treatment with prednisolone with or without azathioprine, with symptom free long-term survival for the majority of patients. For those who do not respond to standard treatment, or who are difficult-to-treat, mycophenolate mofetil and, in the absence of a response, calcineurin inhibitors should be tried in addition to steroids. The pathogenesis of AIH is not fully understood, although there is mounting evidence that genetic susceptibility, molecular mimicry and impaired immunoregulatory networks contribute to the initiation and perpetuation of the autoimmune attack. Liver damage is thought to be mediated primarily by CD4 T-cells, although recent studies support the involvement of diverse populations, including Th17 cells. A deeper understanding of the pathogenesis of AIH is likely to contribute to the development of novel treatments, such as the adoptive transfer of autologous expanded antigenspecific regulatory T-cells, which ultimately aim at restoring tolerance to liver-derived antigens. PMID:26357634

  8. [Recommendations from the Brazilian Society of Rheumatology on the diagnosis and treatment of intestinal parasitic infections in patients with autoimmune rheumatic disorders].

    PubMed

    Braz, Alessandra Sousa; de Andrade, Carlos Augusto Ferreira; da Mota, Licia Maria Henrique; Lima, Caliandra Maria Bezerra Luna

    2015-01-01

    Intestinal parasites - helminths and protozoa - are cosmopolitan diseases which are most prevalent in tropical regions. Patients with diagnoses of autoimmune rheumatic diseases have, due to the underlying disease or its treatment, an increased risk of occurrence of severe manifestations of intestinal parasites. Although the prevalence of these parasitic infections is very high in our environment, not always is the rheumatologist attentive to the need for investigation and treatment of helminthiasis and protozooses before the use of immunomodulatory, immunosuppressive therapies, and of biological drugs that are modifiers of the course of the disease. In this document, the Brazilian Society of Rheumatology establishes general recommendations on the diagnosis and treatment of intestinal parasitic infections in Brazil in patients with autoimmune rheumatic diseases, highlighting rheumatoid arthritis, systemic lupus erythematosus and spondyloarthritis. PMID:25583002

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

    PubMed

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

    2010-01-01

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

  10. Sirolimus for Autoimmune Disease of Blood Cells

    ClinicalTrials.gov

    2016-04-22

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

  11. 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

  12. The role of autoimmunity in premature ovarian failure.

    PubMed

    Ebrahimi, Mahbod; Akbari Asbagh, Firouzeh

    2015-08-01

    Premature ovarian failure (POF) is a heterogeneous syndrome with several causative factors. Autoimmune mechanisms are involved in pathogenesis of 4-30 % of POF cases. The present review focuses on the role of autoimmunity in the pathophysiology of POF. The evidences for an autoimmune etiology are: demonstration of ovarian autoantibodies, the presence of lymphocytic oophoritis, and association with other autoimmune disorders. Several ovarian antigenic targets have been identified in POF patients. The oocyte seems to be the most often targeted cell. Lymphocytic oophoritis is widely present in POF associated adrenal insufficiency. Addison's disease is one of the most common autoimmune disorders associated with POF. Early detection of this potentially life threatening disease was recommended in several studies. The gold standard for detecting autoimmune POF is ovarian biopsy. This procedure is not recommended due to unknown clinical value, expense, and risks. Several immunoassays have been proposed as substitute diagnostic tools. Nevertheless, there is no clinically proven sensitive and specific serum test to confirm the diagnosis of autoimmune POF or to anticipate the patient's chance of developing POF or associated diseases. Some authors suggested the possible effects of immuno-modulating therapy on the resumption of ovarian function and fertility in a selected group of autoimmune POF patients. However, in most instances, this treatment fails to reverse the course of the disease. Numerous studies illustrated that standard treatment outcome for infertility is less effective in the presence of ovarian autoimmunity. The antibody-induced damage could be a pathogenic factor. Nevertheless, the precise cause remains obscure. PMID:26568748

  13. Shared Genetic Relationships Underlying Generalized Vitiligo and Autoimmune Thyroid Disease

    PubMed Central

    2010-01-01

    Background Generalized vitiligo is an autoimmune disease of skin pigmentation that is associated with increased prevalence of other autoimmune diseases, particularly autoimmune thyroid disease (AITD; principally Hashimoto's disease and Graves' disease), both in vitiligo patients and their close relatives, suggesting a heritable predisposition involving, in part, shared susceptibility genes. Summary This review summarizes current knowledge of vitiligo epidemiology and genetics, highlighting recent findings from genome-wide approaches to disease gene identification, emphasizing susceptibility loci shared with other autoimmune diseases, particularly AITD, as well as some important differences. Conclusions Inherited susceptibility to generalized vitiligo involves a number of specific genes, many of which are shared with other autoimmune diseases that are epidemiologically associated with vitiligo, including AITD, confirming a longstanding hypothesis about the genetic basis of these disorders. These genes provide potential therapeutic targets for novel approaches to treatment as well as for approaches to presymptomatic diagnosis and disease prevention in individuals with inherited susceptibility to this group of autoimmune diseases. PMID:20578892

  14. Autoimmune channelopathies in paraneoplastic neurological syndromes.

    PubMed

    Joubert, Bastien; Honnorat, Jrme

    2015-10-01

    Paraneoplastic neurological syndromes and autoimmune encephalitides are immune neurological disorders occurring or not in association with a cancer. They are thought to be due to an autoimmune reaction against neuronal antigens ectopically expressed by the underlying tumour or by cross-reaction with an unknown infectious agent. In some instances, paraneoplastic neurological syndromes and autoimmune encephalitides are related to an antibody-induced dysfunction of ion channels, a situation that can be labelled as autoimmune channelopathies. Such functional alterations of ion channels are caused by the specific fixation of an autoantibody upon its target, implying that autoimmune channelopathies are usually highly responsive to immuno-modulatory treatments. Over the recent years, numerous autoantibodies corresponding to various neurological syndromes have been discovered and their mechanisms of action partially deciphered. Autoantibodies in neurological autoimmune channelopathies may target either directly ion channels or proteins associated to ion channels and induce channel dysfunction by various mechanisms generally leading to the reduction of synaptic expression of the considered channel. The discovery of those mechanisms of action has provided insights on the regulation of the synaptic expression of the altered channels as well as the putative roles of some of their functional subdomains. Interestingly, patients' autoantibodies themselves can be used as specific tools in order to study the functions of ion channels. This article is part of a Special Issue entitled: Membrane channels and transporters in cancers. PMID:25883091

  15. Secondary autoimmune cytopenias in chronic lymphocytic leukemia.

    PubMed

    Rogers, Kerry A; Woyach, Jennifer A

    2016-04-01

    Secondary autoimmune cytopenias in chronic lymphocytic leukemia are distinct clinical entities that require specific management. These autoimmune disorders have a complex pathogenesis that involves both the leukemic cells and the immune environment in which they exist. The mechanism is not the same in all cases, and to varying degrees involves the chronic lymphocytic leukemia (CLL) cells in antibody production, antigen presentation, and stimulation of T cells and bystander polyclonal B cells. Diagnosis of autoimmune cytopenias can be challenging as it is difficult to differentiate between autoimmunity and bone marrow failure due to disease progression. There is a need to distinguish these causes, as prognosis and treatment are not the same. Evidence regarding treatment of secondary autoimmune cytopenias is limited, but many effective options exist and treatment can be selected with severity of disease and patient factors in mind. With new agents to treat CLL coming into widespread clinical use, it will be important to understand how these will change the natural history and treatment of autoimmune cytopenias. PMID:27040709

  16. Smell and autoimmunity: a comprehensive review.

    PubMed

    Perricone, Carlo; Shoenfeld, Netta; Agmon-Levin, Nancy; de Carolis, Caterina; Perricone, Roberto; Shoenfeld, Yehuda

    2013-08-01

    The sense of smell is an ancient sensory modality vital for sampling and perceiving the chemical composition of surrounding environments. Olfaction involves a pathway of biochemical and electrophysiological processes, which allows the conversion of molecular information into sensations. Disturbances in the olfactory function have been investigated mainly in neurological/neurodegenerative disorders such as Alzheimer's and Parkinson's diseases; impaired sense of smell has been associated with depressed mood. Only recently, smell capability was tested in other diseases, particularly autoimmune diseases. Shoenfeld and colleagues opened this chapter showing that patients affected with systemic lupus erythematosus (SLE) have disturbances in their olfactory functions and revealed its association with neuropsychiatric manifestations of the disease. This evidence was confirmed in experimental models and replicated in other SLE populations. The connection between autoimmunity and the sense of smell was lately emphasized by studies on patients with Sjögren's syndrome and in patients with other autoimmune/immune-mediated diseases, such as polydermatomyositis, recurrent spontaneous abortion, and hereditary angioedema. Genetic susceptibility and hormonal and environmental factors may play a role in these conditions. Olfactory receptor gene clusters are located in proximity to key locus of susceptibility for autoimmune diseases such as the major histocompatibility complex, suggesting not only a physic linkage, but a functional association. Nonetheless, gender- and hormone-mediated effects are fundamental in the development of autoimmune diseases. The different connections between smell and autoimmunity, genes and hormones may suggest that this is another tessera of a mosaic which is waiting the answer of Oedipus. PMID:23233263

  17. 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

  18. 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

  19. Novel monogenic diseases causing human autoimmunity.

    PubMed

    Melki, Isabelle; Crow, Yanick J

    2015-12-01

    Fuelled by the on-going sequencing revolution, the last two years have seen a number of exciting discoveries relating to monogenic disorders predisposing to autoimmunity that provide new insights into the function of the human immune system. Here we discuss a selection of these diseases due to mutations in PRKCD, CTLA4, STAT3, IFIH1, TMEM173 and COPA. PMID:26262888

  20. Celiac disease-associated autoimmune endocrinopathies.

    PubMed

    Kumar, V; Rajadhyaksha, M; Wortsman, J

    2001-07-01

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

  1. [Narcolepsy as an autoimmune disease].

    PubMed

    Givaty, Gili; Ganelin-Cohen, Esther

    2013-03-01

    Narcolepsy is a chronic sleep disorder characterized by excessive daytime sleepiness and irresistible sleep attacks that occur during the activities of daily living. Falling asleep in the middle of essential activities such as driving or crossing the street may lead to life-threatening situations. Narcolepsy is estimated to affect 0.002% of the Israeli population. By using animal models, human autopsies and brain biopsies, it has recently been shown that the destruction of the orexin-secreting neurons underlies the pathogenicity of this disease. Orexin is a neurotransmitter involved in the sleep arousal cycle and also in the development of hunger sensations. Based on circumstantial evidence, it is estimated that the autoimmune system is responsible for the destruction of the orexin-secreting neurons. There are several findings in the literature that might connect the autoimmunity with the narcolepsy existence. For instance: narcolepsy is associated with high frequency of specific HLA system alleles, especially DQB1*0602. Furthermore, polymorphism in the alpha chain of the T cell receptors was found among narcolepsy patients. A more direct connection is the discovery of the Trib--an autoantigen. This protein is presented by orexin-secreting neurons and was recently found in narcoleptic patients exclusively, and not in the healthy control group. Nevertheless, there is still no agreement within the scientific community since a direct link between the autoimmune mechanism and narcolepsy has not yet been proved. Several trials using immune modulator therapy did not show any significant improvement. PMID:23713377

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

    PubMed

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

    2014-12-01

    Autoimmune thyroid disease (AITD), known as the most common organ-specific autoimmune disorder, is frequently accompanied by other organ and non-organ-specific autoimmune diseases, including rheumatoid arthritis (RA). Although the exact pathogenic mechanisms of the coexistence of autoimmune disorders are still not completely defined, genetics, immune defects, hormones and environmental factors may play key roles in polyautoimmunity. In this review, the prevalence of AITD and antithyroid autoantibodies in RA patients and rheumatic manifestations in association with thyroid autoimmunity are discussed. Finally, we review the role of genetics in the association of both AITD and RA, especially CTLA-4 and PTPN22 polymorphisms. PMID:25427993

  3. [Narcolepsy as an autoimmune disease].

    PubMed

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

    2015-01-01

    Narcolepsy is a sleep disorder of central origin. Hypocretin deficiency is the essential feature of type 1 narcolepsy. The biological background of type 2 narcolepsy (without cataplexy) is less clear. Infections or other external factors are thought to function as triggers of narcolepsy. After the H1N1 vaccination campaign, the incidence of narcolepsy increased clearly in countries where a vaccine boosted with the AS03 adjuvant was used. According to the current view, the increase of narcolepsy in connection with the pandemic vaccine especially in children and adolescents was associated with the virus component of the vaccine, but the adjuvant may also have boosted the development of autoimmune response. PMID:26245045

  4. 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 ...

  5. Auto-immune encephalitis as differential diagnosis of infectious encephalitis

    PubMed Central

    Armangue, Thaís; Leypoldt, Frank; Dalmau, Josep

    2014-01-01

    Purpose of review To describe the main types of autoimmune encephalitis with special emphasis on those associated with antibodies against neuronal cell surface or synaptic proteins, and the differential diagnosis with infectious encephalitis. Recent findings There is a continuous expansion of the number of cell surface or synaptic proteins that are targets of autoimmunity. The most recently identified include the mGluR5, DPPX, and the GABAAR. In these and previously known autoimmune encephalitis (NMDAR, AMPAR, GABABR, LGI1, CASPR2), the prodromal symptoms or types of presentations often suggest a viral encephalitis. We review here clues that help in the differential diagnosis with infectious encephalitis. Moreover, recent investigations indicate that viral encephalitis (e.g., herpes simplex) can trigger synaptic autoimmunity. In all these disorders immunotherapy is usually effective. Summary Autoimmune encephalitis comprises an expanding group of potentially treatable disorders that should be included in the differential diagnosis of any type of encephalitis. PMID:24792345

  6. Metals and kidney autoimmunity.

    PubMed Central

    Bigazzi, P E

    1999-01-01

    The causes of autoimmune responses leading to human kidney pathology remain unknown. However, environmental agents such as microorganisms and/or xenobiotics are good candidates for that role. Metals, either present in the environment or administered for therapeutic reasons, are prototypical xenobiotics that cause decreases or enhancements of immune responses. In particular, exposure to gold and mercury may result in autoimmune responses to various self-antigens as well as autoimmune disease of the kidney and other tissues. Gold compounds, currently used in the treatment of patients with progressive polyarticular rheumatoid arthritis, can cause a nephrotic syndrome. Similarly, an immune-mediated membranous nephropathy frequently occurred when drugs containing mercury were commonly used. Recent epidemiologic studies have shown that occupational exposure to mercury does not usually result in autoimmunity. However, mercury induces antinuclear antibodies, sclerodermalike disease, lichen planus, or membranous nephropathy in some individuals. Laboratory investigations have confirmed that the administration of gold or mercury to experimental animals leads to autoimmune disease quite similar to that observed in human subjects exposed to these metals. In addition, studies of inbred mice and rats have revealed that a few strains are susceptible to the autoimmune effects of gold and mercury, whereas the majority of inbred strains are resistant. These findings have emphasized the importance of genetic (immunogenetic and pharmacogenetic) factors in the induction of metal-associated autoimmunity. (italic)In vitro(/italic) and (italic)in vivo(/italic) research of autoimmune disease caused by mercury and gold has already yielded valuable information and answered a number of important questions. At the same time it has raised new issues about possible immunostimulatory or immunosuppressive mechanisms of xenobiotic activity. Thus it is evident that investigations of metal-induced renal autoimmunity have the potential to produce new knowledge with relevance to autoimmune disease caused by xenobiotics in general as well as to idiopathic autoimmunity. PMID:10502542

  7. 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

  8. Autoimmune polyglandular syndrome Type 2: the tip of an iceberg?

    PubMed Central

    Betterle, C; Lazzarotto, F; Presotto, F

    2004-01-01

    Autoimmune polyglandular syndromes (APS) are conditions characterized by the association of two or more organ-specific disorders. Type 2 APS is defined by the occurrence of Addison's disease with thyroid autoimmune disease and/or Type 1 diabetes mellitus. Clinically overt disorders are considered only the tip of the autoimmune iceberg, since latent forms are much more frequent. Historical, clinical, genetic, and immunological aspects of Type 2 APS are reviewed. Furthermore, data on 146 personal cases of Type 2 APS are also reported. PMID:15270837

  9. The IRF5–TNPO3 association with systemic lupus erythematosus has two components that other autoimmune disorders variably share

    PubMed Central

    Kottyan, Leah C.; Zoller, Erin E.; Bene, Jessica; Lu, Xiaoming; Kelly, Jennifer A.; Rupert, Andrew M.; Lessard, Christopher J.; Vaughn, Samuel E.; Marion, Miranda; Weirauch, Matthew T.; Namjou, Bahram; Adler, Adam; Rasmussen, Astrid; Glenn, Stuart; Montgomery, Courtney G.; Hirschfield, Gideon M.; Xie, Gang; Coltescu, Catalina; Amos, Chris; Li, He; Ice, John A.; Nath, Swapan K.; Mariette, Xavier; Bowman, Simon; Rischmueller, Maureen; Lester, Sue; Brun, Johan G.; Gøransson, Lasse G.; Harboe, Erna; Omdal, Roald; Cunninghame-Graham, Deborah S.; Vyse, Tim; Miceli-Richard, Corinne; Brennan, Michael T.; Lessard, James A.; Wahren-Herlenius, Marie; Kvarnström, Marika; Illei, Gabor G.; Witte, Torsten; Jonsson, Roland; Eriksson, Per; Nordmark, Gunnel; Ng, Wan-Fai; Anaya, Juan-Manuel; Rhodus, Nelson L.; Segal, Barbara M.; Merrill, Joan T.; James, Judith A.; Guthridge, Joel M.; Hal Scofield, R.; Alarcon-Riquelme, Marta; Bae, Sang-Cheol; Boackle, Susan A.; Criswell, Lindsey A.; Gilkeson, Gary; Kamen, Diane L.; Jacob, Chaim O.; Kimberly, Robert; Brown, Elizabeth; Edberg, Jeffrey; Alarcón, Graciela S.; Reveille, John D.; Vilá, Luis M.; Petri, Michelle; Ramsey-Goldman, Rosalind; Freedman, Barry I.; Niewold, Timothy; Stevens, Anne M.; Tsao, Betty P.; Ying, Jun; Mayes, Maureen D.; Gorlova, Olga Y.; Wakeland, Ward; Radstake, Timothy; Martin, Ezequiel; Martin, Javier; Siminovitch, Katherine; Moser Sivils, Kathy L.; Gaffney, Patrick M.; Langefeld, Carl D.; Harley, John B.; Kaufman, Kenneth M.

    2015-01-01

    Exploiting genotyping, DNA sequencing, imputation and trans-ancestral mapping, we used Bayesian and frequentist approaches to model the IRF5–TNPO3 locus association, now implicated in two immunotherapies and seven autoimmune diseases. Specifically, in systemic lupus erythematosus (SLE), we resolved separate associations in the IRF5 promoter (all ancestries) and with an extended European haplotype. We captured 3230 IRF5–TNPO3 high-quality, common variants across 5 ethnicities in 8395 SLE cases and 7367 controls. The genetic effect from the IRF5 promoter can be explained by any one of four variants in 5.7 kb (P-valuemeta = 6 × 10−49; OR = 1.38–1.97). The second genetic effect spanned an 85.5-kb, 24-variant haplotype that included the genes IRF5 and TNPO3 (P-valuesEU = 10−27–10−32, OR = 1.7–1.81). Many variants at the IRF5 locus with previously assigned biological function are not members of either final credible set of potential causal variants identified herein. In addition to the known biologically functional variants, we demonstrated that the risk allele of rs4728142, a variant in the promoter among the lowest frequentist probability and highest Bayesian posterior probability, was correlated with IRF5 expression and differentially binds the transcription factor ZBTB3. Our analytical strategy provides a novel framework for future studies aimed at dissecting etiological genetic effects. Finally, both SLE elements of the statistical model appear to operate in Sjögren's syndrome and systemic sclerosis whereas only the IRF5–TNPO3 gene-spanning haplotype is associated with primary biliary cirrhosis, demonstrating the nuance of similarity and difference in autoimmune disease risk mechanisms at IRF5–TNPO3. PMID:25205108

  10. 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

  11. Understanding autoimmunity: The ion channel perspective.

    PubMed

    RamaKrishnan, Anantha Maharasi; Sankaranarayanan, Kavitha

    2016-07-01

    Ion channels are integral membrane proteins that orchestrate the passage of ions across the cell membrane and thus regulate various key physiological processes of the living system. The stringently regulated expression and function of these channels hold a pivotal role in the development and execution of various cellular functions. Malfunction of these channels results in debilitating diseases collectively termed channelopathies. In this review, we highlight the role of these proteins in the immune system with special emphasis on the development of autoimmunity. The role of ion channels in various autoimmune diseases is also listed out. This comprehensive review summarizes the ion channels that could be used as molecular targets in the development of new therapeutics against autoimmune disorders. PMID:26854401

  12. Gq-Coupled Receptors in Autoimmunity

    PubMed Central

    Zhang, Lu; Shi, Guixiu

    2016-01-01

    Heterotrimeric G proteins can be divided into Gi, Gs, Gq/11, and G12/13 subfamilies according to their α subunits. The main function of G proteins is transducing signals from G protein coupled receptors (GPCRs), a family of seven transmembrane receptors. In recent years, studies have demonstrated that GPCRs interact with Gq, a member of the Gq/11 subfamily of G proteins. This interaction facilitates the vital role of this family of proteins in immune regulation and autoimmunity, particularly for Gαq, which is considered the functional α subunit of Gq protein. Therefore, understanding the mechanisms through which Gq-coupled receptors control autoreactive lymphocytes is critical and may provide insights into the treatment of autoimmune disorders. In this review, we summarize recent advances in studies of the role of Gq-coupled receptors in autoimmunity, with a focus on their pathologic role and downstream signaling. PMID:26885533

  13. 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

  14. Autoimmunity and the Gut

    PubMed Central

    Campbell, Andrew W.

    2014-01-01

    Autoimmune diseases have increased dramatically worldwide since World War II. This is coincidental with the increased production and use of chemicals both in industrial countries and agriculture, as well as the ease of travel from region to region and continent to continent, making the transfer of a pathogen or pathogens from one part of the world to another much easier than ever before. In this review, triggers of autoimmunity are examined, principally environmental. The number of possible environmental triggers is vast and includes chemicals, bacteria, viruses, and molds. Examples of these triggers are given and include the mechanism of action and method by which they bring about autoimmunity. PMID:24900918

  15. Infection, vaccines and other environmental triggers of autoimmunity.

    PubMed

    Molina, Vered; Shoenfeld, Yehuda

    2005-05-01

    The etiology of autoimmune diseases is still not clear but genetic, immunological, hormonal and environmental factors are considered to be important triggers. Most often autoimmunity is not followed by clinical symptoms unless an additional event such as an environmental factor favors an overt expression. Many environmental factors are known to affect the immune system and may play a role as triggers of the autoimmune mosaic.Infections: bacterial, viral and parasitic infections are known to induce and exacerbate autoimmune diseases, mainly by the mechanism of molecular mimicry. This was studied for some syndromes as for the association between SLE and EBV infection, pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection and more. Vaccines, in several reports were found to be temporally followed by a new onset of autoimmune diseases. The same mechanisms that act in infectious invasion of the host, apply equally to the host response to vaccination. It has been accepted for diphtheria and tetanus toxoid, polio and measles vaccines and GBS. Also this theory has been accepted for MMR vaccination and development of autoimmune thrombocytopenia, MS has been associated with HBV vaccination. Occupational and other chemical exposures are considered as triggers for autoimmunity. A debate still exists about the role of silicone implants in induction of scleroderma like disease.Not only foreign chemicals and agents have been associated with induction of autoimmunity, but also an intrinsic hormonal exposure, such as estrogens. This might explain the sexual dimorphism in autoimmunity.Better understanding of these environmental risk factors will likely lead to explanation of the mechanisms of onset and progression of autoimmune diseases and may lead to effective preventive involvement in specific high-risk groups. So by diagnosing a new patient with autoimmune disease a wide anamnesis work should be done. PMID:16126512

  16. Neurologic autoimmunity: mechanisms revealed by animal models.

    PubMed

    Bradl, Monika; Lassmann, Hans

    2016-01-01

    Over the last decade, neurologic autoimmunity has become a major consideration in the diagnosis and management of patients with many neurologic presentations. The nature of the associated antibodies and their targets has led to appreciation of the importance of the accessibility of the target antigen to antibodies, and a partial understanding of the different mechanisms that can follow antibody binding. This chapter will first describe the basic principles of autoimmune inflammation and tissue damage in the central and peripheral nervous system, and will then demonstrate what has been learnt about neurologic autoimmunity from circumstantial clinical evidence and from passive, active, and occasionally spontaneous or genetic animal models. It will cover neurologic autoimmune diseases ranging from disorders of neuromuscular transmission, peripheral and ganglionic neuropathy, to diseases of the central nervous system, where autoantibodies are either pathogenic and cause destruction or changes in function of their targets, where they are harmless bystanders of T-cell-mediated tissue damage, or are not involved at all. Finally, this chapter will summarize the relevance of current animal models for studying the different neurologic autoimmune diseases, and it will identify aspects where future animal models need to be improved to better reflect the disease reality experienced by affected patients, e.g., the chronicity or the relapsing/remitting nature of their disease. PMID:27112675

  17. Molecular Diagnosis in Autoimmune Skin Blistering Conditions

    PubMed Central

    Otten, J.V.; Hashimoto, T.; Hertl, M.; Payne, A.S.; Sitaru, C.

    2014-01-01

    Blister formation in skin and mucous membranes results from a loss of cell-cell or cell-matrix adhesion and is a common outcome of pathological events in a variety of conditions, including autoimmune and genetic diseases, viral and bacterial infections, or injury by physical and chemical factors. Autoantibodies against structural components maintaining cell-cell and cell-matrix adhesion induce tissue damage in autoimmune blistering diseases. Detection of these autoantibodies either tissue-bound or circulating in serum is essential to diagnose the autoimmune nature of disease. Various immunofluorescence methods as well as molecular immunoassays, including enzyme-linked immunosorbent assay and immunoblotting, belong to the modern diagnostic algorithms for these disorders. There is still a considerable need to increase awareness of the rare autoimmune blistering diseases, which often show a severe, chronic-relapsing course, among physicians and the public. This review article describes the immunopathological features of autoimmune bullous diseases and the molecular immunoassays currently available for their diagnosis and monitoring. PMID:24160488

  18. Autoimmune liver disease panel

    MedlinePlus

    ... Lindor KD. Primary biliary cirrhosis. In: Feldman M, Friedman LS, Brandt LJ, eds. Sleisenger and Fordtran's Gastrointestinal ... Czaia AJ. Autoimmune hepatitis. In: In: Feldman M, Friedman LS, Brandt LJ, eds. Sleisenger and Fordtran's Gastrointestinal ...

  19. Autoimmune Lymphoproliferative Syndrome (ALPS)

    MedlinePlus

    ... About NIAID News & Events Volunteer NIAID > Health & Research Topics > Autoimmune Lymphproliferative Syndrome (ALPS) Skip Website Tools Website Tools Print this page Order publications ​​​​​ Contact Info​ View a list of ...

  20. 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 ...

  1. Autoimmunity in 2014.

    PubMed

    Selmi, Carlo

    2015-10-01

    Our PubMed search for peer-reviewed articles published in the 2014 solar year retrieved a significantly higher number of hits compared to 2013 with a net 28 % increase. Importantly, full articles related to autoimmunity constitute approximately 5 % of immunology articles. We confirm that our understanding of autoimmunity is becoming a translational paradigm with pathogenetic elements rapidly followed by new treatment options. Furthermore, numerous clinical and pathogenetic elements and features are shared among autoimmune diseases, and this is well illustrated in the recent literature. More specifically, the past year witnessed critical revisions of our understanding and management of antiphospholipid syndrome with new exciting data on the pathogenicity of the serum anti-beta2 glycoprotein autoantibody, a better understanding of the current and new treatments for rheumatoid arthritis, and new position papers on important clinical questions such as vaccinations in patients with autoimmune disease, comorbidities, or new classification criteria. Furthermore, data confirming the important connections between innate immunity and autoimmunity via toll-like receptors or the critical role of T regulatory cells in tolerance breakdown and autoimmunity perpetuation were also reported. Lastly, genetic and epigenetic data were provided to confirm that the mosaic of autoimmunity warrants a susceptible individual background which may be geographically determined and contribute to the geoepidemiology of diseases. The 2014 literature in the autoimmunity world should be cumulatively regarded as part of an annus mirabilis in which, on a different level, the 2014 Annual Meeting of the American College of Rheumatology in Boston was attended by over 16,000 participants with over selected 3000 abstracts. PMID:26335699

  2. Viral triggers for autoimmunity

    PubMed Central

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

    2009-01-01

    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

  3. Silica, Silicosis, and Autoimmunity

    PubMed Central

    Pollard, Kenneth Michael

    2016-01-01

    Inhalation of dust containing crystalline silica is associated with a number of acute and chronic diseases including systemic autoimmune diseases. Evidence for the link with autoimmune disease comes from epidemiological studies linking occupational exposure to crystalline silica dust with the systemic autoimmune diseases systemic lupus erythematosus, systemic sclerosis, and rheumatoid arthritis. Although little is known regarding the mechanism by which silica exposure leads to systemic autoimmune disease, there is a voluminous literature on silica exposure and silicosis that may help identify immune processes that precede development of autoimmunity. The pathophysiology of silicosis consists of deposition of silica particles in the alveoli of the lung. Ingestion of these particles by macrophages initiates an inflammatory response, which stimulates fibroblasts to proliferate and produce collagen. Silica particles are encased by collagen leading to fibrosis and the nodular lesions characteristic of the disease. The steps in the development of silicosis, including acute and chronic inflammation and fibrosis, have different molecular and cellular requirements, suggesting that silica-induced inflammation and fibrosis may be mechanistically separate. Significantly, it is unclear whether silica-induced inflammation and fibrosis contribute similarly to the development of autoimmunity. Nonetheless, the findings from human and animal model studies are consistent with an autoimmune pathogenesis that begins with activation of the innate immune system leading to proinflammatory cytokine production, pulmonary inflammation leading to activation of adaptive immunity, breaking of tolerance, and autoantibodies and tissue damage. The variable frequency of these immunological features following silica exposure suggests substantial genetic involvement and gene/environment interaction in silica-induced autoimmunity. However, numerous questions remain unanswered. PMID:27014276

  4. Vaccines, adjuvants and autoimmunity.

    PubMed

    Guimares, Lusa Ea; Baker, Britain; Perricone, Carlo; Shoenfeld, Yehuda

    2015-10-01

    Vaccines and autoimmunity are linked fields. Vaccine efficacy is based on whether host immune response against an antigen can elicit a memory T-cell response over time. Although the described side effects thus far have been mostly transient and acute, vaccines are able to elicit the immune system towards an autoimmune reaction. The diagnosis of a definite autoimmune disease and the occurrence of fatal outcome post-vaccination have been less frequently reported. Since vaccines are given to previously healthy hosts, who may have never developed the disease had they not been immunized, adverse events should be carefully accessed and evaluated even if they represent a limited number of occurrences. In this review of the literature, there is evidence of vaccine-induced autoimmunity and adjuvant-induced autoimmunity in both experimental models as well as human patients. Adjuvants and infectious agents may exert their immune-enhancing effects through various functional activities, encompassed by the adjuvant effect. These mechanisms are shared by different conditions triggered by adjuvants leading to the autoimmune/inflammatory syndrome induced by adjuvants (ASIA syndrome). In conclusion, there are several case reports of autoimmune diseases following vaccines, however, due to the limited number of cases, the different classifications of symptoms and the long latency period of the diseases, every attempt for an epidemiological study has so far failed to deliver a connection. Despite this, efforts to unveil the connection between the triggering of the immune system by adjuvants and the development of autoimmune conditions should be undertaken. Vaccinomics is a field that may bring to light novel customized, personalized treatment approaches in the future. PMID:26275795

  5. Silica, Silicosis, and Autoimmunity.

    PubMed

    Pollard, Kenneth Michael

    2016-01-01

    Inhalation of dust containing crystalline silica is associated with a number of acute and chronic diseases including systemic autoimmune diseases. Evidence for the link with autoimmune disease comes from epidemiological studies linking occupational exposure to crystalline silica dust with the systemic autoimmune diseases systemic lupus erythematosus, systemic sclerosis, and rheumatoid arthritis. Although little is known regarding the mechanism by which silica exposure leads to systemic autoimmune disease, there is a voluminous literature on silica exposure and silicosis that may help identify immune processes that precede development of autoimmunity. The pathophysiology of silicosis consists of deposition of silica particles in the alveoli of the lung. Ingestion of these particles by macrophages initiates an inflammatory response, which stimulates fibroblasts to proliferate and produce collagen. Silica particles are encased by collagen leading to fibrosis and the nodular lesions characteristic of the disease. The steps in the development of silicosis, including acute and chronic inflammation and fibrosis, have different molecular and cellular requirements, suggesting that silica-induced inflammation and fibrosis may be mechanistically separate. Significantly, it is unclear whether silica-induced inflammation and fibrosis contribute similarly to the development of autoimmunity. Nonetheless, the findings from human and animal model studies are consistent with an autoimmune pathogenesis that begins with activation of the innate immune system leading to proinflammatory cytokine production, pulmonary inflammation leading to activation of adaptive immunity, breaking of tolerance, and autoantibodies and tissue damage. The variable frequency of these immunological features following silica exposure suggests substantial genetic involvement and gene/environment interaction in silica-induced autoimmunity. However, numerous questions remain unanswered. PMID:27014276

  6. Rheumatoid factors isolated from patients with autoimmune disorders are derived from germline genes distinct from those encoding the Wa, Po, and Bla cross-reactive idiotypes.

    PubMed Central

    Victor, K D; Randen, I; Thompson, K; Forre, O; Natvig, J B; Fu, S M; Capra, J D

    1991-01-01

    To better understand the structural basis for rheumatoid factor activity, the nucleotide sequence of the light chain variable regions of nine human monospecific IgM rheumatoid factors were analyzed. Rheumatoid factors were isolated from three patients with rheumatoid arthritis, a patient with systemic lupus erythematosus, and a normal individual. The VL gene segments used by these rheumatoid factors are not as restricted as previous work on mixed cryoglobulin rheumatoid factors had suggested. Each of the different VK families is represented and there are two examples where a V lambda gene segment is used. Molecules with structures similar to those of the Wa and Po CRI, characteristic of mixed cryoglobulin rheumatoid factors, are not common among these rheumatoid factors isolated from patients with rheumatoid arthritis. While there are clear examples of rheumatoid factors that are direct copies of germline genes, most of the sequence data suggest that the processes of antigenic selection and somatic mutation contribute significantly to the generation of monospecific rheumatoid factors in patients with autoimmune disease. PMID:2022732

  7. Autoimmunity in Waldenstrm's macroglobulinaemia.

    PubMed

    Jnsson, V; Kierkegaard, A; Salling, S; Molander, S; Andersen, L P; Christiansen, M; Wiik, A

    1999-07-01

    Fifty-seven consecutive patients with Waldenstrm's Macroglobuliemia were studied retrospectively for autoimmune manifestations. 28 patients or 51% (16 women and 13 men) had clinical and/or serological autoimmune manifestations, two or more of these being concomitant in 20 (12 women and 8 men). The predominant findings were Coombs' positive autoimmune hemolytic anemia (16%), seropositive rheumatoid arthritis (16%), inflammatory gastric ulcer with parietal cell autoantibodies (12%), and IgM-cardiolipin syndrome (11%). 40% of the autoimmune manifestations were present at the time of diagnosis of the Waldenstrm's Macroglobulinaemia and 60% were observed over a mean period of 4.7 years. All patients had an IgM M-component. There was no correlation between autoimmunity and the size of the M-component or the degree of hypo-IgG and hypo-IgA gammaglobulinemia. The only correlation between autoimmunity and infection was found in patients with gastric ulcer and parietal cell autoantibodies, in whom the infection was caused by Helicobacter pylori. PMID:10439374

  8. Autoimmunity in 2013.

    PubMed

    Selmi, Carlo

    2014-08-01

    The peer-reviewed publications in the field of autoimmunity published in 2013 represented a significant proportion of immunology articles and grew since the previous year to indicate that more immune-mediated phenomena may recognize an autoimmune mechanism and illustrated by osteoarthritis and atherosclerosis. As a result, our understanding of the mechanisms of autoimmunity is becoming the paradigm for translational research in which the progress in disease pathogenesis for both tolerance breakdown and inflammation perpetuation is rapidly followed by new treatment approaches and clinical management changes. The similarities across the autoimmune disease spectrum outnumber differences, particularly when treatments are compared. Indeed, the therapeutics of autoimmune diseases are based on a growing armamentarium that currently includes monoclonal antibodies and small molecules which act by targeting molecular markers or intracellular mediators with high specificity. Among the over 100 conditions considered as autoimmune, the common grounds are well illustrated by the data reported for systemic lupus erythematosus and rheumatoid arthritis or by the plethora of studies on Th17 cells and biomarkers, particularly serum autoantibodies. Further, we are particularly intrigued by studies on the genomics, epigenetics, and microRNA at different stages of disease development or on the safe and effective use of abatacept acting on the costimulation of T and B cells in rheumatoid arthritis. We are convinced that the data published in 2013 represent a promising background for future developments that will exponentially impact the work of laboratory and clinical scientists over the next years. PMID:24819586

  9. The epigenetics of autoimmunity

    PubMed Central

    Meda, Francesca; Folci, Marco; Baccarelli, Andrea; Selmi, Carlo

    2011-01-01

    The etiology of autoimmune diseases remains largely unknown. Concordance rates in monozygotic twins are lower than 50% while genome-wide association studies propose numerous significant associations representing only a minority of patients. These lines of evidence strongly support other complementary mechanisms involved in the regulation of genes expression ultimately causing overt autoimmunity. Alterations in the post-translational modification of histones and DNA methylation are the two major epigenetic mechanisms that may potentially cause a breakdown of immune tolerance and the perpetuation of autoimmune diseases. In recent years, several studies both in clinical settings and experimental models proposed that the epigenome may hold the key to a better understanding of autoimmunity initiation and perpetuation. More specifically, data support the impact of epigenetic changes in systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis and other autoimmune diseases, in some cases based on mechanistical observations. We herein discuss what we currently know and what we expect will come in the next future. Ultimately, epigenetic treatments already being used in oncology may soon prove beneficial also in autoimmune diseases. PMID:21278766

  10. 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

  11. Autoimmune polyglandular syndrome-3C in a child.

    PubMed

    Turkoglu, Zafer; Kavala, Mukaddes; Kolcak, Ozlem; Zindanci, Ilkin; Can, Burce

    2010-01-01

    Vitiligo is a chronic disorder that causes hypopigmentation in patches of skin. It occurs when the melanocytes, which are derived from neural crest, die or are unable to function. The precise pathogenesis is not yet fully understood but there is evidence suggesting it is caused by a combination of autoimmune, genetic, and neurohumoral factors. Autoimmune polyglandular syndrome (APS) is one of these diseases. APS has a rare incidence; its four subtypes are accompanied by multiple endocrine deficiencies. Autoimmune polyglandular syndrome-3C appears with autoimmune thyroid disease along with one of autoimmune pathologies of skin, neuromuscular system, and nervous system. We report a case of APS-3C in 12-year-old boy with generalized vitiligo, alopecia universalis, and Hashimoto thyroiditis that is the youngest of previous reported cases. PMID:20233565

  12. Autoimmune thrombocytopenic purpura.

    PubMed

    Karpatkin, S

    1980-09-01

    Adult autoimmune throbocytopenic purpura (ATP) is a platelet disorder that develops in certain individuals with a genetic as well as sex (female) predisposition following an environment event (?viral). This results in the production of an IgG antiplatelet antibody capable of reacting with the host's platelets, as well as crossing the placenta. This leads to the rapid clearance and destruction of opsonized platelets by the reticuloendothelial system, particularly the spleen, by greater than tenfold the normal rate. Bound platelet IgG correlates with disease severity, whereas serum antiplatelet IgG does not. It has not been rigorously established whether bound platelet IgG is directed against a platelet antigen or represents an immune complex bound to the platelet Fc receptor. Nevertheless, several lines of evidence suggest that antiplatelet IgG binds directly to a platelet antigen(s). Megakaryocyte number, volume, and mass are increased commensurate with increased platelet turnover. Platelets of increased size, megathrombocytes, are noted on peripheral smear or via platelet volume distribution analysis. Megathrombocyte number is proporationate to megakarocyte number and to platelet turnover. Megathrombocyte diameter is inversely proportional to platelet survival. Antiplatelet antibody is also associated with qualitative platelet functional defects, which are indistinguishable from those noted with thrombopathia (i.e., apparent platelet release defect). Antibody-induced functional defects are probably more common than quantitative thrombocytopenic defects and may represent a significant portion of those women with the "easy bruising" syndrome and normal platelet count. Adults who develop ATP generally develop the chronic variety, which remains permanently with the patient. Treatment should be directed towards maintaining the patient free of purpura, not restoring the platelet count to normal. This can generally be accomplished with a platelet count of > 40,000/cu mm with patients having this disorder. Approximately 50% of patients respond to steroids by a significant elevation of platelet count and improvement of purpura. However, cessation of therapy results in eventual relapse if the disease is of the chronic variety. Splenectomy is successful in approximately 65-75% of patients, resulting in a restoration of the platelet count to normal or safe levels by removing a major source of platelet destruction as well as antibody production; platelet survival improves. At least 50% of patients "in remission" following steroids or splenectomy generally have a compensated thrombocytolytic state in which increased platelet production keeps up with increased platelet destruction. Antiplatelet IgG can often be found in the serum of these patients. Patients refractory to steroids and/or splenectomy present with a serious therapeutic problem. Immunosuppressive therapy is effective in approximately one-third of refractory patients, but often relapses occur, requiring maintenance therapy with potentially mutagenic drugs... PMID:6157441

  13. Autoimmune thrombocytopenic purpura.

    TOXLINE Toxicology Bibliographic Information

    Karpatkin S

    1980-09-01

    Adult autoimmune throbocytopenic purpura (ATP) is a platelet disorder that develops in certain individuals with a genetic as well as sex (female) predisposition following an environment event (?viral). This results in the production of an IgG antiplatelet antibody capable of reacting with the host's platelets, as well as crossing the placenta. This leads to the rapid clearance and destruction of opsonized platelets by the reticuloendothelial system, particularly the spleen, by greater than tenfold the normal rate. Bound platelet IgG correlates with disease severity, whereas serum antiplatelet IgG does not. It has not been rigorously established whether bound platelet IgG is directed against a platelet antigen or represents an immune complex bound to the platelet Fc receptor. Nevertheless, several lines of evidence suggest that antiplatelet IgG binds directly to a platelet antigen(s). Megakaryocyte number, volume, and mass are increased commensurate with increased platelet turnover. Platelets of increased size, megathrombocytes, are noted on peripheral smear or via platelet volume distribution analysis. Megathrombocyte number is proporationate to megakarocyte number and to platelet turnover. Megathrombocyte diameter is inversely proportional to platelet survival. Antiplatelet antibody is also associated with qualitative platelet functional defects, which are indistinguishable from those noted with thrombopathia (i.e., apparent platelet release defect). Antibody-induced functional defects are probably more common than quantitative thrombocytopenic defects and may represent a significant portion of those women with the "easy bruising" syndrome and normal platelet count. Adults who develop ATP generally develop the chronic variety, which remains permanently with the patient. Treatment should be directed towards maintaining the patient free of purpura, not restoring the platelet count to normal. This can generally be accomplished with a platelet count of > 40,000/cu mm with patients having this disorder. Approximately 50% of patients respond to steroids by a significant elevation of platelet count and improvement of purpura. However, cessation of therapy results in eventual relapse if the disease is of the chronic variety. Splenectomy is successful in approximately 65-75% of patients, resulting in a restoration of the platelet count to normal or safe levels by removing a major source of platelet destruction as well as antibody production; platelet survival improves. At least 50% of patients "in remission" following steroids or splenectomy generally have a compensated thrombocytolytic state in which increased platelet production keeps up with increased platelet destruction. Antiplatelet IgG can often be found in the serum of these patients. Patients refractory to steroids and/or splenectomy present with a serious therapeutic problem. Immunosuppressive therapy is effective in approximately one-third of refractory patients, but often relapses occur, requiring maintenance therapy with potentially mutagenic drugs...

  14. 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.

  15. Autoimmune Channelopathies of the Nervous System

    PubMed Central

    Kleopa, Kleopas A

    2011-01-01

    Ion channels are complex transmembrane proteins that orchestrate the electrical signals necessary for normal function of excitable tissues, including the central nervous system, peripheral nerve, and both skeletal and cardiac muscle. Progress in molecular biology has allowed cloning and expression of genes that encode channel proteins, while comparable advances in biophysics, including patch-clamp electrophysiology and related techniques, have made the functional assessment of expressed proteins at the level of single channel molecules possible. The role of ion channel defects in the pathogenesis of numerous disorders has become increasingly apparent over the last two decades. Neurological channelopathies are frequently genetically determined but may also be acquired through autoimmune mechanisms. All of these autoimmune conditions can arise as paraneoplastic syndromes or independent from malignancies. The pathogenicity of autoantibodies to ion channels has been demonstrated in most of these conditions, and patients may respond well to immunotherapies that reduce the levels of the pathogenic autoantibodies. Autoimmune channelopathies may have a good prognosis, especially if diagnosed and treated early, and if they are non-paraneoplastic. This review focuses on clinical, pathophysiologic and therapeutic aspects of autoimmune ion channel disorders of the nervous system. PMID:22379460

  16. Autoimmune pancreatitis--recent advances.

    PubMed

    Novotný, I; Díte, P; Lata, J; Nechutová, H; Kianicka, B

    2010-01-01

    Autoimmune pancreatitis (AIP) is recognized as a distinct clinical entity, identified as a chronic inflammatory process of the pancreas in which the autoimmune mechanism is involved. Clinically and histologically, AIP has two subsets: type 1--lymphoplasmatic sclerosing pancreatitis with abundant infiltration of the pancreas and other affected organs with immunoglobulin G4-positive plasma cells, and type 2--duct centric fibrosis, characterized by granulocyte epithelial lesions in the pancreas without systemic involvement. In the diagnosis of AIP, two diagnostic criterions are used--the HISORt criteria and Asian Diagnostic Criteria. In the differential diagnosis, the pancreatic cancer must be excluded by endosonographically guided pancreatic biopsy. Typical signs of AIP are concomitant disorders in other organs (kidney, liver, biliary tract, salivary glands, colon, retroperitoneum, prostate). Novel clinicopathological entity was proposed as an 'IgG4-related sclerosing disease' (IgG4-RSC). Extensive IgG4-positive plasma cells and T lymphocyte infiltration is a common characteristics of this disease. Recently, IgG4-RSC syndrome was extended to a new entity, characterized by IgG4 hypergammaglobulinemia and IgG4-positive plasma cell infiltration, this being considered an expression of a lymphoproliferative disease, 'IgG4-positive multiorgan lymphoproliferative syndrome'. This syndrome includes Mikulicz's disease, mediastinal fibrosis, autoimmune hypophysitis, and inflammatory pseudotumor--lung, liver, breast. In the therapy of AIP, steroids constitute first-choice treatment. High response to the corticosteroid therapy is an important diagnostic criterion. In the literature, there are no case-control studies that determine if AIP predisposes to pancreatic cancer. Undoubtedly, AIP is currently a hot topic in pancreatology. PMID:20814208

  17. A clinical approach to diagnosis of autoimmune encephalitis.

    PubMed

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

    2016-04-01

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

  18. 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

  19. Triggers and drivers of autoimmunity: lessons from coeliac disease

    PubMed Central

    Sollid, Ludvig M.; Jabri, Bana

    2013-01-01

    Preface Coeliac disease, an inflammatory disease of the small intestine, shares key features with autoimmune disorders, such as susceptibility genes, presence of autoantibodies and T cell-mediated destruction of specific cells. Strikingly, however, continuous exposure to the exogenous dietary antigen gluten and gluten-specific adaptive immunity are required to maintain immunopathology. These observations challenge the notion that autoimmunity requires adaptive immune activation towards self-antigens. Using coeliac disease as an example, we propose that other exogenous factors might be identified as drivers of autoimmune processes, in particular when evidence for T cells with specificity for self-antigens is lacking. PMID:23493116

  20. Autoimmune polyendocrine syndromes: clues to type 1 diabetes pathogenesis

    PubMed Central

    Husebye, Eystein S.; Anderson, Mark S.

    2010-01-01

    Summary Autoimmune diseases like type 1 diabetes are complex in their pathogenesis. One approach to improving our understanding of type 1 diabetes is the study of diseases that represent more extreme examples of autoimmunity. Autoimmune polyendocrine syndromes (APS) are relatively rare diseases that often include type 1 diabetes as part of the disease phenotype. Recently there has been tremendous progress in unraveling some of the underlying mechanisms of APS. Here we highlight the APS disorders with the perspective of the clues they can offer to the pathogenesis and treatment of type 1 diabetes. PMID:20412758

  1. Triggers and drivers of autoimmunity: lessons from coeliac disease.

    PubMed

    Sollid, Ludvig M; Jabri, Bana

    2013-04-01

    Coeliac disease, an inflammatory disease of the small intestine, shares key features with autoimmune disorders, such as susceptibility genes, presence of autoantibodies and T cell-mediated destruction of specific cells. Strikingly, however, continuous exposure to the exogenous dietary antigen gluten and gluten-specific adaptive immunity are required to maintain immunopathology. These observations challenge the notion that autoimmunity requires adaptive immune activation towards self antigens. Using coeliac disease as an example, we propose that other exogenous factors might be identified as drivers of autoimmune processes, in particular when evidence for T cells with specificity for self antigens driving the disease is lacking. PMID:23493116

  2. The expanding spectrum of the Autoimmune Lymphoproliferative Syndromes

    PubMed Central

    Oliveira, João Bosco

    2015-01-01

    1. Purpose of review Several autoimmune lymphoproliferative syndromes have been described lately. We review here the main clinical and laboratory findings of these new disorders. 2. Recent findings The prototypical autoimmune lymphoproliferative syndrome (ALPS) has had its diagnostic criteria modified; somatic mutations in RAS genes were found to cause an ALPS-like syndrome in humans; and mutations in a gene encoding a protein kinase C (PRKCD) were discovered to cause a syndrome of lymphoproliferation, autoimmunity and NK cell defect. 3. Summary The recent discoveries shed light into the molecular pathways governing lymphocyte death, proliferation and immune tolerance in humans. PMID:24240292

  3. Unraveling the autoimmune translational research process layer by layer

    PubMed Central

    Blumberg, Richard S; Dittel, Bonnie; Hafler, David; von Herrath, Matthias; Nestle, Frank O

    2015-01-01

    Autoimmune diseases have a complex etiology and despite great progress having been made in our comprehension of these disorders, there has been limited success in the development of approved medications based on these insights. Development of drugs and strategies for application in translational research and medicine are hampered by an inadequate molecular definition of the human autoimmune phenotype and the organizational models that are necessary to clarify this definition. PMID:22227670

  4. Reconceiving autoimmunity: An overview.

    PubMed

    Tauber, Alfred I

    2015-06-21

    Three interconnected positions are advocated: (1) although serving as a useful model, the immune self does not exist as such; (2) instead of a self/nonself demarcation, the immune system 'sees' itself, i.e., it does not ignore the 'self' or attack the 'other;' but exhibits a spectrum of responses, which when viewed from outside the system appear as discrimination of 'self' and 'nonself' based on certain criteria of reactivity. When immune reactions are conceived in terms of normal physiology and open exchange with the environment, where borders dividing host and foreign are elusive and changing, host defense is only part of the immune system's functions, which actually comprise two basic tasks: protection, i.e., to preserve host integrity, and maintenance of organismic identity. And thus (3) if the spectrum of immunity is enlarged, differentiating low reactive 'autoimmune' reactions from activated immune responses against the 'other' is only a matter of degree. Simply, all immunity is 'autoimmunity,' and the pathologic state of immunity directed at normal constituents of the organism is a particular case of dis-regulation, which appropriately is designated, autoimmune. Other uses of 'autoimmunity' and its congeners function as the semantic remnants of Burnet's original self/nonself theory and should be replaced. A new nomenclature is proposed, concinnity, which more accurately designates the physiology of the animal's ordinary housekeeping economy mediated by the immune system than 'autoimmunity' when used to describe such normal functions. PMID:24880023

  5. Curcumin and autoimmune disease.

    PubMed

    Bright, John J

    2007-01-01

    The immune system has evolved to protect the host from microbial infection; nevertheless, a breakdown in the immune system often results in infection, cancer, and autoimmune diseases. Multiple sclerosis, rheumatoid arthritis, type 1 diabetes, inflammatory bowel disease, myocarditis, thyroiditis, uveitis, systemic lupus erythromatosis, and myasthenia gravis are organ-specific autoimmune diseases that afflict more than 5% of the population worldwide. Although the etiology is not known and a cure is still wanting, the use of herbal and dietary supplements is on the rise in patients with autoimmune diseases, mainly because they are effective, inexpensive, and relatively safe. Curcumin is a polyphenolic compound isolated from the rhizome of the plant Curcuma longa that has traditionally been used for pain and wound-healing. Recent studies have shown that curcumin ameliorates multiple sclerosis, rheumatoid arthritis, psoriasis, and inflammatory bowel disease in human or animal models. Curcumin inhibits these autoimmune diseases by regulating inflammatory cytokines such as IL-1beta, IL-6, IL-12, TNF-alpha and IFN-gamma and associated JAK-STAT, AP-1, and NF-kappaB signaling pathways in immune cells. Although the beneficial effects of nutraceuticals are traditionally achieved through dietary consumption at low levels for long periods of time, the use of purified active compounds such as curcumin at higher doses for therapeutic purposes needs extreme caution. A precise understanding of effective dose, safe regiment, and mechanism of action is required for the use of curcumin in the treatment of human autoimmune diseases. PMID:17569223

  6. Epigenetics in human autoimmunity

    PubMed Central

    STRICKLAND, FAITH M.; RICHARDSON, BRUCE C.

    2010-01-01

    Epigenetic mechanisms are essential for normal development and function of the immune system. Similarly, a failure to maintain epigenetic homeostasis in the immune response due to factors including environmental influences, leads to aberrant gene expression, contributing to immune dysfunction and in some cases the development of autoimmunity in genetically predisposed individuals. This is exemplified by systemic lupus erythematosus, where environmentally induced epigenetic changes contribute to disease pathogenesis in those genetically predisposed. Similar interactions between genetically determined susceptibility and environmental factors are implicated in other systemic autoimmune diseases such as rheumatoid arthritis and scleroderma, as well as in organ specific autoimmunity. The skin is exposed to a wide variety of environmental agents, including UV radiation, and is prone to the development of autoimmune conditions such as atopic dermatitis, psoriasis and some forms of vitiligo, depending on environmental and genetic influences. Herein we review how disruption of epigenetic mechanisms can alter immune function using lupus as an example, and summarize how similar mechanisms may contribute to other human autoimmune rheumatic and skin diseases. PMID:18432408

  7. Autoimmunity and Asbestos Exposure

    PubMed Central

    Pfau, Jean C.; Serve, Kinta M.; Noonan, Curtis W.

    2014-01-01

    Despite a body of evidence supporting an association between asbestos exposure and autoantibodies indicative of systemic autoimmunity, such as antinuclear antibodies (ANA), a strong epidemiological link has never been made to specific autoimmune diseases. This is in contrast with another silicate dust, crystalline silica, for which there is considerable evidence linking exposure to diseases such as systemic lupus erythematosus, systemic sclerosis, and rheumatoid arthritis. Instead, the asbestos literature is heavily focused on cancer, including mesothelioma and pulmonary carcinoma. Possible contributing factors to the absence of a stronger epidemiological association between asbestos and autoimmune disease include (a) a lack of statistical power due to relatively small or diffuse exposure cohorts, (b) exposure misclassification, (c) latency of clinical disease, (d) mild or subclinical entities that remain undetected or masked by other pathologies, or (e) effects that are specific to certain fiber types, so that analyses on mixed exposures do not reach statistical significance. This review summarizes epidemiological, animal model, and in vitro data related to asbestos exposures and autoimmunity. These combined data help build toward a better understanding of the fiber-associated factors contributing to immune dysfunction that may raise the risk of autoimmunity and the possible contribution to asbestos-related pulmonary disease. PMID:24876951

  8. Autoimmune diseases and venous thromboembolism: a review of the literature

    PubMed Central

    Zöller, Bengt; Li, Xinjun; Sundquist, Jan; Sundquist, Kristina

    2012-01-01

    Venous thromboembolism (VTE) is major health problem and is sometimes complicated by lethal pulmonary embolism (PE). Disturbances of the coagulation and anticoagulation systems are important risk factors for VTE. Comparative studies suggest that coagulation and innate immunity have a shared evolutionary origin. It is therefore unsurprising that the immune and coagulation systems are linked, with many molecular components being important for both systems. Systemic inflammation modulates thrombotic responses by suppressing fibrinolysis, upregulating procoagulant, and downregulating anticoagulants, and autoimmune disorders such as systemic lupus erythematosus (SLE), inflammatory bowel disease (IBD), and Behçet’s syndrome have been linked to an increased risk of VTE. Recent reports have further shown that a majority of autoimmune and immune-mediated disorders are linked to an increased risk of venous thrombosis, PE, or VTE. For instance, a Swedish nationwide study found that the risk of PE was increased in the first year after hospitalization for 33 different autoimmune disorders. Especially high risks were noted for several autoimmune diseases such as immune thrombocytopenic purpura, polyarteritis nodosa, polymyositis/dermatomyositis, ulcerative colitis, and SLE. Another study from England, also based on hospitalization data, found that immune-mediated disorders were associated with an increased risk of VTE compared with other medical causes of hospitalization. Multiple mechanisms may operate and disease-specific factors, such as cardiolipin antibodies, have been identified. However, inflammation by itself appears to change the hemostatic balance in a thrombogenic direction. Recent epidemiological studies, together with previous experimental and clinical studies, indicate that autoimmune disorders should not only be viewed as inflammatory disorders, but also hypercoagulable disorders. Research to identify thrombotic risk factors, elucidate the mechanisms involved, and investigate prophylactic regiments is needed. The present review describes the epidemiological, clinical, and experimental evidence for the connection between VTE and autoimmune and immune-mediated disorders. PMID:22937487

  9. Safety of vaccine adjuvants: focus on autoimmunity.

    PubMed

    van der Laan, Jan Willem; Gould, Sarah; Tanir, Jennifer Y

    2015-03-24

    Questions have been recently raised regarding the safety of vaccine adjuvants, particularly in relation to autoimmunity or autoimmune disease(s)/disorder(s) (AID). The International Life Sciences Institute (ILSI) Health and Environmental Sciences Institute (HESI) formed a scientific committee and convened a 2-day workshop, consisting of technical experts from around the world representing academia, government regulatory agencies, and industry, to investigate and openly discuss the issues around adjuvant safety in vaccines. The types of adjuvants considered included oil-in-water emulsions and toll-like receptor (TLR) agonists. The state of science around the use of animal models and biomarkers for the evaluation and prediction of AID were also discussed. Following extensive literature reviews by the HESI committee, and presentations by experts at the workshop, several key points were identified, including the value of animal models used to study autoimmunity and AID toward studying novel vaccine adjuvants; whether there is scientific evidence indicating an intrinsic risk of autoimmunity and AID with adjuvants, or a higher risk resulting from the mechanism of action; and if there is compelling clinical data linking adjuvants and AID. The tripartite group of experts concluded that there is no compelling evidence supporting the association of vaccine adjuvants with autoimmunity signals. Additionally, it is recommended that future research on the potential effects of vaccine adjuvants on AID should consider carefully the experimental design in animal models particularly if they are to be used in any risk assessment, as an improper design and model could result in misleading information. Finally, studies on the mechanistic aspects and potential biomarkers related to adjuvants and autoimmunity phenomena could be developed. PMID:25659277

  10. Evaluation of basal ganglia and thalamic inflammation in children with pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection and tourette syndrome: a positron emission tomographic (PET) study using 11C-[R]-PK11195.

    PubMed

    Kumar, Ajay; Williams, Mitchel T; Chugani, Harry T

    2015-05-01

    We applied PET scanning with (11)C-[R]-PK11195 (PK) to evaluate neuroinflammatory changes in basal ganglia and thalamus in children with clinically diagnosed pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS) and Tourette syndrome. Seventeen children with PANDAS (mean age: 11.4 ± 2.6 years; 13 males), 12 with Tourette syndrome (mean age: 11.0 ± 3.0 years; 10 males), and 15 normal adults (mean age: 28.7 ± 7.9 years; 8 males) underwent dynamic PK PET imaging and binding potential, a measure of ligand-TSPO receptor (expressed by activated microglia) binding, was calculated for basal ganglia and thalamus. Binding potential values, suggesting underlying activated microglia-mediated neuroinflammation, were found to be increased in bilateral caudate and bilateral lentiform nucleus in the PANDAS group and in bilateral caudate nuclei only in the Tourette syndrome group, compared to control group. These differences in the pattern and extent of neuroinflammation also signify a possible difference in pathophysiological etiology between PANDAS and Tourette syndrome patients. PMID:25117419

  11. Multiple autoimmunity, type 1 diabetes (T1DM), autoimmune thyroiditis and thyroid cancer: is there an association? A case report and literature review.

    PubMed

    Karavanaki, Kyriaki; Karayianni, Christina; Vassiliou, Ioannis; Tzanela, Marinella; Sdogou, Triantafyllia; Kakleas, Kostas; Tsentidis, Charalambos; Vakaki, Marina; Soldatou, Alexandra; Kallinikou, Dimitra; Kostaki, Maria; Tsitsopoulos, Stathis; Papathanasiou, Asteroula

    2014-09-01

    Type 1 diabetes mellitus (T1DM) is characterized by selective autoimmune destruction of pancreatic b-cells, resulting in insulin deficiency. Associated autoimmune disorders, such as celiac disease, autoimmune thyroiditis, and gastritis, can coexist in patients with T1DM. These disorders are characterized by the presence of antibodies against tissue transglutaminase (anti-tTG-IgA), thyroglobulin, and thyroid peroxidase (anti-TG, anti-TPO), as well as antibodies against gastric parietal cells. Children with T1DM may also develop organ-specific multiple autoimmunity, with the coexistence of one or more autoimmune disorders. Furthermore, there is a lot of controversy regarding the role of thyroid autoimmunity in the pathogenesis of thyroid cancer. We present a child with T1DM and multiple autoimmunity including autoimmune Hashimoto's thyroiditis (HT), who developed thyroid cancer. The literature on the prevalence of associated autoimmunity in children with T1DM and the prevalence, pathogenesis, and timely diagnosis of thyroid cancer among patients with HT is also reviewed. PMID:24854531

  12. Autoimmune encephalitis: Clinical diagnosis versus antibody confirmation

    PubMed Central

    Cyril, Asha Caroline; Nair, Sruthi S.; Mathai, Annamma; Kannoth, Sudheeran; Thomas, Sanjeev V.

    2015-01-01

    Context: Autoimmune encephalitis is a heterogeneous disorder which is being diagnosed with increasing frequency. The diagnosis of these disorders is based on the detection of autoantibodies and characteristic clinical profiles. Aims: We aimed to study the antibody profile in encephalitis patients with suspected autoimmune etiology presenting to a tertiary care center. Settings and Design: The subjects were selected by screening all patients with clinical profile suggesting autoimmune encephalitis admitted in the neuromedical intensive care unit (ICU) of a tertiary care center in South India. Materials and Methods: Patients who fulfilled modified Zuliani et al.'s, criteria for autoimmune encephalitis were identified during the period December 2009–June 2013. Blood samples from these subjects were screened for six neuronal antibodies. Statistical analysis used: Chi-square test was applied to compare the antibody positive and negative patients. Results: Out of 1,227 patients screened, 39 subjects (14 males: 25 females) were identified with a mean age of 15.95 years and 19 cases were assessed in the acute and 20 in the convalescent phase of the illness. Seizure (87.8 %) was the most common presenting symptom; status epilepticus occurred in 23 (60.5%) patients during the course of the illness. Fourteen (35.9%) patients were N-methyl-D-aspartate receptor (NMDAR) antibody-positive and all were negative for the other antibodies tested. Conclusions: One-third of patients presenting with acute noninfective encephalitis would be positive for NMDAR antibodies with the remaining two-thirds with clinically suspected autoimmune encephalitis being antibody-negative. There are few markers in the clinical and investigative profiles to distinguish antibody-positive and -negative patients. PMID:26713011

  13. EBV and Autoimmunity.

    PubMed

    Ascherio, Alberto; Munger, Kassandra L

    2015-01-01

    Although a role of EBV in autoimmunity is biologically plausible and evidence of altered immune responses to EBV is abundant in several autoimmune diseases, inference on causality requires the determination that disease risk is higher in individuals infected with EBV than in those uninfected and that in the latter it increases following EBV infection. This determination has so far been possible only for multiple sclerosis (MS) and, to some extent, for systemic lupus erythematosus (SLE), whereas evidence is either lacking or not supportive for other autoimmune conditions. In this chapter, we present the main epidemiological findings that justify the conclusion that EBV is a component cause of MS and SLE and possible mechanisms underlying these effects. PMID:26424654

  14. 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

  15. 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

  16. Autoimmune neutropenia preceding Helicobacter pylori-negative MALT lymphoma with nodal dissemination

    PubMed Central

    Harada, Saori; Yamazaki, Sho; Nakamura, Fumihiko; Morita, Ken; Yoshimi, Akihide; Shinozaki-Ushiku, Aya; Fukayama, Masashi; Kurokawa, Mineo

    2014-01-01

    Autoimmune neutropenia (AIN), resulting from granulocyte-specific autoantibodies, is much less frequent than other autoimmune hematologic disorders including autoimmune hemolytic anemia (AIHA) and immune thrombocytopenia (ITP). These autoimmune disorders may precede, synchronize, or follow collagen disorders, viral infections, and lymphoid neoplasms. Herein we present the first case of AIN in association with Helicobacter pylori-negative mucosa-associated lymphoid tissue (MALT) lymphoma with nodal dissemination. In our case, AIN, accompanied by ITP, occurred prior to the clinical manifestation of lymphoma. AIN and ITP were well managed afterwards, but they relapsed in accordance with the recurrence of lymphoma. The administration of prednisolone at 0.5 mg/kg daily alleviated the cytopenias within a week. In general, combination chemotherapy is performed for the treatment of lymphoma-associated autoimmune hematologic disorders and indeed seems to be effective. Our case indicates that corticosteroid monotherapy may be effective for lymphoma-associated AIN especially when AIN precedes the onset of lymphoma. PMID:25337296

  17. Chromosome 18q deletion syndrome with autoimmune diabetes mellitus: putative genomic loci for autoimmunity and immunodeficiency.

    PubMed

    Hogendorf, Anna; Lipska-Zietkiewicz, Beata S; Szadkowska, Agnieszka; Borowiec, Maciej; Koczkowska, Magdalena; Trzonkowski, Piotr; Drozdz, Izabela; Wyka, Krystyna; Limon, Janusz; Mlynarski, Wojciech

    2016-03-01

    A girl with 18q deletion syndrome was diagnosed with autoimmune diabetes mellitus and Hashimoto's thyroiditis at the age of 3 yr. In addition, the girl suffered from recurrent infections due to immunoglobulin A and IgG4 deficiency. She was also found to have CD3+CD4+FoxP3+, CD3+CD4+FoxP3+CD25+, and CD3+CD4+CD25+CD127 regulatory T cells deficiency. The exceptional coincidence of the two autoimmune disorders occurring at an early age, and associated with immune deficiency, implies that genes located on deleted 19.4 Mbp region at 18q21.32-q23 (chr18:58,660,699-78,012,870) might play a role in the pathogenesis of autoimmunity leading to β cell destruction and diabetes. PMID:25403779

  18. The role of autoimmunity in premature ovarian failure

    PubMed Central

    Ebrahimi, Mahbod; Akbari Asbagh, Firouzeh

    2015-01-01

    Premature ovarian failure (POF) is a heterogeneous syndrome with several causative factors. Autoimmune mechanisms are involved in pathogenesis of 4-30 % of POF cases. The present review focuses on the role of autoimmunity in the pathophysiology of POF. The evidences for an autoimmune etiology are: demonstration of ovarian autoantibodies, the presence of lymphocytic oophoritis, and association with other autoimmune disorders. Several ovarian antigenic targets have been identified in POF patients. The oocyte seems to be the most often targeted cell. Lymphocytic oophoritis is widely present in POF associated adrenal insufficiency. Addisonۥs disease is one of the most common autoimmune disorders associated with POF. Early detection of this potentially life threatening disease was recommended in several studies. The gold standard for detecting autoimmune POF is ovarian biopsy. This procedure is not recommended due to unknown clinical value, expense, and risks. Several immunoassays have been proposed as substitute diagnostic tools. Nevertheless, there is no clinically proven sensitive and specific serum test to confirm the diagnosis of autoimmune POF or to anticipate the patient’s chance of developing POF or associated diseases. Some authors suggested the possible effects of immuno-modulating therapy on the resumption of ovarian function and fertility in a selected group of autoimmune POF patients. However, in most instances, this treatment fails to reverse the course of the disease. Numerous studies illustrated that standard treatment outcome for infertility is less effective in the presence of ovarian autoimmunity. The antibody-induced damage could be a pathogenic factor. Nevertheless, the precise cause remains obscure. PMID:26568748

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

    PubMed

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

    2012-05-01

    The association of RASopathies [Noonan syndrome (NS) and Noonan-related syndromes] and autoimmune disorders has been reported sporadically. However, a concomitant evaluation of autoimmune diseases and an assessment of multiple autoantibodies in a large population of patients with molecularly confirmed RASopathy have not been performed. The clinical and laboratory features were analyzed in 42 RASopathy patients, the majority of whom had NS and five individuals had Noonan-related disorders. The following autoantibodies were measured: Anti-nuclear antibodies, anti-double stranded DNA, anti-SS-A/Ro, anti-SS-B/La, anti-Sm, anti-RNP, anti-Scl-70, anti-Jo-1, anti-ribosomal P, IgG and IgM anticardiolipin (aCL), thyroid, anti-smooth muscle, anti-endomysial (AE), anti-liver cytosolic protein type 1 (LC1), anti-parietal cell (APC), anti-mitochondrial (AM) antibodies, anti-liver-kidney microsome type 1 antibodies (LKM-1), and lupus anticoagulant. Six patients (14%) fulfilled the clinical criteria for autoimmune diseases [systemic lupus erythematous, polyendocrinopathy (autoimmune thyroiditis and celiac disease), primary antiphospholipid syndrome (PAPS), autoimmune hepatitis, vitiligo, and autoimmune thyroiditis]. Autoimmune antibodies were observed in 52% of the patients. Remarkably, three (7%) of the patients had specific gastrointestinal and liver autoantibodies without clinical findings. Autoimmune diseases and autoantibodies were frequently present in patients with RASopathies. Until a final conclusion of the real incidence of autoimmunity in Rasopathy is drawn, the physicians should be alerted to the possibility of this association and the need for a fast diagnosis, proper referral to a specialist and ultimately, adequate treatment. PMID:22488759

  20. [Autoimmune hemolytic anemia in children].

    PubMed

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

    2015-01-01

    Autoimmune hemolytic anemia is a rare condition in children which differs from the adult form. It is defined by immune-mediated destruction of red blood cells caused by autoantibodies. Characteristics of the autoantibodies are responsible for the various clinical entities. Classifications of autoimmune hemolytic anemia include warm autoimmune hemolytic anemia, cold autoimmune hemolytic anemia, and paroxysmal cold hemoglobinuria. For each classification, this review discusses the epidemiology, etiology, clinical presentation, laboratory evaluation, and treatment options. PMID:26575109

  1. Autophagy and Autoimmunity Crosstalks

    PubMed Central

    Bhattacharya, Abhisek; Eissa, N. Tony

    2013-01-01

    Autophagy, initially viewed as a conserved bulk-degradation mechanism, has emerged as a central player in a multitude of immune functions. Autophagy is important in host defense against intracellular and extracellular pathogens, metabolic syndromes, immune cell homeostasis, antigen processing and presentation, and maintenance of tolerance. The observation that the above processes are implicated in triggering or exacerbating autoimmunity raises the possibility that autophagy is involved in mediating autoimmune processes, either directly or as a consequence of innate or adaptive functions mediated by the pathway. Genome-wide association studies have shown association between single nucleotide polymorphisms (SNPs) in autophagy related gene 5 (Atg5), and Atg16l1 with susceptibility to systemic lupus erythematosus (SLE) and Crohn’s disease, respectively. Enhanced expression of Atg5 was also reported in blood of mice with experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis (MS), and in T cells isolated from blood or brain tissues from patients with active relapse of MS. This review explores the roles of autophagy pathway in the innate and adaptive immune systems on regulating or mediating the onset, progression, or exacerbation of autoimmune processes. PMID:23596443

  2. Alopecia areata and narcolepsy: a tale of obscure autoimmunity.

    PubMed

    Nigam, Gaurav; Pathak, Charu; Riaz, Muhammad

    2016-01-01

    Alopecia areata is an autoimmune dermatological disorder characterised by loss of hair in one or more discrete patches over the scalp. It has been linked to multiple disorders having an autoimmune origin. Like many autoimmune disorders it tends to be more common in females. To date, only five cases have been reported where alopecia has been associated with narcolepsy. Male gender is less commonly affected by alopecia areata. No case of alopecia areata in males has been associated with narcolepsy to the best of our knowledge. The current case represents the first ever-reported case of alopecia areata in a male patient with narcolepsy type 1. This coexistence is most likely the manifestation of a common underlying pathoimmunological mechanism that has not been completely understood, rather than a random association. PMID:27060069

  3. Autoimmunity in diarrhoeal disease.

    PubMed

    Unsworth, D J; Walker-Smith, J A

    1985-06-01

    Evidence for autoimmunity in diarrhoeal disease is reviewed. Firstly, coeliac disease (CD) is considered. The incidence of tissue-reactive autoantibodies in both adults and children with CD (68% and 65%, respectively) is higher than the incidence of these autoantibodies in controls (6% in normal adults, and 14% and 9% in disease controls drawn respectively from adult and child populations). The R1 antireticulin antibody, when present, was found to disappear after several weeks on a gluten-free diet, but in contrast, other autoantibodies persisted. Secondly, a case is argued for a new disease category, namely "autoimmune enteropathy." Seven cases are reviewed in which patients presented with protracted diarrhoea, a small intestinal enteropathy which failed to heal during periods of total parenteral nutrition, and evidence of a predisposition to autoimmunity (namely, the presence of high titre autoantibodies including one specific for gut epithelium, and/or the presence of associated diseases regarded to be autoimmune). Thirdly, evidence for autoimmunity in inflammatory bowel disease is reviewed and includes discussion of serum goblet cell antibodies and of circulating T cells which participate in antibody-dependent cellular cytotoxicity in vitro using colonic epithelial cells as targets. Finally, an unusual child is described who presented with chronic diarrhoea and a flat small intestinal mucosa, who responded to gluten withdrawal but who later relapsed spontaneously during a strict gluten-free diet. Her mucosa healed only after a period of total parenteral nutrition and treatment with oral steroids. This child's enteropathy was also associated with thyrotoxicosis and a microscopic colitis. PMID:4020570

  4. Risks of myeloid malignancies in patients with autoimmune conditions

    PubMed Central

    Anderson, L A; Pfeiffer, R M; Landgren, O; Gadalla, S; Berndt, S I; Engels, E A

    2009-01-01

    Autoimmune conditions are associated with an elevated risk of lymphoproliferative malignancies, but few studies have investigated the risk of myeloid malignancies. From the US Surveillance Epidemiology and End Results (SEER)-Medicare database, 13 486 myeloid malignancy patients (aged 67+ years) and 160 086 population-based controls were selected. Logistic regression models adjusted for gender, age, race, calendar year and number of physician claims were used to estimate odds ratios (ORs) for myeloid malignancies in relation to autoimmune conditions. Multiple comparisons were controlled for using the Bonferroni correction (P<0.0005). Autoimmune conditions, overall, were associated with an increased risk of acute myeloid leukaemia (AML) (OR 1.29) and myelodysplastic syndrome (MDS, OR 1.50). Specifically, AML was associated with rheumatoid arthritis (OR 1.28), systemic lupus erythematosus (OR 1.92), polymyalgia rheumatica (OR 1.73), autoimmune haemolytic anaemia (OR 3.74), systemic vasculitis (OR 6.23), ulcerative colitis (OR 1.72) and pernicious anaemia (OR 1.57). Myelodysplastic syndrome was associated with rheumatoid arthritis (OR1.52) and pernicious anaemia (OR 2.38). Overall, autoimmune conditions were not associated with chronic myeloid leukaemia (OR 1.09) or chronic myeloproliferative disorders (OR 1.15). Medications used to treat autoimmune conditions, shared genetic predisposition and/or direct infiltration of bone marrow by autoimmune conditions, could explain these excess risks of myeloid malignancies. PMID:19259097

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

    PubMed

    Kasznicki, Jacek; Drzewoski, Józef

    2014-01-01

    We present a case of autoimmune polyglandular syndrome type III (APS III) associated with Hashimoto's disease, type 1 diabetes mellitus, vitiligo and autoimmune urticaria. This rare genetic disorder occurs with unknown frequency in the Polish population. It is characterised by endocrine tissue destruction resulting in the malfunction of multiple organs.Several cases of APS III associated with organ-specific autoimmune diseases such as coeliac disease, hypogonadism and myasthenia gravis, as well as organ-nonspecific or systemic autoimmune diseases such as sarcoidosis, Sjögren syndrome, and rheumatoid arthritis have been described. To the best of our knowledge, we here describe the first case of APS III associated with autoimmune thyroiditis, type 1 diabetes mellitus, vitiligo and autoimmune urticaria in an adult patient. PMID:25185856

  6. Recent Advances in the Genetics of Autoimmune Disease

    PubMed Central

    Gregersen, Peter K.; Olsson, Lina M.

    2010-01-01

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

  7. 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

  8. Alterations in immune function with biologic therapies for autoimmune disease.

    PubMed

    Her, Minyoung; Kavanaugh, Arthur

    2016-01-01

    Autoimmune disorders, including rheumatoid arthritis, inflammatory bowel disease, psoriasis, and others, are characterized by dysregulation of various aspects of normal immunity and inflammation. Biologic agents targeting key components of the dysregulated immune response have dramatically improved patient outcomes and transformed treatment paradigms for a number of systemic inflammatory autoimmune diseases. Despite their excellent efficacy, because they do affect normal immune responsiveness, biologic agents can potentially be associated with a variety of adverse effects. Important potential adverse effects related to the use of biologic agents include immunosuppression, which might result in outcomes such as infection, and autoimmunity, that could result in paradoxical inflammation or even autoimmune disease. In this article the current clinical evidence and immunologic mechanisms of the adverse effects related to biologic agents are discussed. PMID:26768759

  9. The role of gut microbiota in immune homeostasis and autoimmunity

    PubMed Central

    Wu, Hsin-Jung; Wu, Eric

    2012-01-01

    Keeping a delicate balance in the immune system by eliminating invading pathogens, while still maintaining self-tolerance to avoid autoimmunity, is critical for the body’s health. The gut microbiota that resides in the gastrointestinal tract provides essential health benefits to its host, particularly by regulating immune homeostasis. Moreover, it has recently become obvious that alterations of these gut microbial communities can cause immune dysregulation, leading to autoimmune disorders. Here we review the advances in our understanding of how the gut microbiota regulates innate and adaptive immune homeostasis, which in turn can affect the development of not only intestinal but also systemic autoimmune diseases. Exploring the interaction of gut microbes and the host immune system will not only allow us to understand the pathogenesis of autoimmune diseases but will also provide us new foundations for the design of novel immuno- or microbe-based therapies. PMID:22356853

  10. Immunotherapeutic strategies in autoimmune uveitis

    PubMed Central

    Papotto, Pedro Henrique; Marengo, Eliana Blini; Sardinha, Luiz Roberto; Goldberg, Anna Carla; Rizzo, Luiz Vicente

    2014-01-01

    Autoimmune uveitis is an organ-specific disorder characterized by irreversible lesions to the eye that predominantly affect people in their most productive years and is among the leading causes of visual deficit and blindness. Currently available therapies are effective in the treatment of a wide spectrum of uveitis, but are often associated with severe side effects. Here, we review ongoing research with promising immunomodulatory therapeutic strategies, describing their specific features, interactions and the responses triggered by the targeted immune molecules that aim to minimize clinical complications and the likelihood of disease relapse. We first review the main features of the disease, diagnostic tools, and traditional forms of therapy, as well as the animal models predominantly used to understand the pathogenesis and test the novel intervention approaches aiming to control the acute immune and inflammatory responses and to dampen chronic responses. Both exploratory research and clinical trials have targeted either the blockade of effector pathways or of their companion co-stimulatory molecules. Examples of targets are T cell receptors (CD3), their co-stimulatory receptors (CD28, CTLA-4) and corresponding ligands (B7-1 and B7-2, also known as CD80 and CD86), and cytokines like IL-2 and their receptors. Here, we summarize the available evidence on effectiveness of these treatments in human and experimental uveitis and highlight a novel CD28 antagonist monovalent Fab′ antibody, FR104, which has shown preclinical efficacy suppressing effector T cells while enhancing regulatory T cell function and immune tolerance in a humanized graft-versus-host disease (GVHD) mice model and is currently being tested in a mouse autoimmune uveitis model with encouraging results. PMID:24833504

  11. Selenium and Iodine in Autoimmune Thyroiditis.

    PubMed

    Guastamacchia, Edoardo; Giagulli, Vito Angelo; Licchelli, Brunella; Triggiani, Vincenzo

    2015-01-01

    Selenium and iodine are essential for thyroid hormone synthesis and function. Selenium, in form of selenocysteine, is found either in the catalytic center of enzymes involved in the protection of the thyroid gland from free radicals originating during thyroid hormone synthesis, and in three different iodothyronine deiodinases catalyzing the activation and the inactivation of thyroid hormones. Iodine is an essential constituent of thyroid hormones and its deficiency causes different disorders that include goiter, hypothyroidism, reduced fertility and alteration in growth, physical and neurological development. These two micronutrients could be involved in the pathogenesis of autoimmune thyroid diseases, a spectrum of pathological conditions including Hashimoto's thryoiditis, post-partum thyroiditis, the so-called painless thyroiditis, Graves' disease and Graves' ophtalmopathy. Aim of this paper is to review the role played by selenium and iodine in autoimmune thyroiditis. PMID:26088475

  12. Chronic lymphocytic leukemia and autoimmunity: a systematic review

    PubMed Central

    Hodgson, Kate; Ferrer, Gerardo; Montserrat, Emili; Moreno, Carol

    2011-01-01

    Chronic lymphocytic leukemia is frequently associated with immune disturbances. The relationship between chronic lymphocytic leukemia and autoimmune cytopenias, particularly autoimmune hemolytic anemia and immune thrombocytopenia, is well established. The responsible mechanisms, particularly the role of leukemic cells in orchestrating the production of polyclonal autoantibodies, are increasingly well understood. Recent studies show that autoimmune cytopenia is not necessarily associated with poor prognosis. On the contrary, patients with anemia or thrombocytopenia due to immune mechanisms have a better outcome than those in whom these features are due to bone marrow infiltration by the disease. Moreover, fears about the risk of autoimmune hemolysis following single agent fludarabine may no longer be appropriate in the age of chemo-immunotherapy regimens. However, treatment of patients with active hemolysis may pose important problems needing an individualized and clinically sound approach. The concept that autoimmune cytopenia may precede the leukemia should be revisited in the light of recent data showing that autoimmune cytopenia may be observed in monoclonal B-cell lymphocytosis, a condition that can only be detected by using sensitive flow cytometry techniques. On the other hand, there is no evidence of an increased risk of non-hemic autoimmune disorders in chronic lymphocytic leukemia. Likewise, there is no epidemiological proof of an increased risk of chronic lymphocytic leukemia in patients with non-hemic autoimmunity. Finally, since immune disorders are an important part of chronic lymphocytic leukemia, studies aimed at revealing the mechanisms linking the neoplastic and the immune components of the disease should help our understanding of this form of leukemia. PMID:21242190

  13. Autoimmune Bowel Disease

    PubMed Central

    Anderson, F. H.

    1979-01-01

    The gastrointestinal tract is one of the major lymphatic organs of the body. It is capable of many immunological responses and is exposed to more foreign antigens and pathogens than any other part of the body. Because of the complexity of the GI tract and the difficulty in studying normal responses, even the normal physiology of the immunological aspects of the bowel are not fully understood. Definite abnormalities in immunity are apparent in some GI diseases; the three most common are pernicious anemia, ulcerative colitis, and Crohn's disease. Many of the abnormal immune states seen in these diseases, the possibilities of autoimmunity, some of the extra-intestinal manifestations of these diseases and their possible relationship to an autoimmune state are discussed in this article. PMID:21297692

  14. Update on autoimmune hepatitis

    PubMed Central

    Teufel, Andreas; Galle, Peter R; Kanzler, Stephan

    2009-01-01

    Autoimmune hepatitis (AIH) is a necroinflammatory liver disease of unknown etiology that occurs in children and adults of all ages. Characteristics are its autoimmune features, hyperglobulinemia (IgG), and the presence of circulating autoantibodies, as well as a response to immunosuppressant drugs. Current treatment consists of prednisone and azathioprine and in most patients this disease has become very treatable. Over the past 2 years, a couple of new insights into the genetic aspects, clinical course and treatment of AIH have been reported, which will be the focus of this review. In particular, we concentrate on genome-wide microsatellite analysis, a novel mouse model of AIH, the evaluation of a large AIH cohort for overlap syndromes, suggested novel criteria for the diagnosis of AIH, and the latest studies on treatment of AIH with budenoside and mycophenolate mofetil. PMID:19266594

  15. 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

  16. Pregnancy and autoimmune diseases.

    PubMed

    Gordon, Caroline

    2004-06-01

    Until about 15 years ago, the general advice to women with autoimmune rheumatic diseases, especially systemic lupus erythematosus, systemic sclerosis and vasculitic syndromes, was to avoid pregnancy as there was a high risk of maternal and fetal morbidity and mortality. However, it is now clear that these risks can be reduced in general by avoiding pregnancy when the diseases are active and continuing appropriate medication to reduce the chances of disease flare during pregnancy. This article will review the evidence for this advice and will also consider other issues that should be discussed with women before they attempt to become pregnant. This will include the influence of pregnancy on the individual autoimmune diseases, as well as the potential impact of the diseases and drug therapy on fertility and pregnancy outcomes. Anti-phospholipid antibody syndrome has emerged as a major cause of fetal loss, pre-eclampsia and premature birth. The clinical and laboratory diagnosis of this condition will not be covered, but the reader is referred to an excellent recent review. Much of the data on pregnancy and autoimmune rheumatic diseases come from retrospective analyses, but some prospective studies have been reported over the past 10 years. There have been very few meta-analyses or randomized clinical trials. PMID:15158746

  17. Herpesviruses and autoimmunity.

    PubMed

    Posnett, David N

    2008-05-01

    Herpesvirus infection, in particular EBV infection, has been implicated in several major autoimmune diseases, including systemic lupus erythematosus (SLE), multiple sclerosis (MS) and rheumatoid arthritis (RA). Herpesvirus infection has potential roles in both initiating the autoimmune process and exacerbating disease progression. In particular, EBV has a proposed role in initiating the anti-nucleoprotein antibodies that are characteristic of SLE through molecular mimicry. There is also evidence to suggest that there is productive infection with EBV in the brain lesions of MS patients and in the synovium of RA patients. Research has been conducted in a mouse gamma-herpesvirus model, as it serves as a useful model for productive infection within autoimmune target tissues. The novel mechanisms by which EBV could contribute bystander effects by amplification of innate immune responses, along with preclinical and epidemiological studies into the role of herpesviruses in SLE, MS and RA, and clinical studies into the potential benefit of antiviral therapy, are discussed in this review. PMID:18465661

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

    PubMed Central

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

    2015-01-01

    Autoimmune Polyglandular syndrome (APS) are rare condition characterised by presence of immune dysfunction of two or more endocrine glands and other non-endocrine organs. APS is divided into 2 major subtypes based on age of presentation, pattern of disease combinations and mode of inheritance. APS 1(juvenile) usually manifest in early adolescence or in infancy. It is characterised by multiple endocrinal deficiency with mucocutaneous candidiasis and ectodermal dystrophy. Of the endocrine diseases, hypoparathyroidism form an important component followed by Addison’s disease, type 1A diabetes, hypogonadism and thyroid disease. On the other hand APS II usually manifest in 3rd or 4th decade of life with female preponderance. Endocrine diseases commonly include autoimmune thyroid disease (graves or autoimmune thyroiditis), type 1A diabetes, and Addison’s disease. Hypoparathyroidism is of rare occurrence and there is no mucocutaneous candidiasis. We report here a case of APS type II in a 29-year-old male who initially presented with hypothyroidism, which was soon followed by Addison’s disease. The involvement of thyroid gland preceding the involvement of adrenal is of rare occurrence. The patient also had celiac disease which makes the combination further uncommon. PMID:26023582

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

    PubMed

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

    2015-04-01

    Autoimmune Polyglandular syndrome (APS) are rare condition characterised by presence of immune dysfunction of two or more endocrine glands and other non-endocrine organs. APS is divided into 2 major subtypes based on age of presentation, pattern of disease combinations and mode of inheritance. APS 1(juvenile) usually manifest in early adolescence or in infancy. It is characterised by multiple endocrinal deficiency with mucocutaneous candidiasis and ectodermal dystrophy. Of the endocrine diseases, hypoparathyroidism form an important component followed by Addison's disease, type 1A diabetes, hypogonadism and thyroid disease. On the other hand APS II usually manifest in 3rd or 4th decade of life with female preponderance. Endocrine diseases commonly include autoimmune thyroid disease (graves or autoimmune thyroiditis), type 1A diabetes, and Addison's disease. Hypoparathyroidism is of rare occurrence and there is no mucocutaneous candidiasis. We report here a case of APS type II in a 29-year-old male who initially presented with hypothyroidism, which was soon followed by Addison's disease. The involvement of thyroid gland preceding the involvement of adrenal is of rare occurrence. The patient also had celiac disease which makes the combination further uncommon. PMID:26023582

  20. Multiple sclerosis: autoimmune disease or autoimmune reaction?

    PubMed

    Stys, Peter K

    2010-09-01

    Multiple sclerosis (MS) is traditionally considered an autoimmune inflammatory demyelinating disease of the central nervous system (CNS) with much knowledge available to support this view. However, this characterization implies that the primary event is an aberrant immune response directed at CNS antigens, promoting inflammation and later driving progressive axo-glial degeneration. Trials with potent anti-inflammatory agents and detailed neuropathological studies raise questions about this sequence of events. This hypothetical paper argues that MS may be primarily a "cytodegenerative" disease, possibly first involving the oligodendrocyte/myelin unit. Liberation of autoantigens secondarily recruits an immune response, the force of which heavily depends on the host's immune predisposition. Thus, the spectrum of MS from highly aggressive Marburg type, to primary progressive disease with little inflammatory burden, is governed by a "convolution" between the underlying cytodegeneration and the host's immune predilection. Clinical heterogeneity may be a reflection of a variable immune response, whereas in reality, the "real MS" may be a homogeneous degenerative process analogous to well known primary neurodegenerative diseases. PMID:21246931

  1. Immunologic Endocrine Disorders

    PubMed Central

    Michels, Aaron W.; Eisenbarth, George S.

    2010-01-01

    Autoimmunity affects multiple glands in the endocrine system. Animal models and human studies highlight the importance of alleles in HLA (human leukocyte antigen)-like molecules determining tissue specific targeting that with the loss of tolerance leads to organ specific autoimmunity. Disorders such as type 1A diabetes, Grave's disease, Hashimoto's thyroiditis, Addison's disease, and many others result from autoimmune mediated tissue destruction. Each of these disorders can be divided into stages beginning with genetic susceptibility, environmental triggers, active autoimmunity, and finally metabolic derangements with overt symptoms of disease. With an increased understanding of the immunogenetics and immunopathogenesis of endocrine autoimmune disorders, immunotherapies are becoming prevalent, especially in type 1A diabetes. Immunotherapies are being used more in multiple subspecialty fields to halt disease progression. While therapies for autoimmune disorders stop the progress of an immune response, immunomodulatory therapies for cancer and chronic infections can also provoke an unwanted immune response. As a result, there are now iatrogenic autoimmune disorders arising from the treatment of chronic viral infections and malignancies. PMID:20176260

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

    PubMed

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

    2016-02-01

    Nivolumab, a blockade of programmed cell death 1, is now administrated for advanced malignant melanomas. Nivolumab-associated adverse events include organ-specific autoimmune disorders; autoimmune thyroid disease, vitiligo and insulin-dependent diabetes. However, predisposed persons are currently unknown. Here, we report serological aggravation of autoimmune thyroid disease in two cases receiving nivolumab: one with Hashimoto disease and another with probable subclinical Hashimoto disease. We should verify if nivolumab-related hypothyroidism and hyperthyroidism are predisposed to occur in euthyroid individuals with subclinical autoimmune thyroid disease. PMID:26198822

  3. Types of Vestibular Disorders

    MedlinePlus

    ... include complications from aging, autoimmune disorders, and allergies. Acoustic Neuroma Acoustic neuroma (also called a vestibular schwannoma) is a ... This nerve is also referred to as the acoustic nerve, hence the name.) As an acoustic neuroma ...

  4. Thyroid Disorders Overview

    MedlinePlus

    ... the amount of hormones produced by the thyroid. Hypothyroidism Hypothyroidism is a thyroid disorder that occurs when the ... irregularities Depression Dry skin and hair Sluggishness Constipation Hypothyroidism is often caused by Hashimoto's disease, an autoimmune ...

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

    PubMed Central

    Visser, Jeroen; Rozing, Jan; Sapone, Anna; Lammers, Karen; Fasano, Alessio

    2010-01-01

    Autoimmune diseases are characterized by tissue damage and loss of function due to an immune response that is directed against specific organs. This review is focused on celiac disease (CD), an autoimmune enteropathy, and type 1 diabetes (T1D), a hyperglycosaemia caused by a destructive autoimmune process targeting the insulin-producing pancreatic islet cells. Even if environmental factors and genetic susceptibility are clearly involved in the pathogenesis of autoimmunity, for most autoimmune disorders there is no or little knowledge about the causing agent or genetic makeup underlying the disease. In this respect, CD represents a unique autoimmune disorder because a close genetic association with HLA-DQ2 or HLA-DQ8 haplotypes and, more importantly, the environmental trigger (the gliadin fraction of gluten-containing grains wheat, barley, and rye) are known. Conversely, the trigger for autoimmune destruction of pancreatic ß cells in T1D is unclear. Interestingly, recent data suggest that gliadin is also involved in the pathogenesis of T1D. There is growing evidence that increased intestinal permeability plays a pathogenic role in various autoimmune diseases including CD and T1D. Therefore, we hypothesize that besides genetic and environmental factors, loss of intestinal barrier function is necessary to develop autoimmunity. In this review, each of these components will be briefly reviewed. PMID:19538307

  6. Early disease onset and increased risk of other autoimmune diseases in familial generalized vitiligo.

    PubMed

    Laberge, Greggory; Mailloux, Christina M; Gowan, Katherine; Holland, Paulene; Bennett, Dorothy C; Fain, Pamela R; Spritz, Richard A

    2005-08-01

    Generalized vitiligo is an autoimmune disorder in which acquired white patches of skin and overlying hair result from autoimmune loss of melanocytes from involved areas. Although usually sporadic, family clustering of vitiligo may occur, in a non-Mendelian pattern typical of multifactorial, polygenic inheritance. Sporadic vitiligo is associated with autoimmune thyroid disease, pernicious anemia, Addison's disease, and lupus; these same disorders occur at increased frequency in patients' first-degree relatives. Here, we studied 133 'multiplex' generalized vitiligo families, with multiple affected family members. The age of onset of vitiligo is earlier in these 'multiplex' families than in patients with sporadic vitiligo. Affected members of the multiplex vitiligo families have elevated frequencies of autoimmune thyroid disease, rheumatoid arthritis, psoriasis, adult-onset insulin-dependent diabetes mellitus, pernicious anemia, and Addison's disease. Probands' unaffected siblings have elevated frequencies of most of these same autoimmune diseases, particularly if the proband had non-vitiligo autoimmune disease. Familial generalized vitiligo is thus characterized by earlier disease onset and a broader repertoire of associated autoimmune diseases than sporadic vitiligo. This mostly likely reflects a greater inherited genetic component of autoimmune susceptibility in these families. These findings have important implications for autoimmune disease surveillance in families in which multiple members are affected with vitiligo. PMID:16029422

  7. Proteome-wide survey of the autoimmune target repertoire in autoimmune polyendocrine syndrome type 1.

    PubMed

    Landegren, Nils; Sharon, Donald; Freyhult, Eva; Hallgren, Åsa; Eriksson, Daniel; Edqvist, Per-Henrik; Bensing, Sophie; Wahlberg, Jeanette; Nelson, Lawrence M; Gustafsson, Jan; Husebye, Eystein S; Anderson, Mark S; Snyder, Michael; Kämpe, Olle

    2016-01-01

    Autoimmune polyendocrine syndrome type 1 (APS1) is a monogenic disorder that features multiple autoimmune disease manifestations. It is caused by mutations in the Autoimmune regulator (AIRE) gene, which promote thymic display of thousands of peripheral tissue antigens in a process critical for establishing central immune tolerance. We here used proteome arrays to perform a comprehensive study of autoimmune targets in APS1. Interrogation of established autoantigens revealed highly reliable detection of autoantibodies, and by exploring the full panel of more than 9000 proteins we further identified MAGEB2 and PDILT as novel major autoantigens in APS1. Our proteome-wide assessment revealed a marked enrichment for tissue-specific immune targets, mirroring AIRE's selectiveness for this category of genes. Our findings also suggest that only a very limited portion of the proteome becomes targeted by the immune system in APS1, which contrasts the broad defect of thymic presentation associated with AIRE-deficiency and raises novel questions what other factors are needed for break of tolerance. PMID:26830021

  8. Proteome-wide survey of the autoimmune target repertoire in autoimmune polyendocrine syndrome type 1

    PubMed Central

    Landegren, Nils; Sharon, Donald; Freyhult, Eva; Hallgren, Åsa; Eriksson, Daniel; Edqvist, Per-Henrik; Bensing, Sophie; Wahlberg, Jeanette; Nelson, Lawrence M.; Gustafsson, Jan; Husebye, Eystein S.; Anderson, Mark S.; Snyder, Michael; Kämpe, Olle

    2016-01-01

    Autoimmune polyendocrine syndrome type 1 (APS1) is a monogenic disorder that features multiple autoimmune disease manifestations. It is caused by mutations in the Autoimmune regulator (AIRE) gene, which promote thymic display of thousands of peripheral tissue antigens in a process critical for establishing central immune tolerance. We here used proteome arrays to perform a comprehensive study of autoimmune targets in APS1. Interrogation of established autoantigens revealed highly reliable detection of autoantibodies, and by exploring the full panel of more than 9000 proteins we further identified MAGEB2 and PDILT as novel major autoantigens in APS1. Our proteome-wide assessment revealed a marked enrichment for tissue-specific immune targets, mirroring AIRE’s selectiveness for this category of genes. Our findings also suggest that only a very limited portion of the proteome becomes targeted by the immune system in APS1, which contrasts the broad defect of thymic presentation associated with AIRE-deficiency and raises novel questions what other factors are needed for break of tolerance. PMID:26830021

  9. 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

  10. High prevalence of infections and autoimmunity in patients with thymoma.

    PubMed

    Holbro, Andreas; Jauch, Annaïse; Lardinois, Didier; Tzankov, Alexander; Dirnhofer, Stephan; Hess, Christoph

    2012-03-01

    The thymus selects T cells, thus ensuring T cell tolerance. Thymoma can be associated with immune dysregulation manifesting as autoimmunity and/or immunodeficiency. Immune dysregulation in thymoma patients has only been described in case reports and small case series. The current study was a retrospective single-center study, covering the period 1/2000 to 12/2010. Clinical data were collected by chart review. We identified 29 patients with thymoma. The median age at diagnosis was 60 years (range: 23-87). Median follow-up time was 1,326 days (range: 15-3,710), and 20 patients (69%) were alive at last follow-up. Overall, in 13 of 29 patients (45%) autoimmunity and infection were observed in 7 of 29 (24%) and 3 of 29 patients (10%) infection and autoimmunity only was observed, respectively. Both opportunistic and nonopportunistic infections were recorded. Myasthenia gravis (10 of 29 patients) was the most frequent autoimmune disease. Additional entities included pemphigus, pure red cell aplasia, lichen planus, Sjögren's syndrome, systemic lupus erythematosus (n = 2 each), and cutaneous lupus erythematosus, sarcoidosis, vitiligo, polymyositis, and chronic inflammatory demyelinating polyradiculoneuropathy (n = 1 each). Six of 29 patients (21%) had more than 1 autoimmune disorder. In thymoma patients, infection, autoimmunity, and in particular a combination of both pose a challenge to treating physicians. Prospective multicenter studies are required to more precisely define the thymoma-associated immune dysregulation syndrome. PMID:22261388

  11. Biologics for the treatment of autoimmune renal diseases.

    PubMed

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

    2016-04-01

    Biological therapeutics (biologics) that target autoimmune responses and inflammatory injury pathways have a marked beneficial impact on the management of many chronic diseases, including rheumatoid arthritis, psoriasis, inflammatory bowel disease, and ankylosing spondylitis. Accumulating data suggest that a growing number of renal diseases result from autoimmune injury - including lupus nephritis, IgA nephropathy, anti-neutrophil cytoplasmic antibody-associated glomerulonephritis, autoimmune (formerly idiopathic) membranous nephropathy, anti-glomerular basement membrane glomerulonephritis, and C3 nephropathy - and one can speculate that biologics might also be applicable to these diseases. As many autoimmune renal diseases are relatively uncommon, with long natural histories and diverse outcomes, clinical trials that aim to validate potentially useful biologics are difficult to design and/or perform. Some excellent consortia are undertaking cohort studies and clinical trials, but more multicentre international collaborations are needed to advance the introduction of new biologics to patients with autoimmune renal disorders. This Review discusses the key molecules that direct injurious inflammation and the biologics that are available to modulate them. The opportunities and challenges for the introduction of relevant biologics into treatment protocols for autoimmune renal diseases are also discussed. PMID:26949177

  12. High Prevalence of Antinuclear Antibodies in Children with Thyroid Autoimmunity

    PubMed Central

    Segni, Maria; Pucarelli, Ida; Truglia, Simona; Turriziani, Ilaria; Serafinelli, Chiara; Conti, Fabrizio

    2014-01-01

    Background. Antinuclear antibodies (ANA) are a hallmark of many autoimmune diseases and can be detected many years before disease onset. Autoimmune thyroid diseases (AITD) are frequently associated with other organ- and non-organ-specific autoimmune disorders. Objectives. To assess the prevalence of ANA in pediatric patients with AITD and their clinical correlations. Methods. Ninety-three consecutive pediatric patients with AITD were enrolled (86 children with chronic lymphocytic thyroiditis and 7 with Graves' disease). ANA, anti-double DNA (anti-dsDNA) antibodies, anti-extractable nuclear antigen (anti-ENA), anti-cyclic citrullinated peptide antibodies (anti-CCP), and rheumatoid factor (RF) was obtained. Signs and symptoms potentially related to rheumatic diseases in children were investigated by a questionnaire. Results. ANA positivity was found in 66/93 children (71%), anti-ENA in 4/93 (4.3%), anti-dsDNA in 1/93 (1.1%), RF in 3/93 (3.2%), and anti-CCP in none. No significant differences were found between the ANA-positive and ANA-negative groups with respect to age, sex, L-thyroxine treatment, or prevalence of other autoimmune diseases. Overall, parental autoimmunity was found in 23%. Conclusions. ANA positivity was demonstrated in 71% of children with AITD. ANA positivity was not related to overt immune-rheumatic diseases. However, because the positivity of ANA can occur even many years before the onset of systemic autoimmune diseases, prospective studies are warranted. PMID:24741574

  13. Targeting Dendritic Cell Function during Systemic Autoimmunity to Restore Tolerance

    PubMed Central

    Mackern-Oberti, Juan P.; Vega, Fabián; Llanos, Carolina; Bueno, Susan M.; Kalergis, Alexis M.

    2014-01-01

    Systemic autoimmune diseases can damage nearly every tissue or cell type of the body. Although a great deal of progress has been made in understanding the pathogenesis of autoimmune diseases, current therapies have not been improved, remain unspecific and are associated with significant side effects. Because dendritic cells (DCs) play a major role in promoting immune tolerance against self-antigens (self-Ags), current efforts are focusing at generating new therapies based on the transfer of tolerogenic DCs (tolDCs) during autoimmunity. However, the feasibility of this approach during systemic autoimmunity has yet to be evaluated. TolDCs may ameliorate autoimmunity mainly by restoring T cell tolerance and, thus, indirectly modulating autoantibody development. In vitro induction of tolDCs loaded with immunodominant self-Ags and subsequent cell transfer to patients would be a specific new therapy that will avoid systemic immunosuppression. Herein, we review recent approaches evaluating the potential of tolDCs for the treatment of systemic autoimmune disorders. PMID:25229821

  14. MicroRNA control in the development of systemic autoimmunity

    PubMed Central

    2013-01-01

    Mammalian immune responses are intended to eradicate microbial pathogens and thus protect individuals from the harmful effects of such infections. However, unresolved inflammation can be devastating to the host and cause tissue damage and organ malfunction. Immune responses can even mistakenly target self-antigens and mediate autoimmune inflammation. Consequently, a variety of cellular and molecular mechanisms have evolved to control the inflammatory responses, and many of these safeguards or triggers are perturbed in the setting of autoimmunity. In this review, we discuss the emerging roles of cellular non-coding RNAs, and in particular microRNAs (miRNAs), in the regulation of autoimmune inflammation. How miRNAs function to impact the onset, magnitude, and resolution of inflammatory responses and recent observations regarding links between miRNAs and specific autoimmune disorders will be addressed. Finally, the diagnostic and therapeutic relevance of miRNAs involved in autoimmunity will be considered. It is clear that, taken together, mammalian miRNAs are integral to the pathogenesis of mammalian autoimmune diseases and may be effective targets of next-generation therapeutics aimed at eradicating tissue inflammation. PMID:23379780

  15. The Immunopathogenesis of Chronic Autoimmune Thyroiditis One Century after Hashimoto

    PubMed Central

    Weetman, Anthony P

    2013-01-01

    Hakaru Hashimoto described 4 patients with a hitherto unknown cause for goitre, struma lymphomatosa, a century ago. He was careful to distinguish this from Riedel thyroiditis but it has become clear that fibrosis and atrophy of the thyroid are indeed components of Hashimoto thyroiditis, and in rare cases IgG4-related sclerosing disease may be an outcome. Although the cause of the lymphocytic infiltration was unknown to Hashimoto, we now know through the pioneering studies of N.R. Rose and E. Witebsky [J Immunol 1956;76:417427] that this condition is the archetype for autoimmune destruction as a disease mechanism. In the last two decades in particular, there has been huge interest in unravelling the genetic basis for this and related autoimmune disorders. The list of polymorphisms associated with autoimmune thyroid disease grows each year, and in the case of vitiligo, which is frequently found in association with thyroid autoimmunity, we know that 27 separate susceptibility loci account for less than 20% of the heritability of this condition. Environmental and existential factors may turn out to be just as complex in number and in interactions. We can thus imagine a Swiss cheese model for the causation of autoimmune thyroid disease, in which the effects of cumulative weaknesses line up like the holes in slices of cheese to allow the catastrophic event of autoimmune destruction to occur. PMID:24783026

  16. The immunopathogenesis of chronic autoimmune thyroiditis one century after hashimoto.

    PubMed

    Weetman, Anthony P

    2013-01-01

    Hakaru Hashimoto described 4 patients with a hitherto unknown cause for goitre, struma lymphomatosa, a century ago. He was careful to distinguish this from Riedel thyroiditis but it has become clear that fibrosis and atrophy of the thyroid are indeed components of Hashimoto thyroiditis, and in rare cases IgG4-related sclerosing disease may be an outcome. Although the cause of the lymphocytic infiltration was unknown to Hashimoto, we now know through the pioneering studies of N.R. Rose and E. Witebsky [J Immunol 1956;76:417-427] that this condition is the archetype for autoimmune destruction as a disease mechanism. In the last two decades in particular, there has been huge interest in unravelling the genetic basis for this and related autoimmune disorders. The list of polymorphisms associated with autoimmune thyroid disease grows each year, and in the case of vitiligo, which is frequently found in association with thyroid autoimmunity, we know that 27 separate susceptibility loci account for less than 20% of the heritability of this condition. Environmental and existential factors may turn out to be just as complex in number and in interactions. We can thus imagine a 'Swiss cheese' model for the causation of autoimmune thyroid disease, in which the effects of cumulative weaknesses line up - like the holes in slices of cheese - to allow the catastrophic event of autoimmune destruction to occur. PMID:24783026

  17. 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

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

    ERIC Educational Resources Information Center

    Swedo, Susan E.; Grant, Paul J.

    2005-01-01

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

  19. Neuronal Surface Antibody-Mediated Autoimmune Encephalitis

    PubMed Central

    Linnoila, Jenny J.; Rosenfeld, Myrna R.; Dalmau, Josep

    2016-01-01

    In the past few years, many autoimmune encephalitides have been identified, with specific clinical syndromes and associated antibodies against neuronal surface antigens. There is compelling evidence that many of these antibodies are pathogenic and most of these encephalitides are highly responsive to immunotherapies. The clinical spectra of some of these antibody-mediated syndromes, especially those reported in only a few patients, are evolving. Others, such as anti-N-methyl-D-aspartate (NMDA) receptor encephalitis, are well characterized. Diagnosis involves recognizing the specific syndromes and identifying the antibody in a patient’s cerebrospinal fluid (CSF) and/or serum. These syndromes are associated with variable abnormalities in CSF, magnetic resonance imaging, and electroencephalography. Treatment is often multidisciplinary and should be focused upon neutralizing the effects of antibodies and eliminating their source. Overlapping disorders have been noted, with some patients having more than one neurologic autoimmune disease. In other patients, viral infections such as herpes simplex virus encephalitis trigger robust antineuronal autoimmune responses. PMID:25369441

  20. Genetics Home Reference: autoimmune lymphoproliferative syndrome

    MedlinePlus

    ... immune system may attack red blood cells (autoimmune hemolytic anemia ), white blood cells (autoimmune neutropenia), or platelets (autoimmune ... years later, most frequently as a combination of hemolytic anemia and thrombocytopenia, also called Evans syndrome. People with ...

  1. Autoimmune diseases and myelodysplastic syndromes.

    PubMed

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

    2016-05-01

    Immune dysregulation and altered T-cell hemostasis play important roles in the pathogenesis of myelodysplastic syndromes (MDS). Recent studies suggest an increased risk of MDS among patients with autoimmune diseases. Here, we investigated the prevalence of autoimmune diseases among MDS patients, comparing characteristics and outcomes in those with and without autoimmune diseases. From our study group of 1408 MDS patients, 391 (28%) had autoimmune disease, with hypothyroidism being the most common type, accounting for 44% (n = 171) of patients (12% among all MDS patients analyzed). Other autoimmune diseases with ≥5% prevalence included idiopathic thrombocytopenic purpura in 12% (n = 46), rheumatoid arthritis in 10% (n = 41), and psoriasis in 7% (n = 28) of patients. Autoimmune diseases were more common in female MDS patients, those with RA or RCMD WHO subtype, and those who were less dependent on red blood cell transfusion. Median overall survival (OS) was 60 months (95% CI, 50-70) for patients with autoimmune diseases versus 45 months (95% CI, 40-49) for those without (log-rank test, P = 0.006). By multivariate analysis adjusting for revised IPSS and age >60 years, autoimmune diseases were a statistically significant independent factor for OS (HR 0.78; 95% CI, 0.66-0.92; P = 0.004). The rate of acute myeloid leukemia (AML) transformation was 23% (n = 89) in MDS patients with autoimmune disease versus 30% (n = 301) in those without (P = 0.011). Patient groups did not differ in response to azacitidine or lenalidomide treatment. Autoimmune diseases are prevalent among MDS patients. MDS patients with autoimmune diseases have better OS and less AML transformation. Am. J. Hematol. 91:E280-E283, 2016. © 2016 Wiley Periodicals, Inc. PMID:26875020

  2. [Autoimmune thyroiditis and thyroid cancer].

    PubMed

    Krátký, Jan; Jiskra, Jan

    2015-10-01

    Association between autoimmune thyroiditis (CLT) and thyroid cancer remains not clear. Although both diseases often occur simultaneously in histological samples, it is not yet clear whether CLT can be regarded as a risk factor for thyroid malignancy. This review focus on the known epidemiological and molecular genetics links between both diseases. Most studies have shown a significant association between thyroid cancer and positive antibodies to thyroglobulin and histological evidence of CLT, as well. Both disorders share some risk factors (greater incidence in women, in areas with adequate supply of iodine and in patients after radiotherapy of the neck) and molecular genetics linkage. For example: RET/PTC rearrangements could be more often found in carcinomas associated with CLT, but this mutation could be found in benign lesions such as CLT, as well. CLT seems to be a positive prognostic factor in patients with differentiated thyroid cancer. It is associated with less invasive forms of tumor, lower occurrence of infiltrated lymphatic nodes and a lower risk of recurrence. PMID:26486481

  3. The Autoimmune Basis of Narcolepsy

    PubMed Central

    Mahlios, Josh; De la Herrán-Arita, Alberto K.; Mignot, Emmanuel

    2013-01-01

    Narcolepsy is a neurological disorder characterized by excessive daytime sleepiness, cataplexy, hypnagonic hallucinations, sleep paralysis, and disturbed nocturnal sleep patterns. Narcolepsy is caused by the loss of hypocretin (orexin)-producing neurons in the lateral hypothalamus. Evidence, such as a strong association with HLA DQB1*06:02, strongly suggests an autoimmune basis targeting hypocretin neurons. Genome-wide association studies have strengthened the association between narcolepsy and immune system gene polymorphisms, including the identification of polymorphisms in the T cell receptor alpha locus, TNFSF4 (also called OX40L), Cathepsin H (CTSH) the purinergic receptor P2RY11, and the DNA methyltransferase DNMT1. Recently, attention has been raised regarding a spike in cases of childhood narcolepsy in 2010 following the 2009 H1N1 pandemic (pH1N1) in China and vaccination with Pandemrix, an adjuvanted H1N1 vaccine that was used in Europe. How the immune system may be involved in disease initiation and/or progression remains a challenge to researchers. Potential immunological pathways that could lead to the specific elimination of hypocretin producing neurons include molecular mimicry or bystander activation, and are likely a combination of genetic and environmental factors, such as upper airway infections. PMID:23725858

  4. The autoimmune basis of narcolepsy.

    PubMed

    Mahlios, Josh; De la Herrán-Arita, Alberto K; Mignot, Emmanuel

    2013-10-01

    Narcolepsy is a neurological disorder characterized by excessive daytime sleepiness, cataplexy, hypnagonic hallucinations, sleep paralysis, and disturbed nocturnal sleep patterns. Narcolepsy is caused by the loss of hypocretin (orexin)-producing neurons in the lateral hypothalamus. Evidence, such as a strong association with HLA DQB1*06:02, strongly suggests an autoimmune basis targeting hypocretin neurons. Genome-wide association studies have strengthened the association between narcolepsy and immune system gene polymorphisms, including the identification of polymorphisms in the T cell receptor alpha locus, TNFSF4 (also called OX40L), Cathepsin H (CTSH) the purinergic receptor P2RY11, and the DNA methyltransferase DNMT1. Recently, attention has been raised regarding a spike in cases of childhood narcolepsy in 2010 following the 2009 H1N1 pandemic (pH1N1) in China and vaccination with Pandemrix, an adjuvanted H1N1 vaccine that was used in Europe. How the immune system may be involved in disease initiation and/or progression remains a challenge to researchers. Potential immunological pathways that could lead to the specific elimination of hypocretin producing neurons include molecular mimicry or bystander activation, and are likely a combination of genetic and environmental factors, such as upper airway infections. PMID:23725858

  5. Treatment of autoimmune hemolytic anemias

    PubMed Central

    Zanella, Alberto; Barcellini, Wilma

    2014-01-01

    Autoimmune hemolytic anemia (AIHA) is a relatively uncommon disorder caused by autoantibodies directed against self red blood cells. It can be idiopathic or secondary, and classified as warm, cold (cold hemagglutinin disease (CAD) and paroxysmal cold hemoglobinuria) or mixed, according to the thermal range of the autoantibody. AIHA may develop gradually, or have a fulminant onset with life-threatening anemia. The treatment of AIHA is still not evidence-based. The first-line therapy for warm AIHA are corticosteroids, which are effective in 70–85% of patients and should be slowly tapered over a time period of 6–12 months. For refractory/relapsed cases, the current sequence of second-line therapy is splenectomy (effective approx. in 2 out of 3 cases but with a presumed cure rate of up to 20%), rituximab (effective in approx. 80–90% of cases), and thereafter any of the immunosuppressive drugs (azathioprine, cyclophosphamide, cyclosporin, mycophenolate mofetil). Additional therapies are intravenous immunoglobulins, danazol, plasma-exchange, and alemtuzumab and high-dose cyclophosphamide as last resort option. As the experience with rituximab evolves, it is likely that this drug will be located at an earlier point in therapy of warm AIHA, before more toxic immunosuppressants, and in place of splenectomy in some cases. In CAD, rituximab is now recommended as first-line treatment. PMID:25271314

  6. [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

  7. 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

  8. 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

  9. TDP-43 Frontotemporal Lobar Degeneration and Autoimmune Disease

    PubMed Central

    Miller, Zachary A.; Rankin, Katherine P.; Graff-Radford, Neill R.; Takada, Leonel T.; Sturm, Virginia E.; Cleveland, Clare M.; Criswell, Lindsey A.; Jaeger, Philipp A.; Stan, Trisha; Heggeli, Kristin A.; Hsu, Sandy Chan; Karydas, Anna; Khan, Baber K.; Grinberg, Lea T.; Gorno-Tempini, Maria Luisa; Boxer, Adam L.; Rosen, Howard J.; Kramer, Joel H.; Coppola, Giovanni; Geschwind, Daniel H.; Rademakers, Rosa; Seeley, William W.; Wyss-Coray, Tony; Miller, Bruce L.

    2013-01-01

    Background The aetiology and pathogenesis of non-genetic forms of frontotemporal dementia (FTD) is unknown and even with the genetic forms of FTD, pathogenesis remains elusive. Given the association between systemic inflammation and other neurodegenerative processes, links between autoimmunity and FTD need to be explored. Objective To describe the prevalence of systemic autoimmune disease in semantic variant primary progressive aphasia (svPPA), a clinical cohort, and in progranulin (PGRN) mutation carriers compared to neurologically healthy normal controls (NC) and Alzheimer’s disease (AD) as dementia controls. Design Case control. Setting Academic medical centres. Participants 129 svPPA, 39 PGRN, 186 NC, and 158 AD patients underwent chart review for autoimmune conditions. A large subset of svPPA, PGRN, and NC cohorts underwent serum analysis for tumor necrosis factor α (TNF-α) levels. Outcome Measures Chi-square comparison of autoimmune prevalence and follow up logistic regression. Results There was a significantly increased risk of autoimmune disorders clustered around inflammatory arthritides, cutaneous disorders, and gastrointestinal conditions in the svPPA and PGRN cohorts. Elevated TNF-α levels were observed in svPPA and PGRN compared to NC. Conclusions svPPA and PGRN are associated with increased prevalence of specific and related autoimmune diseases compared to NC and AD. These findings suggest a unique pattern of systemic inflammation in svPPA and PGRN and open new research avenues for understanding and treating disorders associated with underlying transactive response DNA-binding protein 43 (TDP-43) aggregation. PMID:23543794

  10. Emerging role of interleukin-33 in autoimmune diseases

    PubMed Central

    Pei, Cheng; Barbour, Mark; Fairlie-Clarke, Karen J; Allan, Debbie; Mu, Rong; Jiang, Hui-Rong

    2014-01-01

    Interleukin-33 (IL-33) is a member of the IL-1 cytokine family. It predominantly induces type 2 immune responses and thus is protective against atherosclerosis and nematode infections but contributes to allergic airway inflammation. Interleukin-33 also plays a pivotal role in the development of many autoimmune diseases through mechanisms that are still not fully understood. In this review, we focus on the recent advances in understanding of the expression and function of IL-33 in some autoimmune disorders, aiming to provide insight into its potential role in disease development. PMID:24116703

  11. 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

  12. Prevalence of coeliac disease in patients with thyroid autoimmunity.

    PubMed

    Valentino, R; Savastano, S; Tommaselli, A P; Dorato, M; Scarpitta, M T; Gigante, M; Micillo, M; Paparo, F; Petrone, E; Lombardi, G; Troncone, R

    1999-01-01

    The occurrence of autoimmune thyroid disorders among patients with coeliac disease (CD) is well documented, but the exact prevalence of CD among patients with autoimmune thyroid diseases (ATD) is as yet unclear. We screened 150 newly diagnosed patients with ATD by serum endomysial antibody detection (EmA). In 5 subjects (3.3%) EmA positivity was found; all underwent jejunal biopsy. On gluten-free diet an excellent clinical and histological response was recorded with an improvement of hypothyroidism and reduction of the thyroxine dosage. Our data suggest a significant high prevalence (3.3%) of CD in patients with ATD, in particular with Hashimoto's thyroiditis. PMID:10461017

  13. Autoimmune hemolytic anemia.

    PubMed

    Dacie, J V

    1975-10-01

    Warm-type autoantibodies of autoimmune hemolytic anemia (AIHA) are usually IgG but may be IgM or IgA. They are usual Rh specific. Cold-type antibodies are IgM or IgG (Donath-Landsteiner [DL] antibody). IgM antibodies are usually anit-l (occasionally anti-i) and DL antibodies anti-P. The warm IgG antibodies do not fix complement (C); they cause red blood cell (RBC) destruction predominantly in the spleen as the result of interaction between fixing; they cause RBC destruction either by intravascular lysis (complement sequence completed) or by interaction between C3-coated RBCs and phagocytes in liver and spleen. Gentic factors, immunoglobulin deficiency, somatic mutation, viral infections and drugs, and failure of T-lymphocyte function, all probably play a part in breaking immunological tolerance and the development of AIHA. PMID:1164110

  14. Immunomodulation of Autoimmune Arthritis by Herbal CAM.

    PubMed

    Venkatesha, Shivaprasad H; Rajaiah, Rajesh; Berman, Brian M; Moudgil, Kamal D

    2011-01-01

    Rheumatoid arthritis (RA) is a debilitating autoimmune disease of global prevalence. The disease is characterized by synovial inflammation leading to cartilage and bone damage. Most of the conventional drugs used for the treatment of RA have severe adverse reactions and are quite expensive. Over the years, increasing proportion of patients with RA and other immune disorders are resorting to complementary and alternative medicine (CAM) for their health needs. Natural plant products comprise one of the most popular CAM for inflammatory and immune disorders. These herbal CAM belong to diverse traditional systems of medicine, including traditional Chinese medicine, Kampo, and Ayurvedic medicine. In this paper, we have outlined the major immunological pathways involved in the induction and regulation of autoimmune arthritis and described various herbal CAM that can effectively modulate these immune pathways. Most of the information about the mechanisms of action of herbal products in the experimental models of RA is relevant to arthritis patients as well. The study of immunological pathways coupled with the emerging application of genomics and proteomics in CAM research is likely to provide novel insights into the mechanisms of action of different CAM modalities. PMID:21234398

  15. Immunomodulation of Autoimmune Arthritis by Herbal CAM

    PubMed Central

    Venkatesha, Shivaprasad H.; Rajaiah, Rajesh; Berman, Brian M.; Moudgil, Kamal D.

    2011-01-01

    Rheumatoid arthritis (RA) is a debilitating autoimmune disease of global prevalence. The disease is characterized by synovial inflammation leading to cartilage and bone damage. Most of the conventional drugs used for the treatment of RA have severe adverse reactions and are quite expensive. Over the years, increasing proportion of patients with RA and other immune disorders are resorting to complementary and alternative medicine (CAM) for their health needs. Natural plant products comprise one of the most popular CAM for inflammatory and immune disorders. These herbal CAM belong to diverse traditional systems of medicine, including traditional Chinese medicine, Kampo, and Ayurvedic medicine. In this paper, we have outlined the major immunological pathways involved in the induction and regulation of autoimmune arthritis and described various herbal CAM that can effectively modulate these immune pathways. Most of the information about the mechanisms of action of herbal products in the experimental models of RA is relevant to arthritis patients as well. The study of immunological pathways coupled with the emerging application of genomics and proteomics in CAM research is likely to provide novel insights into the mechanisms of action of different CAM modalities. PMID:21234398

  16. Neuroimmunology: An Expanding Frontier in Autoimmunity

    PubMed Central

    Höftberger, Romana

    2015-01-01

    Anti-neuronal autoimmune encephalitis (AIE) comprises a recently characterized group of immune-mediated disorders that result in limbic, multifocal, or diffuse encephalitis due to direct interaction of autoantibodies with neuronal surface or synaptic proteins. The pathological effects of the autoantibodies vary according to the target antigen but when they are removed, neuronal dysfunction is commonly reversed. Ongoing research on AIE constantly increases the number of novel autoantibodies and expands the spectrum of neurological syndromes that are important in the differential diagnosis of psychiatric illness, dementia, or viral encephalitis. This review summarizes recent advances in AIE, focusing on pathogenetic mechanisms and novel associations with other CNS disorders such as neurodegeneration, relapsing symptoms post-herpes simplex virus encephalitis, and demyelinating diseases. In addition, an algorithmic approach to detect and characterize neuronal cell surface autoantibodies is proposed. PMID:25972873

  17. Immunodeficiency and Autoimmune Enterocolopathy Linked to NFAT5 Haploinsufficiency

    PubMed Central

    Boland, Brigid S.; Widjaja, Christella E.; Banno, Asoka; Zhang, Bing; Kim, Stephanie H.; Stoven, Samantha; Peterson, Michael R.; Jones, Marilyn C.; Su, H. Irene; Crowe, Sheila E.; Bui, Jack D.; Ho, Samuel B.; Okugawa, Yoshinaga; Goel, Ajay; Marietta, Eric V.; Khosroheidari, Mahdieh; Jepsen, Kristen L.; Aramburu, Jose; Lopez-Rodriguez, Cristina; Sandborn, William J.; Murray, Joseph A.; Harismendy, Olivier; Chang, John T.

    2015-01-01

    The link between autoimmune diseases and primary immunodeficiency syndromes has been increasingly appreciated. Immunologic evaluation of a young man with autoimmune enterocolopathy and unexplained infections revealed evidence of immunodeficiency, including IgG subclass deficiency, impaired antigen-induced lymphocyte proliferation, reduced cytokine production by CD8+ T lymphocytes, and decreased numbers of natural killer (NK) cells. Genetic evaluation identified haploinsufficiency of NFAT5, a transcription factor regulating immune cell function and cellular adaptation to hyperosmotic stress, as a possible cause of this syndrome. Inhibition or deletion of NFAT5 in normal human and murine cells recapitulated several of the immune deficits identified in the patient. These results provide evidence of a primary immunodeficiency disorder associated with organ-specific autoimmunity linked to NFAT5 deficiency. PMID:25667416

  18. Rare association of insulin autoimmune syndrome with ankylosing spondylitis

    PubMed Central

    Raizada, Nishant; Rahaman, S H; Kandasamy, D

    2015-01-01

    Summary Insulin autoimmune syndrome (IAS) is a rare cause of hyperinsulinemic hypoglycaemia, which is known to occur in association with the use of sulfhydryl-containing drugs and autoimmune disorders. We describe a patient with hitherto an unreported association of IAS with ankylosing spondylitis. We have also performed and described a simplified method of polyethylene glycol (PEG) precipitation of an insulin bound antibody in the serum. Learning points IAS should be considered in differential diagnosis of endogenous hyperinsulinemic hypoglycaemia. Ankylosing spondylitis can be associated with IAS apart from several other autoimmune diseases. Very high serum insulin levels (100–10 000 μU/ml) are frequently seen in IAS. When faced with very high serum insulin before suspecting insulinoma, it is advisable that PEG precipitation of serum be done to identify antibody bound insulin. A clinical suspicion of IAS can avoid expensive imaging and unnecessary surgery in affected patients. PMID:26527431

  19. Toll-Like Receptors in the Pathogenesis of Autoimmune Diseases

    PubMed Central

    Mohammad Hosseini, Akbar; Majidi, Jafar; Baradaran, Behzad; Yousefi, Mehdi

    2015-01-01

    Human Toll-like receptors (TLRs) are a family of transmembrane receptors, which play a key role in both innate and adaptive immune responses. Beside of recognizing specific molecular patterns that associated with different types of pathogens, TLRs may also detect a number of self-proteins and endogenous nucleic acids. Activating TLRs lead to the heightened expression of various inflammatory genes, which have a protective role against infection. Data rising predominantly from human patients and animal models of autoimmune disease indicate that, inappropriate triggering of TLR pathways by exogenous or endogenous ligands may cause the initiation and/or perpetuation of autoimmune reactions and tissue damage. Given their important role in infectious and non-infectious disease process, TLRs and its signaling pathways emerge as appealing targets for therapeutics. In this review, we demonstrate how TLRs pathways could be involved in autoimmune disorders and their therapeutic application. PMID:26793605

  20. Questions and Answers on Autoimmunity and Autoimmune Diseases

    MedlinePlus

    ... Take our Survey Information List of Diseases & Info ‎Women and Autoimmunity The Common Thread Coping Tools InFocus Newsletter Questions & Answers Fundraising Grassroots Fundraising Workplace Giving Special Events AARDA on Facebook Copyright © 2004 - ...

  1. 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

  2. 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

  3. 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 diseases. PMID:25763008

  4. Bone involvement in clusters of autoimmune diseases: just a complication?

    PubMed

    Lombardi, Francesca; Franzese, Adriana; Iafusco, Dario; del Puente, Antonio; Esposito, Antonella; Prisco, Francesco; Troncone, Riccardo; Valerio, Giuliana

    2010-02-01

    Bone loss, described in individual groups of patients with Type 1 diabetes (T1D), autoimmune thyroid disease (ATD) or celiac disease (CD) is usually viewed as a complication of these diseases. There is increasing evidence that alterations in the immune system may directly affect bone mass. Clustering of autoimmune diseases in the same individual might predispose to higher risk of osteopenia due to imbalance in immune regulation. The aim of this study was to evaluate bone involvement in clusters of the most common autoimmune diseases (T1D, ATD and CD) in children. The study was performed at a tertiary care center for the care of pediatric diabetes. One-hundred-two patients with T1D alone or associated with ATD and/or CD were studied; 13 patients had cluster of three autoimmune diseases. Amplitude-dependent speed of sound (AD-SoS) was measured by phalangeal quantitative ultrasound and expressed as standard deviation score (SDS). AD-SoS SDS < -2 was considered indicative of osteopenia. Osteopenia was equally distributed among children with T1D alone (8.1%), T1D associated with ATD (7.7%) or CD (10.3%), while it was 53.8% in patients presenting with three autoimmune diseases. Poor compliance to gluten-free diet increased osteopenia to 18.8% in patients with T1D and CD and 80% in patients with three autoimmune disorders. No difference among groups was found with regard to gluco-metabolic control, calcium metabolism, thyroid function. In conclusion bone impairment in multiple autoimmune diseases might be considered not only a complication due to endocrine or nutritional mechanisms, but also a consequence of an immunoregulatory imbalance. Alterations of homeostatic mechanisms might explain an imbalance of osteoclast activity leading to osteopenia. PMID:19815104

  5. [Autoimmune mechanisms in endocrinology--the polyglandular autoimmune endocrine syndrome].

    PubMed

    Hrnciar, J; Hrnciarová, M

    1991-06-01

    Autoimmune endocrinopathies belong to so-called organ specific autoimmune diseases. These diseases combine very often and from the polyglandular autoimmune endocrine syndrome (PAES), where autoantibodies either destroy or stimulate individual endocrine glands or hormone receptors in target tissues. Thus a wide range of combinations of hypofunctional or hyperfunctional clinical syndromes develops. PAES is a good natural model of endocrine polyautoaggressiveness. In its development the following aetiopathogenetic factors participate: 1. Hereditary familial disposition, expressed e.g. by certain inherited HHS genes (e.g. A1, B8, DR 3, 4). 2. Aberrant expression of these DR genes on endocrine organs due to bacterial or viral infections, pregnancy, stimulation of the thyroid gland by TSH or immunoglobulins (TSIg). 3. Antigenic mimicri and the presentation of autoantigens to immunocompetent cells. 4. Impaired immunoregulation--antigen specific insufficiency of suppressor T lymphocytes. 5. Local and general amplification reaction to an autoimmune process. 6. The development and autoreproduction of organ specific autoimmune endocrine disease and its development into the final stage of endocrine disease where autoantibodies may disappear. The diagnosis of PAES in clinical practice is difficult. Common immunological tests are not very conclusive. To assess a polyglandular affection we found useful the multiaxial synchronous test where stimulation of several hypothalamic releasing hormones combined with a hypoglycaemic stimulus is used. Autoimmune lymphocytic hypophysitis is part of PAES. In clinical practice this syndrome is therefore frequently incorrectly diagnosed and then incorrectly treated. PMID:1897135

  6. Adaptive and innate immune modulators of inflammation and autoimmunity.

    PubMed

    Moudgil, Kamal D

    2015-10-01

    Both genetic and environmental factors contribute to the pathogenesis of inflammatory and autoimmune diseases. The association of specific major histocompatibility complex (MHC) alleles with susceptibility to particular autoimmune diseases is well known, although the mechanistic aspects of this link are not fully unraveled yet. Furthermore, the prevalence of many autoimmune diseases is much higher in females than in males. Intensive efforts are currently being directed to defining the role of sex hormones, the hypothalamic–pituitary–adrenal (HPA) axis, and other modifying factors in this sexual dimorphism. Among the environmental factors, emerging understanding of the interplay between the gut microbiota and the immune system has opened up a new frontier of biomedical research with a renewed perspective of host-environment interactions. In addition, besides specific T helper subsets and their cytokine products, the roles of the scavenger receptors, the inflammasome, the newer cytokines of the IL-1 (e.g., IL-33, IL-37) and IL-12 (e.g., IL-27, IL-35) families, and the soluble mediators produced by adipocytes (adipokines) (e.g., leptin, adiponectin) in the pathogenesis of inflammation, autoimmunity, and metabolic disorders are increasingly being realized. In this special issue, "Cytokines in Immune Pathology and Therapy," second volume, leading experts have shared their research work and perspectives on the above-mentioned cytokines and other modulators of inflammation and autoimmunity. An outline of 15 articles in volume 2 is presented here. Volume 1 of this special issue containing 14 articles was published recently. PMID:26535443

  7. Vascular endothelial growth factor (VEGF) in autoimmune diseases.

    PubMed

    Carvalho, Jozélio Freire; Blank, Miri; Shoenfeld, Yehuda

    2007-05-01

    Vascular endothelial growth factor (VEGF) is a potent stimulating factor for angiogenesis and vascular permeability. There are eight isoforms with different and sometimes overlapping functions. The mechanisms of action are under investigation with emerging insights into overlapping pathways and cross-talk between other receptors such as the neuropilins, which were not previously associated to angiogenesis. VEGF has important physiological actions on embryonic development, healing, and menstrual cycle. It also has a great role in pathological conditions that are associated to autoimmune diseases. There is considerable evidence in various autoimmune diseases such as in systemic lupus erythematosus, rheumatoid arthritis, and multiple sclerosis of an interrelationship between the VEGF system and theses disorders. Serum levels of VEGF correlate with disease activity in a large number of autoimmune diseases and fall with the use of standard therapy. We raised the possible future therapeutic strategies in autoimmune diseases with the anti-VEGF or anti-VEGFR (receptor). So far, this therapy has been used in cancer and macular ocular degeneration in diabetes. This review outlines the evidence for VEGF participation in various autoimmune diseases and proposes lines for future research in this field. PMID:17340192

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

    PubMed

    Lundin, Knut E A; Wijmenga, Cisca

    2015-09-01

    Coeliac disease is a treatable, gluten-induced disease that often occurs concurrently with other autoimmune diseases. In genetic studies since 2007, a partial genetic overlap between these diseases has been revealed and further insights into the pathophysiology of coeliac disease and autoimmunity have been gained. However, genetic screening is not sensitive and specific enough to accurately predict disease development. The current method to diagnose individuals with coeliac disease is serological testing for the presence of autoantibodies whilst the patient is on a regular, gluten-containing diet, followed by gastroduodenoscopy with duodenal biopsy. Serological test results can also predict the probability of coeliac disease development, even if asymptomatic. In patients with autoimmune diseases known to occur alongside coeliac disease (particularly type 1 diabetes mellitus or thyroid disorders), disease screening-and subsequent treatment if coeliac disease is detected-could have beneficial effects on progression or potential complications of both diseases, owing to the effectiveness of gluten-free dietary interventions in coeliac disease. However, whether diagnosis of coeliac disease and subsequent dietary treatment can prevent autoimmune diseases is debated. In this Review, the genetic and immunological features of coeliac disease, overlap with other autoimmune diseases and implications for current screening strategies will be discussed. PMID:26303674

  9. Dyslipidaemia in Rheumatological Autoimmune Diseases

    PubMed Central

    Toms, Tracey E; Panoulas, Vasileios F; Kitas, George D

    2011-01-01

    Autoimmunity forms the basis of many rheumatological diseases, and may contribute not only to the classical clinical manifestations but also to the complications. Many of the autoimmune rheumatological diseases, including rheumatoid arthritis and systemic lupus erythematosus are associated with an excess cardiovascular morbidity and mortality. Much of this excess cardiovascular risk can be attributed to atherosclerotic disease. Atherosclerosis is a complex pathological process, with dyslipidaemia and inflammation fundamental to all stages of plaque evolution. The heightened inflammatory state seen in conjunction with many rheumatological diseases may accelerate plaque formation, both through direct effects on the arterial wall and indirectly through inflammation-mediated alterations in the lipid profile. Alongside these factors, antibodies produced as part of the autoimmune nature of these conditions may lead to alterations in the lipid profile and promote atherosclerosis. In this review, we discuss the association between several of the rheumatological autoimmune diseases and dyslipidaemia, and the potential cardiovascular impact this may confer. PMID:21660202

  10. Sex differences in autoimmune diseases

    PubMed Central

    2011-01-01

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

  11. 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

  12. Adjuvants and autoimmunity.

    PubMed

    Israeli, E; Agmon-Levin, N; Blank, M; Shoenfeld, Y

    2009-11-01

    Some adjuvants may exert adverse effects upon injection or, on the other hand, may not trigger a full immunological reaction. The mechanisms underlying adjuvant adverse effects are under renewed scrutiny because of the enormous implications for vaccine development. In the search for new and safer adjuvants, several new adjuvants were developed by pharmaceutical companies utilizing new immunological and chemical innovations. The ability of the immune system to recognize molecules that are broadly shared by pathogens is, in part, due to the presence of special immune receptors called toll-like receptors (TLRs) that are expressed on leukocyte membranes. The very fact that TLR activation leads to adaptive immune responses to foreign entities explains why so many adjuvants used today in vaccinations are developed to mimic TLR ligands. Alongside their supportive role, adjuvants were found to inflict by themselves an illness of autoimmune nature, defined as 'the adjuvant diseases'. The debatable question of silicone as an adjuvant and connective tissue diseases, as well as the Gulf War syndrome and macrophagic myofaciitis which followed multiple injections of aluminium-based vaccines, are presented here. Owing to the adverse effects exerted by adjuvants, there is no doubt that safer adjuvants need to be developed and incorporated into future vaccines. Other needs in light of new vaccine technologies are adjuvants suitable for use with mucosally delivered vaccines, DNA vaccines, cancer and autoimmunity vaccines. In particular, there is demand for safe and non-toxic adjuvants able to stimulate cellular (Th1) immunity. More adjuvants were approved to date besides alum for human vaccines, including MF59 in some viral vaccines, MPL, AS04, AS01B and AS02A against viral and parasitic infections, virosomes for HBV, HPV and HAV, and cholera toxin for cholera. Perhaps future adjuvants occupying other putative receptors will be employed to bypass the TLR signaling pathway completely in order to circumvent common side effects of adjuvant-activated TLRs such as local inflammation and the general malaise felt because of the costly whole-body immune response to antigen. PMID:19880572

  13. Autoimmune Hepatitis – Approach to Diagnosis

    PubMed Central

    Czaja, Albert J.

    2006-01-01

    Abstract and Definition Abstract Context Autoimmune hepatitis has diverse features that can delay its diagnosis and the institution of potentially lifesaving corticosteroid therapy. Objective Review the clinical, laboratory, and histologic features of autoimmune hepatitis and promulgate routine application of its codified diagnostic criteria. Data Sources Reference lists and MEDLINE. Study Selection All clinically pertinent published observations that indicate the diversity of manifestations and pitfalls in diagnosis. Data Extraction Findings that had common clinical relevance and the potential to confuse the diagnosis or delay institution of therapy were selected. Data Synthesis Autoimmune hepatitis can present acutely and have histologic features of centrilobular zone 3 inflammation. Many patients may be asymptomatic, but they frequently have severe or advanced disease and typically develop symptoms later. Autoantibodies are reflective of immune-mediated mechanisms, but they are not diagnostic, pathogenic, or even required for the diagnosis. Genetic factors affect susceptibility, clinical phenotype, and treatment outcome, and they may be clues to indigenous etiologic agents. Autoimmune hepatitis can recur or develop de novo after liver transplantation, and it should be considered in all transplanted patients with allograft dysfunction. Diagnostic criteria have been codified, and a scoring system quantifies the strength of the diagnosis and accommodates atypical or deficient features. Conclusion Autoimmune hepatitis is an important diagnosis to consider in all patients with chronic hepatitis of undetermined cause. Definition Autoimmune hepatitis is a nonresolving inflammation of the liver of unknown cause.[1] It is characterized by the presence of interface hepatitis on histologic examination, hypergammaglobulinemia, and autoantibodies. There are no features that are absolutely diagnostic, and the existence of the condition can be established only by recognition of a constellation of compatible features and the exclusion of other diseases.[1] Drug-induced liver diseases, especially those related to minocycline or diclofenac toxicity; hereditary conditions, most notably Wilson disease; chronic viral infections with hepatitis B or C viruses; and the chronic cholestatic disorders of primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) must be excluded by appropriate laboratory, serologic, and histologic investigations.[2] The sine qua non of the diagnosis is the presence of interface hepatitis in liver biopsy tissue (Figure 1).[1] Plasma cell infiltration strengthens the histologic diagnosis (Figure 2), but it can occur in other forms of acute and chronic liver disease.[1] Furthermore, the absence of plasma cell infiltration does not preclude the diagnosis. Other histologic features include panacinar (lobular) hepatitis (Figure 3)[1,3] and centrilobular (Rappaport zone 3) necrosis (Figure 4).[3–6] In the latter instance, successive liver tissue examinations have demonstrated transition from the centrilobular zone 3 pattern to the classical pattern of interface hepatitis during the course of the disease.[7] Centrilobular zone 3 necrosis may be an early histologic manifestation of autoimmune hepatitis and provide clues to a toxic, ischemic, or metabolic basis for the condition. PMID:16926794

  14. Rheumatic fever, autoimmunity, and molecular mimicry: the streptococcal connection.

    PubMed

    Cunningham, Madeleine W

    2014-01-01

    The group A streptococcus, Streptococcus pyogenes, and its link to autoimmune sequelae, has acquired a new level of understanding. Studies support the hypothesis that molecular mimicry between the group A streptococcus and heart or brain are important in directing immune responses in rheumatic fever. Rheumatic carditis, Sydenham chorea and a new group of behavioral disorders called pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections are reviewed with consideration of autoantibody and T cell responses and the role of molecular mimicry between the heart, brain and group A streptococcus as well as how immune responses contribute to pathogenic mechanisms in disease. In rheumatic carditis, studies have investigated human monoclonal autoantibodies and T cell clones for their crossreactivity and their mechanisms leading to valve damage in rheumatic heart disease. Although studies of human and animal sera from group A streptococcal diseases or immunization models have been crucial in providing clues to molecular mimicry and its role in the pathogenesis of rheumatic fever, study of human monoclonal autoantibodies have provided important insights into how antibodies against the valve may activate the valve endothelium and lead to T cell infiltration. Passive transfer of anti-streptococcal T cell lines in a rat model of rheumatic carditis illustrates effects of CD4+ T cells on the valve. Although Sydenham chorea has been known as the neurological manifestation of rheumatic fever for decades, the combination of autoimmunity and behavior is a relatively new concept linking brain, behavior and neuropsychiatric disorders with streptococcal infections. In Sydenham chorea, human mAbs and their expression in transgenic mice have linked autoimmunity to central dopamine pathways as well as dopamine receptors and dopaminergic neurons in basal ganglia. Taken together, the studies reviewed provide a basis for understanding streptococcal sequelae and how immune responses against group A streptococci influence autoimmunity and inflammatory responses in the heart and brain. PMID:24892819

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

    PubMed

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

    2013-06-15

    Vitiligo is more common in people with certain autoimmune diseases. Here we studied the association between vitiligo and autoimmune diseases. In this case control study, 86 patients with vitiligo were questioned about the location of vitiligo, family history, treatment and therapeutic response. All patients were examined both clinically and with laboratory tests to detect the presence of autoimmune disorders including autoimmune thyroid disease, pernicious anemia, insulin dependent diabetes, and Systemic Lupus Erythematic (SLE) and Addison disease. We compared the prevalence of autoimmune disorder in vitiligo patients with that in a group of age-and gender-matched normal population. Average age of disease onset was 21.8 +/- 11 years; 61% of patients were female and 39% were male. The most common locations of vitiligo were hands (33.7%) and face (32.1%). The most common pattern of onset was vulgaris type (40%). Nearly one-fourth of patients had a positive family history of vitiligo. Prevalence of thyroid disorders in vitiligo patients and control group was 21.1 and 7%, respectively. The difference was statistically significant (p = 0.008). The most common autoimmune disorder in patient with vitiligo was hypothyroidism. Family history had a poor prognostic effect on response to therapy. PMID:24494526

  16. Autoimmune diseases and rehabilitation.

    PubMed

    Flachenecker, Peter

    2012-01-01

    This review gives an overview of the rehabilitation of autoimmune diseases. After general remarks on rehabilitation, the effects of acute and chronic exercises on inflammatory markers are summarized. Most of the available literature deals with rheumatoid arthritis (RA) and multiple sclerosis (MS), and therefore, rehabilitation of these diseases is described in more detail. Exercise is the main component in the rehabilitation of patients with RA and aims at increasing physical capacity, muscle strength, aerobic endurance, cardiovascular fitness and functional abilities, and helps to prevent secondary deconditioning due to reduced activity levels. Since MS causes a wide range of symptoms, the rehabilitation of these patients requires a multidisciplinary approach and encompasses physiotherapy, exercise therapy, hippotherapy, cognitive rehabilitation, psychological therapy, strategies to improve fatigue and coping programs. The ultimate goal of rehabilitation is to enable patients with chronic conditions to reach and maintain their optimal physical, sensory, intellectual, psychological and social functional levels, and to attain independence and self-determination as far as possible. PMID:21619946

  17. Autoimmune-Featured Interstitial Lung Disease

    PubMed Central

    Vij, Rekha; Strek, Mary E.

    2011-01-01

    Background: Patients with interstitial lung disease (ILD) may have features of an autoimmune disorder that do not meet the diagnostic criteria for connective tissue diseases. We determined the prevalence and characteristics of autoimmune-featured ILD (AIF-ILD) and compared these with those of idiopathic pulmonary fibrosis (IPF) and known connective tissue disease-related ILD (CTD-ILD). Methods: Patients with ILD who did not meet the criteria for a connective tissue disease were defined as having AIF-ILD if they had a sign or symptom suggestive of a connective tissue disease and a serologic test reflective of an autoimmune process. Clinical characteristics, high-resolution CT images, and lung biopsy specimens were analyzed and compared with those of patients with IPF and CTD-ILD. Survival was evaluated using a Kaplan-Meier curve. Results: Two hundred subjects completed the questionnaire and serologic testing. AIF-ILD was identified in 32%, IPF in 29%, and CTD-ILD in 19%. Gender, age, and race differed among groups (P < .01). Sixty-two percent of patients with AIF-ILD had a typical usual interstitial pneumonia (UIP) pattern on CT images. In 31 patients with AIF-ILD, lung biopsy specimens showed UIP in 81% and nonspecific interstitial pneumonia in 6%. Patients with AIF-ILD and IPF had similar survival, worse than those with CTD-ILD (P < .01). Antinuclear antibody (ANA) titers ≥ 1:1280 were associated with improved survival in patients with AIF-ILD (P = .02). Conclusions: Systematic evaluation of symptoms and serologic tests in ILD can identify AIF-ILD. A UIP pattern on CT images and histopathology is common in AIF-ILD. Although survival for patients with AIF-ILD is poor, ANA titers ≥ 1:1280 are associated with improved survival. PMID:21565966

  18. A case of autoimmune epilepsy associated with anti-leucine-rich glioma inactivated subunit 1 antibodies manifesting electrical shock-like sensations and transparent sadness

    PubMed Central

    Murata, Yoshiko; Watanabe, Osamu; Taniguchi, Go; Sone, Daichi; Fujioka, Mao; Okazaki, Mitsutoshi; Nakagawa, Eiji; Watanabe, Yutaka; Watanabe, Masako

    2015-01-01

    Autoimmune epilepsy is an isolated phenotype of autoimmune encephalitis, which may be suspected in patients with unexplained adult-onset seizure disorders or resistance to antiepileptic drugs (AEDs). Antibodies against leucine-rich glioma inactivated subunit 1 of the voltage-gated potassium channel (VGKC) complex, recently termed anti-LGI-1 antibodies, are one of the causes of autoimmune epilepsies. Bizarre symptoms with extremely short duration and high frequency are clues to the possible presence of autoimmune epilepsy with anti-LGI-1 antibodies. Precise diagnosis is important because autoimmune epilepsy is treatable and the prognosis can be predicted. PMID:26543815

  19. Thyroid-associated orbitopathy is linked to gastrointestinal autoimmunity.

    PubMed

    Ponto, K A; Schuppan, D; Zwiener, I; Binder, H; Mirshahi, A; Diana, T; Pitz, S; Pfeiffer, N; Kahaly, G J

    2014-10-01

    Common autoimmune disorders tend to co-exist in the same subjects and cluster in families. The objective of this study was to determine the prevalence of autoimmune co-morbidity in patients with autoimmune thyroid disease (AITD) with and without thyroid-associated orbitopathy (TAO). This was a cross-sectional study conducted at an academic tertiary referral centre. Of 1310 patients with AITD [n = 777 or 59% with Graves' disease (GD) and n = 533, 41% with Hashimoto's thyroiditis (HT)] followed at a specialized joint thyroid-eye out-patient clinic, 176 (13·4%) had an adult type of the autoimmune polyglandular syndrome, 129 (9·8%) type 1 diabetes, 111 (8·5%) coeliac disease, 60 (4·6%) type A autoimmune gastritis, 57 (4·4%) vitiligo and 25 (1·9%) Addison's disease. Coeliac disease and autoimmune gastritis were associated positively with GD [odds ratio (OR) = 2·18; P = 0·002 and OR = 6·52; P < 0·001], whereas type 1 diabetes, Addison's disease, autoimmune primary hypogonadism, alopecia areata, rheumatoid arthritis and Sjögren's syndrome were 'protective' for GD and thus linked to HT, OR = 0·49 (P < 0·001), 0·06 (P < 0·001), 0·25 (P < 0·001), 0·50 (P = 0·090) and 0·32 (P = 0·003), respectively. Of 610 (46·6%) AITD patients with TAO, 584 (95·7%) and 26 (4·3%) had GD and HT, respectively (P < 0·001). TAO was most prevalent in GD patients with coeliac disease (94%, OR = 1·87, P < 0·001). Multivariate analysis showed high OR for coeliac disease and autoimmune gastritis (3·4 and 4·03, both P < 0·001) pertaining to the association with TAO while type 1 diabetes, Addison's disease and alopecia areata were protective for TAO. In patients with TAO, coeliac disease is the most prevalent co-morbid autoimmune condition and rates are increased compared to GD patients without TAO. PMID:24903731

  20. Thyroid-associated orbitopathy is linked to gastrointestinal autoimmunity

    PubMed Central

    Ponto, K A; Schuppan, D; Zwiener, I; Binder, H; Mirshahi, A; Diana, T; Pitz, S; Pfeiffer, N; Kahaly, G J

    2014-01-01

    Common autoimmune disorders tend to co-exist in the same subjects and cluster in families. The objective of this study was to determine the prevalence of autoimmune co-morbidity in patients with autoimmune thyroid disease (AITD) with and without thyroid-associated orbitopathy (TAO). This was a cross-sectional study conducted at an academic tertiary referral centre. Of 1310 patients with AITD [n = 777 or 59% with Graves' disease (GD) and n = 533, 41% with Hashimoto's thyroiditis (HT)] followed at a specialized joint thyroid–eye out-patient clinic, 176 (13·4%) had an adult type of the autoimmune polyglandular syndrome, 129 (9·8%) type 1 diabetes, 111 (8·5%) coeliac disease, 60 (4·6%) type A autoimmune gastritis, 57 (4·4%) vitiligo and 25 (1·9%) Addison's disease. Coeliac disease and autoimmune gastritis were associated positively with GD [odds ratio (OR) = 2·18; P = 0·002 and OR = 6·52; P < 0·001], whereas type 1 diabetes, Addison's disease, autoimmune primary hypogonadism, alopecia areata, rheumatoid arthritis and Sjögren's syndrome were ‘protective’ for GD and thus linked to HT, OR = 0·49 (P < 0·001), 0·06 (P < 0·001), 0·25 (P < 0·001), 0·50 (P = 0·090) and 0·32 (P = 0·003), respectively. Of 610 (46·6%) AITD patients with TAO, 584 (95·7%) and 26 (4·3%) had GD and HT, respectively (P < 0·001). TAO was most prevalent in GD patients with coeliac disease (94%, OR = 1·87, P < 0·001). Multivariate analysis showed high OR for coeliac disease and autoimmune gastritis (3·4 and 4·03, both P < 0·001) pertaining to the association with TAO while type 1 diabetes, Addison's disease and alopecia areata were protective for TAO. In patients with TAO, coeliac disease is the most prevalent co-morbid autoimmune condition and rates are increased compared to GD patients without TAO. PMID:24903731

  1. Immune Disorder HSCT Protocol

    ClinicalTrials.gov

    2016-01-09

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

  2. Hyposplenism, adult coeliac disease, and autoimmunity.

    PubMed Central

    Bullen, A W; Hall, R; Gowland, G; Rajah, S; Losowsky, M S

    1981-01-01

    Functional hyposplenism is associated with a variety of disorders including coeliac disease. The aims of this study were to estimate the need for a small intestinal biopsy in the investigation of hyposplenism, and to assess the relationship of autoimmunity to hyposplenism and coeliac disease. During one year, the features of hyposplenism were found in blood films of 27 patients who had not had a splenectomy. Ten patients were already known to have coeliac disease. Intestinal biopsy was performed in another 13 patients; coeliac disease was diagnosed in six. Of the 23 patients biopsied, coeliac disease was present in 16 (70%). Autoantibodies were detected in significantly more patients with hyposplenism than in healthy controls (P less than 0.05), and in significantly more coeliacs with hyposplenism than coeliacs with normal blood films (P less than 0.01). The increased incidence of autoantibodies in coeliacs with hyposplenism compared with other coeliacs was not associated with a difference in the incidence of HLA-B8. Small bowel biopsy should be carried out in the investigation of unexplained hyposplenism. There may be a link between hyposplenism and the autoimmune manifestations of coeliac disease. PMID:7461474

  3. 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

  4. 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

  5. Autoimmune myelofibrosis and systemic lupus erythematosus in a middle-aged male presenting only with severe anemia: a case report.

    PubMed

    Pundole, Xerxes; Konoplev, Sergej; Oo, Thein Hlaing; Lu, Huifang

    2015-05-01

    Autoimmune myelofibrosis is a distinct clinicopathologic entity that occasionally occurs with autoimmune disorders such as systemic lupus erythematosus (SLE) and rheumatoid arthritis. Most cases of autoimmune myelofibrosis have been reported in female patients with a known history of SLE. We report a case of a middle-aged male patient with an unusual presentation of SLE and autoimmune myelofibrosis who presented only with severe anemia initially and was later diagnosed with SLE and autoimmune myelofibrosis. The patient's condition improved dramatically after treatment with corticosteroids.SLE and autoimmune myelofibrosis is a rare but potentially devastating condition. Anemia maybe the only presenting symptom in addition to bone marrow fibrosis and careful clinical and laboratory assessment is imperative. Corticosteroids maybe useful and spare patients from bone marrow transplantation. PMID:25984660

  6. The Vogt-Koyanagi-Harada syndrome: association with autoimmune polyglandular syndrome type 1.

    PubMed Central

    Jovic, N. S.; Nesovic, M.; Vranjesevic, D. N.; Ciric, J.; Marinkovic, D. M.; Bonaci, B.

    1996-01-01

    We describe a young woman with primary adrenal insufficiency, hypoparathyroidism (autoimmune polyglandular syndrome type 1), Graves disease, vitiligo, and alopecia universalis. Five years after the diagnosis, she presented with recurrent ophthalmological and neurological disorders as features of Vogt-Koyanagi-Harada syndrome. A marked therapeutic response was noted on systemic high-dose corticosteroid treatment. To the best of our knowledge, such a spectre of autoimmune diseases has not been reported previously. PMID:8796218

  7. Autoimmune-associated lymphoid tyrosine phosphatase is a gain-of-function variant.

    PubMed

    Vang, Torkel; Congia, Mauro; Macis, Maria Doloretta; Musumeci, Lucia; Orrú, Valeria; Zavattari, Patrizia; Nika, Konstantina; Tautz, Lutz; Taskén, Kjetil; Cucca, Francesco; Mustelin, Tomas; Bottini, Nunzio

    2005-12-01

    A SNP in the gene PTPN22 is associated with type 1 diabetes, rheumatoid arthritis, lupus, Graves thyroiditis, Addison disease and other autoimmune disorders. T cells from carriers of the predisposing allele produce less interleukin-2 upon TCR stimulation, and the encoded phosphatase has higher catalytic activity and is a more potent negative regulator of T lymphocyte activation. We conclude that the autoimmune-predisposing allele is a gain-of-function mutant. PMID:16273109

  8. Dietary lipids and risk of autoimmune disease.

    PubMed

    Fernandes, G

    1994-08-01

    In summary, it is well established that moderate calorie restriction or reduction in overall high calorie food intake prevents or forestalls the development of age-associated disease incidence such as breast cancer and renal disease in rodents. A similar approach could also readily be applied in humans for preventing the risk and rise of life-shortening diseases. Many age-associated diseases, particularly autoimmune diseases with viral etiology, appear to be exacerbated in the presence of adverse lipid intake such as an increased level of vegetable oils or trans-fatty acids from the usage of hydrogenated dietary oils. At present, nearly 35-40% of the total calories are from dietary fats and/or of lipid origin. Although usage of saturated fat, which increases cardiovascular disease, has been reduced to a large extent in the United States, consumption of both monounsaturated and polyunsaturated fats of omega-6 origin has either increased or simply been substituted in place of saturated fats. Further, for the past 50 years, a significant reduction in highly polyunsaturated fat consumption such as marine oil has also occurred specifically in the United States. The reduction in omega-3 lipids of marine or vegetable source occurs primarily because of short shelf life due to rancidity. However, the increased consumption of omega-6 or a vegetable source of oils and decreased omega-3 intake may increase in vivo the production of free radicals and higher proinflammatory cytokines. Our ongoing studies reveal that proinflammatory vegetable oil could increase autoimmune disease by increasing the free radical formation by decreasing the antioxidant enzyme mRNA levels, thereby further decreasing immune function, particularly the production of anti-inflammatory cytokines such as IL-2 and TGF beta mRNA levels. In contrast, omega-3 lipid intake in the presence of an antioxidant supplement appears to exert protection against autoimmunity by enhancing antioxidant enzymes and TGF beta mRNA levels and by preventing the rise in oncogene expression. However, detailed studies are required to establish the protective and deleterious role of different commonly consumed lipids or dietary oils by the general population, particularly during middle and aging years. Further, we also propose that combining nonsteroidal drug therapy along with moderate calorie reduction in the presence of more protective omega-3 dietary lipids of either marine or vegetable source and decreasing the levels of mono- and polyunsaturated lipids may provide additional protection against the age-associated rise in malignancy and autoimmune disorders. PMID:8050192

  9. Helicobacter pylori and autoimmune diseases

    PubMed Central

    Hasni, S; Ippolito, A; Illei, GG

    2013-01-01

    Helicobacter pylori (H. pylori) is a widely prevalent microbe, with between 50 and 80% of the population infected worldwide. Clinically, infection with H. pylori is commonly associated with peptic ulcer disease, but many of those infected remain asymptomatic. H. pylori has evolved a number of means to affect the host immune response and has been implicated in many diseases mitigated by immune dysregulation, such as immune thrombocytopenic purpura (ITP), atrophic gastritis, and mucosa associated lymphoid tissue (MALT) lymphoma. Autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis, and Sjogren’s syndrome, are the result of a dysregulated host immune system which targets otherwise healthy tissues. The exact etiology of autoimmune diseases is unclear, but it has long been suggested that exposure to certain environmental agents, such as viral and bacterial infection or chemical exposures, in genetically susceptible individuals may be the catalyst for the initiation of autoimmune processes. Because of its prevalence and ability to affect human immune function, many researchers have hypothesized that H. pylori might contribute to the development of autoimmune diseases. In this article, we review the available literature regarding the role of chronic H. pylori infection in various autoimmune disease states. PMID:21902767

  10. 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

  11. 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

  12. 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

  13. Th17 Cells in Immunity and Autoimmunity

    PubMed Central

    Bedoya, Simone Kennedy; Lam, Brandon; Lau, Kenneth; Larkin, Joseph

    2013-01-01

    Th17 and IL-17 play important roles in the clearance of extracellular bacterial and fungal infections. However, strong evidence also implicates the Th17 lineage in several autoimmune disorders including multiple sclerosis, psoriasis, rheumatoid arthritis, inflammatory bowel disease, systemic lupus erythematosus, and asthma. The Th17 subset has also been connected with type I diabetes, although whether it plays a role in the pathogenicity of or protection from the disease remains a controversial issue. In this review we have provided a comprehensive overview of Th17 pathogenicity and function, including novel evidence for a protective role of Th17 cells in conjunction with the microbiota gut flora in T1D onset and progression. PMID:24454481

  14. Infantile cytomegalovirus-associated autoimmune hemolytic anemia.

    PubMed

    Murray, J C; Bernini, J C; Bijou, H L; Rossmann, S N; Mahoney, D H; Morad, A B

    2001-01-01

    Autoimmune hemolytic anemia (AIHA) is a hematologic disorder that is rarely seen in infants and young children. Most cases are associated with viral or bacterial infection, but the immunologic events leading to hemolysis are poorly understood. We describe two infants with severe cytomegalovirus (CMV)-associated warm antibody AIHA. One case was immunohematologically analyzed and showed suggestive evidence that endogenous anti-CMV IgG antibodies were the pathogenic antibodies leading to hemolysis, implicating a possible causal relationship between AIHA and CMV infection. Both patients were ultimately treated with intravenous CMV immune globulin, with subsequent improvement. These cases suggest that investigation for the presence of CMV in infantile AIHA is warranted and that CMV immune globulin should be considered as a therapeutic option. PMID:11464992

  15. Th17 cells in immunity and autoimmunity.

    PubMed

    Bedoya, Simone Kennedy; Lam, Brandon; Lau, Kenneth; Larkin, Joseph

    2013-01-01

    Th17 and IL-17 play important roles in the clearance of extracellular bacterial and fungal infections. However, strong evidence also implicates the Th17 lineage in several autoimmune disorders including multiple sclerosis, psoriasis, rheumatoid arthritis, inflammatory bowel disease, systemic lupus erythematosus, and asthma. The Th17 subset has also been connected with type I diabetes, although whether it plays a role in the pathogenicity of or protection from the disease remains a controversial issue. In this review we have provided a comprehensive overview of Th17 pathogenicity and function, including novel evidence for a protective role of Th17 cells in conjunction with the microbiota gut flora in T1D onset and progression. PMID:24454481

  16. Localized Autoimmune Pancreatitis

    PubMed Central

    Cao, Zhe; Tian, Rui; Zhang, Taiping; Zhao, Yupei

    2015-01-01

    Abstract Autoimmune pancreatitis (AIP) is a rare disease with clinical presentations that greatly mimic pancreatic cancer (PC). It is critical for clinicians to distinguish AIP from PC because their treatments and prognoses are entirely different. Typical images show characteristic features such as diffuse pancreatic swelling and strictures of the main pancreatic duct (MPD). However, AIP may present as a localized pancreatic mass, in which case it is very difficult to differentiate from PC. Here, we report a case of a 40-year-old man with computed tomography (CT) imaging studies confirming an area of low-density neoplasm in the uncinate process of the pancreas with dilation in the common biliary duct (CBD) and MPD. Increased uptake in the uncinate mass was observed by positron emission tomography (PET)/CT scan, which strongly suggested PC. Further laboratory analyses showed a marked elevation of serum IgG4. Because there was not enough evidence to rule out a diagnosis of malignancy, a histopathological biopsy became the criterion standard. An endoscopic ultrasound (EUS)-guided needle biopsy failed. As an alternative, a pancreaticoduodenectomy was conducted for the biopsy, and pathological analysis confirmed IgG4-related sclerotic chronic pancreatitis with moderate lymphoplasmacellular infiltration. We suggest that an accurate preoperative diagnosis for localized AIP with MPD and CBD obstructions mimicking PC is of great importance. Radiological imaging findings, particularly observations of diffused enlargement of the pancreas and delayed enhancement during the venous and portal phases, are essential for diagnosing AIP. Careful consideration should be given if serum IgG4 was taken as a special indicator for a differential diagnosis between AIP and PC. A history of IgG4-related diseases involving the biliary, lacrimal, salivary, retroperitoneal, renal, or pulmonary systems should also be highlighted. Thus, the pathology of extrapancreatic organs can be utilized as diagnostic evidence when the pathology for a pancreatic mass is not available, as in the case presented here. Furthermore, cautious use of hormone therapy is indicated for patients who cannot be ruled out as having PC. The results of future studies on localized AIP are eagerly awaited. PMID:26496272

  17. The genetics of generalized vitiligo and associated autoimmune diseases.

    PubMed

    Spritz, Richard A

    2006-01-01

    Generalized vitiligo is an acquired disorder in which patches of depigmented skin, overlying hair, and oral mucosa result from progressive autoimmune loss of melanocytes from the involved areas. Although vitiligo is perhaps the most common pigmentary disorder, insufficiently clear clinical definition of the disorder and lack of a good laboratory animal model have inhibited progress in understanding its pathobiology, its environmental triggers, and in developing specific and effective therapeutic approaches. Vitiligo results from a complex interaction of environmental, genetic, and immunologic factors, which ultimately contribute to melanocyte destruction, resulting in the characteristic depigmented lesions. In the past few years, studies of the genetic epidemiology of generalized vitiligo have led to the recognition that vitiligo is part of a broader, genetically-determined, autoimmune/autoinflammatory diathesis. Attempts to identify genes involved in vitiligo susceptibility have involved both allelic association studies of candidate genes and genome-wide linkage analyses to discover new genes, and these studies have begun to shed light on the mechanisms of vitiligo pathogenesis. It is anticipated that the discovery of biological pathways of vitiligo pathogenesis will provide novel therapeutic and prophylactic targets for future approaches to the treatment and prevention of vitiligo and its associated autoimmune diseases. PMID:16289692

  18. TCR-mediated hyper-responsiveness of autoimmune Galphai2(-/-) mice is an intrinsic naïve CD4(+) T cell disorder selective for the Galphai2 subunit.

    PubMed

    Huang, Tiffany T; Zong, Yumei; Dalwadi, Harnisha; Chung, Chan; Miceli, M Carrie; Spicher, Karsten; Birnbaumer, Lutz; Braun, Jonathan; Aranda, Richard

    2003-11-01

    Heterotrimeric Gi signaling regulates immune homeostasis, since autoimmunity occurs upon disruption of this pathway. However, the role of the lymphocyte-expressed Galphai subunits (Galphai2 and 3) on T cell activation and cytokine production is poorly understood. To examine this role, we studied T lymphocytes from mice deficient in the Galphai2 or Galphai3 subunits. Galphai2(-/-) but not Galphai3(-/-) splenocytes were hyper-responsive for IFN-gamma and IL-4 production following activation through the TCR. Galphai2(-/-) T cells had a relaxed costimulatory requirement for IL-2 secretion and proliferation compared to wild-type cells. Purified naïve Galphai2(-/-) T cells produced more IL-2 than naïve wild-type T cells following TCR activation, indicating that the hyper-responsive cytokine profile was not due to the expanded Galphai2(-/-) memory T cells, but involved an intrinsic T cell alteration. Cytokine hyper-responsiveness was not seen when purified Galphai2(-/-) T cells were stimulated with phorbol myristic acetate/ionomycin, localizing the alteration to a proximal TCR-specific signaling pathway. Galphai2(-/-) CD4(+) T cells were distinguished from wild-type or Galphai3(-/-) T cells by a globally augmented TCR-induced calcium response. These findings indicate that Galphai2(-/-) mice have an intrinsic CD4(+) T cell abnormality in TCR signaling which may be one cause of augmented T cell effector function and Galphai2(-/-) autoimmune susceptibility. PMID:14565934

  19. 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 ...

  20. 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 Sjgren's syndrome (SS), systemic lupus erythematosus (SLE), multiple sclerosis (MS), rheumatoid arthritis (RA), systemic sclerosis (SSc), and psoriasis. PMID:25687121

  1. Therapeutic Potential of Hyporesponsive CD4+ T Cells in Autoimmunity

    PubMed Central

    Maggi, Jaxaira; Schafer, Carolina; Ubilla-Olguín, Gabriela; Catalán, Diego; Schinnerling, Katina; Aguillón, Juan C.

    2015-01-01

    The interaction between dendritic cells (DCs) and T cells is crucial on immunity or tolerance induction. In an immature or semi-mature state, DCs induce tolerance through T-cell deletion, generation of regulatory T cells, and/or induction of T-cell anergy. Anergy is defined as an unresponsive state that retains T cells in an “off” mode under conditions in which immune activation is undesirable. This mechanism is crucial for the control of T-cell responses against self-antigens, thereby preventing autoimmunity. Tolerogenic DCs (tDCs), generated in vitro from peripheral blood monocytes of healthy donors or patients with autoimmune pathologies, were shown to modulate immune responses by inducing T-cell hyporesponsiveness. Animal models of autoimmune diseases confirmed the impact of T-cell anergy on disease development and progression in vivo. Thus, the induction of T-cell hyporesponsiveness by tDCs has become a promising immunotherapeutic strategy for the treatment of T-cell-mediated autoimmune disorders. Here, we review recent findings in the area and discuss the potential of anergy induction for clinical purposes. PMID:26441992

  2. Role of Sortilin in Models of Autoimmune Neuroinflammation.

    PubMed

    Reuter, Eva; Weber, Juliane; Paterka, Magdalena; Ploen, Robert; Breiderhoff, Tilman; van Horssen, Jack; Willnow, Thomas E; Siffrin, Volker; Zipp, Frauke

    2015-12-15

    The proneurotrophin receptor sortilin is a protein with dual functions, being involved in intracellular protein transport, as well as cellular signal transduction. The relevance of the receptor for various neuronal disorders, such as dementia, seizures, and brain injury, is well established. In contrast, little is known about the role of sortilin in immune cells and inflammatory diseases. The aim of our study was to elucidate the distribution of sortilin in different immune cell types in mice and humans and to analyze its function in autoimmune CNS inflammation. Sortilin was expressed most profoundly in murine and human macrophages and dendritic cells and to a much lesser extent in B and T cells. In dendritic cells, sortilin had an impact on Ag processing. Accordingly, sortilin was highly expressed by infiltrated perivascular myeloid cells, mainly in vessel cuffs, in the CNS of patients suffering from multiple sclerosis, the most common inflammatory autoimmune disease of the CNS. Yet, sortilin gene-targeted mice (Sort1(-/-)) and chimeras deficient in sortilin in the immune system were as susceptible as wild-type littermates to T cell-dependent experimental autoimmune encephalomyelitis. Considering our results and recent data from other investigators, we conclude that the proneurotrophin receptor sortilin plays a role in innate, rather than in adaptive, immune processes and, thus, not in autoimmune neuroinflammation. PMID:26566674

  3. Possible Role of Autoimmunity in Patients with Premature Ovarian Insufficiency

    PubMed Central

    Košir Pogačnik, Renata; Meden Vrtovec, Helena; Vizjak, Alenka; Uršula Levičnik, Alenka; Slabe, Nina; Ihan, Alojz

    2014-01-01

    Background: To evaluate the involvement of immune abnormality in patients with idiopathic premature ovarian insufficiency (POI). In addition to the known etiology, autoimmune disorders may be a pathologic mechanism for POI. Materials and Methods: Our study was a prospective controlled trial. Twenty women with POI, reasons other than autoimmune excluded, were enrolled in this study. The control group consisted of 17 healthy women. In both groups, family and personal history were taken and the levels of follicle stimulating hormone, luteinizing hormone, thyroid-stimulating hormone, prolactin, anti-Müllerian hormone, inhibin B, antithyroglobulin and antithyroid peroxidase antibodies were determined. Antiovarian antibodies and subpopulations of peripheral blood T-lymhocytes were also determined. Results: Participants in the study group exhibited hypergonadotropichypogonadism, while high levels of follicle stimulating hormone and low levels of inhibin B and anti-Müllerian hormone were observed. In 16 (80%) patients, POI was associated in their personal and familial history with another autoimmune disease. Fifty percent of patients presented highly elevated antithyroid antibodies. The lymphocyte subset, especially B cells, was significantly higher (p=0.014), and peripheral regulatory lymphocytes CD25+ high were significantly lower (p=0.015) in the study group than in the control group. Anti- ovarian antibodies were detected in 20% of patients with POI. Conclusion: We presume that the presence of anti-ovarian antibodies together with abnormalities of cellular immunity may in some cases potentially represent the involvement of an autoimmune mechanism in idiopathic POI. PMID:24520498

  4. 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

  5. T cells in multiple sclerosis and experimental autoimmune encephalomyelitis

    PubMed Central

    Fletcher, J M; Lalor, S J; Sweeney, C M; Tubridy, N; Mills, K H G

    2010-01-01

    Multiple sclerosis (MS) is a demyelinating inflammatory disorder of the central nervous system (CNS), which involves autoimmune responses to myelin antigens. Studies in experimental autoimmune encephalomyelitis (EAE), an animal model for MS, have provided convincing evidence that T cells specific for self-antigens mediate pathology in these diseases. Until recently, T helper type 1 (Th1) cells were thought to be the main effector T cells responsible for the autoimmune inflammation. However more recent studies have highlighted an important pathogenic role for CD4+ T cells that secrete interleukin (IL)-17, termed Th17, but also IL-17-secreting γδ T cells in EAE as well as other autoimmune and chronic inflammatory conditions. This has prompted intensive study of the induction, function and regulation of IL-17-producing T cells in MS and EAE. In this paper, we review the contribution of Th1, Th17, γδ, CD8+ and regulatory T cells as well as the possible development of new therapeutic approaches for MS based on manipulating these T cell subtypes. PMID:20682002

  6. Mercury and nickel allergy: risk factors in fatigue and autoimmunity.

    PubMed

    Sterzl, Ivan; Procházková, Jarmila; Hrdá, Pavlína; Bártová, Jirina; Matucha, Petr; Stejskal, Vera DM

    1999-01-01

    This study examined the presence of hypersensitivity to dental and environmental metals in patients with clinical disorders complicated with chronic fatigue syndrome. Three groups of patients were examined through medical history, dental examination, and by using a modified test of blast transformation for metals-MELISA(R). The three groups consisted of the following: 22 patients with autoimmune thyroiditis with or without polyglandular autoimmune activation; 28 fatigued patients free from endocrinopathy; and 22 fatigued professionals without evidence of autoimmunity. As controls, a population sample or 13 healthy subjects without any evidence of metal sensitivity was included. Healthy controls did not complain of marked fatigue and their laboratory tests did not show signs of autoimmunity and endocrinopathy. We have found that fatigue, regardless of the underlying disease, is primarily associated with hypersensitivity to inorganic mercury and nickel. The lymphocyte stimulation by other metals was similar in fatigued and control groups. To evaluate clinical relevance of positive in vitro findings, the replacement of amalgam with metal-free restorations was performed in some of the patients. At a six-month follow-up, patients reported considerably alleviated fatigue and disappearance of many symptoms previously encountered; in parallel, lymphocyte responses to metals decreased as well. We suggest that metal-driven inflammation may affect the hypothalamic-pituitary-adrenal axis (HPA axis) and indirectly trigger psychosomatic multisymptoms characterizing chronic fatigue syndrome, fibromyalgia, and other diseases of unknown etiology. PMID:11462117

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

    PubMed Central

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

    2015-01-01

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

  8. Effect of TACI signaling on humoral immunity and autoimmune diseases.

    PubMed

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

    2015-01-01

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

  9. Cellular mechanisms of CCL22-mediated attenuation of autoimmune diabetes.

    PubMed

    Bischoff, Loraine; Alvarez, Sigrid; Dai, Derek L; Soukhatcheva, Galina; Orban, Paul C; Verchere, C Bruce

    2015-04-01

    Autoimmune destruction of insulin-producing β cells in type 1 diabetes and islet transplantation involves a variety of immune pathways but is primarily mediated by self-reactive T cells. Chemokines can modulate local immune responses in inflammation and tumors by recruiting immune cells. We have reported that expression of the chemokine CCL22 in pancreatic β cells in the NOD mouse prevents autoimmune attack by recruiting T regulatory cells (Tregs), protecting mice from diabetes. In this study we show that invariant NKT cells are also recruited to CCL22-expressing islet transplants and are required for CCL22-mediated protection from autoimmunity. Moreover, CCL22 induces an influx of plasmacytoid dendritic cells, which correlates with higher levels of IDO in CCL22-expressing islet grafts. In addition to its chemotactic properties, we found that CCL22 activates Tregs and promotes their ability to induce expression of IDO by dendritic cells. Islet CCL22 expression thus produces a tolerogenic milieu through the interplay of Tregs, invariant NKT cells, and plasmacytoid dendritic cells, which results in suppression of effector T cell responses and protection of β cells. The immunomodulatory properties of CCL22 could be harnessed for prevention of graft rejection and type 1 diabetes as well as other autoimmune disorders. PMID:25740943

  10. 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

  11. Polyglandular autoimmune syndrome type I.

    PubMed

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

    2012-12-01

    Polyglandular Autoimmune Syndrom type 1 (PAS-1) or Autoimmune PolyEndocrinopathy Candidiasis-Ectodermal-Dystrophy (APECED) is a rare recessive autosomal disease related to Autoimmune Regulator (AIRE) gene mutations. AIRE is mainly implicated in central and peripheric immune tolerance. Diagnosis was classically based on presence of at least two out of three "majors" criterions of Whitaker's triad (candidiasis, autoimmune hypoparathyroidism and adrenal insufficiency). Presence of one criterion was sufficient when a sibling was previously diagnosed. However, some atypic or poorly symptomatic variants do not correspond to these criterions. As a matter of fact, digestive (malabsorption, pernicious anemia, hepatitis), cutaneous (alopecia, vitiligo, enamel dysplasia) or ophtalmological (keratitis) components could prevail. In these cases, diagnosis could be made by molecular genetics. Prognosis is influenced by genetic (AIRE mutations, HLA), hormonal and environmental (infections) factors. Potentially letal components (hepatitis and severe malabsorption) could be treated by immunosuppressors. Candidiasis and other infections should be carefully screened and treated before beginning those therapies, in order to avoid severe systemic infections. PMID:23182677

  12. Fc?RIIB and autoimmunity.

    PubMed

    Espli, Marion; Smith, Kenneth G C; Clatworthy, Menna R

    2016-01-01

    Autoimmune diseases are characterized by adaptive immune responses against self-antigens, including humoral responses resulting in the production of autoantibodies. Autoantibodies generate inflammation by activating complement and engaging Fc? receptors (Fc?Rs). The inhibitory receptor Fc?RIIB plays a central role in regulating the generation of autoantibodies and their effector functions, which include activation of innate immune cells and the cellular arm of the adaptive immune system, via effects on antigen presentation to CD4 T cells. Polymorphisms in Fc?RIIB have been associated with susceptibility to autoimmunity but protection against infections in humans and mice. In the last few years, new mechanisms by which Fc?RIIB controls the adaptive immune response have been described. Notably, Fc?RIIB has been shown to regulate germinal center B cells and dendritic cell migration, with potential impact on the development of autoimmune diseases. Recent work has also highlighted the implication of Fc?RIIB on the regulation of the innate immune system, via inhibition of Toll-like receptor- and complement receptor-mediated activation. This review will provide an update on the role of Fc?RIIB in adaptive immune responses in autoimmunity, and then focus on their emerging function in innate immunity. PMID:26683154

  13. Iodine, thyroid autoimmunity and cancer.

    PubMed

    Fiore, Emilio; Latrofa, Francesco; Vitti, Paolo

    2015-03-01

    This review focuses on two different topics: (a) iodine and autoimmune thyroid disease (AITD) and (b) AITD and papillary thyroid carcinoma (PTC). Iodine intake modifies the expression of thyroid diseases and has been associated with induction of AITD. Thyroglobulin (Tg) is an important target in iodine-induced autoimmune response due to post-translational modifications of iodinated Tg, as suggested in animal models. We have shown that the unmasking of a cryptic epitope on Tg contributes to iodine-induced thyroid autoimmunity in humans. The relationship between AITD and PTC has been suggested in many studies. The presence of two different mechanisms has been hypothesized, one typical of AITD and the other of an immune reaction to PTC. We have shown that in AITD, the pattern of Tg recognition by anti-Tg antibodies (TgAb) is 'restricted' to the immunodominant regions of Tg, while in patients with non-AITD, such as nodular goiter and PTC devoid of thyroid lymphocytic infiltration at histology, TgAb show a less restricted epitopic pattern and bind also to other regions of Tg. Thyroid function may also affect the frequency of PTC, the risk of cancer increasing with serum TSH levels. We have shown that this mechanism, rather than thyroiditis per se, plays a major role in the association of PTC with Hashimoto's thyroiditis, as a consequence of the autoimmune process leading to a progressive increase of serum TSH in these patients. PMID:25960959

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2016-04-01

    C3 glomerulonephritis (C3GN) results from genetic or acquired dysregulation of the alternative complement pathway. A subset of patients may have clinical and biochemical characteristics compatible with an autoimmune disorder. We studied a cohort of 85 patients with confirmed C3GN (2007-2014), of which ten patients (3 male, 7 female; mean age 38.5 years) had an associated autoimmune disorder. All patients had abnormal ANA titers, 6 also had positive ds-DNA titers. At the time of presentation with C3GN, all 7 female patients had autoimmune-related presentations. Of the 3 male patients, only 1 patient had autoimmune-related presentations. Kidney biopsy showed predominantly mesangial proliferative or membranoproliferative glomerulonephritis. In 5 patients, the alternative pathway was evaluated. All had allele variants/polymorphisms associated with C3GN. One patient was also positive for C3Nefs. Treatment varied form conservative management to the use of prednisone alone or with cytotoxic therapy. Mean serum creatinine decreased from 2.0 to 1.4 mg/dL while proteinuria decreased from 2300 to 994 mg/24 h in 8 patients with follow-up. The study highlights the association between C3GN and autoimmune disorders, particularly in female patients. The study suggests that an autoimmune milieu may act as a trigger for the development of C3GN in genetically susceptible patients. Short-term prognosis of C3GN associated with autoimmune disorders appears excellent. PMID:26187133

  16. IL-17 silencing does not protect nonobese diabetic mice from autoimmune diabetes.

    PubMed

    Joseph, Julie; Bittner, Stefan; Kaiser, Fabian M P; Wiendl, Heinz; Kissler, Stephan

    2012-01-01

    The long-held view that many autoimmune disorders are primarily driven by a Th1 response has been challenged by the discovery of Th17 cells. Since the identification of this distinct T cell subset, Th17 cells have been implicated in the pathogenesis of several autoimmune diseases, including multiple sclerosis and rheumatoid arthritis. Type 1 diabetes has also long been considered a Th1-dependent disease. In light of the emerging role for Th17 cells in autoimmunity, several recent studies investigated the potential of this subset to initiate autoimmune diabetes. However, direct evidence supporting the involvement of Th17 cells in actual pathogenesis, particularly during spontaneous onset, is lacking. In this study, we sought to directly address the role of IL-17, the cytokine by which Th17 cells are primarily characterized, in the pathogenesis of autoimmune diabetes. We used lentiviral transgenesis to generate NOD mice in which IL-17 is silenced by RNA interference. The loss of IL-17 had no effect on the frequency of spontaneous or cyclophosphamide-induced diabetes. In contrast, IL-17 silencing in transgenic NOD mice was sufficient to reduce the severity of myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis, consistent with reports that IL-17 deficiency is protective in this experimental model of multiple sclerosis. We concluded that IL-17 is dispensable, at least in large part, in the pathogenesis of autoimmune diabetes. PMID:22116823

  17. A coding polymorphism in NALP1 confers risk for autoimmune Addison's disease and type 1 diabetes.

    PubMed

    Magitta, N F; Bøe Wolff, A S; Johansson, S; Skinningsrud, B; Lie, B A; Myhr, K-M; Undlien, D E; Joner, G; Njølstad, P R; Kvien, T K; Førre, Ø; Knappskog, P M; Husebye, E S

    2009-03-01

    Variants in the gene encoding NACHT leucine-rich-repeat protein 1 (NALP1), an important molecule in innate immunity, have recently been shown to confer risk for vitiligo and associated autoimmunity. We hypothesized that sequence variants in this gene may be involved in susceptibility to a wider spectrum of autoimmune diseases. Investigating large patient cohorts from six different autoimmune diseases, that is autoimmune Addison's disease (n=333), type 1 diabetes (n=1086), multiple sclerosis (n=502), rheumatoid arthritis (n=945), systemic lupus erythematosus (n=156) and juvenile idiopathic arthritis (n=505), against 3273 healthy controls, we analyzed four single nucleotide polymorphisms (SNPs) in NALP1. The major allele of the coding SNP rs12150220 revealed significant association with autoimmune Addison's disease compared with controls (OR=1.25, 95% CI: 1.06-1.49, P=0.007), and with type 1 diabetes (OR=1.15, 95% CI: 1.04-1.27, P=0.005). Trends toward the same associations were seen in rheumatoid arthritis, systemic lupus erythematosus and, although less obvious, multiple sclerosis. Patients with juvenile idiopathic arthritis did not show association with NALP1 gene variants. The results indicate that NALP1 and the innate immune system may be implicated in the pathogenesis of many autoimmune disorders, particularly organ-specific autoimmune diseases. PMID:18946481

  18. Screening Autoimmune Anti-neuronal Antibodies in Pediatric Patients with Suspected Autoimmune Encephalitis

    PubMed Central

    Kim, Soo Yeon; Choi, Sun Ah; Ryu, Hye Won; Kim, Hunmin; Lim, Byung Chan; Hwang, Hee; Chae, Jong-Hee; Choi, Jieun; Kim, Ki Joong; Hwang, Yong Seung; Lee, Soon-Tae; Chu, Kon; Lee, Sang Kun

    2014-01-01

    Background and Purpose: The aim of this study was to identify and describe the pediatric autoimmune encephalitis cases positive for anti-neuronal antibody tests. Methods: Screening of six anti-neuronal antibodies in 23 children with suspected autoimmune encephalitis was performed by cell-based indirect immunofluorescence test with patients’ serum or cerebrospinal fluid. Results: Among the 23 cases enrolled here, eight patients (35%) were positive for the anti-N-methyl-d-aspartate (NMDA) receptor antibody and one patient (4%) was positive for the anti-contactin-associated protein-like 2 (CASPR2) antibody. In the anti-NMDA receptor antibody-positive group, seizure and movement disorders were the most prominent features and were present in all patients. A tumor was present in only one patient. Three patients with infant- and toddler-onset disease did not exhibit a classic multistage illness. In addition to seizure and dyskinesia, aphasia or mutism without severe consciousness impairment was present in all three patients. These atypical clinical presentations may suggest different pathomechanism of anti-NMDA receptor encephalitis among these age groups. The patient who was positive for the anti-CASPR2 antibody was an 8-year-old girl who presented with fever, encephalopathy, and seizure. Neuromyotonia or other dyskinesia was not present. Conclusions: Eight anti-NMDA receptor antibody positive patients and one CASPR2 positive patient were identified from the screening of six anti-neuronal antibodies in pediatric patients suspected with autoimmune encephalitis. Developmental regression specifically for language skills was suggested as one of the atypical clinical features in infants and toddler onset anti-NMDA receptor antibody positive patients. PMID:25625089

  19. New insights into immune mechanisms underlying autoimmune diseases of the gastrointestinal tract.

    PubMed

    Di Sabatino, Antonio; Lenti, Marco Vincenzo; Giuffrida, Paolo; Vanoli, Alessandro; Corazza, Gino Roberto

    2015-12-01

    Recent progresses in the immune mechanisms implicated in chronic inflammatory disorders have led to a more in-depth knowledge of the pathogenesis of autoimmune diseases of the gastrointestinal tract, including autoimmune atrophic gastritis, celiac disease, autoimmune enteropathy and ulcerative colitis. While the pathogenic role of specific circulating autoantibodies, i.e., respectively anti-parietal cell, anti-tissue transglutaminase, anti-enterocyte and anti-neutrophil cytoplasmic, is still controversial, some common T-cell mediated mechanisms for inflammation - increase in T helper cell type 1/type 17 pro-inflammatory cytokines- or losing self-tolerance-abnormal regulatory T cell function - are recognized as crucial mediators of the tissue damage causing atrophy of the stomach mucosa in autoimmune atrophic gastritis, villous flattening of the small bowel in celiac disease and autoimmune enteropathy, and mucosal ulceration of the colon in ulcerative colitis. This review deals with novel advances in the immunological bases of the aforementioned autoimmune gastrointestinal disorders, and it also highlights immune mechanisms of progression from chronic inflammation to cancer and implications for new therapeutic targets. PMID:26275585

  20. Peroxisome Proliferator-Activated Receptor-γ in Thyroid Autoimmunity

    PubMed Central

    Ferrari, Silvia Martina; Fallahi, Poupak; Vita, Roberto; Benvenga, Salvatore

    2015-01-01

    Peroxisome proliferator-activated receptor- (PPAR-) γ expression has been shown in thyroid tissue from patients with thyroiditis or Graves' disease and furthermore in the orbital tissue of patients with Graves' ophthalmopathy (GO), such as in extraocular muscle cells. An increasing body of evidence shows the importance of the (C-X-C motif) receptor 3 (CXCR3) and cognate chemokines (C-X-C motif) ligand (CXCL)9, CXCL10, and CXCL11, in the T helper 1 immune response and in inflammatory diseases such as thyroid autoimmune disorders. PPAR-γ agonists show a strong inhibitory effect on the expression and release of CXCR3 chemokines, in vitro, in various kinds of cells, such as thyrocytes, and in orbital fibroblasts, preadipocytes, and myoblasts from patients with GO. Recently, it has been demonstrated that rosiglitazone is involved in a higher risk of heart failure, stroke, and all-cause mortality in old patients. On the contrary, pioglitazone has not shown these effects until now; this favors pioglitazone for a possible use in patients with thyroid autoimmunity. However, further studies are ongoing to explore the use of new PPAR-γ agonists in the treatment of thyroid autoimmune disorders. PMID:25722716

  1. The genetics of generalized vitiligo and associated autoimmune diseases.

    PubMed

    Spritz, Richard A

    2007-08-01

    Vitiligo is an acquired disorder in which patches of depigmented skin and often overlying hair, and mucous membranes, are the result of progressive autoimmune loss of melanocytes from the involved areas. Considered the most common pigmentary disorder, vitiligo involves complex interaction of environmental and genetic factors that ultimately contribute to melanocyte destruction, resulting in the characteristic depigmented lesions. In the past few years, studies of the genetic epidemiology of vitiligo have led to the recognition that generalized vitiligo is part of a broader autoimmune disease diathesis. Attempts to identify genes involved in susceptibility to generalized vitiligo have involved gene expression studies, genetic association studies of candidate genes, and genome-wide linkage analyses to discover new genes. These studies have begun to yield results that shed light on the mechanisms of vitiligo pathogenesis. It is anticipated that the discovery of biological pathways of vitiligo pathogenesis will provide novel targets for future approaches to the treatment and prevention of vitiligo and its associated autoimmune diseases. PMID:17630960

  2. 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

  3. Rituximab resistant evans syndrome and autoimmunity in Schimke immuno-osseous dysplasia

    PubMed Central

    2011-01-01

    Autoimmunity is often observed among individuals with primary immune deficiencies; however, the frequency and role of autoimmunity in Schimke immuno-osseous dysplasia (SIOD) has not been fully assessed. SIOD, which is caused by mutations of SMARCAL1, is a rare autosomal recessive disease with its prominent features being skeletal dysplasia, T cell deficiency, and renal failure. We present a child with severe SIOD who developed rituximab resistant Evans syndrome (ES). Consistent with observations in several other immunodeficiency disorders, a review of SIOD patients showed that approximately a fifth of SIOD patients have some features of autoimmune disease. To our best knowledge this case represents the first patient with SIOD and rituximab resistant ES and the first study of autoimmune disease in SIOD. PMID:21914180

  4. In Vivo Visualization of (Auto)Immune Processes in the Central Nervous System of Rodents.

    PubMed

    Schläger, Christian; Litke, Tanja; Flügel, Alexander; Odoardi, Francesca

    2016-01-01

    The CNS is effectively shielded from the periphery by the blood-brain barrier (BBB) which limits the entry of cells and solutes. However, in autoimmune disorders such as multiple sclerosis, immune cells can overcome this barrier and induce the formation of CNS inflammatory lesions. Recently, two-photon laser scanning microscopy (TPLSM) has made it possible to visualize autoimmune processes in the living CNS in real time. However, along with a high microscopy standard, this technique requires an advanced surgical procedure to access the region of interest. Here, we describe in detail the necessary methodological steps to visualize (auto)immune processes in living rodent tissue. We focus on the procedures to image the leptomeningeal vessels of the thoracic spinal cord during transfer experimental autoimmune encephalomyelitis in LEW rats (AT EAE) and in active EAE in C57BL/6 mice (aEAE). PMID:25549830

  5. The analysis of genetics and associated autoimmune diseases in Chinese vitiligo patients.

    PubMed

    Zhang, Zheng; Xu, Sheng-Xin; Zhang, Feng-Yu; Yin, Xian-Yong; Yang, Sen; Xiao, Feng-Li; Du, Wen-Hui; Wang, Jian-Feng; Lv, Yong-Mei; Tang, Hua-Yang; Zhang, Xue-Jun

    2009-02-01

    Vitiligo is a common skin and hair depigmentary disorder that results from selective destruction of melanocytes. It occurs in a typical multifactorial, polygenic inheritance. Several studies have indicated that vitiligo is associated with some autoimmune diseases. In this paper we examined 6,516 vitiligo patients including clinical characteristics, familial involvement, and their association with other autoimmune diseases. Compared with sporadic vitiligo probands, familial vitiligo probands have earlier age onset and longer disease duration. The prevalences of four autoimmune diseases namely rheumatoid arthritis, chronic urticaria, alopecia areata and psoriasis, were significantly elevated in generalized vitiligo probands and their first-degree relatives. The prevalences of chronic urticaria, rheumatoid arthritis, psoriasis were much higher in familial generalized vitiligo probands. In addition, the prevalences of diabetes mellitus and asthma were also higher in familial vitiligo probands. These findings indicate that generalized vitiligo may share common genetic aetiologic links with other autoimmune diseases, and the genetic component of familial generalized vitiligo is stronger. PMID:18839195

  6. 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

  7. Association of Extrahepatic Manifestations with Autoimmune Hepatitis.

    PubMed

    Wong, Guan Wee; Heneghan, Michael A

    2015-01-01

    For many patients with autoimmune hepatitis (AIH), the presence of extrahepatic features is well recognised both at the time of presentation and during long-term follow-up. Concomitant 'autoimmune disorders' have been described in 20-50% of patients with AIH, both in adults and children. Indeed, the presence of these associated phenomena has been incorporated into both the original and revised International AIH group scoring systems as an aid to codifying the diagnosis. In acute index presentations, non-specific joint pains sometimes flitting in nature have been reported in 10-60% of patients, and while joint swelling is uncommon, rheumatoid arthritis and mixed connective tissue disease have been reported in 2-4% of patients with AIH. For a majority of patients, these joint symptoms resolve within days of the introduction of immunosuppressive therapy. Rarer features at index presentation include a maculopapular skin rash and unexplained fever, which are features that tend to resolve quickly with treatment. Interestingly, joint pain and stiffness are also well recognised in the context of steroid withdrawal and cessation in AIH. The occasional co-presentation of AIH with coeliac disease is clinically important (1-6%), since for some patients, there is a risk of immunosuppression malabsorption, thus delaying effective treatment. Similarly, the co-existence of selective IgA deficiency (IgAD) can occur in patients with coeliac disease or in isolation. Selective IgAD as a co-existing extraheaptic feature seems to be more common in paediatric patients with AIH. For these patients, they are at an increased risk of respiratory and sinus infections. Although, typically associated with primary sclerosing cholangitis, the presence of inflammatory bowel disease (IBD; both Crohn's disease and ulcerative colitis) has been described in 2-8% of patients with AIH. Interestingly, for patients with autoimmune sclerosing cholangitis, a distinct pattern of IBD has been recently described. Other conditions have been reported at a lower frequency, including Sjogren's syndrome 1-7%, systemic lupus erythematosus 1-3% and glomerulonephritis 1%. Rarer still and at a frequency of <1% include fibrosing alveolitis, haemolytic anaemia, uveitis, mononeuritis multiplex, polymyositis and multiple sclerosis. In contrast, the reported associations between AIH and thyroiditis 8-23%, diabetes 1-10% and psoriasis 3% are commonly seen and notable in clinical practice. PMID:26641498

  8. Forced-exercise attenuates experimental autoimmune neuritis.

    PubMed

    Calik, Michael W; Shankarappa, Sahadev A; Stubbs, Evan B

    2012-07-01

    Physical inactivity in combination with a sedentary lifestyle is strongly associated with an increased risk of development of inflammatory-mediated diseases, including autoimmune disorders. Recent studies suggest that anti-inflammatory effects of physical exercise may be of therapeutic value in some affected individuals. In this study, we determined the effects of forced-exercise (treadmill running) on the development and progression of experimental autoimmune neuritis (EAN), an established animal model of Guillain-Barré syndrome. Adult male Lewis rats were subjected to sedentary (control) or forced-exercise (1.2 km per day, 5 days a week) for three weeks prior to induction of EAN. P2 (53-78)-immunized sedentary control rats developed a monophasic course of EAN beginning on post-injection day 12.33 ± 0.59 (n = 18) and reaching peak severity on day 15.83 ± 0.35 (n = 18). At near peak of disease, ankle- and sciatic notch-evoked compound muscle action potential (CMAP) amplitudes in sedentary control rats were reduced (~50%) while motor nerve conduction velocity (MNCV) was slowed (~30%) compared with pre-induction evoked responses. In marked contrast, rats undergoing forced-exercise exhibited a significantly less severe clinical course of EAN beginning on post-injection day 12.63 ± 0.53 (n = 16) and reaching peaking severity on day 14.69 ± 0.73 (n = 16). At near peak of disease, ankle- and sciatic-notch-evoked CMAP amplitudes in forced-exercised rats were preserved while EAN-associated slowing of MNCV was modestly attenuated by exercise. Three weeks of forced-exercise reduced by 46% total plasma corticosterone content while elevating the levels of corticosteroid binding globulin. We conclude from this study that forced-exercise administered prior to and during development of EAN affords a novel measure of protection against autoimmune-associated deficits in peripheral nerve evoked responses independent of steroid-induced immune suppression. PMID:22569066

  9. 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

  10. 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

  11. Antibodies to neurofascin exacerbate adoptive transfer experimental autoimmune neuritis.

    PubMed

    Yan, Weixing; Nguyen, Toan; Yuki, Nobuhiro; Ji, Qiuhong; Yiannikas, Con; Pollard, John D; Mathey, Emily K

    2014-12-15

    Guillain-Barré syndrome and chronic inflammatory demyelinating polyneuropathy are autoimmune disorders of the peripheral nervous system in which autoantibodies are implicated in the disease pathogenesis. Recent work has focused on the nodal regions of the myelinated axon as potential autoantibody targets. Here we screened patient sera for autoantibodies to neurofascin and assessed the pathophysiological relevance of anti-neurofascin antibodies in vivo. Levels of anti-neurofascin antibodies were higher in sera from patients with Guillain-Barré syndrome and chronic inflammatory demyelinating polyneuropathy when compared with those of controls. Anti-neurofascin antibodies exacerbated and prolonged adoptive transfer experimental autoimmune neuritis and caused conduction defects when injected intraneurally. PMID:25262157

  12. Autoimmune myasthenia gravis: emerging clinical and biological heterogeneity

    PubMed Central

    Meriggioli, Matthew N; Sanders, Donald B

    2009-01-01

    Acquired myasthenia gravis (MG) is an autoimmune disorder of the neuromuscular junction in which patients experience fluctuating skeletal muscle weakness that often affects selected muscle groups preferentially. The target of the autoimmune attack in most cases is the skeletal muscle acetylcholine receptor (AChR), but in others, non-AChR components of the neuromuscular junction, such as the muscle-specific receptor tyrosine kinase, are targeted. The pathophysiological result is muscle endplate dysfunction and consequent fatigable muscle weakness. Clinical presentations vary substantially, both for anti-AChR positive and negative MG, and accurate diagnosis and selection of effective treatment depends on recognition of less typical as well as classic disease phenotypes. Accumulating evidence suggests that clinical MG subgroups might respond differently to treatment. In this Review, we provide current information about the epidemiology, immunopathogenesis, clinical presentations, diagnosis, and treatment of MG, including emerging therapeutic strategies. PMID:19375665

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

    PubMed

    Zhang, Zimu; Zhang, Rongxin

    2015-10-01

    Epigenetics is the study of heritable changes in genome function without underlying modifications in their nucleotide sequence. Disorders of epigenetic processes, which involve DNA methylation, histone modification, non-coding RNA and nucleosome remodeling, may influence chromosomal stability and gene expression, resulting in complicated syndromes. In the past few years, it has been disclosed that identified epigenetic alterations give rise to several typical human autoimmune diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and multiple sclerosis (MS). These emerging epigenetic studies provide new insights into autoimmune diseases. The identification of specific epigenetic dysregulation may inspire more discoveries of other uncharacterized mechanisms. Further elucidation of the biological functions and clinical significance of these epigenetic alterations may be exploited for diagnostic biomarkers and therapeutic benefits. PMID:26026695

  14. [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

  15. Proteome analysis of brain in murine experimental autoimmune encephalomyelitis.

    PubMed

    Fazeli, Abolhassan Shahzadeh; Nasrabadi, Davood; Sanati, Mohammad Hossein; Pouya, Alireza; Ibrahim, Saleh M; Baharvand, Hossein; Salekdeh, Ghasem Hosseini

    2010-08-01

    Multiple sclerosis is considered a prototype inflammatory autoimmune disorder of the CNS. Experimental autoimmune encephalomyelitis (EAE) induced by myelin oligodendrocyte glycoprotein is one of the best-characterized animal models of multiple sclerosis. Comprehensive understanding of gene expression in EAE can help identify genes that are important in drug response and pathogenesis. We applied a 2-DE-based proteomics approach to analyze the protein expression pattern of the brain in healthy and EAE samples. Of more than 1000 protein spots we analyzed, 70 showed reproducible and significant changes in EAE compared to controls. Of these, 42 protein spots could be identified using MALDI TOF-TOF-MS. They included mitochondrial and structural proteins as well as proteins involved in ionic and neurotransmitter release, blood barriers, apoptosis, and signal transduction. The possible role of these proteins in the responses of mice to animal models of multiple sclerosis is discussed. PMID:20540118

  16. 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

  17. Autoimmune diseases and reproductive aging

    PubMed Central

    Bove, Riley

    2013-01-01

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

  18. 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

  19. Sex steroids in autoimmune diseases.

    PubMed

    Martocchia, A; Stefanelli, M; Cola, S; Falaschi, P

    2011-01-01

    A sexual dysmorphism in the immune response has been described and females display an increased incidence of autoimmune diseases. Experimental data show that sex steroids influence immune cell development and have immunomodulatory effects. The distribution, the action (genomic and nongenomic), the sex and tissue-depending expression pattern of estrogen, progesterone and androgen receptors and their functional disruptions in corresponding receptor knockout animals will be discussed, pointing out the difference among sex steroid hormones. Recent advances indicate an immunomodulatory role of sex steroids in the pathogenesis of systemic lupus erythematosus, multiple sclerosis and rheumatoid arthritis. The outcomes of the clinical trials will help to find the best use of sex steroids in combination with current therapeutic drugs in autoimmune diseases. Sex steroid receptor modulating drugs will provide new therapeutic approaches in these pathologies. PMID:21463254

  20. Animal Models of Autoimmune Neuropathy

    PubMed Central

    Soliven, Betty

    2014-01-01

    The peripheral nervous system (PNS) comprises the cranial nerves, the spinal nerves with their roots and rami, dorsal root ganglia neurons, the peripheral nerves, and peripheral components of the autonomic nervous system. Cell-mediated or antibody-mediated immune attack on the PNS results in distinct clinical syndromes, which are classified based on the tempo of illness, PNS component(s) involved, and the culprit antigen(s) identified. Insights into the pathogenesis of autoimmune neuropathy have been provided by ex vivo immunologic studies, biopsy materials, electrophysiologic studies, and experimental models. This review article summarizes earlier seminal observations and highlights the recent progress in our understanding of immunopathogenesis of autoimmune neuropathies based on data from animal models. PMID:24615441

  1. The Autoimmune Model of Schizophrenia

    PubMed Central

    Adams, D. D.; Knight, J. G.; Ebringer, A.

    2012-01-01

    Schizophrenia is of mysterious causation. It is not infectious, not congenital, but shows familial aggregation, the Mendelian genetics indicating involvement of multiple codominant genes with incomplete penetrance. This is the pattern for autoimmune diseases, such as Graves' disease of the thyroid, where forbidden clones of B lymphocytes develop, and cause thyrotoxicosis by secreting autoantibodies that react with the thyroid gland's receptor for thyroid-stimulating hormone from the pituitary gland. In 1982, Knight postulated that autoantibodies affecting the function of neurons in the limbic region of the brain are a possible cause of schizophrenia. Today, this is even more probable, with genes predisposing to schizophrenia having being found to be immune response genes, one in the MHC and two for antibody light chain V genes. Immune response genes govern the immune repertoire, dictating the genetic risk of autoimmune diseases. The simplest test for an autoimmune basis of schizophrenia would be trial of immunosuppression with prednisone in acute cases. The urgent research need is to find the microbial trigger, as done by Ebringer for rheumatoid arthritis and for ankylosing spondylitis. This could lead to prophylaxis of schizophrenia by vaccination against the triggering microbe. PMID:23738211

  2. [Autoimmune hepatitis induced by isotretionine].

    PubMed

    Guzman Rojas, Patricia; Gallegos Lopez, Roxana; Ciliotta Chehade, Alessandra; Scavino, Yolanda; Morales, Alejandro; Tagle, Martín

    2016-01-01

    We describe a case of a teenage patient with the diagnosis of drug induced autoimmune hepatitis. The patient is a 16 years old female, with the past medical history of Hashimoto’s hypothyroidism controlled with levothyroxine, who started treatment with Isotretionin (®Accutane) 20 mg q/12 hours for a total of 3 months for the treatment of severe acne. The physical examination was within normal limits and the results of the laboratory exams are: Baseline values of ALT 28 U/L, AST 28 U/L. Three months later: AST 756 U/L, ALT 1199U/L, alkaline phosphatase 114 U/L, with normal bilirrubin levels throughout the process. The serology studies were negative for all viral hepatitis; ANA titers were positive (1/160) and igG levels were also elevated. A liver biopsy was performed, and was compatible with the diagnosis of autoimmune hepatitis. Corticosteroid therapy was started with Prednisone 40 mg per day one week after stopping the treatment with isotretionin, observing an improvement in the laboratory values. We describe this case and review the world literature since there are no reported cases of Isotretinoin-induced autoimmune hepatitis. PMID:27131947

  3. HYPERAUTOFLUORESCENT RING IN AUTOIMMUNE RETINOPATHY

    PubMed Central

    LIMA, LUIZ H.; GREENBERG, JONATHAN P.; GREENSTEIN, VIVIENNE C.; SMITH, R. THEODORE; SALLUM, JULIANA M. F.; THIRKILL, CHARLES; YANNUZZI, LAWRENCE A.; TSANG, STEPHEN H.

    2015-01-01

    Purpose To report the presence of a hyperautofluorescent ring and corresponding spectral-domain optical coherence tomography (SD-OCT) features seen in patients with autoimmune retinopathy. Methods All eyes were evaluated by funduscopic examination, full-fleld electroretinography, fundus autofluorescence, and SD-OCT. Further confirmation of the diagnosis was obtained with immunoblot and immunohistochemistry testing of the patient’s serum. Humphrey visual fields and microperimetry were also performed. Results Funduscopic examination showed atrophic retinal pigment epithelium (RPE) associated with retinal artery narrowing but without pigment deposits. The scotopic and photopic full-field electroretinograms were nondetectable in three patients and showed a cone–rod pattern of dysfunction in one patient. Fundus autofluorescence revealed a hyperautofluorescent ring in the parafoveal region, and the corresponding SD-OCT demonstrated loss of the photoreceptor inner segment–outer segment junction with thinning of the outer nuclear layer from the region of the hyperautofluorescent ring toward the retinal periphery. The retinal layers were generally intact within the hyperautofluorescent ring, although the inner segment–outer segment junction was disrupted, and the outer nuclear layer and photoreceptor outer segment layer were thinned. Conclusion This case series revealed the structure of the hyperautofluorescent ring in autoimmune retinopathy using SD-OCT. Fundus autofluorescence and SD-OCT may aid in the diagnosis of autoimmune retinopathy and may serve as a tool to monitor its progression. PMID:22218149

  4. Gender and risk of autoimmune diseases: possible role of estrogenic compounds.

    PubMed Central

    Ahmed, S A; Hissong, B D; Verthelyi, D; Donner, K; Becker, K; Karpuzoglu-Sahin, E

    1999-01-01

    A striking common feature of many autoimmune diseases in humans and experimental animals, despite differences in pathology, is that females are highly susceptible to autoimmune conditions compared to males. In several animal models, estrogens promote, whereas androgens abrogate, B-cell-mediated autoimmune diseases. To understand mechanisms by which estrogens regulate autoimmunity, it is first necessary to decipher estrogen effects on the normal immune system. Estrogen treatment of nonautoimmune mice diminished lymphocyte numbers in both developmental and mature lymphoid organs. Estrogen dysregulated T- and B-cell balance by inducing selective T-cell hypoactivity and B-cell hyperactivity. Even though estrogen did not alter the relative percentages of splenic T-cell subsets, splenic lymphocytes had a reduced proliferative response to T-cell stimulants and were refractory to rescue from activation-induced apoptosis compared to cells from placebo-treated mice. In contrast, estrogen induced B-cell hyperactivity (promoted autoantibodies to double-stranded DNA and phospholipids, increased numbers of plasma cells, and increased autoantibody yield per B cell). Note that treatment of normal mice with estrogen can alter T- and B-cell regulation and overcome B-cell tolerance to result in autoimmunity in normal individuals. Could environmental estrogens promote some human autoimmune disorders? Is there a link between environmental estrogens and autoimmune disorders, especially since these disorders are reported possibly more frequently? These provocative questions warrant investigation. Our findings on immunomodulatory effects may serve as a benchmark to examine whether endocrine-disrupting chemicals will have similar immunologic effects. Images Figure 1 Figure 2 PMID:10502531

  5. Systemic Autoimmunity in TAM Triple Knockout Mice Causes Inflammatory Brain Damage and Cell Death

    PubMed Central

    Li, Qiutang; Lu, Qingjun; Lu, Huayi; Tian, Shifu; Lu, Qingxian

    2013-01-01

    The Tyro3, Axl and Mertk (TAM) triply knockout (TKO) mice exhibit systemic autoimmune diseases, with characteristics of increased proinflammatory cytokine production, autoantibody deposition and autoreactive lymphocyte infiltration into a variety of tissues. Here we show that TKO mice produce high level of serum TNF-α and specific autoantibodies deposited onto brain blood vessels. The brain-blood barrier (BBB) in mutant brains exhibited increased permeability for Evans blue and fluorescent-dextran, suggesting a breakdown of the BBB in the mutant brains. Impaired BBB integrity facilitated autoreactive T cells infiltrating into all regions of the mutant brains. Brain autoimmune disorder caused accumulation of the ubiquitin-reactive aggregates in the mutant hippocampus, and early formation of autofluorescent lipofuscins in the neurons throughout the entire brains. Chronic neuroinflammation caused damage of the hippocampal mossy fibers and neuronal apoptotic death. This study shows that chronic systemic inflammation and autoimmune disorders in the TKO mice cause neuronal damage and death. PMID:23840307

  6. Celiac disease as an autoimmune condition

    PubMed Central

    Sur, Genel; Lupan, Iulia; Tilinca, Mariana; Deleanu, Diana

    2014-01-01

    Autoimmune diseases have become a major medical problem of recent years. Celiac disease is an autoimmune disease model. The aim of our study was to follow the changes in the clinical autoimmunity picture of the celiac disease from recent years. The study of autoimmunity in celiac disease has focused on associated diseases with the aforementioned disease: type 1 diabetes mellitus, thyroid autoimmunity disease, Graves disease, Hashimoto's disease, systemic lupus erythematosus, systemic sclerosis, spondyloarthritis, hyperprolactinemia, Turner syndrome, Addison's disease, sensory neuronopathies. Immune reactivity to tissue transglutaminase targeted autoantibodies and other autoantigens, including transglutaminase 3, actin, ganglioside, collagen, calreticulin or zonulin which have been reported in the celiac disease. New research directions given by celiac disease autoimmunity, interleukin 1, interleukin 2, protein tyrosine phosphatase non-receptor type 22, CD4+CD25+ T lymphocytes, cytotoxic T-lymphocyte antigen 4, infection with Necator americanus and definitive identification of pathogenic T cell epitopes, seem to provide a solution in celiac disease treatment. PMID:26155154

  7. The role of dendritic cells in autoimmunity

    PubMed Central

    Ganguly, Dipyaman; Haak, Stefan; Sisirak, Vanja; Reizis, Boris

    2014-01-01

    Dendritic cells (DCs) initiate and shape both the innate and adaptive immune responses. Accordingly, recent evidence from clinical studies and experimental models implicates DCs in the pathogenesis of most autoimmune diseases. However, fundamental questions remain unanswered concerning the actual roles of DCs in autoimmunity, both in general and, in particular, in specific diseases. In this Review, we discuss the proposed roles of DCs in immunological tolerance, the effect of the gain or loss of DCs on autoimmunity and DC-intrinsic molecular regulators that help to prevent the development of autoimmunity. We also review the emerging roles of DCs in several autoimmune diseases, including autoimmune myocarditis, multiple sclerosis, psoriasis, type 1 diabetes and systemic lupus erythematosus. PMID:23827956

  8. Immune Complex-Mediated Autoimmunity in a Patient With Smith-Magenis Syndrome (del 17p11.2)

    PubMed Central

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

    2014-01-01

    Smith-Magenis syndrome (SMS) is a sporadic congenital disorder involving multiple organ systems caused by chromosome 17p11.2 deletions. Smith-Magenis syndrome features craniofacial and skeletal anomalies, cognitive impairment, and neurobehavioral abnormalities. In addition, some SMS patients may exhibit hypogammaglobulinemia. We report the first case of SMS-associated autoimmunity in a woman who presented with adult onset of multiple autoimmune disorders, including systemic lupus erythematosus, antiphospholipid antibody syndrome, and autoimmune hepatitis. Molecular analysis using single-nucleotide polymorphism array confirmed a de novo 3.8-Mb deletion (breakpoints, chr17: 16,660,721–20,417,975), resulting in haploinsufficiency for TACI (transmembrane activator and CAML interactor). Our data are consistent with potential loss of function for the BAFF (B cell–activating factor) receptor TACI as a contributing factor to human autoimmune phenomena. PMID:25036569

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

    PubMed

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

    2014-08-01

    Smith-Magenis syndrome (SMS) is a sporadic congenital disorder involving multiple organ systems caused by chromosome 17p11.2 deletions. Smith-Magenis syndrome features craniofacial and skeletal anomalies, cognitive impairment, and neurobehavioral abnormalities. In addition, some SMS patients may exhibit hypogammaglobulinemia. We report the first case of SMS-associated autoimmunity in a woman who presented with adult onset of multiple autoimmune disorders, including systemic lupus erythematosus, antiphospholipid antibody syndrome, and autoimmune hepatitis. Molecular analysis using single-nucleotide polymorphism array confirmed a de novo 3.8-Mb deletion (breakpoints, chr17: 16,660,721-20,417,975), resulting in haploinsufficiency for TACI (transmembrane activator and CAML interactor). Our data are consistent with potential loss of function for the BAFF (B cell-activating factor) receptor TACI as a contributing factor to human autoimmune phenomena. PMID:25036569

  10. Vaccines and autoimmune diseases of the adult.

    PubMed

    Orbach, Hedi; Agmon-Levin, Nancy; Zandman-Goddard, Gisele

    2010-02-01

    Infectious agents contribute to the environmental factors involved in the development of autoimmune diseases possibly through molecular mimicry mechanisms. Hence, it is feasible that vaccinations may also contribute to the mosaic of autoimmunity. Evidence for the association of vaccinations and the development of these diseases is presented in this review. Infrequently reported post-vaccination autoimmune diseases include systemic lupus erythematosus, rheumatoid arthritis, inflammatory myopathies, multiple sclerosis, Guillain-Barré syndrome, and vasculitis. In addition, we will discuss macrophagic myofasciitis, aluminum containing vaccines, and the recent evidence for autoimmunity following the use of human papillomavirus vaccine. PMID:20193633

  11. Genetic association, seasonal infections and autoimmune basis of narcolepsy

    PubMed Central

    Singh, Abinav Kumar; Mahlios, Josh; Mignot, Emmanuel

    2014-01-01

    In recent years, a growing number of potential autoimmune disorders affecting neurons in the central nervous system have been identified, including narcolepsy. Narcolepsy is a lifelong sleep disorder characterized by excessive daytime sleepiness with irresistible sleep attacks, cataplexy (sudden bilateral loss of muscle tone), hypnagogic hallucinations, and abnormalities of Rapid Eye Movement sleep. Narcolepsy is generally a sporadic disorder and is caused by the loss of hypocretin (orexin)-producing neurons in the hypothalamus region of the brain. Studies have established that more than 90% of patients have a genetic association with HLA DQB1*06:02. Genome-wide association analysis shows a strong association between narcolepsy and polymorphisms in the TCR? locus and weaker associations within TNFSF4 (also called OX40L), Cathepsin H and the P2RY11-DNMT1 (purinergic receptor subtype P2Y11 to DNMT1, a DNA methytransferase) loci, suggesting an autoimmune basis. Mutations in DNMT1 have also been reported to cause narcolepsy in association with a complex neurological syndrome, suggesting the importance of DNA methylation in the pathology. More recently, narcolepsy was identified in association with seasonal streptococcus, H1N1 infections and following AS03-adjuvanted pH1N1 influenza vaccination in Northern Europe. Potential immunological pathways responsible for the loss of hypocretin producing neurons in these cases may be molecular mimicry or bystander activation. Specific autoantibodies or T cells cross-reactive with hypocretin neurons have not yet been identified, however, thus narcolepsy does not meet Witebskys criteria for an autoimmune disease. As the brain is not an easily accessible organ, mechanisms of disease initiation and progression remain a challenge to researchers. PMID:23497937

  12. Genetic association, seasonal infections and autoimmune basis of narcolepsy.

    PubMed

    Singh, Abinav Kumar; Mahlios, Josh; Mignot, Emmanuel

    2013-06-01

    In recent years, a growing number of potential autoimmune disorders affecting neurons in the central nervous system have been identified, including narcolepsy. Narcolepsy is a lifelong sleep disorder characterized by excessive daytime sleepiness with irresistible sleep attacks, cataplexy (sudden bilateral loss of muscle tone), hypnagogic hallucinations, and abnormalities of Rapid Eye Movement sleep. Narcolepsy is generally a sporadic disorder and is caused by the loss of hypocretin (orexin)-producing neurons in the hypothalamus region of the brain. Studies have established that more than 90% of patients have a genetic association with HLA DQB1*06:02. Genome-wide association analysis shows a strong association between narcolepsy and polymorphisms in the TCRα locus and weaker associations within TNFSF4 (also called OX40L), Cathepsin H and the P2RY11-DNMT1 (purinergic receptor subtype P2Y11 to DNMT1, a DNA methytransferase) loci, suggesting an autoimmune basis. Mutations in DNMT1 have also been reported to cause narcolepsy in association with a complex neurological syndrome, suggesting the importance of DNA methylation in the pathology. More recently, narcolepsy was identified in association with seasonal streptococcus, H1N1 infections and following AS03-adjuvanted pH1N1 influenza vaccination in Northern Europe. Potential immunological pathways responsible for the loss of hypocretin producing neurons in these cases may be molecular mimicry or bystander activation. Specific autoantibodies or T cells cross-reactive with hypocretin neurons have not yet been identified, however, thus narcolepsy does not meet Witebsky's criteria for an autoimmune disease. As the brain is not an easily accessible organ, mechanisms of disease initiation and progression remain a challenge to researchers. PMID:23497937

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

    PubMed Central

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

    1999-01-01

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

  14. Role of Endocannabinoid Activation of Peripheral CB1 Receptors in the Regulation of Autoimmune Disease

    PubMed Central

    Sido, Jessica Margaret; Nagarkatti, Prakash S.; Nagarkatti, Mitzi

    2014-01-01

    The impact of the endogenous cannabinoids (AEA, 2-AG, PEA, and virodamine) on the immune cell expressed cannabinoid receptors (CB1, CB2, TRPV-1, and GPR55) and consequent regulation of immune function is an exciting area of research with potential implications in the prevention and treatment of inflammatory and autoimmune diseases. Despite significant advances in understanding the mechanisms through which cannabinoids regulate immune functions, not much is known about the role of endocannabinoids in the pathogenesis or prevention of autoimmune diseases. Inasmuch as CB2 expression on immune cells and its role has been widely reported, the importance of CB1 in immunological disorders has often been overlooked especially because it is not highly expressed on naive immune cells. Therefore, the current review aims at delineating the effect of endocannabinoids on CB1 receptors in T cell driven autoimmune diseases. This review will also highlight some autoimmune diseases in which there is evidence indicating a role for endocannabinoids in the regulation of autoimmune pathogenesis. Overall, based on the evidence presented using the endocannabinoids, specifically AEA, we propose that the peripheral CB1 receptor is involved in the regulation and amelioration of inflammation associated with autoimmune diseases. PMID:24911431

  15. Autoimmune hemolytic anemia caused by cold agglutinins in a young pregnant woman.

    PubMed

    Batalias, Labros; Trakakis, Eftihios; Loghis, Costas; Salabasis, Costas; Simeonidis, George; Karanikolopoulos, Panagiotis; Kassanos, Demetrios; Salamalekis, Emmanuel

    2006-04-01

    Autoimmune hemolytic anemia is a rare disorder. A 34-year old woman presented with thrombophlebitis after her first delivery, during puerperium. A high titer of cold agglutinins was found. Lymphomas, systemic lupus erythematosus, and tumors were excluded. She conceived again. Due to the anemia she had frequent blood transfusions and she delivered at 38 weeks of gestation. PMID:16854701

  16. CELL-MEDIATED IMMUNITY AND INTERFERON GAMMA IN AUTOIMMUNE VITILIGO OF SMYTH LINE CHICKENS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Vitiligo is a common acquired hypopigmentary disorder characterized by a loss of epidermal pigment cells (melanocytes). The Smyth line (SL) chicken is the only animal model for autoimmune vitiligo that recapitulates the entire spectrum of clinical and biological manifestations of the human disease....

  17. 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

  18. Pituitary autoantibodies in autoimmune polyendocrine syndrome type 1.

    PubMed

    Bensing, Sophie; Fetissov, Sergueï O; Mulder, Jan; Perheentupa, Jaakko; Gustafsson, Jan; Husebye, Eystein S; Oscarson, Mikael; Ekwall, Olov; Crock, Patricia A; Hökfelt, Tomas; Hulting, Anna-Lena; Kämpe, Olle

    2007-01-16

    Autoimmune polyendocrine syndrome type 1 (APS1) is a rare autosomal recessive disorder caused by mutations in the autoimmune regulator (AIRE) gene. High titer autoantibodies (Aabs) toward intracellular enzymes are a hallmark for APS1 and serve as diagnostic markers and predictors for disease manifestations. In this study, we aimed to identify pituitary autoantigens in patients with APS1. A pituitary cDNA expression library was screened with APS1 sera and a tudor domain containing protein 6 (TDRD6) cDNA clone was isolated. Positive immunoreactivity against in vitro translated TDRD6 fragments was shown in 42/86 (49%) APS1 patients but not in patients with other autoimmune diseases or in healthy controls. By using immunohistochemistry, sera from 3/6 APS1 patients with growth hormone (GH) deficiency showed immunostaining of a small number of guinea pig anterior pituitary cells, and 40-50% of these cells were GH-positive. No such immunostaining was seen with sera from healthy controls. The APS1 Aab-positive, GH-negative cells may represent a novel subpopulation of anterior pituitary cells. In addition, 4/6 patient sera showed staining of a fiber-plexus in the pituitary intermediate lobe recognizing enzymes of monoamine and GABA synthesis. Thus, we have identified TDRD6 as a major autoantigen in APS1 patients and shown that several sera from GH-deficient patients stain specific cell populations and nerves in the pituitary gland. PMID:17215373

  19. Autoimmunity and dysmetabolism of human acquired immunodeficiency syndrome.

    PubMed

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

    2016-06-01

    Acquired immunodeficiency syndrome (AIDS) remains ill-defined by lists of symptoms, infections, tumors, and disorders in metabolism and immunity. Low CD4 cell count, severe loss of body weight, pneumocystis pneumonia, and Kaposi's sarcoma are the major disease indicators. Lines of evidence indicate that patients living with AIDS have both immunodeficiency and autoimmunity. Immunodeficiency is attributed to deficits in the skin- and mucosa-defined innate immunity, CD4 T cells and regulatory T cells, presumably relating human immunodeficiency virus (HIV) infection. The autoimmunity in AIDS is evident by: (1) overproduction of autoantibodies, (2) impaired response of CD4 cells and CD8 cells, (3) failure of clinical trials of HIV vaccines, and (4) therapeutic benefits of immunosuppression following solid organ transplantation and bone marrow transplantation in patients at risk of AIDS. Autoantibodies are generated in response to antigens such as debris and molecules de novo released from dead cells, infectious agents, and catabolic events. Disturbances in metabolic homeostasis occur at the interface of immunodeficiency and autoimmunity in the development of AIDS. Optimal treatments favor therapeutics targeting on the regulation of metabolism to restore immune homeostasis. PMID:26676359

  20. Lymphopenia in occupational pulmonary silicosis with or without autoimmune disease

    PubMed Central

    Subra, J F; Renier, G; Reboul, P; Tollis, F; Boivinet, R; Schwartz, P; Chevailler, A

    2001-01-01

    An increased prevalence of autoimmune diseases such as rheumatoid arthritis has been demonstrated in silica-exposed patients. The aim of this study was to determine the peripheral blood lymphocyte phenotype in a population of silicotic workers employed in the slate mines of the district. Silicosis was assessed in 58 patients according to the International Labor Office's criteria. Clinical and biological data including flow cytometric evaluation of the lymphocyte subsets were compared with those from 41 healthy volunteers. The silicotic patients had a higher prevalence of autoimmune diseases (6/58 versus 0/41: P < 0·05) and of elevated antinuclear antibody titres compared to the control group. A very significant decrease of total lymphocyte count (P < 0·001) involving B, T and Natural Killer cells was found in silicotic patients as compared with matched healthy volunteers. A significant increase in the percentage of activated T cells (12·3%) was observed in the silicotic group as compared to 6·5% in the control group (P = 5 × 10−5). Our results show that in silicotic patients, the absolute number of circulating lymphocytes is diminished with an increased proportion of activated T cells. Whether these findings could predispose to the development of autoimmune disorders is discussed. PMID:11737074

  1. Defective removal of ribonucleotides from DNA promotes systemic autoimmunity

    PubMed Central

    Günther, Claudia; Kind, Barbara; Reijns, Martin A.M.; Berndt, Nicole; Martinez-Bueno, Manuel; Wolf, Christine; Tüngler, Victoria; Chara, Osvaldo; Lee, Young Ae; Hübner, Norbert; Bicknell, Louise; Blum, Sophia; Krug, Claudia; Schmidt, Franziska; Kretschmer, Stefanie; Koss, Sarah; Astell, Katy R.; Ramantani, Georgia; Bauerfeind, Anja; Morris, David L.; Cunninghame Graham, Deborah S.; Bubeck, Doryen; Leitch, Andrea; Ralston, Stuart H.; Blackburn, Elizabeth A.; Gahr, Manfred; Witte, Torsten; Vyse, Timothy J.; Melchers, Inga; Mangold, Elisabeth; Nöthen, Markus M.; Aringer, Martin; Kuhn, Annegret; Lüthke, Kirsten; Unger, Leonore; Bley, Annette; Lorenzi, Alice; Isaacs, John D.; Alexopoulou, Dimitra; Conrad, Karsten; Dahl, Andreas; Roers, Axel; Alarcon-Riquelme, Marta E.; Jackson, Andrew P.; Lee-Kirsch, Min Ae

    2014-01-01

    Genome integrity is continuously challenged by the DNA damage that arises during normal cell metabolism. Biallelic mutations in the genes encoding the genome surveillance enzyme ribonuclease H2 (RNase H2) cause Aicardi-Goutières syndrome (AGS), a pediatric disorder that shares features with the autoimmune disease systemic lupus erythematosus (SLE). Here we determined that heterozygous parents of AGS patients exhibit an intermediate autoimmune phenotype and demonstrated a genetic association between rare RNASEH2 sequence variants and SLE. Evaluation of patient cells revealed that SLE- and AGS-associated mutations impair RNase H2 function and result in accumulation of ribonucleotides in genomic DNA. The ensuing chronic low level of DNA damage triggered a DNA damage response characterized by constitutive p53 phosphorylation and senescence. Patient fibroblasts exhibited constitutive upregulation of IFN-stimulated genes and an enhanced type I IFN response to the immunostimulatory nucleic acid polyinosinic:polycytidylic acid and UV light irradiation, linking RNase H2 deficiency to potentiation of innate immune signaling. Moreover, UV-induced cyclobutane pyrimidine dimer formation was markedly enhanced in ribonucleotide-containing DNA, providing a mechanism for photosensitivity in RNase H2–associated SLE. Collectively, our findings implicate RNase H2 in the pathogenesis of SLE and suggest a role of DNA damage–associated pathways in the initiation of autoimmunity. PMID:25500883

  2. Abnormal intestinal permeability and microbiota in patients with autoimmune hepatitis

    PubMed Central

    Lin, Rui; Zhou, Lu; Zhang, Jie; Wang, Bangmao

    2015-01-01

    Background: Autoimmune hepatitis (AIH) is a chronic, progressive, and immunologically mediated inflammatory liver disorder. The etiology of AIH still remains unknown. The aim of this study was to investigate the changes in intestinal permeability, bacterial translocation, and intestinal microbiome in patients with AIH and to evaluate the correlations of those changes with the stages of the disease. Methods: 24 patients with autoimmune hepatitis and 8 healthy volunteers were recruited for this study. We assessed (1) the integrity of tight junctions within the gut by immunohistochemical analysis of zona occludens-1 and occludin expression in duodenal biopsy specimens; (2) changes in the enteric microbiome by 16S rDNA quantitative PCR; and (3) the presence of bacterial translocation by the level of lipopolysaccharide (LPS) using ELISA. Results: Increased intestinal permeability, derangement of the microbiome and bacterial translocation occurred in AIH, which correlated with the severity of the disease. Conclusions: Autoimmune hepatitis is associated with leaky gut and intestinal microbiome dysbiosis. The impaired intestinal barrier may play an important role in the pathogenesis of AIH. PMID:26191211

  3. Celiac disease: pathophysiology, clinical manifestations, and associated autoimmune conditions.

    PubMed

    Barker, Jennifer M; Liu, Edwin

    2008-01-01

    The clinical spectrum of celiac disease continues to evolve. What was once thought to be a rare disorder affecting young children is now recognized to be very common with a range of symptoms from asymptomatic disease to severely affected persons. Screening for celiac disease has become relatively easily with reliable antibodies against self-antigens (TG) and modified environmental antigens (DGP). Diagnosis is confirmed by small intestinal biopsy with characteristic changes graded by the Marsh score. Elimination of gluten from the diet has been the standard of care for the last half century. Patients often have difficulty adhering to a gluten-free diet, and the failure of symptoms, antibody levels, or pathologic changes to improve after initiating the diet may be largely due to this difficulty. The genetic risk for celiac disease is largely related to HLA genotypes, with over 90% of subjects with celiac disease positive for DQ2 and the remainder positive for DQ8. The HLA association with celiac disease is largely accountable for its link to other autoimmune diseases, including type 1 diabetes and autoimmune thyroid disease, and the majority of risk for celiac disease in these populations is related to HLA genotype. Celiac disease also carries an increased risk for type 1 diabetes and autoimmune thyroid disease. Genetic syndromes such as Turner and Down syndromes are associated with an increased risk for celiac disease. Practitioners can identify groups of subjects at high risk for celiac disease and perform screening with celiac disease-related antibodies. PMID:19048738

  4. Anatabine ameliorates experimental autoimmune thyroiditis.

    PubMed

    Caturegli, Patrizio; De Remigis, Alessandra; Ferlito, Marcella; Landek-Salgado, Melissa A; Iwama, Shintaro; Tzou, Shey-Cherng; Ladenson, Paul W

    2012-09-01

    Tobacco smoking favorably influences the course of Hashimoto thyroiditis, possibly through the antiinflammatory proprieties of nicotine. In this study we tested anatabine, another tobacco alkaloid, in a model of experimental autoimmune thyroiditis. Experimental autoimmune thyroiditis was induced by different doses of thyroglobulin, to produce a disease of low, moderate, or high severity, in 88 CBA/J female mice: 43 drank anatabine supplemented water and 45 regular water. Mice were bled after immunization and killed to assess thyroid histopathology, thyroglobulin antibodies, T(4), and thyroid RNA expression of 84 inflammatory genes. We also stimulated in vitro a macrophage cell line with interferon-γ or lipopolysaccharide plus or minus anatabine to quantitate inducible nitric oxide synthase and cyclooxygenase 2 protein expression. Anatabine reduced the incidence and severity of thyroiditis in the moderate disease category: only 13 of 21 mice (62%) developed thyroid infiltrates when drinking anatabine as compared with 22 of 23 (96%) controls (relative risk 0.59, P = 0.0174). The median thyroiditis severity was 0.5 and 2.0 in anatabine and controls, respectively (P = 0.0007 by Wilcoxon rank sum test). Anatabine also reduced the antibody response to thyroglobulin on d 14 (P = 0.029) and d 21 (P = 0.045) after immunization and improved the recovery of thyroid function on d 21 (P = 0.049). In the thyroid transcriptome, anatabine restored expression of IL-18 and IL-1 receptor type 2 to preimmunization levels. Finally, anatabine suppressed in a dose-dependent manner macrophage production of inducible nitric oxide synthase and cyclooxygenase 2. Anatabine ameliorates disease in a model of autoimmune thyroiditis, making the delineation of its mechanisms of action and potential clinical utility worthwhile. PMID:22807490

  5. Narcolepsy, 2009 A(H1N1) pandemic influenza, and pandemic influenza vaccinations: what is known and unknown about the neurological disorder, the role for autoimmunity, and vaccine adjuvants.

    PubMed

    Ahmed, S Sohail; Schur, Peter H; MacDonald, Noni E; Steinman, Lawrence

    2014-05-01

    The vaccine safety surveillance system effectively detected a very rare adverse event, narcolepsy, in subjects receiving AS03-adjuvanted A(H1N1) pandemic vaccine made using the European inactivation/purification protocol. The reports of increased cases of narcolepsy in non-vaccinated subjects infected with wild A(H1N1) pandemic influenza virus suggest a role for the viral antigen(s) in disease development. However, additional investigations are needed to better understand what factor(s) in wild influenza infection trigger(s) narcolepsy in susceptible hosts. An estimated 31 million doses of European AS03-adjuvanted A(H1N1) pandemic vaccine were used in more than 47 countries. The Canadian AS03-adjuvanted A(H1N1) pandemic vaccine was used with high coverage in Canada where an estimated 12 million doses were administered. As no similar narcolepsy association has been reported to date with the AS03-adjuvanted A(H1N1) pandemic vaccine made using the Canadian inactivation/purification protocol, this suggests that the AS03 adjuvant alone may not be responsible for the narcolepsy association. To date, no narcolepsy association has been reported with the MF59®-adjuvanted A(H1N1) pandemic vaccine. This review article provides a brief background on narcolepsy, outlines the different types of vaccine preparations including the ones for influenza, reviews the accumulated evidence for the safety of adjuvants, and explores the association between autoimmune diseases and natural infections. It concludes by assimilating the historical observations and recent clinical studies to formulate a feasible hypothesis on why vaccine-associated narcolepsy may not be solely linked to the AS03 adjuvant but more likely be linked to how the specific influenza antigen component of the European AS03-adjuvanted pandemic vaccine was prepared. Careful and long-term epidemiological studies of subjects who developed narcolepsy in association with AS03-adjuvanted A(H1N1) pandemic vaccine prepared with the European inactivation/purification protocol are needed. PMID:24559657

  6. 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-associated autoimmune responses. The active suppression is mediated by the CD4+ CD25+ immunoregulatory cells and is associated with the downregulation of Th1-type cytokines and upregulation of the secretion of IL-10 and the immunosuppressive cytokine transforming growth factor beta. PMID:16608409

  7. Peripheral Nervous System Manifestations in Systemic Autoimmune Diseases

    PubMed Central

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

    2014-01-01

    The peripheral nervous system refers to parts of the nervous system outside the brain and spinal cord. Systemic autoimmune diseases can affect both the central and peripheral nervous systems in a myriad of ways and through a heterogeneous number of mechanisms leading to many different clinical manifestations. As a result, neurological complications of these disorders can result in significant morbidity and mortality. The most common complication of peripheral nervous system (PNS) involvement is peripheral neuropathy, with symptoms of numbness, sensory paresthesias, weakness, or gait imbalance. The neuropathy may be multifocal and asymmetric or, less frequently, distal and symmetric. PMID:25705295

  8. Anti-NMDA receptor encephalitis, autoimmunity, and psychosis

    PubMed Central

    Kayser, Matthew S.; Dalmau, Josep

    2014-01-01

    Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a recently-discovered synaptic autoimmune disorder in which auto-antibodies target NMDARs in the brain, leading to their removal from the synapse. Patients manifest with prominent psychiatric symptoms – and in particular psychosis – early in the disease course. This presentation converges with long-standing evidence on multiple fronts supporting the glutamatergic model of schizophrenia. We review mechanisms underlying disease in anti-NMDAR encephalitis, and discuss its role in furthering our understanding of neural circuit dysfunction in schizophrenia. PMID:25458857

  9. Multiple intracranial hemorrhages in pregnancy: A common autoimmune etiology

    PubMed Central

    Pahadiya, Hans Raj; Lakhotia, Manoj; Gandhi, Ronak; Choudhary, Akanksha; Madan, Shiva

    2016-01-01

    Systemic lupus erythematosus (SLE) is an autoimmune disorder, primarily affect female in fertile age. Pregnancy in SLE female is a high-risk situation which can adversely affect maternal-fetal dyad. SLE can flare during pregnancy or in postpartum period. We describe a case of a young pregnant female who presented because of right hemiparesis due multiple hemorrhages in the brain. The first presentation of the SLE with multiple intracranial hemorrhages in pregnancy, preceding the other characteristic clinical symptoms is rare. Here, we high lighten the major neurological issues and maternal-fetal dyad issues in SLE pregnancy and treatment strategies for management of SLE in pregnancy. PMID:27114665

  10. Mapping of an autoimmunity susceptibility locus (AIS1) to chromosome 1p31.3-p32.2.

    PubMed

    Alkhateeb, Asem; Stetler, Gary L; Old, William; Talbert, Janet; Uhlhorn, Cynthia; Taylor, Melanie; Fox, Angela; Miller, Cynthia; Dills, Diana G; Ridgway, E Chester; Bennett, Dorothy C; Fain, Pamela R; Spritz, Richard A

    2002-03-15

    Generalized vitiligo is a common autoimmune disorder in which patchy loss of skin and hair pigmentation results from loss of pigment-forming melanocytes from the involved regions. Vitiligo occurs with a frequency of about 1% in most populations, and is highly associated with other autoimmune disorders, particularly Hashimoto thyroiditis. Most cases of vitiligo are sporadic, although some cases cluster in families, and the disorder is thought to be oligogenic in origin. We have studied a large family cluster in which vitiligo and Hashimoto thyroiditis occur in numerous individuals. A whole-genome scan of 24 family members, including 14 affected with autoimmune disease, showed significant linkage of an oligogenic autoimmune susceptibility locus, termed AIS1, to a 14.4 cM interval in 1p31.3-p32.2. A two-locus analysis of Hashimoto thyroiditis in family members segregating an AIS1 susceptibility allele showed suggestive linkage to markers in chromosome 6p22.3-q14.1, in a region spanning both the major histocompatibility complex and AITD1, a susceptibility locus for autoimmune thyroid disease. Our results indicate that the 1p AIS1 locus is associated with susceptibility to autoimmunity, particularly vitiligo, in this family, and that a chromosome 6 locus, most likely AITD1, may mediate the occurrence of Hashimoto's thyroiditis in AIS1-susceptible family members. PMID:11912181

  11. Autoimmune and Neoplastic Thyroid Diseases Associated with Hepatitis C Chronic Infection

    PubMed Central

    Fallahi, Poupak; Ferrari, Silvia Martina; Politti, Ugo; Giuggioli, Dilia; Ferri, Clodoveo

    2014-01-01

    Frequently, patients with hepatitis C virus (HCV) chronic infection have high levels of serum anti-thyroperoxidase and/or anti-thyroglobulin autoantibodies, ultrasonographic signs of chronic autoimmune thyroiditis, and subclinical hypothyroidism, in female gender versus healthy controls, or hepatitis B virus infected patients. In patients with “HCV-associated mixed cryoglobulinemia” (MC + HCV), a higher prevalence of thyroid autoimmune disorders was shown not only compared to controls, but also versus HCV patients without cryoglobulinemia. Patients with MC + HCV or HCV chronic infection show a higher prevalence of papillary thyroid cancer than controls, in particular in patients with autoimmune thyroiditis. Patients with HCV chronic infection, or with MC + HCV, in presence of autoimmune thyroiditis, show higher serum levels of T-helper (Th)1 (C-X-C motif) ligand 10 (CXCL10) chemokine, but normal levels of Th2 (C-C motif) ligand 2 chemokine, than patients without thyroiditis. HCV thyroid infection could act by upregulating CXCL10 gene expression and secretion in thyrocytes recruiting Th1 lymphocytes that secrete interferon-γ and tumor necrosis factor-α. These cytokines might induce a further CXCL10 secretion by thyrocytes, thus perpetuating the immune cascade, which may lead to the appearance of autoimmune thyroid disorders in genetically predisposed subjects. A careful monitoring of thyroid function, particularly where nodules occur, is recommended in HCV patients. PMID:25374602

  12. Autoimmune and neoplastic thyroid diseases associated with hepatitis C chronic infection.

    PubMed

    Fallahi, Poupak; Ferrari, Silvia Martina; Politti, Ugo; Giuggioli, Dilia; Ferri, Clodoveo; Antonelli, Alessandro

    2014-01-01

    Frequently, patients with hepatitis C virus (HCV) chronic infection have high levels of serum anti-thyroperoxidase and/or anti-thyroglobulin autoantibodies, ultrasonographic signs of chronic autoimmune thyroiditis, and subclinical hypothyroidism, in female gender versus healthy controls, or hepatitis B virus infected patients. In patients with "HCV-associated mixed cryoglobulinemia" (MC + HCV), a higher prevalence of thyroid autoimmune disorders was shown not only compared to controls, but also versus HCV patients without cryoglobulinemia. Patients with MC + HCV or HCV chronic infection show a higher prevalence of papillary thyroid cancer than controls, in particular in patients with autoimmune thyroiditis. Patients with HCV chronic infection, or with MC + HCV, in presence of autoimmune thyroiditis, show higher serum levels of T-helper (Th)1 (C-X-C motif) ligand 10 (CXCL10) chemokine, but normal levels of Th2 (C-C motif) ligand 2 chemokine, than patients without thyroiditis. HCV thyroid infection could act by upregulating CXCL10 gene expression and secretion in thyrocytes recruiting Th1 lymphocytes that secrete interferon-γ and tumor necrosis factor-α. These cytokines might induce a further CXCL10 secretion by thyrocytes, thus perpetuating the immune cascade, which may lead to the appearance of autoimmune thyroid disorders in genetically predisposed subjects. A careful monitoring of thyroid function, particularly where nodules occur, is recommended in HCV patients. PMID:25374602

  13. Autoimmune autonomic ganglionopathy with reversible cognitive impairment

    PubMed Central

    Gibbons, Christopher H.; Centi, Justin; Vernino, Steven; Freeman, Roy

    2012-01-01

    Background Autoimmune autonomic ganglionopathy (AAG) is a rare disorder of antibody mediated impaired transmission across the autonomic ganglia resulting in severe autonomic failure. Some patients with AAG report cognitive impairment of unclear etiology despite treatment of autonomic symptoms. Objectives To investigate the relationship between orthostatic hypotension, antibody titers and cognitive impairment in patients with AAG. Design Prospective cohort. Setting Academic medical center. Participants Three patients with AAG underwent neuropsychological testing before and after cycles of plasma exchange in both the seated and standing position to determine the effects of orthostatic hypotension and antibody titers on cognition. Main Outcome Measures Patient responses to neuropsychological tests were measured by percent change from baseline in the seated and standing positions pre- and post-plasma exchange to determine the effects of orthostatic hypotension and antibody titers on cognition. Results Orthostatic hypotension and elevated antibody titer were associated independently with neuropsychological impairment (P<0.05), particularly in domains of executive function, sustained attention, and working memory. Cognitive dysfunction improved, even in the seated normotensive position, after plasmapheresis and consequent reduction in antibody levels. Conclusion The data presented in this study demonstrate reversible cognitive impairment is independently associated with both orthostatic hypotension and elevated nicotinic acetylcholine receptor autoantibodies thereby expanding the clinical spectrum of autonomic ganglionopathy and, in so doing, providing an additional treatable cause of cognitive impairment. PMID:22158721

  14. The prevalence of thyroid autoimmunity in patients with urticaria: a systematic review and meta-analysis.

    PubMed

    Pan, Xi-Feng; Gu, Jian-Qiu; Shan, Zhong-Yan

    2015-04-01

    Thyroid autoimmunity is the most common organ-specific autoimmune disorder, which is characterized by the production of thyroid autoantibodies and lymphocytic infiltration into the thyroid. The majority cases of chronic urticaria have unknown (idiopathic) causes, with about 30-40 % possibly having an autoimmune substrate. Considering that autoimmune factors may be the common features of both thyroid autoimmunity and urticaria, it is likely that both entities may coexist within the same patient. A number of studies have investigated the association between thyroid autoimmunity and urticaria. However, most of these studies are relatively small sample size, the power achieved in those studies was not sufficient to detect whether there is an association between urticaria and thyroid autoimmunity. The aim of this study is to combine primary data from all relevant studies to produce reliable estimates of the associations between thyroid autoantibodies and urticaria. Literature databases were searched including Medline, Embase, Web of Science, Chinese Wanfang, and CBM databases from January 1980 to December 2013. A total of 14,203 urticaria cases and 12,339 non-urticaria controls were included in this study. From these data, the odds ratio (OR) with 95% confidence interval (95% CI) was calculated. The meta-analysis results showed that the prevalence of positive thyroid autoantibodies in patients with urticaria was higher than non-urticaria controls (TgAb: OR 6.55, 95% CI 3.19-13.42, P<0.00001, I2=67%; TmAb: OR 4.51, 95% CI 2.78-7.33, P<0.00001, I2=47%; TPOAb: OR 8.71, 95% CI 6.89-11.01, P<0.00001, I2=20%, respectively). The results of this meta-analysis suggested that patients with urticaria were more likely to have thyroid autoimmunity than the control groups. PMID:25064381

  15. Telomere Dysfunction, Autoimmunity and Aging

    PubMed Central

    Hohensinner, Philipp J.; Goronzy, Jörg J.; Weyand, Cornelia M.

    2011-01-01

    Immune aging is associated with loss of critical immune functions, such as host protection from infection and malignancy. Unexpectedly, immunosenescence also renders the host susceptible to inflammation, which may translate into tissue-damaging disease as the senescent immune system loses its ability to maximize inflammatory protection while minimizing inflammatory injury. On the other hand, chronic inflammation associated with immune-mediated disease represents a profound stress factor for the immune system, affecting cellular turn-over, replication and exhaustion. Immune cell longevity is tightly connected to the functional integrity of telomeres which are regulated by cell multiplication, exposure to oxidative stress and DNA repair mechanisms. Lymphocytes are amongst the few cell types that can actively elongate telomeres through the action of telomerase. In patients with the autoimmune disease rheumatoid arthritis (RA), telomerase deficiency is associated with prematurity of immune aging. Patients with RA have other defects in DNA repair mechanisms, including the kinase Ataxia telangiectasia mutated (ATM), critically involved in the repair of DNA double strand breaks. ATM deficiency in RA shortens lymphocyte survival. Dynamics of telomeric length and structure are beginning to be understood and have distinct patterns in different autoimmune diseases, suggesting a multitude of molecular mechanisms defining the interface between chronic immune stimulation and progressive aging of the immune system. PMID:22396899

  16. Autoimmune etiology of generalized vitiligo.

    PubMed

    Le Poole, I Caroline; Luiten, Rosalie M

    2008-01-01

    Vitiligo is characterized by progressive skin depigmentation resulting from an autoimmune response targeting epidermal melanocytes. Melanocytes are particularly immunogenic by virtue of the contents of their melanosomes, generating the complex radical scavenging molecule melanin in a process that involves melanogenic enzymes and structural components, including tyrosinase, MART-1, gp100, TRP-2 and TRP-1. These molecules are also prime targets of the immune response in both vitiligo and melanoma. The immunogenicity of melanosomal proteins can partly be explained by the dual role of melanosomes, involved both in melanin synthesis and processing of exogenous antigens. Melanocytes are capable of presenting antigens in the context of MHC class II, providing HLA-DR+ melanocytes in perilesional vitiligo skin the option of presenting melanosomal antigens in response to trauma and local inflammation. Type I cytokine-mediated immunity to melanocytes in vitiligo involves T cells reactive with melanosomal antigens, similar to T cells observed in melanoma. In vitiligo, however, T cell tuning allows T cells with higher affinity for melanocyte differentiation antigens to enter the circulation after escaping clonal deletion in primary lymphoid organs. The resulting efficacious and progressive autoimmune response to melanocytes provides a roadmap for melanoma therapy. PMID:18460889

  17. 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

  18. Cystic Lesions in Autoimmune Pancreatitis

    PubMed Central

    Gompertz, Macarena; Morales, Claudia; Aldana, Hernán; Castillo, Jaime; Berger, Zoltán

    2015-01-01

    Autoimmune pancreatitis (AIP) can be chronic or recurrent, but frequently completely reversible after steroid treatment. A cystic lesion in AIP is a rare finding, and it can mimic a pancreatic cystic neoplasm. Difficulties in an exact diagnosis interfere with treatment, and surgery cannot be avoided in some cases. We report the history of a 63-year-old male presenting with jaundice and pruritus. AIP was confirmed by imaging and elevated IgG4 blood levels, and the patient completely recovered after corticosteroid therapy. One year later, he presented with a recurrent episode of AIP with elevated IgG4 levels, accompanied by the appearance of multiple intrapancreatic cystic lesions. All but 1 of these cysts disappeared after steroid treatment, but the remaining cyst in the pancreatic head was even somewhat larger 1 year later. Pancreatoduodenectomy was finally performed. Histology showed the wall of the cystic lesion to be fibrotic; the surrounding pancreatic tissue presented fibrosis, atrophy and lymphoplasmacytic infiltration by IgG4-positive cells, without malignant elements. Our case illustrates the rare possibility that cystic lesions can be part of AIP. These pseudocysts appear in the pancreatic segments involved in the autoimmune disease and can be a consequence of the local inflammation or related to ductal strictures. Steroid treatment should be initiated, after which these cysts can completely disappear with recovery from AIP. Surgical intervention may be necessary in some exceptional cases. PMID:26675058

  19. IP-10 in autoimmune thyroiditis.

    PubMed

    Ruffilli, I; Ferrari, S M; Colaci, M; Ferri, C; Fallahi, P; Antonelli, A

    2014-08-01

    The interferon-γ-inducible protein 10 (IP-10) was initially identified as a chemokine that is induced by interferon (IFN)-γ. IP-10 exerts its function through binding to chemokine (C-X-C motif) receptor 3 (CXCR3). IP-10 and its receptor, CXCR3, appear to contribute to the pathogenesis of many autoimmune diseases, organ specific (such as type 1 diabetes, Graves' disease and ophthalmopathy), or systemic (such as systemic lupus erythematosus, mixed cryoglobulinemia, Sjogren syndrome, or systemic sclerosis). The secretion of IP-10 by (CD)4+, CD8+, and natural killer is dependent on IFN-γ. Under the influence of IFN-γ, IP-10 is secreted by thyrocytes. Determination of high level of IP-10 in peripheral fluids is therefore a marker of a T helper 1 orientated immune response. High levels of circulating IP-10, have been shown in patients with autoimmune thyroiditis (AT). Among patients with AT, IP-10 levels were significantly higher in those with a hypoechoic ultrasonographic pattern, which is a sign of a more severe lympho-monocytic infiltration, and in those with hypothyroidism. For these reasons, it has been postulated that IP-10 could be a marker of a stronger and more aggressive inflammatory response in the thyroid, subsequently leading to thyroid destruction and hypothyroidism. Further studies are needed to investigate whether IP-10 is a novel therapeutic target in AT. PMID:24977661

  20. 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

  1. Helicobacter pylori and skin autoimmune diseases

    PubMed Central

    Magen, Eli; Delgado, Jorge-Shmuel

    2014-01-01

    Autoimmune skin diseases are characterized by dysregulation of the immune system resulting in a loss of tolerance to skin self-antigen(s). The prolonged interaction between the bacterium and host immune mechanisms makes Helicobacter pylori (H. pylori) a plausible infectious agent for triggering autoimmunity. Epidemiological and experimental data now point to a strong relation of H. pylori infection on the development of many extragastric diseases, including several allergic and autoimmune diseases. H. pylori antigens activate cross-reactive T cells and induce autoantibodies production. Microbial heat shock proteins (HSP) play an important role of in the pathogenesis of autoimmune diseases because of the high level of sequence homology with human HSP. Eradication of H. pylori infection has been shown to be effective in some patients with chronic autoimmune urticaria, psoriasis, alopecia areata and Schoenlein-Henoch purpura. There is conflicting and controversial data regarding the association of H. pylori infection with Behets 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

  2. 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

  3. Autoimmune mechanisms in pernicious anaemia & thyroid disease.

    PubMed

    Osborne, David; Sobczyńska-Malefora, Agata

    2015-09-01

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

  4. Diagnosis and classification of autoimmune gastritis.

    PubMed

    Toh, Ban-Hock

    2014-01-01

    Autoimmune gastritis is a silent and highly prevalent disease that only becomes clinically manifested with progression to corpus atrophy and development of iron deficient or B12-deficient (pernicious) anaemia. Autoimmune gastritis is associated with autoimmune thyroiditis and type 1 diabetes mellitus. Corpus atrophy may be complicated by gastric carcinoids and gastric cancer. Laboratory diagnosis of autoimmune gastritis rests on serum biomarkers of antibody to parietal cell H/K ATPase and intrinsic factor and corpus atrophy on serum biomarkers of gastrin and pepsinogen levels. Subjects with asymptomatic parietal cell antibody should be regularly assessed for serum biomarkers for progression to corpus atrophy, development of iron and B12 deficiency anaemia and for associated autoimmune thyroiditis and type 1 diabetes mellitus. PMID:24424193

  5. Lithium-associated transient thyrotoxicosis in 4 Chinese women with autoimmune thyroiditis.

    PubMed

    Chow, C C; Lee, S; Shek, C C; Wing, Y K; Ahuja, A; Cockram, C S

    1993-06-01

    Four Chinese female patients who suffered from manic-depressive disorder and underlying autoimmune thyroiditis developed transient episodes of thyrotoxicosis during maintenance lithium therapy. Endocrinologically speaking, three of them had "Hashitoxicosis", while the other had silent lymphocytic thyroiditis. Albeit rare among Western patients, such lithium-associated thyroid dysfunctions appeared to be more likely to occur in Hong Kong Chinese. They seemed to involve multiple aetiological factors, such as autoimmune thyroid disease, the toxic and immunomodulatory roles of lithium and perhaps genetic and dietary factors. Because of their self-limiting nature, the importance of avoiding unnecessary and potentially deleterious antithyroid treatment is emphasised. PMID:8363533

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

    PubMed

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

    2016-01-01

    Autoimmune blistering diseases are a heterogeneous group of disorders that mostly affect the skin and mucous membranes. Occasionally, other organ systems may be involved, depending on the unique pathophysiology of each disease. Cicatricial pemphigoid, pemphigus vulgaris, and paraneoplastic pemphigus are distinct entities, but all have the potential to have cutaneous and ocular involvement. Awareness and early recognition of ocular involvement in these diseases is important given the increased risk for vision loss and blindness with delay in management. Several skin diseases may be associated with involvement of the external eye. The most common autoimmune diseases are cicatricial pemphigoid, pemphigus vulgaris, and paraneoplastic pemphigus. PMID:26903186

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

    PubMed

    McKinnon, John E; Maksimowicz-McKinnon, Kathleen

    2016-01-01

    Vaccines hold promise both for the prevention of infections and as potential immunologic therapy for patients with autoimmune disease (AD). These patients are at high risk for both common and opportunistic infections, but this risk can be significantly reduced and even obviated with the use of recommended available vaccines. Unfortunately, patients with ADs are not routinely offered or provided indicated vaccinations and have higher rates of complications from vaccine-preventable illnesses than patients without ADs. In addition, vaccine therapy is currently under study for the treatment of autoimmune disorders, with early studies demonstrating immunomodulatory effects that may counter undesired immune activation and alleviate disease activity. PMID:26408802

  8. Autoimmune Hemolytic Anemia in Children: Mayo Clinic Experience.

    PubMed

    Sankaran, Janani; Rodriguez, Vilmarie; Jacob, Eapen K; Kreuter, Justin D; Go, Ronald S

    2016-04-01

    We studied 35 pediatric patients with autoimmune hemolytic anemia seen at Mayo Clinic from 1994 to 2014. The median age was 10.0 years and 65.7% were males. Most had warm antibodies (80.0%) and some secondary to viral (14.3%) or autoimmune disorders (31.4%). Seven (20.0%) patients presented with Evans syndrome, 3 of whom also had common variable immunodeficiency. The median hemoglobin at diagnosis was 6.1 g/dL and 62.8% patients required red cell transfusions. The severity of anemia was worse among children below 10 years (median 5.5 vs. 7.0 g/dL, P=0.01). Steroid was the initial treatment for 88.5% patients, with overall response rate of 82.7% (68.5% complete, 14.2% partial) and median response duration of 10.7 months (range, 0.2 to 129.7+ mo). After median follow-up of 26.6 months, 8 (22.8%) patients relapsed. Salvage treatments included splenectomy, intravenous immunoglobulin, rituximab, and mycophenolate mofetil. Infectious complications occurred in 9 (25.7%) patients and 1 patient died of cytomegalovirus infection. Four patients had cold agglutinin disease and 3 (75.0%) responded to steroids. Autoimmune hemolytic anemia is a rare disorder in pediatric population and most respond well to steroids regardless of the type of antibody. Infectious complications are common and screening for immunodeficiency is recommended among those with Evans syndrome. PMID:26925716

  9. The potential utility of B cell-directed biologic therapy in autoimmune diseases

    PubMed Central

    2007-01-01

    Increasing awareness of the importance of aberrant B cell regulation in autoimmunity has driven the clinical development of novel B cell-directed biologic therapies with the potential to treat a range of autoimmune disorders. The first of these drugs—rituximab, a chimeric monoclonal antibody against the B cell-specific surface marker CD20—was recently approved for treating rheumatoid arthritis in patients with an inadequate response to other biologic therapies. The aim of this review is to discuss the potential use of rituximab in the management of other autoimmune disorders. Results from early phase clinical trials indicate that rituximab may provide clinical benefit in systemic lupus erythematosus, Sjögren’s syndrome, vasculitis, and thrombocytopenic purpura. Numerous case reports and several small pilot studies have also been published reporting the use of rituximab in conditions such as myositis, antiphospholipid syndrome, Still’s disease, and multiple sclerosis. In general, the results from these preliminary studies encourage further testing of rituximab therapy in formalized clinical trials. Based on results published to date, it is concluded that rituximab, together with other B cell-directed therapies currently under clinical development, is likely to provide an important new treatment option for a number of these difficult-to-treat autoimmune disorders. PMID:17957371

  10. Transmethylation in immunity and autoimmunity

    PubMed Central

    Lawson, Brian R.; Eleftheriadis, Theodoros; Tardif, Virginie; Gonzalez-Quintial, Rosana; Baccala, Roberto; Kono, Dwight H.; Theofilopoulos, Argyrios N.

    2013-01-01

    The activation of immune cells is mediated by a network of signaling proteins that can undergo post-translational modifications critical for their activity. Methylation of nucleic acids or proteins can have major effects on gene expression as well as protein repertoire diversity and function. Emerging data indicate that indeed many immunologic functions, particularly those of T cells, including thymic education, differentiation and effector function are highly dependent on methylation events. The critical role of methylation in immunocyte biology is further documented by evidence that autoimmune phenomena may be curtailed by methylation inhibitors. Additionally, epigenetic alterations imprinted by methylation can also exert effects on normal and abnormal immune responses. Further work in defining methylation effects in the immune system is likely to lead to a more detailed understanding of the immune system and may point to the development of novel therapeutic approaches. PMID:22364920

  11. Successful pregnancy with autoimmune cirrhosis.

    PubMed

    Braga, António; Braga, Jorge

    2016-01-01

    Pregnancy with liver cirrhosis is a rare and dangerous event that exposes mother and fetus to potentially lethal risks. During pregnancy, hepatic decompensation could suffice and the development of hepatic failure and encephalopathy could occur. The incidence of obstetric complications is also increased with a high rate of pre-eclampsia, postpartum bleeding, preterm delivery and stillbirth. We report a case of a 27-year-old woman with autoimmune hepatitis and liver cirrhosis complicated by splenomegaly, oesophageal varices and severe thrombocytopaenia. During pregnancy, close clinical and analytical surveillance was performed. She was medicated with corticosteroids, azathioprine and propranolol. At the 25th week of gestation, an upper gastrointestinal endoscopy was performed to control oesophageal varices. This patient had an uneventful pregnancy until 37 weeks. At 37th week of gestation, after spontaneous rupture of membranes, signs of acute fetal distress were observed, and an urgent caesarean was performed. Good neonatal and maternal outcomes were achieved. PMID:26825934

  12. The 'hygiene hypothesis' for autoimmune and allergic diseases: an update.

    PubMed

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

    2010-04-01

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

  13. Targeting ion channels for the treatment of autoimmune neuroinflammation

    PubMed Central

    Bittner, Stefan

    2013-01-01

    Pharmacological targeting of ion channels has long been recognized as an attractive strategy for the treatment of various diseases. Multiple sclerosis (MS) is an autoimmune disorder of the central nervous system with a prominent neurodegenerative component. A multitude of different cell types are involved in the complex pathophysiology of this disorder, including cells of the immune system (e.g. T and B lymphocytes and microglia), the neurovascular unit (e.g. endothelial cells and astrocytes) and the central nervous system (e.g. astrocytes and neurons). The pleiotropic expression and function of ion channels gives rise to the attractive opportunity of targeting different players and pathophysiological aspects of MS by the modulation of ion channel function in a cell-type and context-specific manner. We discuss the emerging knowledge about ion channels in the context of autoimmune neuroinflammation. While some pharmacological targets are at the edge of clinical translation, others have only recently been discovered and are still under investigation. Special focus is given to those candidates that could be attractive novel targets for future therapeutic approaches in neuroimmune autoinflammation. PMID:23997817

  14. Immunoadsorption therapy in autoimmune encephalitides

    PubMed Central

    Golombeck, Kristin S.; Bien, Corinna; Abu-Tair, Mariam; Brand, Marcus; Bulla-Hellwig, Michael; Lohmann, Hubertus; Münstermann, Dieter; Pavenstädt, Hermann; Thölking, Gerold; Valentin, Rainer; Wiendl, Heinz; Melzer, Nico; Bien, Christian G.

    2016-01-01

    Objective: It was hypothesized that in encephalitides with autoantibodies directed to CNS surface antigens an antibody-removing intervention might speed up recovery. Methods: The outcome of autoimmune encephalitis in 19 patients with antibodies against surface antigens (leucine-rich, glioma inactivated 1 [LGI1], n = 3; contactin-associated protein-2 [CASPR2], n = 4; NMDA receptor [NMDAR], n = 7) and intracellular antigens (glutamic acid decarboxylase [GAD], n = 5) after immunoadsorption in addition to corticosteroid therapy was evaluated retrospectively. Modified Rankin scale (mRS) scores and data on seizures, memory, and antibody titers directly after immunoadsorption (early follow-up) and after a median of 4 months (late follow-up) were compiled. Results: Immediately after immunoadsorption, 9 of 14 patients with antibodies against LGI1, CASPR2, or NMDAR (64%), but none with GAD antibodies, had improved by at least one mRS point. Five of the 7 patients with LGI1 or CASRP2 antibodies had become seizure-free, and 2 patients with NMDAR antibodies had a memory improvement of more than 1 SD of a normal control population. At late follow-up, 12 of 14 patients with surface antibodies had improved (86%), and none of the patients with GAD antibodies. Conclusions: It is suggested that addition of immunoadsorption to immunosuppression therapy in patients with surface antibodies may accelerate recovery. This supports the pathogenic role of surface antibodies. Classification of evidence: This study provides Class IV evidence that immunoadsorption combined with immunosuppression therapy is effective in patients with autoimmune encephalitis with surface antibodies. PMID:26977423

  15. Cognitive Impairments Preceding and Outlasting Autoimmune Limbic Encephalitis

    PubMed Central

    Gross, Robert; Davis, Jennifer; Roth, Julie; Querfurth, Henry

    2016-01-01

    Mild cognitive impairment (MCI) can be the initial manifestation of autoimmune limbic encephalitis (ALE), a disorder that at times presents a diagnostic challenge. In addition to memory impairment, clinical features that might suggest this disorder include personality changes, agitation, insomnia, alterations of consciousness, and seizures. Once recognized, ALE typically responds to treatment with immune therapies, but long-term cognitive deficits may remain. We report two cases of patients with MCI who were ultimately diagnosed with ALE with antibodies against the voltage gated potassium channel complex. Months after apparent resolution of their encephalitides, both underwent neuropsychological testing, which demonstrated persistent cognitive deficits, primarily in the domains of memory and executive function, for cases 1 and 2, respectively. A brief review of the literature is included. PMID:26881156

  16. Cutting-edge issues in autoimmune orchitis.

    PubMed

    Silva, Clovis A; Cocuzza, Marcello; Borba, Eduardo F; Bonfá, Eloísa

    2012-04-01

    Autoimmune orchitis is a relevant cause of decreased fecundity in males, and it is defined as a direct aggression to the testis with the concomitant presence of anti-sperm antibodies (ASA). The presence of these specific antibodies has been observed in approximately 5-12% of infertile male partners. Primary autoimmune orchitis is defined by isolated infertility with ASA but without evidence of a systemic disease. Secondary causes of orchitis and/or testicular vasculitis are uniformly associated with autoimmune diseases, mainly in primary vasculitis such as polyarteritis nodosa, Behçet's disease, and Henoch-Schönlein purpura. The overall frequencies of acute orchitis and ASA in rheumatic diseases are 2-31% and 0-50%, respectively. The pathogenesis of primary/secondary autoimmune orchitis is not completely understood but probably involves the access of immune cells to the testicular microenvironment due to inflammation, infection or trauma, leading to apoptosis of spermatocytes and spermatids. Glucocorticoids and immunosuppressive drugs are indicated in autoimmune orchitis-associated active systemic autoimmune diseases. However, there are no standardized treatment options, and the real significance of ASA in infertile men is still controversial. Assisted reproductive technologies such as intrauterine insemination, in vitro fertilization, and intracytoplasmic sperm injection (ICSI) are therapeutic options for male infertility associated with these autoantibodies. ICSI is considered to be the best choice for patients with severe sperm autoimmunity, particularly in males with low semen counts or motility. PMID:21842235

  17. 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

  18. A Cytomegalovirus Peptide-Specific Antibody Alters Natural Killer Cell Homeostasis and Is Shared in Several Autoimmune Diseases.

    PubMed

    Liu, Yu; Mu, Rong; Gao, Ya-Ping; Dong, Jie; Zhu, Lei; Ma, Yuyuan; Li, Yu-Hui; Zhang, He-Qiu; Han, Dong; Zhang, Yu; McInnes, Iain B; Zhang, Jingang; Shen, Beifen; Yang, Guang; Li, Zhan-Guo

    2016-03-01

    Human cytomegalovirus (hCMV), a ubiquitous beta-herpesvirus, has been associated with several autoimmune diseases. However, the direct role of hCMV in inducing autoimmune disorders remains unclear. Here we report the identification of an autoantibody that recognizes a group of peptides with a conserved motif matching the Pp150 protein of hCMV (anti-Pp150) and is shared among patients with various autoimmune diseases. Anti-Pp150 also recognizes the single-pass membrane protein CIP2A and induces the death of CD56(bright) NK cells, a natural killer cell subset whose expansion is correlated with autoimmune disease. Consistent with this finding, the percentage of circulating CD56(bright) NK cells is reduced in patients with several autoimmune diseases and negatively correlates with anti-Pp150 concentration. CD56(bright) NK cell death occurs via both antibody- and complement-dependent cytotoxicity. Our findings reveal that a shared hCMV-induced autoantibody is involved in the decrease of CD56(bright) NK cells and may thus contribute to the onset of autoimmune disorders. PMID:26962948

  19. Metronomic maintenance chemotherapy in patients presenting with paraneoplastic autoimmune hepatitis with recurrent thymic carcinoma.

    PubMed

    Kivrak Salim, Derya; Mutlu, Hasan; Karakurt Eryilmaz, Melek; Yalçin Musri, Fatma; Tural, Deniz; Coşkun, Hasan Şenol

    2016-04-01

    Autoimmune hepatitis is a rarely seen autoimmune paraneoplastic syndrome of thymic carcinoma. Chemotherapy may be an effective choice in the treatment of primary tumor and paraneoplastic disorder. In this case, we report a 32-year-old man presented with increased liver enzymes and cholestasis with a history of thymoma surgically removed four years ago. Liver biopsy showed chronic active autoimmune hepatitis. Computed tomography scan showed pulmonary metastases and pleural mass as a recurrence of thymic carcinoma, proven by biopsy. After four cycles of cisplatin plus adriamycin plus cyclophosphamide plus vincristine and six cycles of paclitaxel plus gemcitabine, maintenance metronomic cyclophosphamide plus etoposide regimen was offered to the patient. Complete biological signs of hepatitis without need for steroids or immune suppressors and complete radiologic response in primary tumor were achieved. Maintenance metronomic chemotherapy regimens may be an alternative to the current treatment options in patients with thymic carcinomas. PMID:25231462

  20. Induction of regulatory T cells: A role for probiotics and prebiotics to suppress autoimmunity.

    PubMed

    Dwivedi, Mitesh; Kumar, Prasant; Laddha, Naresh C; Kemp, E Helen

    2016-04-01

    Regulatory T cells (Tregs) are comprised of a heterogeneous population of cells that play a vital role in suppressing inflammation and maintaining immune tolerance. Given the crucial role of Tregs in maintaining immune homeostasis, it is probably not surprising that many microbial species and their metabolites have the potential to induce Tregs. There is now great interest in the therapeutic potential of probiotics and prebiotics based strategies for a range of autoimmune disorders. This review will summarise recent findings concerning the role of probiotics and prebiotics in induction of Tregs to ameliorate the autoimmune conditions. In addition, the article is focused to explain the different mechanisms of Treg induction and function by these probiotics and prebiotics, based on the available studies till date. The article further proposes that induction of Tregs by probiotics and prebiotics could lead to the development of new therapeutic approach towards curbing the autoimmune response and as an alternative to detrimental immunosuppressive drugs. PMID:26774011

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

    PubMed Central

    Kahlenberg, J. Michelle; Kaplan, Mariana J.

    2013-01-01

    The innate immune system utilizes many approaches for defense against invading microorganisms, including complement-mediated lysis, engulfment, formation of neutrophil extracellular traps (NETs) and release of antimicrobial peptides (AMPs). While classically thought to be driven by adaptive immunity, the development of autoimmune diseases such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) is increasingly associated with dysregulated innate immune pathways. An emerging theme within this literature is the contribution of AMPs to the development of autoimmune disorders. This is best exemplified in atopic dermatitis and psoriasis where the defensins and the single human cathelicidin, LL-37, may contribute to disease. Further, in the past few years, a role for LL-37 has emerged in the pathogenesis of SLE, RA, atherosclerosis and possibly other diseases. This review discusses the role of LL-37 and its murine ortholog, mCRAMP, in the modulation of immune and inflammatory pathways and their effects on autoimmune and inflammatory diseases. PMID:24185823

  2. Beneficial effect of testosterone in the treatment of chronic autoimmune thyroiditis in rats

    SciTech Connect

    Ahmed, S.A.; Young, P.R.; Penhale, W.J.

    1986-01-01

    Early thymectomy and sublethal irradiation of normal rats consistently induces a sex-dependent chronic autoimmune thyroiditis. Females are much more susceptible to this autoimmune disorder than are males. The possible therapeutic effects of testosterone (Te) on established autoimmune thyroiditis has been investigated in this model. The pathologic condition of the gland before treatment was monitored by a thyroid grafting and extirpation techniques. Te administration by either parenteral injection or implantation caused significant regression of established thyroiditis. Repeated doses of Te ester in oil were found to be more effective than powdered free-Te given by implantation, and frequently produced complete resolution of chronic lesions involving the entire gland. In these thyroids, there was reappearance of normal thyroid architecture and complete absence of mononuclear cellular infiltration. However, no inhibitory effect on serum autoantibody production to thyroglobulin was noted with any form of Te treatment. These observations strengthen the concept that cellular rather than humoral mechanisms are involved in the pathogenesis of thyroiditis.

  3. Cutting edge issues in autoimmune gastritis.

    PubMed

    Toh, Ban-Hock; Chan, James; Kyaw, Tin; Alderuccio, Frank

    2012-06-01

    Autoimmune gastritis is the outcome of a pathological CD4 T cell-mediated autoimmune response directed against the gastric H/K-ATPase. Silent initially, the gastric lesion becomes manifest in humans by the development of megaloblastic pernicious anemia arising from vitamin B12 deficiency. Cutting edge issues in this disease relate to its epidemiology, immunogenetics, a role for Helicobacter pylori as an infective trigger through molecular mimicry, its immunopathogenesis, associated organ-specific autoimmune diseases, laboratory diagnosis, and approaches to curative therapy. PMID:21174235

  4. 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

  5. Low-dose interleukin-2 therapy: a driver of an imbalance between immune tolerance and autoimmunity.

    PubMed

    Kosmaczewska, Agata

    2014-01-01

    For many years, the role of interleukin-2 (IL-2) in autoimmune responses was established as a cytokine possessing strong pro-inflammatory activity. Studies of the past few years have changed our knowledge on IL-2 in autoimmune chronic inflammation, suggesting its protective role, when administered at low-doses. The disrupted balance between regulatory and effector T cells (Tregs and Teffs, respectively) is a characteristic of autoimmune diseases, and is dependent on homeostatic cytokines, including IL-2. Actually, inherent defects in the IL-2 signaling pathway and/or levels leading to Treg compromised function and numbers as well as Th17 expansion have been attributed to autoimmune disorders. In this review, we discuss the role of IL-2 in the pathogenesis of autoimmune diseases. In particular, we highlight the impact of the dysregulated IL-2 pathway on disruption of the Treg/Th17 balance, reversal of which appears to be a possible mechanism of the low-dose IL-2 treatment. The negative effects of IL-2 on the differentiation of follicular helper T cells (Tfh) and pathogenic Th17 cells, both of which contribute to autoimmunity, is emphasized in the paper as well. We also compare the current IL-2-based therapies of animal and human subjects with immune-mediated diseases aimed at boosting the Treg population, which is the most IL-2-dependent cell subset desirable for sufficient control of autoimmunity. New perspectives of therapeutic approaches focused on selective delivery of IL-2 to inflamed tissues, thus allowing local activity of IL-2 to be combined with its reduced systemic and pleiotropic toxicity, are also proposed in this paper. PMID:25322151

  6. Low-Dose Interleukin-2 Therapy: A Driver of an Imbalance between Immune Tolerance and Autoimmunity

    PubMed Central

    Kosmaczewska, Agata

    2014-01-01

    For many years, the role of interleukin-2 (IL-2) in autoimmune responses was established as a cytokine possessing strong pro-inflammatory activity. Studies of the past few years have changed our knowledge on IL-2 in autoimmune chronic inflammation, suggesting its protective role, when administered at low-doses. The disrupted balance between regulatory and effector T cells (Tregs and Teffs, respectively) is a characteristic of autoimmune diseases, and is dependent on homeostatic cytokines, including IL-2. Actually, inherent defects in the IL-2 signaling pathway and/or levels leading to Treg compromised function and numbers as well as Th17 expansion have been attributed to autoimmune disorders. In this review, we discuss the role of IL-2 in the pathogenesis of autoimmune diseases. In particular, we highlight the impact of the dysregulated IL-2 pathway on disruption of the Treg/Th17 balance, reversal of which appears to be a possible mechanism of the low-dose IL-2 treatment. The negative effects of IL-2 on the differentiation of follicular helper T cells (Tfh) and pathogenic Th17 cells, both of which contribute to autoimmunity, is emphasized in the paper as well. We also compare the current IL-2-based therapies of animal and human subjects with immune-mediated diseases aimed at boosting the Treg population, which is the most IL-2-dependent cell subset desirable for sufficient control of autoimmunity. New perspectives of therapeutic approaches focused on selective delivery of IL-2 to inflamed tissues, thus allowing local activity of IL-2 to be combined with its reduced systemic and pleiotropic toxicity, are also proposed in this paper. PMID:25322151

  7. 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

  8. Celiac Disease and Autoimmune-Associated Conditions

    PubMed Central

    Lauret, Eugenia; Rodrigo, Luis

    2013-01-01

    Celiac disease (CD) is frequently accompanied by a variety of extradigestive manifestations, thus making it a systemic disease rather than a disease limited to the gastrointestinal tract. This is primarily explained by the fact that CD belongs to the group of autoimmune diseases. The only one with a known etiology is related to a permanent intolerance to gluten. Remarkable breakthroughs have been achieved in the last decades, due to a greater interest in the diagnosis of atypical and asymptomatic patients, which are more frequent in adults. The known presence of several associated diseases provides guidance in the search of oligosymptomatic cases as well as studies performed in relatives of patients with CD. The causes for the onset and manifestation of associated diseases are diverse; some share a similar genetic base, like type 1 diabetes mellitus (T1D); others share pathogenic mechanisms, and yet, others are of unknown nature. General practitioners and other specialists must remember that CD may debut with extraintestinal manifestations, and associated illnesses may appear both at the time of diagnosis and throughout the evolution of the disease. The implementation of a gluten-free diet (GFD) improves the overall clinical course and influences the evolution of the associated diseases. In some cases, such as iron deficiency anemia, the GFD contributes to its disappearance. In other disorders, like T1D, this allows a better control of the disease. In several other complications and/or associated diseases, an adequate adherence to a GFD may slow down their evolution, especially if implemented during an early stage. PMID:23984314

  9. Somatic KRAS mutations associated with a human nonmalignant syndrome of autoimmunity and abnormal leukocyte homeostasis

    PubMed Central

    Niemela, Julie E.; Lu, Lianghao; Fleisher, Thomas A.; Davis, Joie; Caminha, Iusta; Natter, Marc; Beer, Laurel A.; Dowdell, Kennichi C.; Pittaluga, Stefania; Raffeld, Mark; Rao, V. Koneti

    2011-01-01

    Somatic gain-of-function mutations in members of the RAS subfamily of small guanosine triphosphatases are found in > 30% of all human cancers. We recently described a syndrome of chronic nonmalignant lymphadenopathy, splenomegaly, and autoimmunity associated with a mutation in NRAS affecting hematopoietic cells, and initially we classified the disease as a variant of the autoimmune lymphoproliferative syndrome. Here, we demonstrate that somatic mutations in the related KRAS gene can also be associated with a nonmalignant syndrome of autoimmunity and breakdown of leukocyte homeostasis. The activating KRAS mutation impaired cytokine withdrawal–induced T-cell apoptosis through the suppression of the proapoptotic protein BCL-2 interacting mediator of cell death and facilitated proliferation through p27kip1 down-regulation. These defects could be corrected in vitro by mitogen-activated protein kinase/extracellular signal-regulated kinase kinase 1 or phosphatidyl inositol-3 kinase inhibition. We suggest the use of the term RAS-associated autoimmune leukoproliferative disease to differentiate this disorder from autoimmune lymphoproliferative syndrome. PMID:21079152

  10. Somatic KRAS mutations associated with a human nonmalignant syndrome of autoimmunity and abnormal leukocyte homeostasis.

    PubMed

    Niemela, Julie E; Lu, Lianghao; Fleisher, Thomas A; Davis, Joie; Caminha, Iusta; Natter, Marc; Beer, Laurel A; Dowdell, Kennichi C; Pittaluga, Stefania; Raffeld, Mark; Rao, V Koneti; Oliveira, João B

    2011-03-10

    Somatic gain-of-function mutations in members of the RAS subfamily of small guanosine triphosphatases are found