Wiersinga, Wilmar M.
Autoimmune thyroid disease (AITD) is a multifactorial disease in which autoimmunity against thyroid antigens develops against a particular genetic background facilitated by exposure to environmental factors. Immunogenicity of the major thyroid antigens thyroid peroxidase, thyroglobulin (TG) and
Autoimmune gastritis is a chronic inflammatory disease with destruction of parietal cells of the corpus and fundus of the stomach. The known consequence is vitamin B12 deficiency and, consequently, pernicious anemia. However, loss of parietal cells reduces secretion of gastric acid which is also required for absorption of inorganic iron; thus, iron deficiency is commonly found in patients with autoimmune gastritis. This usually precedes vitamin B12 deficiency and is found mainly in young women. Patients with chronic iron deficiency, especially those refractory to oral iron therapy, should therefore be evaluated for the presence of autoimmune gastritis.
... exact cause of autoimmune disorders is unknown. One theory is that some microorganisms (such as bacteria or ... M. is also a founding member of Hi-Ethics and subscribes to the principles of the Health ...
Full Text Available Background: Autoimmune pancreatitis is a recently described type of pancreatitis of presumed autoimmune etiology. Autoimmune pancreatitis is often misdiagnosed as pancreatic cancer difficult, since their clinical presentations are often similar. The concept of autoimmune pancreatitis was first published in 1961. Since then, autoimmune pancreatitis has often been treated not as an independent clinical entity but rather as a manifestation of systemic disease. The overall prevalence and incidence of the disease have yet to be determined, but three series have reported the prevalence as between 5 and 6 % of all patients with chronic pancreatitis. Patient vary widely in age, but most are older than 50 years. Patients with autoimmune pancreatitis usually complain of the painless jaundice, mild abdominal pain and weight loss. There is no laboratory hallmark of the disease, even if cholestatic profiles of liver dysfunction with only mild elevation of amylase and lipase levels have been reported.Conclusions: Proposed diagnostic criteria contains: (1 radiologic imaging, diffuse enlargement of the pancreas and diffusely irregular narrowing of the main pancreatic duct, (2 laboratory data, elevated levels of serum ã-globulin and/or IgG, specially IgG4, or the presence of autoantibodies and (3 histopathologic examination, fibrotic change with dense lymphoplasmacytic infiltration in the pancreas. For correct diagnosis of autoimmune pancreatitis, criterion 1 must be present with criterion 2 and/or 3. Autoimmune pancreatitis is frequently associated with rheumatoid arthritis, Sjogren’s syndrome, inflammatory bowel disease, tubulointersticial nephritis, primary sclerosing cholangitis and idiopathic retroperitoneal fibrosis. Pancreatic biopsy using an endoscopic ultrasound-guided fine needle aspiration biopsy is the most important diagnostic method today. Treatment with corticosteroids leads to the and resolution of pancreatic inflamation, obstruction and
Krarup, Therese; Hagen, Claus
during pregnancy or postpartum, but also occurs in males and children. AH is often associated with other autoimmune diseases, most frequently with Hashimoto's thyroiditis. The symptoms are caused by enlargement of the pituitary gland and disturbances of the hormone function. Treatment is either...
Vergani, D; Mieli-Vergani, G
Autoimmune hepatitis (AIH) is characterised histologically by interface hepatitis, and serologically by the presence of non-organ and liver specific autoantibodies and increased levels of immunoglobulin G. Its onset is often ill-defined, frequently mimicing acute hepatitis. AIH usually responds to immunosuppressive treatment, which should be instituted as soon as diagnosis is made. Two types of AIH are recognized according to seropositivity for smooth muscle and/or antinuclear antibody (SMA/ANA, type 1 AIH) or liver kidney microsomal type 1 antibody (LKM1, type 2 AIH). There is a female predominance in both. LKM1 positive patients tend to present more acutely, at a younger age and commonly have immunoglobulin A deficiency, while duration of symptoms before diagnosis, clinical signs, family history of autoimmunity, presence of associated autoimmune disorders, response to treatment and long-term prognosis are similar in the 2 groups. Susceptibility to AIH type 1 is conferred by possession of HLA DR3 and DR4, while to AIH type 2 by possession of HLA DR7. Liver damage is likely to derive from an immune reaction to liver cell antigens, possibly triggered by a mechanism of molecular mimicry, where immune responses to external pathogens, e.g. viruses, become directed towards structurally similar self-components. In AIH this process would be perpetuated by impairment in immune regulation.
Yusri Dianne Jurnalis
Full Text Available AbstrakHepatitis autoimun merupakan penyakit inflamasi hati yang berat dengan penyebab pasti yang tidak diketahui yang mengakibatkan morbiditas dan mortalitas yang tinggi. Semua usia dan jenis kelamin dapat dikenai dengan insiden tertinggi pada anak perempuan usia prepubertas, meskipun dapat didiagnosis pada usia 6 bulan. Hepatitis autoimun dapat diklasifikasikan menjadi 2 bagian berdasarkan adanya antibodi spesifik: Smooth Muscle Antibody (SMA dengan anti-actin specificity dan/atau Anti Nuclear Antibody (ANA pada tipe 1 dan Liver-Kidney Microsome antibody (LKM1 dan/atau anti-liver cytosol pada tipe 2. Gambaran histologisnya berupa “interface hepatitis”, dengan infiltrasi sel mononuklear pada saluran portal, berbagai tingkat nekrosis, dan fibrosis yang progresf. Penyakit berjalan secara kronik tetapi keadaan yang berat biasanya menjadi sirosis dan gagal hati.Tipe onset yang paling sering sama dengan hepatitis virus akut dengan gagal hati akut pada beberapa pasien; sekitar sepertiga pasien dengan onset tersembunyi dengan kelemahan dan ikterik progresif ketika 10-15% asimptomatik dan mendadak ditemukan hepatomegali dan/atau peningkatan kadar aminotransferase serum. Adanya predominasi perempuan pada kedua tipe. Pasien LKM1 positif menunjukkan keadaan lebih akut, pada usia yang lebih muda, dan biasanya dengan defisiensi Immunoglobulin A (IgA, dengan durasi gejala sebelum diagnosis, tanda klinis, riwayat penyakit autoimun pada keluarga, adanya kaitan dengan gangguan autoimun, respon pengobatan dan prognosis jangka panjang sama pada kedua tipe.Kortikosteroid yang digunakan secara tunggal atau kombinasi azathioprine merupakan terapi pilihan yang dapat menimbulkan remisi pada lebih dari 90% kasus. Strategi terapi alternatif adalah cyclosporine. Penurunan imunosupresi dikaitkan dengan tingginya relap. Transplantasi hati dianjurkan pada penyakit hati dekom-pensata yang tidak respon dengan pengobatan medis lainnya.Kata kunci : hepatitis Autoimmune
Autoimmune hepatitis is chronic liver disease with two subtypes, type 1 with anti nuclear or smooth muscle antibodies and type 2 with LKM1 or LC1 antibodies, and both with hypergammaglobulinemia and typical histology. Prevalence of AIH is between 10 to 17 per 100000 in Europe. Up to 20-40 % of cases present with acute hepatitis. Budesonide can be used as a first line induction therapy in non-cirrhotic patients, and tiopurines, mercaptopurine or mycophenolic acid as maintenance therapies. Patients not responding to conventional therapy can be treated with ciclosporin, tacrolimus or rituximab or finally with liver transplantation.
Liver disease test panel - autoimmune ... Autoimmune disorders are a possible cause of liver disease. The most common of these diseases are autoimmune hepatitis and primary biliary cholangitis (formerly called primary biliary cirrhosis). This group of tests ...
Anderson, Mark S.
Context: The endocrine system is a common target in pathogenic autoimmune responses, and there has been recent progress in our understanding, diagnosis, and treatment of autoimmune endocrine diseases.
Majumder, Shounak; Takahashi, Naoki; Chari, Suresh T
Autoimmune pancreatitis (AIP) is a chronic fibroinflammatory disease of the pancreas that belongs to the spectrum of immunoglobulin G-subclass4-related diseases (IgG4-RD) and typically presents with obstructive jaundice. Idiopathic duct-centric pancreatitis (IDCP) is a closely related but distinct disease that mimics AIP radiologically but manifests clinically most commonly as recurrent acute pancreatitis in young individuals with concurrent inflammatory bowel disease. IgG4 levels are often elevated in AIP and normal in IDCP. Histologically, lymphoplasmacytic acinar inflammation and storiform fibrosis are seen in both. In addition, the histologic hallmark of IDCP is the granulocyte epithelial lesion: intraluminal and intraepithelial neutrophils in medium-sized and small ducts with or without granulocytic acinar inflammation often associated with destruction of ductal architecture. Initial treatment of both AIP and IDCP is with oral corticosteroids for duration of 4 weeks followed by a gradual taper. Relapses are common in AIP and relatively uncommon in IDCP, a relatively rare disease for which the natural history is not well understood. For patients with relapsing AIP, treatment with immunomodulators and more recently rituximab has been recommended. Although rare instances of pancreaticobiliary malignancy has been reported in patients with AIP, overall the lifetime risk of developing pancreatic cancer does not appear to be elevated.
Bizzaro, Nicola; Antico, Antonio; Villalta, Danilo
Alterations in the immune response of patients with autoimmune diseases may predispose to malignancies, and a link between chronic autoimmune gastritis and gastric cancer has been reported in many studies. Intestinal metaplasia with dysplasia of the gastric corpus-fundus mucosa and hyperplasia of chromaffin cells, which are typical features of late-stage autoimmune gastritis, are considered precursor lesions. Autoimmune gastritis has been associated with the development of two types of gastric neoplasms: intestinal type and type I gastric carcinoid. Here, we review the association of autoimmune gastritis with gastric cancer and other autoimmune features present in gastric neoplasms. PMID:29373557
de Oliveira, Felipe L; Gatto, Mariele; Bassi, Nicola; Luisetto, Roberto; Ghirardello, Anna; Punzi, Leonardo; Doria, Andrea
Galectin-3 (gal-3) is a β-galactoside-binding lectin, which regulates cell-cell and extracellular interactions during self/non-self-antigen recognition and cellular activation, proliferation, differentiation, migration and apoptosis. It plays a significant role in cellular and tissue pathophysiology by organizing niches that drive inflammation and immune responses. Gal-3 has some therapeutic potential in several diseases, including chronic inflammatory disorders, cancer and autoimmune diseases. Gal-3 exerts a broad spectrum of functions which differs according to its intra- or extracellular localization. Recombinant gal-3 strategy has been used to identify potential mode of action of gal-3; however, exogenous gal-3 may not reproduce the functions of the endogenous gal-3. Notably, gal-3 induces monocyte-macrophage differentiation, interferes with dendritic cell fate decision, regulates apoptosis on T lymphocytes and inhibits B-lymphocyte differentiation into immunoglobulin secreting plasma cells. Considering the influence of these cell populations in the pathogenesis of several autoimmune diseases, gal-3 seems to play a role in development of autoimmunity. Gal-3 has been suggested as a potential therapeutic agent in patients affected with some autoimmune disorders. However, the precise role of gal-3 in driving the inflammatory process in autoimmune or immune-mediated disorders remains elusive. Here, we reviewed the involvement of gal-3 in cellular and tissue events during autoimmune and immune-mediated inflammatory diseases. © 2015 by the Society for Experimental Biology and Medicine.
Anaya, Juan-Manuel; Ramirez-Santana, Carolina; Alzate, Maria A; Molano-Gonzalez, Nicolas; Rojas-Villarraga, Adriana
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.
Rapin, Nicolas; Mosekilde, Erik; Lund, Ole
Autoimmune diseases damage host tissue, which, in turn, may trigger a stronger immune response. Systems characterized by such positive feedback loops can display co-existing stable steady states. In a mathematical model of autoimmune disease, one steady state may correspond to the healthy state...
Anderson, Mark S
The endocrine system is a common target in pathogenic autoimmune responses, and there has been recent progress in our understanding, diagnosis, and treatment of autoimmune endocrine diseases. Rapid progress has recently been made in our understanding of the genetic factors involved in endocrine autoimmune diseases. Studies on monogenic autoimmune diseases that include endocrine phenotypes like autoimmune polyglandular syndrome type 1 and immune dysregulation, polyendocrinopathy, enteropathy, X-linked have helped reveal the role of key regulators in the maintenance of immune tolerance. Highly powered genetic studies have found and confirmed many new genes outside of the established role of the human leukocyte antigen locus with these diseases, and indicate an essential role of immune response pathways in these diseases. Progress has also been made in identifying new autoantigens and the development of new animal models for the study of endocrine autoimmunity. Finally, although hormone replacement therapy is still likely to be a mainstay of treatment in these disorders, there are new agents being tested for potentially treating and reversing the underlying autoimmune process. Although autoimmune endocrine disorders are complex in etiology, these recent advances should help contribute to improved outcomes for patients with, or at risk for, these disorders.
Full Text Available 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, 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.
Rizzo, Leonardo F L; Mana, Daniela L; Bruno, Oscar D
The term thyroiditis comprises a group of thyroid diseases characterized by the presence of inflammation, including autoimmune and non-autoimmune entities. It may manifest as an acute illness with severe thyroid pain (subacute thyroiditis and infectious thyroiditis), and conditions in which the inflammation is not clinically evident evolving without pain and presenting primarily thyroid dysfunction and/or goiter (drug-induced thyroiditis and Riedel thyroiditis). The aim of this review is to provide an updated approach on non-autoimmune thyroiditis and its clinical, diagnostic and therapeutic aspects.
Winfield, J B; Jarjour, W N
At birth, the immune system is biased toward recognition of microbial antigens in order to protect the host from infection. Recent data suggest that an important initial line of defense in this regard involves autologous stress proteins, especially conserved peptides of hsp60, which are presented to T cells bearing gamma delta receptors by relatively nonpolymorphic class lb molecules. Natural antibodies may represent a parallel B cell mechanism. Through an evolving process of "physiological" autoreactivity and selection by immunodominant stress proteins common to all prokaryotes, B and T cell repertoires expand during life to meet the continuing challenge of infection. Because stress proteins of bacteria are homologous with stress proteins of the host, there exists in genetically susceptible individuals a constant risk of autoimmune disease due to failure of mechanisms for self-nonself discrimination. That stress proteins actually play a role in autoimmune processes is supported by a growing body of evidence which, collectively, suggests that autoreactivity in chronic inflammatory arthritis involves, at least initially, gamma delta cells which recognize epitopes of the stress protein hsp60. Alternate mechanisms for T cell stimulation by stress proteins undoubtedly also exist, e.g., molecular mimicry of the DR beta third hypervariable region susceptibility locus for rheumatoid arthritis by a DnaJ stress protein epitope in gram-negative bacteria. While there still is confusion with respect to the most relevant stress protein epitopes, a central role for stress proteins in the etiology of arthritis appears likely. Furthermore, insight derived from the work thus far in adjuvant-induced arthritis already is stimulating analyses of related phenomena in autoimmune diseases other than those involving joints. Only limited data are available in the area of humoral autoimmunity to stress proteins. Autoantibodies to a number of stress proteins have been identified in SLE and
Muratori, Luigi; Deleonardi, Gaia; Lalanne, Claudine; Barbato, Erica; Tovoli, Alessandra; Libra, Alessia; Lenzi, Marco; Cassani, Fabio; Muratori, Paolo
The detection of diagnostic autoantibodies such as antinuclear antibodies (ANA), anti-smooth muscle antibodies (SMA), anti-liver/kidney microsomal type 1 (anti-LKM1), anti-liver cytosol type 1 (anti-LC1) and anti-soluble liver antigen (anti-SLA) is historically associated with the diagnosis of autoimmune hepatitis. When autoimmune hepatitis is suspected, the detection of one or any combination of diagnostic autoantibodies, by indirect immunofluorescence or immuno-enzymatic techniques with recombinant antigens, is a pivotal step to reach a diagnostic score of probable or definite autoimmune hepatitis. Diagnostic autoantibodies (ANA, SMA, anti-LKM1, anti-LC1, anti-SLA) are a cornerstone in the diagnosis of autoimmune hepatitis. Other ancillary autoantibodies, associated with peculiar clinical correlations, appear to be assay-dependent and institution-specific, and validation studies are needed. © 2015 S. Karger AG, Basel.
Guimarães, Luísa Eça; Baker, Britain; Perricone, Carlo; Shoenfeld, Yehuda
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. Copyright © 2015 Elsevier Ltd. All rights reserved.
Full Text Available Eosinophils are multifunctional granulocytes that contribute to initiation and modulation of inflammation. Their role in asthma and parasitic infections has long been recognized. Growing evidence now reveals a role for eosinophils in autoimmune diseases. In this review, we summarize the function of eosinophils in inflammatory bowel diseases, neuromyelitis optica, bullous pemphigoid, autoimmune myocarditis, primary biliary cirrhosis, eosinophilic granulomatosis with polyangiitis, and other autoimmune diseases. Clinical studies, eosinophil-targeted therapies, and experimental models have contributed to our understanding of the regulation and function of eosinophils in these diseases. By examining the role of eosinophils in autoimmune diseases of different organs, we can identify common pathogenic mechanisms. These include degranulation of cytotoxic granule proteins, induction of antibody-dependent cell-mediated cytotoxicity, release of proteases degrading extracellular matrix, immune modulation through cytokines, antigen presentation, and prothrombotic functions. The association of eosinophilic diseases with autoimmune diseases is also examined, showing a possible increase in autoimmune diseases in patients with eosinophilic esophagitis, hypereosinophilic syndrome, and non-allergic asthma. Finally, we summarize key future research needs.
Diny, Nicola L.; Rose, Noel R.; Čiháková, Daniela
Eosinophils are multifunctional granulocytes that contribute to initiation and modulation of inflammation. Their role in asthma and parasitic infections has long been recognized. Growing evidence now reveals a role for eosinophils in autoimmune diseases. In this review, we summarize the function of eosinophils in inflammatory bowel diseases, neuromyelitis optica, bullous pemphigoid, autoimmune myocarditis, primary biliary cirrhosis, eosinophilic granulomatosis with polyangiitis, and other autoimmune diseases. Clinical studies, eosinophil-targeted therapies, and experimental models have contributed to our understanding of the regulation and function of eosinophils in these diseases. By examining the role of eosinophils in autoimmune diseases of different organs, we can identify common pathogenic mechanisms. These include degranulation of cytotoxic granule proteins, induction of antibody-dependent cell-mediated cytotoxicity, release of proteases degrading extracellular matrix, immune modulation through cytokines, antigen presentation, and prothrombotic functions. The association of eosinophilic diseases with autoimmune diseases is also examined, showing a possible increase in autoimmune diseases in patients with eosinophilic esophagitis, hypereosinophilic syndrome, and non-allergic asthma. Finally, we summarize key future research needs. PMID:28496445
Tirosh, Amir; Mandel, Dror; Mimouni, Francis B; Zimlichman, Eyal; Shochat, Tzippora; Kochba, Ilan
Previous research has suggested an inverse relationship between T-helper 2-related atopic disorders, such as asthma, and T-helper 1-related autoimmune diseases. One controversial hypothesis postulates that asthma provides a protective effect for the development of autoimmune-related disorders. To assess the rate of newly diagnosed autoimmune disorders in a large cohort of young adults. Using cross-sectional data from the Israeli Defense Force database, the authors analyzed the prevalence of autoimmune disorders in asthmatic and nonasthmatic military personnel between 1980 and 2003. A follow-up study traced newly diagnosed autoimmune disorders among asthmatic and nonasthmatic individuals from the time of enrollment in military service until discharge (22 and 36 months for women and men, respectively). General community. 307,367 male and 181,474 female soldiers in compulsory military service who were between 18 and 21 years of age. Cases of type 1 diabetes mellitus, vasculitis, immune thrombocytopenic purpura, inflammatory bowel disease, rheumatoid arthritis, and the antiphospholipid syndrome. Of 488,841 participants at enrollment, significantly more women than men had autoimmune disorders. Compared with asthmatic women, nonasthmatic women had a significantly higher prevalence of all autoimmune disorders except for the antiphospholipid syndrome. Type 1 diabetes mellitus, vasculitis, and rheumatoid arthritis were less prevalent in men with asthma than in those without. During the follow-up period, vasculitis and rheumatoid arthritis were more frequently diagnosed in nonasthmatic persons of both sexes. There was a significantly higher incidence of immune thrombocytopenic purpura, inflammatory bowel disease, and the antiphospholipid syndrome in nonasthmatic women and a statistically significantly higher incidence of type 1 diabetes mellitus in nonasthmatic men. The study was limited to a population of young military recruits; therefore, its findings are not necessarily
Coati, Irene; Fassan, Matteo; Farinati, Fabio; Graham, David Y; Genta, Robert M; Rugge, Massimo
Western countries are seeing a constant decline in the incidence of Helicobacter pylori-associated gastritis, coupled with a rising epidemiological and clinical impact of autoimmune gastritis. This latter gastropathy is due to autoimmune aggression targeting parietal cells through a complex interaction of auto-antibodies against the parietal cell proton pump and intrinsic factor, and sensitized T cells. Given the specific target of this aggression, autoimmune gastritis is typically restricted to the gastric corpus-fundus mucosa. In advanced cases, the oxyntic epithelia are replaced by atrophic (and metaplastic) mucosa, creating the phenotypic background in which both gastric neuroendocrine tumors and (intestinal-type) adenocarcinomas may develop. Despite improvements in our understanding of the phenotypic changes or cascades occurring in this autoimmune setting, no reliable biomarkers are available for identifying patients at higher risk of developing a gastric neoplasm. The standardization of autoimmune gastritis histology reports and classifications in diagnostic practice is a prerequisite for implementing definitive secondary prevention strategies based on multidisciplinary diagnostic approaches integrating endoscopy, serology, histology and molecular profiling.
Bright, John J
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.
John, Seby; Hajj-Ali, Rula A
Autoimmune diseases are a group of heterogeneous inflammatory disorders characterized by systemic or localized inflammation, leading to ischemia and tissue destruction. These include disorders like systemic lupus erythematosus and related diseases, systemic vasculitides, and central nervous system (CNS) vasculitis (primary or secondary). Headache is a very common manifestation of CNS involvement of these diseases. Although headache characteristics can be unspecific and often non-diagnostic, it is important to recognize because headache can be the first manifestation of CNS involvement. Prompt recognition and treatment is necessary not only to treat the headache, but also to help prevent serious neurological sequelae that frequently accompany autoimmune diseases. In this review, we discuss headache associated with autoimmune diseases along with important mimics. © 2014 American Headache Society.
Dilas, Ljiljana Todorović; Icin, Tijana; Paro, Jovanka Novaković; Bajkin, Ivana
Autoimmune diseases are chronic conditions initiated by the loss of immunological tolerance to self-antigens. They constitute heterogeneous group of disorders, in which multiple alterations in the immune system result in a spectrum of syndromes that either target specific organs or affect the body systematically. Recent epidemiological studies have shown a possible shift of one autoimmune disease to another or the fact that more than one autoimmune disease may coexist in a single patient or in the same family. Numerous autoimmune diseases have been shown to coexist frequently with thyroid autoimmune diseases. AUTOIMMNUNE THYROID DISEASE AND OTHER ORGAN SPECIFIC NON-ENDOCRINE AUTOIMMUNE DISEASES: This part of the study reviews the prevalence of autoimmune thyroid disease coexisting with: pernicious anaemia, vitiligo, celiac disease, autoimmune liver disease, miastenia gravis, alopecia areata and sclerosis multiplex, and several recommendations for screening have been given. AUTOIMMUNE THYROID DISEASE AND OTHER ORGAN NON-SPECIFIC NON-ENDOCRINE AUTOIMMUNE DISEASES: Special attention is given to the correlation between autoimmune thyroid disease and rheumatoid arthritis, systemic lupus erythematosus, syndrome Sjögren, systemic sclerosis and mixed connective tissue disease. Screening for autoimmune thyroid diseases should be recommended in everyday clinical practice, in patients with primary organ-specific or organ non-specific autoimmune disease. Otherwise, in patients with primary thyroid autoimmune disease, there is no good reason of seeking for all other autoimmune diseases, although these patients have a greater risk of developing other autoimmune disease. Economic aspects of medicine require further analyzing of these data, from cost/benefit point of view to justified either mandatory screening or medical practitioner judgment.
Drexhage, H.A.; Wiersinga, W.M.
These proceedings give an almost complete picture of what is presently known on the autoimmune aspects of both functional and growth disturbances of the thyroid gland. It comprises 12 reviews on main areas of present research, each followed by shorter communications of work in progress relevant to the topic. (Auth.)
Lim, Thien Thien
To provide an overview of paraneoplastic autoimmune disorders presenting with various movement disorders. The spectrum of paraneoplastic autoimmune disorders has been expanding with the discovery of new antibodies against cell surface and intracellular antigens. Many of these paraneoplastic autoimmune disorders manifest as a form of movement disorder. With the discovery of new neuronal antibodies, an increasing number of idiopathic or neurodegenerative movement disorders are now being reclassified as immune-mediated movement disorders. These include anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis which may present with orolingual facial dyskinesia and stereotyped movements, CRMP-5 IgG presenting with chorea, anti-Yo paraneoplastic cerebellar degeneration presenting with ataxia, anti-VGKC complex (Caspr2 antibodies) neuromyotonia, opsoclonus-myoclonus-ataxia syndrome, and muscle rigidity and episodic spasms (amphiphysin, glutamic acid decarboxylase, glycine receptor, GABA(A)-receptor associated protein antibodies) in stiff-person syndrome. Movement disorders may be a presentation for paraneoplastic autoimmune disorders. Recognition of these disorders and their common phenomenology is important because it may lead to the discovery of an occult malignancy. Copyright © 2017 Elsevier Ltd. All rights reserved.
Brahim, Imane; Brahim, Ikram; Hazime, Raja; Admou, Brahim
Autoimmune hepatopathies (AIHT) including autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC) and autoimmune cholangitis (AIC), represent an impressive entities in clinical practice. Their pathogenesis is not perfectly elucidated. Several factors are involved in the initiation of hepatic autoimmune and inflammatory phenomena such as genetic predisposition, molecular mimicry and/or abnormalities of T-regulatory lymphocytes. AIHT have a wide spectrum of presentation, ranging from asymptomatic forms to severe acute liver failure. The diagnosis of AIHT is based on the presence of hyperglobulinemia, cytolysis, cholestasis, typical even specific circulating auto-antibodies, distinctive of AIH or PBC, and histological abnormalities as well as necrosis and inflammation. Anti-F actin, anti-LKM1, anti-LC1 antibodies permit to distinguish between AIH type 1 and AIH type 2. Anti-SLA/LP antibodies are rather associated to more severe hepatitis, and particularly useful for the diagnosis of seronegative AIH for other the antibodies. Due to the relevant diagnostic value of anti-M2, anti-Sp100, and anti-gp210 antibodies, the diagnosis of PBC is more affordable than that of PSC and AIC. Based on clinical data, the immunological diagnosis of AIHT takes advantage of the various specialized laboratory techniques including immunofluorescence, immunodot or blot, and the Elisa systems, provided of a closer collaboration between the biologist and the physician. Copyright © 2017 Elsevier Masson SAS. All rights reserved.
Mieli-Vergani, Giorgina; Vergani, Diego
Liver disorders with a likely autoimmune pathogenesis in childhood include autoimmune hepatitis (AIH), autoimmune sclerosing cholangitis (ASC), and de novo AIH after liver transplantation. AIH is divided into two subtypes according to seropositivity for smooth muscle and/or antinuclear antibody (SMA/ANA, type 1) or liver kidney microsomal antibody (LKM1, type 2). There is a female predominance in both. LKM1 positive patients tend to present more acutely, at a younger age, and commonly have partial IgA deficiency, while duration of symptoms before diagnosis, clinical signs, family history of autoimmunity, presence of associated autoimmune disorders, response to treatment, and long-term prognosis are similar in both groups. The most common type of paediatric sclerosing cholangitis is ASC. The clinical, biochemical, immunological, and histological presentation of ASC is often indistinguishable from that of AIH type 1. In both, there are high IgG, non-organ specific autoantibodies, and interface hepatitis. Diagnosis is made by cholangiography. Children with ASC respond to immunosuppression satisfactorily and similarly to AIH in respect to remission and relapse rates, times to normalization of biochemical parameters, and decreased inflammatory activity on follow up liver biopsies. However, the cholangiopathy can progress. There may be evolution from AIH to ASC over the years, despite treatment. De novo AIH after liver transplantation affects patients not transplanted for autoimmune disorders and is strikingly reminiscent of classical AIH, including elevated titres of serum antibodies, hypergammaglobulinaemia, and histological findings of interface hepatitis, bridging fibrosis, and collapse. Like classical AIH, it responds to treatment with prednisolone and azathioprine. De novo AIH post liver transplantation may derive from interference by calcineurin inhibitors with the intrathymic physiological mechanisms of T-cell maturation and selection. Whether this condition is a
Full Text Available 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.
Stepanov, Alexey; Lomakin, Yakov; Gabibov, Alexander; Belogurov, Alexey
The mammalian immune system is a nearly perfect defensive system polished by a hundred million years of evolution. Unique flexibility and adaptivity have created a virtually impenetrable barrier to numerous exogenous pathogens that are assaulting us every moment. Unfortunately, triggers that remain mostly enigmatic will sometimes persuade the immune system to retarget against self-antigens. This civil war remains underway, showing no mercy and taking no captives, eventually leading to irreversible pathological changes in the human body. Research that has emerged during the last two decades has given us hope that we may have a chance to overcome autoimmune diseases using a variety of techniques to "reset" the immune system. In this report, we summarize recent advances in utilizing short polypeptides - mostly fragments of autoantigens - in the treatment of autoimmune neurodegeneration. Copyright© Bentham Science Publishers; For any queries, please email at firstname.lastname@example.org.
Full Text Available Most of the studies have shown a higher risk for subclinical and clinical hypothyroidism, antithyroid autoantibodies [overall antithyroid peroxidase antibodies (TPOAb], and in general, thyroid autoimmunity, overall in the female gender in patients with sarcoidosis (S. A significantly higher prevalence of clinical hypothyroidism and Graves’ disease was also described in female S patients with respect to controls. Gallium-67 (Ga-67 scyntigraphy in S patients, in the case of thyroid uptake, suggests the presence of aggressive autoimmune thyroiditis and hypothyroidism. For this reason, ultrasonography and thyroid function should be done in the case of Ga-67 thyroid uptake. In conclusion, thyroid function, TPOAb measurement, and ultrasonography should be done to assess the clinical profile in female S patients, and the ones at high risk (female individuals, with TPOAb positivity, and hypoechoic and small thyroid should have periodically thyroid function evaluations and suitable treatments.
Napier, Catherine; Pearce, Simon H S
Addison's disease is a rare autoimmune disorder. In the developed world, autoimmune adrenalitis is the commonest cause of primary adrenal insufficiency, where the majority of patients have circulating antibodies against the key steroidogenic enzyme 21-hydroxylase. A complex interplay of genetic, immunological and environmental factors culminates in symptomatic adrenocortical insufficiency, with symptoms typically developing over months to years. Biochemical evaluation and further targeted investigations must confirm primary adrenal failure and establish the underlying aetiology. The diagnosis of adrenocortical insufficiency will necessitate lifelong glucocorticoid and mineralocorticoid replacement therapy, aiming to emulate physiological patterns of hormone secretion to achieve well-being and good quality of life. Education of patients and healthcare professionals is essential to minimise the risk of a life-threatening adrenal crisis, which must be promptly recognised and aggressively managed when it does occur. This article provides an overview of our current understanding of the natural history and underlying genetic and immunological basis of this condition. Future research may reveal novel therapeutic strategies for patient management. Until then, optimisation of pharmacological intervention and continued emphasis on education and empowerment of patients should underpin the management of individuals with autoimmune Addison's disease. Copyright © 2012. Published by Elsevier Masson SAS.
Ponto, Katharina A; Kahaly, George J
Autoimmune thyrotoxicosis or Graves' disease (GD) is the most common cause of hyperthyroidism in the United States (full text available online: http://education.amjmed.com/pp1/249). GD occurs more often in women (ratio 5:1) and has a population prevalence of 1-2%. A genetic determinant to the susceptibility to GD is suspected because of familial clustering of the disease, a high sibling recurrence risk, and the familial occurrence of thyroid autoantibodies. GD is a systemic autoimmune thyroid disorder characterized by the infiltration of immune effector cells and thyroid-antigen-specific T cells into the thyroid and thyroid stimulating hormone receptor (TSHR) expressing tissues, i.e. orbit, skin, with the production of autoantibodies to well-defined thyroidal antigens. Stimulatory autoantibodies in GD activate the TSHR leading to thyroid hyperplasia and unregulated thyroid hormone production and secretion. Diagnosis of GD is straightforward in a patient with a diffusely enlarged, heterogeneous, hypervascular (increased Doppler flow on neck ultrasound) thyroid gland, associated orbitopathy, biochemically confirmed thyrotoxicosis, positive TSHR autoantibodies, and often a family history of autoimmune disorders. Copyright © 2012. Published by Elsevier Inc.
Muratori, Paolo; Granito, Alessandro; Pappas, Georgios; Muratori, Luigi; Lenzi, Marco; Bianchi, Francesco B
Autoimmune liver disease (ALD) includes a spectrum of diseases which comprises both cholestatic and hepatitic forms: autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC) and the so called "overlap" syndromes where hepatitic and cholestatic damage coexists. All these diseases are characterized by an extremely high heterogeneity of presentation, varying from asymptomatic, acute (as in a subset of AIH) or chronic (with aspecific symptoms such as fatigue and myalgia in AIH or fatigue and pruritus in PBC and PSC). The detection and characterization of non organ specific autoantibodies plays a major role in the diagnostic approach of autoimmune liver disease; anti nuclear reactivities (ANA) and anti smooth muscle antibodies (SMA) mark type 1 AIH, liver kidney microsomal antibody type 1 (LKM1) and liver cytosol type 1 (LC1) are the serological markers of type 2 AIH; antimitochondrial antibodies (AMA) are associated with PBC, while no specific marker is found in PSC, since anticytoplasmic neutrophil antibodies with perinuclear pattern (atypical p-ANCA or p-ANNA) are also detected in a substantial proportion of type 1 AIH cases. Treatment options rely on immunosoppressive therapy (steroids and azathioprine) in AIH and on ursodeoxycholic acid in cholestatic conditions; in all these diseases liver transplantation remains the only therapeutical approach for the end stage of liver disease.
Full Text Available Autoimmune hepatitis is a chronic immune-mediated disease of the liver. In childhood, autoimmune liver disorders include autoimmune hepatitis type I and II, autoimmune sclerosing cholangitis, Coombs-positive giant cell hepatitis, and de novo autoimmune hepatitis after liver transplantation. Autoimmune liver disease has a more aggressive course in children, especially autoimmune hepatitis type II. Standard therapy is a combination of corticosteroids and azathioprine. Around 80 % of children with autoimmune liver disease show a rapid response to combination therapy. The non-responders are treated with more potent drugs, otherwise autoimmune disease progresses to cirrhosis of the liver and the child needs liver transplantation as rescue therapy.
Bueverov, A O
The immunosuppresive drugs, primarily glucocorticosteroids, serve as the basis for the pathogenetic treatment of autoimmune diseases of the liver. In autoimmune hepatitis, immunosuppressive therapy induces and maintains persistent remission in most patients while in primary biliary cirrhosis and primary sclerosing cholangitis, its capacities are substantially limited. Ursodeoxycholic acid is used as the basic drug in predominantly occurring intrahepatic cholestasis. The treatment of cross autoimmune syndromes generally requires the choice of a combination of drugs.
Full Text Available Introduction Autoimmune hepatitis (AIH is a disease of unknown etiology. In pregnancy, it may have mild clinical course as well as can lead to liver failure, or exacerbation of clinical symptoms. In pregnant women the severity of symptoms is often observed between the second and third trimester, and in the puerperium. The disease is marked by enhanced activity of Th lymphocytes, which hepatocytes recognize as foreign antigens. This results in interleukin production activating B lymphocytes, and the production of specific antibodies attacking and destroying the hepatocytes. Case report A 35-year old patient, CII PII, 7 Hbd, with autoimmune hepatitis reported for a check-up. Her first pregnancy was 18 years ago, without history of underlying disease, carried to term without complications. The woman gave birth to a baby-son weighing 3,280g, 10 points Apgar. The delivery was spontaneous and uneventful. The patient got pregnant after an 18-year break. When she twice-tested positively for pregnancy, the treatment with azathioprine was switched to prednisolone. Over the pregnancy the patient was hospitalized 4 times, in 25, 29, 35, and 37 week of gestation due to a threat of preterm delivery, and pregnancy-related cholestasis associated with AIH. In 37 week of gestation, delivery was induced, and she gave birth to a healthy male, weighing 2,650 g, body height of 49 cm, 10 points Apgar scale. The liver function improved and stabilized after the delivery. Treatment with prednisolone has been continued, and the patient’s condition is still controlled. Pregnant patients with autoimmune hepatitis often experience exacerbation of the disease, especially in the third trimester, and in the postpartum period. This case shows that with proper care it is possible to continue and terminate pregnancy safely for the mother and her newly born baby.
Trombetta, Amelia Chiara; Meroni, Marianna; Cutolo, Maurizio
From the middle of the 19th century, it is known that endocrine and immune systems interact bi-directionally in different processes that ensure organism homeostasis. Endocrine and nervous systems have a pivotal role in the balancing of pro- and anti-inflammatory functions of immune system, and constitute a complex circadian neuroendocrine network. Autoimmune diseases have in fact a complex pathogenic origin in which the importance of endocrine system was demonstrated. In this chapter, we will mention the structure and function of steroidal hormones involved in the neuroendocrine immune network and we will address the ways in which endocrine and immune systems influence each other, in a bi-directional fashion. Adrenal hormones, sex hormones, vitamin D, and melatonin and prolactin importantly all contribute to the homeostasis of the immune system. Indeed, some of the steroidal hormone activities determine inhibition or stimulation of immune system components, in both physiological (i.e. suppression of an unwanted response in pregnancy, or stimulation of a protective response in infections) and pathological conditions. We will finally mention the rationale for optimization of exogenous administration of glucocorticoids in chronic autoimmune diseases, and the latest developments concerning these drugs. © 2017 S. Karger AG, Basel.
Muratori, Luigi; Muratori, Paolo; Granito, Alessandro; Pappas, Giorgios; Cassani, Fabio; Lenzi, Marco
Autoimmune hepatitis is a chronic liver disease of unknown aetiology characterized by interface hepatitis, hypergammaglobulinaemia and circulating autoantibodies. In the last decade a number of advancements have been made in the field of clinical and basic research: the simplified diagnostic criteria, the complete response defined as normalization of transaminase levels, the molecular identification of the antigenic targets of anti-liver cytosol antibody type 1 and anti-soluble liver antigen, the detection of anti-actin antibodies, the description of de novo autoimmune hepatitis after liver transplantation for non-autoimmune liver diseases, the characterization of autoimmune hepatitis with overlapping features of primary biliary cirrhosis or primary sclerosing cholangitis, the preliminary experience with novel treatment strategies based on cyclosporine, mycophenolate mofetil and budesonide, the role played by "impaired" regulatory T cells and the development of novel animal models of autoimmune hepatitis. Copyright © 2010 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.
Full Text Available Premature ovarian failure (POF, also termed as primary ovarian insufficiency (POI, is a highly heterogenous condition affecting 0.5-3.0% of women in childbearing age. These young women comprise quite a formidable group with unique physical and psychological needs that require special attention. Premature ovarian senescence (POS in all of its forms evolves insidiously as a basically asymptomatic process, leading to complete loss of ovarian function, and POI/POF diagnoses are currently made at relatively late stages. Well-known and well-documented risk factors exist, and the presence or suspicion of autoimmune disorder should be regarded as an important one. Premature ovarian failure is to some degree predictable in its occurrence and should be considered while encountering young women with loss of menstrual regularity, especially when there is a concomitant dysfunction in the immune system.
Psychoneuroimmunology is a relatively young field of research that investigates interactions between central nervous and immune system. The brain modulates the immune system by the endocrine and autonomic nervous system. Vice versa, the immune system modulates brain activity including sleep and body temperature. Based on a close functional and anatomical link, the immune and nervous systems act in a highly reciprocal manner. From fever to stress, the influence of one system on the other has evolved in an intricate manner to help sense danger and to mount an appropriate adaptive response. Over recent decades, reasonable evidence has emerged that these brain-to-immune interactions are highly modulated by psychological factors which influence immunity and autoimmune disease. For several diseases, the relevance of psychoneuroimmunological findings has already been demonstrated.
Mieli-Vergani, Giorgina; Vergani, Diego
AIH, ASC, and de novo AIH after liver transplantation are childhood liver diseases of an autoimmune nature. The mode of presentation of AIH in childhood is variable, and the disease should be suspected and excluded in all children presenting with symptoms and signs of prolonged or severe acute liver disease. Although corticosteroids are effective in all types of childhood AIH, patients with LKM1 have a higher frequency of acute hepatic failure and relapse after corticosteroid withdrawal than do patients with ANA/SMA. ASC occurs commonly in the absence of inflammatory bowel disease, requires cholangiography for diagnosis, and improves during corticosteroid therapy. The development of AIH de novo in children who undergo liver transplantation for nonautoimmune liver disease may reflect interference with the maturation of T cells by immunosuppressive drugs.
Bliddal, Sofie; Nielsen, Claus Henrik; Feldt-Rasmussen, Ulla
Autoimmune thyroid disease (AITD) is often observed together with other autoimmune diseases. The coexistence of two or more autoimmune diseases in the same patient is referred to as polyautoimmunity, and AITD is the autoimmune disease most frequently involved. The occurrence of polyautoimmunity h...
Delévaux, I; Chamoux, A; Aumaître, O
The etiology of auto-immune disorders is multifactorial. Stress is probably a participating factor. Indeed, a high proportion of patients with auto-immune diseases report uncommon stress before disease onset or disease flare. The biological consequences of stress are increasingly well understood. Glucocorticoids and catecholamines released by hypothalamic-pituitary-adrenal axis during stress will alter the balance Th1/Th2 and the balance Th17/Treg. Stress impairs cellular immunity, decreases immune tolerance and stimulates humoral immunity exposing individuals to autoimmune disease among others. The treatment for autoimmune disease should include stress management. Copyright © 2012 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.
Kahaly, George J; Schuppan, Detlef
Celiac disease (CD) is a small-intestinal inflammatory disease that is triggered by the ingestion of the storage proteins (gluten) of wheat, barley and rye. Endocrine autoimmunity is prevalent in patients with CD and their relatives. The genes that predispose to endocrine autoimmune diseases, e.g. type 1 diabetes, autoimmune thyroid diseases, and Addison's disease, i.e. DR3-DQ2 and DR4-DQ8, are also the major genetic determinants of CD, which is the best understood HLA-linked disease. Thus, up to 30% of first-degree relatives both of patients with CD and/or endocrine autoimmunity are affected by the other disease. In CD, certain gluten proteins bind with high affinity to HLA-DQ2 or -DQ8 in the small-intestinal mucosa, to activate gluten-specific T cells which are instrumental in the destruction of the resorptive villi. Here, the autoantigen tissue transglutaminase increases the T cell response by generating deamidated gluten peptides that bind more strongly to DQ2 or DQ8. Classical symptoms such as diarrhea and consequences of malabsorption like anemia and osteoporosis are often absent in patients with (screening-detected) CD, but this absence does not significantly affect these patients' incidence of endocrine autoimmunity. Moreover, once autoimmunity is established, a gluten-free diet is not able to induce remission. However, ongoing studies attempt to address how far a gluten-free diet may prevent or retard the development of CD and endocrine autoimmunity in children at risk. The close relationship between CD and endocrine autoimmunity warrants a broader immune genetic and endocrine screening of CD patients and their relatives. © 2015 S. Karger AG, Basel.
Full Text Available Autoimmune thyroiditis (AIT is generally associated with hypothyroidism. It affects ~2% of the female population and 0.2% of the male population. The evidence of thyroid function- and thyroid autoantibody-unrelated microproteinuria in almost half of patients with AIT and sometimes heavy proteinuria as in the nephrotic syndrome point to a link of AIT with renal disease. The most common renal diseases observed in AIT are membranous nephropathy, membranoproliferative glomerulonephritis, minimal change disease, IgA nephropathy, focal segmental glomerulosclerosis, antineutrophil cytoplasmic autoantibody (ANCA vasculitis, and amyloidosis. Different hypotheses have been put forward regarding the relationship between AIT and glomerulopathies, and several potential mechanisms for this association have been considered. Glomerular deposition of immunocomplexes of thyroglobulin and autoantibodies as well as the impaired immune tolerance for megalin (a thyrotropin-regulated glycoprotein expressed on thyroid cells are the most probable mechanisms. Cross-reactivity between antigens in the setting of genetic predisposition has been considered as a potential mechanism that links the described association between ANCA vasculitis and AIT.
Ana Maria Abreu Velez
Full Text Available Autoimmune bullous skin diseases (ABDs are uncommon, potentially fatal diseases of skin and mucous membranes which are associated with deposits of autoantibodies and complement against distinct molecules of the epidermis and dermal/epidermal basement membrane zone (BMZ. These autoantibodies lead to a loss in skin molecular integrity, which manifests clinically as formation of blisters or erosions. In pemphigus vulgaris, loss of adhesion occurs within the epidermis. The pioneering work of Ernst H. Beutner, Ph.D. and Robert E. Jordon, M.D. confirmed the autoimmune nature of these diseases. Walter F. Lever, M.D. contributed significantly to our understanding of the histopathologic features of these diseases. Walter Lever, M.D. and Ken Hashimoto, M.D. contributed electron microscopic studies of these diseases, especially in pemphigus vulgaris and bullous pemphigoid. In bullous pemphigoid (BP, linear IgA bullous dermatosis, epidermolysis bullosa acquisita (EBA and dermatitis herpetiformis (DH, loss of adhesion takes place within or underneath the BMZ. Classic EBA demonstrates extensive skin fragility; DH is commonly associated with gluten-sensitive enteropathy, and manifests clinically with pruritic papulovesicles on the extensor surfaces of the extremities and the lumbosacral area. The clinical spectrum of bullous pemphigoid includes tense blisters, urticarial plaques, and prurigo-like eczematous lesions. Pemphigoid gestationis mostly occurs during the last trimester of pregnancy, and mucous membrane pemphigoid primarily involves the oral mucosa and conjunctivae and leads to scarring. Linear IgA bullous dermatosis manifests with tense blisters in a „cluster of jewels”-like pattern in childhood (chronic bullous disease of childhood and is more clinically heterogeneous in adulthood. Many of the autoantigens in these disorders are known and have been well characterized. ABDs may be influenced by both genetic and exogenous factors. The diagnoses of
Mieli-Vergani, G; Vergani, D
Autoimmune liver disorders are characterised by an inflammatory liver histology, circulating non-organ specific autoantibodies and increased levels of immunoglobulin G (IgG) in the absence of a known aetiology. They respond to immunosuppressive treatment, which should be instituted as soon as diagnosis is made. Liver disorders with a likely autoimmune pathogenesis include autoimmune hepatitis (AIH) and autoimmune sclerosing cholangitis (ASC). Two types of AIH are recognised according to seropositivity for smooth muscle and/or antinuclear antibody (SMA/ANA, type 1) or liver kidney microsomal antibody (LKM1, type 2). There is a female predominance in both. LKM1-positive patients tend to present more acutely, at a younger age, and commonly have immunoglobulin A (IgA) deficiency, while duration of symptoms before diagnosis, clinical signs, family history of autoimmunity, presence of associated autoimmune disorders, response to treatment and long-term prognosis are similar in both groups. The most common type of paediatric sclerosing cholangitis is ASC. The clinical, biochemical, immunological and histological presentation of ASC is often indistinguishable from that of AIH. In both, there are high IgG, non-organ specific autoantibodies and interface hepatitis. Diagnosis is made by cholangiography. Children with ASC respond to immunosuppression satisfactorily and similarly to AIH in respect to remission and relapse rates, times to normalisation of biochemical parameters and decreased inflammatory activity on follow-up liver biopsies. However, the cholangiopathy can progress and there may be an evolution from AIH to ASC over the years, despite treatment. Whether the juvenile autoimmune form of sclerosing cholangitis and AIH are 2 distinct entities, or different aspects of the same condition, remains to be elucidated.
Pras, Eran; Neumann, Ron; Zandman-Goddard, Gisele; Levy, Yair; Assia, Ehud I; Shoenfeld, Yehuda; Langevitz, Pnina
The uveal tract represents the vascular organ of the eye. In addition to providing most of the blood supply to the intraocular structures, it acts as a conduit for immune cells, particularly lymphocytes, to enter the eye. Consequently, the uveal tract is represented in many intraocular inflammatory processes. Uveitis is probably a misnomer unless antigens within the uvea are the direct targets of the inflammatory process. A better term of the condition is "intraocular inflammation" (IOI). To review the presence of IOI in autoimmune diseases, the immunopathogenic mechanisms leading to disease, and treatment. We reviewed the English medical literature by using MEDLINE (1984-2003) employing the terms "uveitis," "intraocular inflammation," and "autoimmune diseases." An underlying autoimmune disease was identified in up to 40% of patients with IOI, and included spondyloarthropathies, Behcets disease, sarcoidosis, juvenile chronic arthritis, Vogt-Koyanagi-Harada syndrome (an inflammatory syndrome including uveitis with dermatologic and neurologic manifestations), immune recovery syndrome, and uveitis with tubulointerstitial disease. The immunopathogenesis of IOI involves enhanced T-cell response. Recently, guidelines for the use of immunosuppressive drugs for inflammatory eye disease were established and include: corticosteroids, azathioprine, methotrexate, mycophenolate mofetil, cyclosporine, tacrolimus, cyclophosphamide, and chlorambucil. New therapies with limited experience include the tumor necrosis factor alpha inhibitors, interferon alfa, monoclonal antibodies against lymphocyte surface antigens, intravenous immunoglobulin (IVIG), and the intraocular delivery of immunosuppressive agents. An underlying autoimmune disease was identified in up to 40% of patients with IOI. Immunosuppressive drugs, biologic agents, and IVIG are employed for the treatment of IOI in autoimmune diseases.
Cronin, Edmond M
Autoimmune hepatitis is a rare, chronic inflammatory disorder which has been associated with a number of other auto-immune conditions. However, there are no reports in the medical literature of an association with microscopic (lymphocytic) colitis. We report the case of a 53-year-old woman with several autoimmune conditions, including lymphocytic colitis, who presented with an acute hepatitis. On the basis of the clinical features, serology, and histopathology, we diagnosed autoimmune hepatitis. To our knowledge, this is the first report of autoimmune hepatitis in association with lymphocytic colitis, and lends support to the theory of an autoimmune etiology for lymphocytic colitis.
Zen, Yoh; Bogdanos, Dimitrios P; Kawa, Shigeyuki
Before the concept of autoimmune pancreatitis (AIP) was established, this form of pancreatitis had been recognized as lymphoplasmacytic sclerosing pancreatitis or non-alcoholic duct destructive chronic pancreatitis based on unique histological features. With the discovery in 2001 that serum IgG4 concentrations are specifically elevated in AIP patients, this emerging entity has been more widely accepted. Classical cases of AIP are now called type 1 as another distinct subtype (type 2 AIP) has been identified. Type 1 AIP, which accounts for 2% of chronic pancreatitis cases, predominantly affects adult males. Patients usually present with obstructive jaundice due to enlargement of the pancreatic head or thickening of the lower bile duct wall. Pancreatic cancer is the leading differential diagnosis for which serological, imaging, and histological examinations need to be considered. Serologically, an elevated level of IgG4 is the most sensitive and specific finding. Imaging features include irregular narrowing of the pancreatic duct, diffuse or focal enlargement of the pancreas, a peri-pancreatic capsule-like rim, and enhancement at the late phase of contrast-enhanced images. Biopsy or surgical specimens show diffuse lymphoplasmacytic infiltration containing many IgG4+ plasma cells, storiform fibrosis, and obliterative phlebitis. A dramatic response to steroid therapy is another characteristic, and serological or radiological effects are normally identified within the first 2 or 3 weeks. Type 1 AIP is estimated as a pancreatic manifestation of systemic IgG4-related disease based on the fact that synchronous or metachronous lesions can develop in multiple organs (e.g. bile duct, salivary/lacrimal glands, retroperitoneum, artery, lung, and kidney) and those lesions are histologically identical irrespective of the organ of origin. Several potential autoantigens have been identified so far. A Th2-dominant immune reaction and the activation of regulatory T-cells are assumed
Full Text Available Abstract Before the concept of autoimmune pancreatitis (AIP was established, this form of pancreatitis had been recognized as lymphoplasmacytic sclerosing pancreatitis or non-alcoholic duct destructive chronic pancreatitis based on unique histological features. With the discovery in 2001 that serum IgG4 concentrations are specifically elevated in AIP patients, this emerging entity has been more widely accepted. Classical cases of AIP are now called type 1 as another distinct subtype (type 2 AIP has been identified. Type 1 AIP, which accounts for 2% of chronic pancreatitis cases, predominantly affects adult males. Patients usually present with obstructive jaundice due to enlargement of the pancreatic head or thickening of the lower bile duct wall. Pancreatic cancer is the leading differential diagnosis for which serological, imaging, and histological examinations need to be considered. Serologically, an elevated level of IgG4 is the most sensitive and specific finding. Imaging features include irregular narrowing of the pancreatic duct, diffuse or focal enlargement of the pancreas, a peri-pancreatic capsule-like rim, and enhancement at the late phase of contrast-enhanced images. Biopsy or surgical specimens show diffuse lymphoplasmacytic infiltration containing many IgG4+ plasma cells, storiform fibrosis, and obliterative phlebitis. A dramatic response to steroid therapy is another characteristic, and serological or radiological effects are normally identified within the first 2 or 3 weeks. Type 1 AIP is estimated as a pancreatic manifestation of systemic IgG4-related disease based on the fact that synchronous or metachronous lesions can develop in multiple organs (e.g. bile duct, salivary/lacrimal glands, retroperitoneum, artery, lung, and kidney and those lesions are histologically identical irrespective of the organ of origin. Several potential autoantigens have been identified so far. A Th2-dominant immune reaction and the activation of
Autoimmune pancreatitis (AIP) is a rare disease, the pathophysiological understanding of which has been greatly improved over the last years. The most common form, type 1 AIP belongs to the IgG4-related diseases and must be distinguished from type 2 AIP, which is a much rarer entity associated with chronic inflammatory bowel disease. Clinically, there is an overlap with pancreatic cancer. Imaging and further criteria, such as serological and histological parameters are utilized for a differentiation between both entities in order to select the appropriate therapy and to avoid the small but ultimately unnecessary number of pancreatectomies. The diagnostics of AIP are complex, whereby the consensus criteria of the International Association of Pancreatology have become accepted as the parameters for discrimination. These encompass five cardinal criteria and one therapeutic criterion. By applying these criteria AIP can be diagnosed with a sensitivity of 84.9 %, a specificity of 100 % and an accuracy of 93.8 %. The diagnosis of AIP is accomplished by applying several parameters of which two relate to imaging. As for the routine diagnostics of the pancreas these are ultrasound, computed tomography (CT) and magnetic resonance imaging (MRI). Important for the differential diagnosis is the exclusion of signs of local and remote tumor spread for which CT and MRI are established. The essential diagnostic parameter of histology necessitates sufficient sample material, which cannot usually be acquired by a fine needle biopsy. CT or MRI are the reference standard methods for identification of the optimal puncture site and imaging-assisted (TruCut) biopsy. In patients presenting with unspecific upper abdominal pain, painless jaundice combined with the suspicion of a pancreatic malignancy in imaging but a mismatch of secondary signs of malignancy, AIP should also be considered as a differential diagnosis. As the diagnosis of AIP only partially relies on imaging radiologists also
Full Text Available Abstract 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.
Full Text Available Since the discovery of RNA interference (RNAi, excitement has grown over its potential therapeutic uses. Targeting RNAi pathways provides a powerful tool to change biological processes post-transcriptionally in various health conditions such as cancer or autoimmune diseases. Optimum design of shRNA, siRNA, and miRNA enhances stability and specificity of RNAi-based approaches whereas it has to reduce or prevent undesirable immune responses or off-target effects. Recent advances in understanding pathogenesis of autoimmune diseases have allowed application of these tools in vitro as well as in vivo with some degree of success. Further research on the design and delivery of effectors of RNAi pathway and underlying molecular basis of RNAi would warrant practical use of RNAi-based therapeutics in human applications. This review will focus on the approaches used for current therapeutics and their applications in autoimmune diseases, including rheumatoid arthritis and Sjögren’s syndrome.
Khan, Farah Aziz; Al-Jameil, Noura; Khan, Mohammad Fareed; Al-Rashid, May; Tabassum, Hajera
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.
Bosch, A.J.T.; Bolinger, B.; Keck, S.; Štěpánek, Ondřej; Ozga, A.J.; Galati-Fournier, V.; Stein, J.V.; Palmer, E.
Roč. 316, jaro (2017), s. 21-31 ISSN 0008-8749 R&D Projects: GA ČR GJ16-09208Y Institutional support: RVO:68378050 Keywords : T cell * Tolerance * Autoimmunity Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Immunology Impact factor: 3.172, year: 2016
Vanderlocht, Joris; van der Cruys, Mart; Stals, Frans; Bakker-Jonges, Liesbeth; Damoiseaux, Jan
Autoantibody detection for autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC) and autoimmune gastritis (AIG) is traditionally performed by IIF on a combination of tissues. Multiplex line/dot blots (LIA/DIA) offer multiple advantages, i.e. automation, objective reading, no interfering reactivities, no coincidental findings. In the current study we evaluated automated DIA (D-Tek) for detecting autoantibodies related to autoimmune diseases of the gastrointestinal tract. We tested samples of the Dutch EQC program and compared the results with the consensus of the participating labs. For the autoimmune liver diseases and AIG, respectively, 64 and 36 samples were tested. For anti-mitochondrial and anti-smooth muscle antibodies a concordance rate of 97% and 88% was observed, respectively. The concordance rate for anti-parietal cell antibodies was 92% when samples without EQC consensus (n=15) were excluded. For antibodies against intrinsic factor a concordance of 96% was observed. For all these antibodies discrepancies were identified that relate to the different test characteristics and the preponderance of IIF utilizing labs in the EQC program. In conclusion, we observed good agreement of the tested DIA blots with the consensus results of the Dutch EQC program. Taken together with the logistic advantages these blots are a good alternative for autoantibody detection in the respective diseases. A large prospective multicenter study is warranted to position these novel tests further in the whole spectrum of assays for the detection of these antibodies in a routine autoimmune laboratory. Copyright © 2017 Elsevier B.V. All rights reserved.
Autoimmune diseases are characterized by tissue damage and loss of function due to an immune response that is directed against specific organs. This review is focused on the role of impaired intestinal barrier function on autoimmune pathogenesis. Together with the gut-associated lymphoid tissue and the neuroendocrine network, the intestinal epithelial barrier, with its intercellular tight junctions, controls the equilibrium between tolerance and immunity to non-self antigens. Zonulin is the only physiologic modulator of intercellular tight junctions described so far that is involved in trafficking of macromolecules and, therefore, in tolerance/immune response balance. When the zonulin pathway is deregulated in genetically susceptible individuals, autoimmune disorders can occur. This new paradigm subverts traditional theories underlying the development of these diseases and suggests that these processes can be arrested if the interplay between genes and environmental triggers is prevented by re-establishing the zonulin-dependent intestinal barrier function. Both animal models and recent clinical evidence support this new paradigm and provide the rationale for innovative approaches to prevent and treat autoimmune diseases.
Full Text Available Vitiligo represents the most common cause of acquired skin, hair, and oral depigmentation, affecting 0.5–1% of the population worldwide. It is clinically characterized by the appearance of disfiguring circumscribed skin macules following melanocyte destruction by autoreactive cytotoxic T lymphocytes. Patients affected by vitiligo usually show a poorer quality of life and are more likely to suffer from depressive symptoms, particularly evident in dark-skinned individuals. Although vitiligo is a non-fatal disease, exposure of affected skin to UV light increases the chance of skin irritation and predisposes to skin cancer. In addition, vitiligo has been associated with other rare systemic disorders due to the presence of melanocytes in other body districts, such as in eyes, auditory, nervous, and cardiac tissues, where melanocytes are thought to have roles different from that played in the skin. Several pathogenetic models have been proposed to explain vitiligo onset and progression, but clinical and experimental findings point mainly to the autoimmune hypothesis as the most qualified one. In this context, it is of relevance the strong association of vitiligo with other autoimmune diseases, in particular with autoimmune thyroid disorders, such as Hashimoto thyroiditis and Graves’ disease. In this review, after a brief overview of vitiligo and its pathogenesis, we will describe the clinical association between vitiligo and autoimmune thyroid disorders and discuss the possible underlying molecular mechanism(s.
Vialettes, Bernard; Dubois-Leonardon, Noémie
Type 2 autoimmune polyendocrine syndromes (APS-2) are the most frequent disorders associating several organ-specific autoimmune diseases. Their high prevalence is due to the fact that the main manifestations of APS-2, such as thyroidal autoimmunity, type 1 diabetes, autoimmune gastric atrophy and vitiligo, are common diseases. APS-2 represents a clinical model that can serve to help unravel the mechanisms underlying autoimmunity. Diagnosis of APS-2 is a challenge for the clinician, especially in poorly symptomatic forms, and may require systematic screening based on measurement of autoantibodies and functional markers.
Full Text Available Laboratory testing is of great value when evaluating a patient with a suspected autoimmune disease. The results can confirm a diagnosis, estimate disease severity, aid in assessing prognosis and are useful to follow disease activity. Components of the laboratory exam include complete blood count with differential, comprehensive metabolic panel, inflammatory markers, autoantibodies, and flow cytometry. Currently, autoimmunity laboratories are very vibrant owing to the constant and increasing availability of new tests, mainly due to the detection of new autoantibodies. The main characteristic that differentiates the autoimmunity laboratory from other laboratories is the use of immunoassays such as enzyme-linked immunosorbent assay (ELISA, as basic techniques which determines antibodies (autoantibodies and not antigens. For this reason, immunoassay techniques must employ antigens as reagents. However, over the last few years, a significant trend at autoimmunity laboratories has been the gradual replacement of immunofluorescence microscopy by immunoassay. Nowadays the revolution of new technology has taken place significantly, for examples; recombinant DNA technology has allowed the production of large quantities of antigens for autoantibody analysis. Flow cytometry for the analysis of microsphere-based immunoassays allows the simultaneous measurement of several autoantibodies. In the same way, autoantigen microarrays provide a practical means to analyse biological fluids in the search for a high number of autoantibodies. We are now at the beginning of an era of multiplexed analysis, with a high capacity of autoantibody specificities. The future tendency in this field will include immunoassays with greater analytical sensitivity, specificity, simultaneous multiplexed capability, the use of protein microarrays, and the use of other technologies such as microfluidics.
Kamisawa, Terumi; Takuma, Kensuke; Hara, Seiichi; Tabata, Taku; Kuruma, Sawako; Inaba, Yoshihiko; Gopalakrishna, Rajesh; Egawa, Naoto; Itokawa, Fumihide; Itoi, Takao
Autoimmune pancreatitis (AIP) is a newly developed concept for a peculiar type of pancreatitis, and at present is recognized as a pancreatic lesion reflecting IgG4-related systemic disease. It is of utmost importance to differentiate AIP from pancreatic cancer to avoid unnecessary surgery. The current management strategies for AIP, including its clinical features, diagnostic criteria, clinical subtypes, steroid therapy and prognosis are discussed, based on our 66 AIP cases and papers searched in PubMed from 1992 to March 2011, using the term 'autoimmune pancreatitis'. A new clinicopathological entity, an 'IgG4-related sclerosing disease' is also mentioned. AIP should be considered in the differential diagnosis in elderly male patients presented with obstructive jaundice and pancreatic mass. Steroids are a standard therapy for AIP, but their regimen including maintenance therapy should be evaluated in prospective trials.
Full Text Available Research shows that autoimmune encephalitis is associated with sleep disorders. Paraneoplastic neurological syndrome (PNS with Ma2 antibodies can cause sleep disorders, particularly narcolepsy and rapid eye movement sleep behavior disorder (RBD. Limbic encephalitis (LE and Morvan syndrome, associated with voltage - gated potassium channel (VGKC-complex antibodies, which include leucine-rich glioma-inactivated 1 (LGI1 antibody and contactin-associated protein 2 (Caspr2, can result in profound insomnia and other sleep disorders. Central neurogenic hypoventilation are found in patients with anti-N-methyl-D-aspartate (NMDA receptor encephalitis, whereas obstructive sleep apnea (OSA, stridor and parasomnia are prominent features of encephalopathy associated with IgLON5 antibodies. Sleep disorders are cardinal manifestations in patients with autoimmune encephalitis. Immunotherapy possiblely can improve clinical symptoms and prognosis in a positive way. DOI: 10.3969/j.issn.1672-6731.2017.10.004
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
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. Copyright © 2012 Elsevier Ltd. All rights reserved.
Full Text Available Autoimmune diseases (AIDs are the result of specific immune responses directed against structures of the self. In normal conditions, the molecules recognized as “self” are tolerated by immune system, but when the self-tolerance is lost, the immune system could react against molecules from the body, causing the loss of self-tolerance, and subsequently the onset of AID that differs for organ target and etiology. Autoimmune thyroid disease (ATD is caused by the development of autoimmunity against thyroid antigens and comprises Hashimoto’s thyroiditis and Graves disease. They are frequently associated with other organ or non-organ specific AIDs, such as myasthenia gravis (MG. In fact, ATD seems to be the most associated pathology to MG. The etiology of both diseases is multifactorial and it is due to genetic and environmental factors, and each of them has specific characteristics. The two pathologies show many commonalities, such as the organ-specificity with a clear pathogenic effect of antibodies, the pathological mechanisms, such as deregulation of the immune system and the implication of the genetic predisposition. They also show some differences, such as the mode of action of the antibodies and therapies. In this review that focuses on ATD and MG, the common features and the differences between the two diseases are discussed.
Full Text Available Introduction. Isolated pancreatic and peripancreatic tuberculosis is a challenging diagnosis due to its rarity and variable presentation. Pancreatic tuberculosis can mimic pancreatic carcinoma. Similarly, autoimmune pancreatitis can appear as a focal lesion resembling pancreatic malignancy. Endoscopic ultrasound-guided fine needle aspiration provides an effective tool for differentiating between benign and malignant pancreatic lesions. The immune processes involved in immunoglobulin G4 related systemic diseases and tuberculosis appear to have some similarities. Case Report. We report a case of a 59-year-old Southeast Asian male who presented with fever, weight loss, and obstructive jaundice. CT scan revealed pancreatic mass and enlarged peripancreatic lymph nodes. Endoscopic ultrasound-guided fine needle aspiration confirmed the presence of mycobacterium tuberculosis. Patient also had high immunoglobulin G4 levels suggestive of autoimmune pancreatitis. He was started on antituberculosis medications and steroids. Clinically, he responded to treatment. Follow-up imaging showed findings suggestive of chronic pancreatitis. Discussion. Pancreatic tuberculosis and autoimmune pancreatitis can mimic pancreatic malignancy. Accurate diagnosis is imperative as unnecessary surgical intervention can be avoided. Endoscopic ultrasound-guided fine needle aspiration seems to be the diagnostic test of choice for pancreatic masses. Long-term follow-up is warranted in cases of chronic pancreatitis.
LIMA, LUIZ H.; GREENBERG, JONATHAN P.; GREENSTEIN, VIVIENNE C.; SMITH, R. THEODORE; SALLUM, JULIANA M. F.; THIRKILL, CHARLES; YANNUZZI, LAWRENCE A.; TSANG, STEPHEN H.
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
Lopomo, Angela; Berrih-Aknin, Sonia
Autoimmune diseases (AIDs) are the result of specific immune responses directed against structures of the self. In normal conditions, the molecules recognized as “self” are tolerated by immune system, but when the self-tolerance is lost, the immune system could react against molecules from the body, causing the loss of self-tolerance, and subsequently the onset of AID that differs for organ target and etiology. Autoimmune thyroid disease (ATD) is caused by the development of autoimmunity against thyroid antigens and comprises Hashimoto’s thyroiditis and Graves disease. They are frequently associated with other organ or non-organ specific AIDs, such as myasthenia gravis (MG). In fact, ATD seems to be the most associated pathology to MG. The etiology of both diseases is multifactorial and it is due to genetic and environmental factors, and each of them has specific characteristics. The two pathologies show many commonalities, such as the organ-specificity with a clear pathogenic effect of antibodies, the pathological mechanisms, such as deregulation of the immune system and the implication of the genetic predisposition. They also show some differences, such as the mode of action of the antibodies and therapies. In this review that focuses on ATD and MG, the common features and the differences between the two diseases are discussed. PMID:28751878
E. A. Potrokhova
Full Text Available The review discusses the effect of vitamin D on the tolerogenic modulation of an immune response, its relationship to cells of the monocyte-macrophage series, including dendritic cells, monocytes, and macrophages, in the context of the impact of the expression of anti-inflammatory proinflammatory cytokines in some autoimmune diseases (rheumatoid arthritis, systemic scleroderma, multiple sclerosis, type 1 diabetes mellitus, systemic lupus erythematosus, and Crohn`s disease. It discusses the role of vitamin D in the development of innate and adaptive immunity. Despite some conflicting evidence, the immune regulatory function of vitamin D is generally directed toward inhibition of the components of innate and acquired immunity, which are responsible for the induction of autoimmune reactions; in this connection there are a growing number of publications devoted to the issues of vitamin D supplementation in patients with autoimmune diseases, the preventive effect of vitamin D intake on the risk of an abnormality and that of therapeutic doses of the vitamin on its course. The maintenance of the threshold value for serum 25(OHD3 at least 30 ng/ml, which is achieved by the intake of about 2000 IU of vitamin D, is shown to be required for its immune regulatory function. The data given raise the question as to whether it is necessity to revise the Russian recommended daily dietary allowances for vitamin D through its infant food fortification.
Schneider, Alexander; Michaely, Henrik; Rückert, Felix; Weiss, Christel; Ströbel, Philipp; Belle, Sebastian; Hirth, Michael; Wilhelm, Torsten J; Haas, Stephan L; Jesenofsky, Ralf; Schönberg, Stefan; Marx, Alexander; Singer, Manfred V; Ebert, Matthias P; Pfützer, Roland H; Löhr, J Matthias
We had developed the Unifying-Autoimmune-Pancreatitis-Criteria (U-AIP) to diagnose autoimmune pancreatitis (AiP) within the M-ANNHEIM classification of chronic pancreatitis. In 2011, International-Consensus-Diagnostic-Criteria (ICDC) to diagnose AiP have been published. We had applied the U-AIP long before the ICDC were available. The aims of the study were, first, to describe patients with AiP diagnosed by the U-AIP; second, to compare diagnostic accuracies of the U-AIP and other diagnostic systems; third, to evaluate the clinical applicability of the U-AIP. From 1998 until 2008, we identified patients with AiP using U-AIP, Japanese-, Korean-, Asian-, Mayo-HISORt-, Revised-Mayo-HISORt- and Italian-criteria. We retrospectively verified the diagnosis by ICDC and Revised-Japanese-2011-criteria, compared diagnostic accuracies of all systems and evaluated all criteria in consecutive patients with pancreatitis (2009 until 2010, Pancreas-Outpatient-Clinic-Cohort, n = 84). We retrospectively validated our diagnostic approach in consecutive patients with a pancreatic lesion requiring surgery (Surgical-Cohort, n = 98). Overall, we identified 21 patients with AiP. Unifying-Autoimmune-Pancreatitis-Criteria and ICDC presented the highest diagnostic accuracies (each 98.8%), highest Youden indices (each 0.95238), and highest proportions of diagnosed patients (each n = 20/21, U-AIP/ICDC vs. other diagnostic systems, p Pancreatitis-Criteria revealed a satisfactory clinical applicability and offered an additional approach to diagnose AiP. Copyright © 2017 IAP and EPC. Published by Elsevier B.V. All rights reserved.
Full Text Available The occurrence of three or more autoimmune disorders in one patient defines multiple autoimmune syndrome. The pathogenesis of multiple autoimmune syndrome is not known yet and environmental triggers and genetic susceptibility have been suggested to be involved. Herein, we report a 47-year-old woman who had Hashimoto’s thyroiditis, vitiligo and newly diagnosed ulcerative colitis. Diagnosis of ulcerative colitis was confirmed with histopathologic examination. This case presents a new combination of multiple autoimmune syndrome.
Eaton, William W.; Rose, N.R.; Kalaydijan, A.
An epidemiologic study of the autoimmune diseases taken together has not been done heretofore. The National Patient Register of Denmark is used to estimate the population prevalence of 31 possible or probable autoimmune diseases. Record linkage is used to estimate 465 pairwise co-morbidities in i......An epidemiologic study of the autoimmune diseases taken together has not been done heretofore. The National Patient Register of Denmark is used to estimate the population prevalence of 31 possible or probable autoimmune diseases. Record linkage is used to estimate 465 pairwise co...
Full Text Available Artem Minalyan,1 Jihane N Benhammou,1 Aida Artashesyan,1 Michael S Lewis,2 Joseph R Pisegna1 1Division of Gastroenterology, Hepatology and Parenteral Nutrition, 2Department of Pathology and Laboratory Medicine, VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA Abstract: At present there is no universally accepted classification for gastritis. The first successful classification (The Sydney System that is still commonly used by medical professionals was first introduced by Misiewicz et al in Sydney in 1990. In fact, it was the first detailed classification after the discovery of Helicobacter pylori by Warren and Marshall in 1982. In 1994, the Updated Sydney System was proposed during the International Workshop on the Histopathology of Gastritis followed by the publication in The American Journal of Surgical Pathology by Dixon et al. Using the new classification, distinction between atrophic and nonatrophic gastritis was revised, and the visual scale grading was incorporated. According to the Updated Sydney System Classification, atrophic gastritis is categorized into multifocal (H. pylori, environmental factors, specific diet and corpus-predominant (autoimmune. Since metaplasia is a key histological characteristic in patients with atrophic gastritis, it has been recommended to use the word “metaplastic” in both variants of atrophic gastritis: autoimmune metaplastic atrophic gastritis (AMAG and environmental metaplastic atrophic gastritis. Although there are many overlaps in the course of the disease and distinction between those two entities may be challenging, the aim of this review article was to describe the etiology, epidemiology, pathogenesis, diagnosis, clinical manifestations and treatment in patients with AMAG. However, it is important to mention that H. pylori is the most common etiologic factor for the development of gastritis in the world. Keywords: autoimmune gastritis, pernicious anemia, gastric carcinoid
Full Text Available The study of autoimmunity mediated by immunoglobulin E (IgE autoantibodies, which may be termed autoallergy, is in its infancy. It is now recognized that systemic lupus erythematosus, bullous pemphigoid (BP, and chronic urticaria, both spontaneous and inducible, are most likely to be mediated, at least in part, by IgE autoantibodies. The situation in other conditions, such as autoimmune uveitis, rheumatoid arthritis, hyperthyroid Graves’ disease, autoimmune pancreatitis, and even asthma, is far less clear but evidence for autoallergy is accumulating. To be certain of an autoallergic mechanism, it is necessary to identify both IgE autoantibodies and their targets as has been done with the transmembrane protein BP180 and the intracellular protein BP230 in BP and IL-24 in chronic spontaneous urticaria. Also, IgE-targeted therapies, such as anti-IgE, must have been shown to be of benefit to patients as has been done with both of these conditions. This comprehensive review of the literature on IgE-mediated autoallergy focuses on three related questions. What do we know about the prevalence of IgE autoantibodies and their targets in different diseases? What do we know about the relevance of IgE autoantibodies in different diseases? What do we know about the cellular and molecular effects of IgE autoantibodies? In addition to providing answers to these questions, based on a broad review of the literature, we outline the current gaps of knowledge in our understanding of IgE autoantibodies and describe approaches to address them.
Full text: Immunoglobulin G4-related disease was recognized as a systemic disease since various extrapancreatic lesions were observed in patients with autoimmune pancreatitis (AIP). The real etiology and pathogenesis of IgG4-RD is still not clearly understood. Moreover the exact role of IgG4 or IgG4-positive plasma cells in this disease has not yet been elucidated. only some inconsistent biological features such as hypergammaglobulinemia or hypocomplementemia support the autoimmune nature of the disease process. various names have been ascribed to this clinicopathological entity including IgG4-related sclerosing disease, IgG4-related systemic sclerosing disease, IgG4-related disease, IgG4-related autoimmune disease, hyper-IgG4 disease and IgG4-related systemic disease. The extrapancreatic lesions of IgG4-RD also exhibit the same characteristic histologic features including dense lymphoplasmacytic infiltrate, massive storiform fibrosis, and obliterative phlebitis as seen in IgG4-related pancreatitis. Abdominal manifestations include the following organs/systems: Bile ducts: Sclerosing cholangitis; Gallbladder and liver: Acalculous sclerosis cholecytitis with diffuse wall thickening; hepatic inflammatory pseudotumorts; Kidneys: round or wedge-shaped renal cortical nodules, peripheral cortical; lesions, mass like lesions or renal pelvic involvement; Prostate, urethra, seminal vesicle, vas deferens, uterine cervix; Autoimmune prostatitis; Retroperitoneum: Retroperitoneal fibrosis. thin or mildly thick homogeneous soft tissue lesion surrounding the abdominal aorta and its branches but also bulky masses causing hydronephroureterosis; Mesentery: Sclerosing mesenteritis usually involving the root of the mesentery; Bowel: Inflammatory bowel diseases mimicking Crohn’s disease or ulcerative colitis. various types of sclerosing nodular lesions of the bowel wall; Stomach: Gastritis, gastric ulcers and focal masses mimicking submucosal tumor; omentum: Infiltration mimicking
Roshini Sarah Abraham
Full Text Available 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 CD21low 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.
Wiebolt, Janneke; Koeleman, Bobby P C; van Haeften, Timon W
The endocrine system is a frequent target in pathogenic autoimmune responses. Type 1 diabetes and autoimmune thyroid disease are the prevailing examples. When several diseases cluster together in one individual, the phenomenon is called autoimmune polyglandular syndrome. Progress has been made in understanding the genetic factors involved in endocrine autoimmune diseases. Studies on monogenic autoimmune diseases such as autoimmune polyglandular syndrome type 1, immunodysregulation, polyendocrinopathy, enteropathy, X-linked and primary immune deficiencies helped uncover the role of key regulators in the preservation of immune tolerance. Alleles of the major histocompatibility complex have been known to contribute to the susceptibility to most forms of autoimmunity for more than 3 decades. Furthermore, sequencing studies revealed three non-major histocompatibility complex loci and some disease specific loci, which control T lymphocyte activation or signalling. Recent genome-wide association studies (GWAS) have enabled acceleration in the identification of novel (non-HLA) loci and hence other relevant immune response pathways. Interestingly, several loci are shared between autoimmune diseases, and surprisingly some work in opposite direction. This means that the same allele which predisposes to a certain autoimmune disease can be protective in another. Well powered GWAS in type 1 diabetes has led to the uncovering of a significant number of risk variants with modest effect. These studies showed that the innate immune system may also play a role in addition to the adaptive immune system. It is anticipated that next generation sequencing techniques will uncover other (rare) variants. For other autoimmune disease (such as autoimmune thyroid disease) GWAS are clearly needed. © 2010 The Authors. European Journal of Clinical Investigation © 2010 Stichting European Society for Clinical Investigation Journal Foundation.
Full Text Available Autoimmune diseases are known to have association with each other but it is very rare to see multiple autoimmune diseases in one patient. The combination of at least three autoimmune diseases in the same patient is referred to as multiple autoimmune syndrome. The case we are reporting features multiple autoimmune syndrome with five different conditions. The patient had type 1 diabetes mellitus, autoimmune hemolytic anemia, systemic lupus erythematosus, vitiligo, and psoriasis. Psoriasis has rarely been reported previously under the spectrum of autoimmune syndrome. Although the relationship of autoimmune conditions with each other has been explored in the past, this case adds yet another dimension to the unique evolution of autoimmune pathologies. The patient presented with a combination of five autoimmune diseases, which makes it consistent type three multiple autoimmune syndromes with the addition of psoriasis. The current case is unique in this aspect that the combination of these five autoimmune disorders has never been reported in the past.
Full Text Available 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.
Full Text Available The autoimmune thyroid diseases (AITD are complex diseases which are caused by an interaction between susceptibility genes and environmental triggers. Genetic susceptibility in combination with external factors (e.g. dietary iodine is believed to initiate the autoimmune response to thyroid antigens. Abundant epidemiological data, including family and twin studies, point to a strong genetic influence on the development of AITD. Various techniques have been employed to identify the genes contributing to the etiology of AITD, including candidate gene analysis and whole genome screening. These studies have enabled the identification of several loci (genetic regions that are linked with AITD, and in some of these loci, putative AITD susceptibility genes have been identified. Some of these genes/loci are unique to Graves' disease (GD and Hashimoto's thyroiditis (HT and some are common to both the diseases, indicating that there is a shared genetic susceptibility to GD and HT. The putative GD and HT susceptibility genes include both immune modifying genes (e.g. HLA, CTLA-4 and thyroid specific genes (e.g. TSHR, Tg. Most likely, these loci interact and their interactions may influence disease phenotype and severity.
Andersen, Yuki M.F.; Egeberg, Alexander; Gislason, Gunnar H.
Background An increased susceptibility to autoimmune disease has been shown in patients with atopic dermatitis (AD), but data remain scarce and inconsistent. Objective We examined the co-occurrence of selected autoimmune diseases in adult patients with AD. Methods Nationwide health registers were...
... common in particular ethnic groups? Genetic Changes The cause of autoimmune Addison disease is complex and not completely understood. A combination ... is not caused by an autoimmune reaction. Other causes include infections that ... adrenal glands. Addison disease can also be one of several features of ...
Espejo, C.; Penkowa, Milena; Saez-Torres, I.
Neurobiology, experimental autoimmune encephalomyelitis IFN-d, multiple sclerosis, neurodegeneration, oxidative stress......Neurobiology, experimental autoimmune encephalomyelitis IFN-d, multiple sclerosis, neurodegeneration, oxidative stress...
Johnson, Matthew B; Hattersley, Andrew T; Flanagan, Sarah E
The most common endocrine diseases, type 1 diabetes, hyperthyroidism, and hypothyroidism, are the result of autoimmunity. Clustering of autoimmune endocrinopathies can result from polygenic predisposition, or more rarely, may present as part of a wider syndrome due to a mutation within one of seven genes. These monogenic autoimmune diseases show highly variable phenotypes both within and between families with the same mutations. The average age of onset of the monogenic forms of autoimmune endocrine disease is younger than that of the common polygenic forms, and this feature combined with the manifestation of other autoimmune diseases, specific hallmark features, or both, can inform clinicians as to the relevance of genetic testing. A genetic diagnosis can guide medical management, give an insight into prognosis, inform families of recurrence risk, and facilitate prenatal diagnoses. Copyright © 2016 Elsevier Ltd. All rights reserved.
Jørgensen, Kristian T; Rostgaard, Klaus; Bache, Iben
OBJECTIVE: In terms of number of X chromosomes, women with Turner's syndrome cytogenetically resemble men. An increased risk of autoimmune diseases has been observed among women with Turner's syndrome. This study was undertaken to investigate whether the autoimmune disease profile in women...... with Turner's syndrome is characterized by diseases with a female or male predominance. METHODS: Using the Danish Cytogenetic Central Register, the Danish National Patient Register, and the Danish Civil Registration System, we estimated relative risk of 46 different autoimmune diseases in a cohort of 798...... Danish women with Turner's syndrome followed up for 12,461 person-years between 1980 and 2004. Standardized incidence ratios (SIRs) of first hospitalization for autoimmune disease and 95% confidence intervals (95% CIs) were used as measures of relative risk. RESULTS: The overall risk of autoimmune...
Batool F. Kirmani
Full Text Available Status epilepticus is a neurological emergency with increased morbidity and mortality. Urgent diagnosis and treatment are crucial to prevent irreversible brain damage. In this mini review, we will discuss the recent advances in the diagnosis and treatment of autoimmune status epilepticus (ASE, a rare form of the disorder encountered in the intensive care unit. ASE can be refractory to anticonvulsant therapy and the symptoms include subacute onset of short-term memory loss with rapidly progressive encephalopathy, psychiatric symptoms with unexplained new-onset seizures, imaging findings, CSF pleocytosis, and availability of antibody testing makes an earlier diagnosis of ASE possible. Neuroimmunomodulatory therapies are the mainstay in the treatment of ASE. The goal is to maximize the effectiveness of anticonvulsant agents and find an optimal combination of therapies while undergoing immunomodulatory therapy to reduce morbidity and mortality.
John J. Miles
Full Text Available Helminths have evolved to become experts at subverting immune surveillance. Through potent and persistent immune tempering, helminths can remain undetected in human tissues for decades. Redirecting the immunomodulating “talents” of helminths to treat inflammatory human diseases is receiving intensive interest. Here, we review therapies using live parasitic worms, worm secretions, and worm-derived synthetic molecules to treat autoimmune disease. We review helminth therapy in both mouse models and clinical trials and discuss what is known on mechanisms of action. We also highlight current progress in characterizing promising new immunomodulatory molecules found in excretory/secretory products of helminths and their potential use as immunotherapies for acute and chronic inflammatory diseases.
Full Text Available A young female presented with bilateral subacute onset of progressive decrease in night vision and reduced peripheral field of vision. The short duration and rapid progression of symptoms along with the lack of family history of night blindness prompted a diagnosis of autoimmune retinopathy (AIR. Fundus fluorescein angiography, optical coherence tomography, visual fields, and electroretinogram were suggestive of AIR. A differential diagnosis of retinitis pigmentosa (RP was also made. Antiretinal autoantibodies were detected in the blood sample. Treatment was with oral steroids and subsequently oral immunosuppressive agents. Visual acuity was maintained, fundus examination reverted to normal, and investigations repeated at every visit were stable with improvement in visual fields. Our case suggests that AIR, if diagnosed early and treated appropriately, may have a good outcome and should be considered in patients with an atypical presentation of RP.
Ghiringhelli, Paolo; Chelazzi, Paolo; Chelazzi, Giovanni; Bellintani, Claudio; Rania, Simone
The present case report refers to a multiorgan autoimmune disease manifesting following thymectomy performed for a benign thymoma. This disease is characterized by hypothyroidism, severe myasthenia, polymyositis and alopecia which are organ-specific diseases probably with a different time of onset but which are all an expression of the same immunopathologic process occurring in individuals who have a genetic predisposition. Characteristic of the present case is not only the association of the different immunopathologic clinical pictures but also the rather difficult differential diagnosis between a hypothyroidism-related myopathy and polymyositis. It was possible to formulate the diagnosis by integrating the results of clinical and laboratory evaluation with the therapeutic outcome. The onset of the syndrome was attributed to the withdrawal, following surgery, of the inhibitory effects of the thymoma on some clones of autoreactive lymphocytes.
Rodrigo Oliveira Moreira
Full Text Available CONTEXT: Insulin autoimmune syndrome (IAS, Hirata disease is a rare cause of hypoglycemia in Western countries. It is characterized by hypoglycemic episodes, elevated insulin levels, and positive insulin antibodies. Our objective is to report a case of IAS identified in South America. CASE REPORT: A 56-year-old Caucasian male patient started presenting neuroglycopenic symptoms during hospitalization due to severe trauma. Biochemical evaluation confirmed hypoglycemia and abnormally high levels of insulin. Conventional imaging examinations were negative for pancreatic tumor. Insulin antibodies were above the normal range. Clinical remission of the episodes was not achieved with verapamil and steroids. Thus, a subtotal pancreatectomy was performed due to the lack of response to conservative treatment and because immunosuppressants were contraindicated due to bacteremia. Histopathological examination revealed diffuse hypertrophy of beta cells. The patient continues to have high insulin levels but is almost free of hypoglycemic episodes.
Longhi, Maria Serena; Ma, Yun; Mieli-Vergani, Giorgina; Vergani, Diego
The histological lesion of interface hepatitis, with its dense portal cell infiltrate consisting of lymphocytes, monocytes/macrophages and plasma cells, was the first to suggest an autoaggressive cellular immune attack in the pathogenesis of autoimmune hepatitis (AIH). Immunohistochemical studies, focused on the phenotype of inflammatory cells infiltrating the liver parenchyma, have shown a predominance of alphabeta-T cells. Amongst these cells, the majority have been CD4 helper/inducers, while a sizeable minority have consisted of CD8 cytotoxic/suppressors. Lymphocytes on non-T cell lineage included natural killer cells, monocytes/macrophages and B lymphocytes. For autoimmunity to arise, the self-antigenic peptide, embraced by an human leukocyte antigen (HLA) class II molecule, must be presented to an uncommitted T helper (T(H)0) lymphocyte by professional antigen-presenting cells. Once activated and according to the presence in the milieu of interleukin 12 (IL-12) or IL-4, T(H)0 lymphocytes can differentiate into T(H)1 cells, which are pivotal to macrophage activation; enhance HLA class I expression, rendering liver cells vulnerable to CD8 T-cell attack; and induce HLA class II expression on hepatocytes; or they can differentiate into T(H)2 cells, which produce IL-4, IL-10 and IL-13, cytokines favouring autoantibody production by B lymphocytes. Autoantigen recognition is tightly controlled by regulatory mechanisms, such as those exerted by CD4+CD25(high) regulatory T cells. Numerical and functional regulatory T cell impairment characterises AIH and permits the perpetuation of effector immune responses with ensuing persistent liver destruction. Advances in the study of autoreactive T cells stem mostly from AIH type 2, where the main autoantigen, cytochrome P450IID6 (CYP2D6), is known to enable characterisation of antigen-specific immune responses. Copyright 2010 S. Karger AG, Basel.
Silva, Clovis A; Cocuzza, Marcello; Borba, Eduardo F; Bonfá, Eloísa
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.
Silva, C A; Cocuzza, M; Carvalho, J F; Bonfá, E
Autoimmune orchitis is characterized by testis inflammation and the presence of specific antisperm antibodies (ASA). It is classified in two categories. Primary autoimmune orchitis is defined by infertility and asymptomatic orchitis associated with ASA (100%) directed to the basement membrane or seminiferous tubules in infertile men, without any systemic disease and usually asymptomatic. Secondary autoimmune orchitis is characterized by symptomatic orchitis and/or testicular vasculiti`s associated with a systemic autoimmune disease, particularly vasculitis. These patients typically demonstrate testicular pain, erythema and/or swelling. ASA in secondary autoimmune orchitis have been reported in up to 50% of patients, especially in systemic lupus erythematosus patients. The pathogenesis of primary as well as secondary autoimmune orchitis is still unknown. Although the etiology is likely to be multifactorial, testicular inflammation, infection or trauma may induce T cell response with pro-inflammatory cytokine production with a consequent blood-testis-barrier permeability alteration, ASA production and apoptosis of spermatocytes and spermatids. ASA is known to cause immobilization and/or agglutination of spermatozoa, which may block sperm-egg interaction resulting in infertility. Assisted reproduction has been used as an efficient option in primary cases and immunosuppressive therapy for secondary autoimmune orchitis, although there is no double-blind, randomized trial to confirm the efficacy of any treatment regimens for these conditions. Copyright © 2014 Elsevier B.V. All rights reserved.
Vassilatou, E; Papadavid, E; Papastamatakis, P; Alexakos, D; Koumaki, D; Katsimbri, P; Hadjidakis, D; Dimitriadis, G; Rigopoulos, D
Common autoimmune diseases tend to coexist in the same patients. Few studies have examined the possible association between autoimmune thyroiditis and psoriasis or psoriatic arthritis (PsA), with inconsistent results. To investigate the prevalence of autoimmune thyroiditis in psoriatic patients with or without PsA, living in an iodine-sufficient area. We studied prospectively, 114 psoriatic patients with disease duration of 5-38 years, 30 of them with PsA, and 286 age- and body mass index (BMI)-matched subjects without psoriasis or known thyroid disease or autoimmune disease. A detailed medical history was obtained from all participants and clinical examination and laboratory evaluation was performed. Psoriasis severity was assessed with Psoriasis Area and Severity Index (PASI). Autoimmune thyroiditis was defined by the presence of positive autoantibodies to thyroid peroxidase and/or thyroglobulin. There was no difference in the prevalence of autoimmune thyroiditis between psoriatic patients and controls (20.2% vs. 19.6%). The prevalence of autoimmune thyroiditis in male and female psoriatic patients was similar (9.6% and 10.5% respectively), in contrast to the increased, as expected, prevalence in female vs. male controls (14.7% vs. 4.9%, P thyroiditis were similar in psoriatic patients and controls (7.9% and 7.0% respectively). Autoimmune thyroiditis in psoriatic patients was not related with age of psoriasis onset, psoriasis duration, PASI score, PsA and obesity. These data support that psoriatic patients with or without PsA do not have an increased risk for autoimmune thyroiditis. © 2016 European Academy of Dermatology and Venereology.
Zerwas, Stephanie; Larsen, Janne Tidselbak; Petersen, Liselotte
higher hazards of eating disorders for children and adolescents with autoimmune or autoinflammatory diseases: 36% higher hazard for anorexia nervosa, 73% for bulimia nervosa, and 72% for an eating disorder not otherwise specified. The association was particularly strong in boys. Parental autoimmune...... or autoinflammatory disease history was associated with significantly increased odds for anorexia nervosa (odds ratio [OR] = 1.13, confidence interval [CI] = 1.01-1.25), bulimia nervosa (OR = 1.29; CI = 1.08-1.55) and for an eating disorder not otherwise specified (OR = 1.27; CI = 1.13-1.44). CONCLUSIONS: Autoimmune...
Chew, Fiona L M; Tajunisah, Iqbal
To describe a case of retinal phlebitis associated with autoimmune hemolytic anemia. Observational case report. A 44-year-old Indian man diagnosed with autoimmune hemolytic anemia presented with a 1-week history of blurred vision in both eyes. Fundus biomicroscopy revealed bilateral peripheral retinal venous sheathing and cellophane maculopathy. Fundus fluorescent angiogram showed bilateral late leakage from the peripheral venous arcades and submacular fluid accumulation. The retinal phlebitis resolved following a blood transfusion and administration of systemic steroids. Retinopathy associated with autoimmune hemolytic anemia is not well known. This is thought to be the first documentation of retinal phlebitis occurring in this condition.
Full Text Available Chikungunya infection has recently re-emerged as an important arthropod-borne disease in Thailand. Recently, Southern Thailand was identified as a potentially endemic area for the chikungunya virus. Here, we report a case of severe musculoskeletal complication, presenting with muscle weakness and swelling of the limbs. During the investigation to exclude autoimmune muscular inflammation, high titers of antinuclear antibody were detected. This is the report of autoimmunity detection associated with an arbovirus infection. The symptoms can mimic autoimmune polymyositis disease, and the condition requires close monitoring before deciding to embark upon prolonged specific treatment with immunomodulators.
like autoimmune thyroiditis, celiac disease and ulcerative colitis, with about 25% having cirrhosis at ... to immunosuppressive therapy. Keywords: Autoimmune hepatitis, Autoimmune liver disease, Chronic liver disease, Nigeria ... who is also exposed to environmental triggering factors.2,5,8 Subsequently, the autoimmune.
M.J. van Heerde (Marianne)
textabstractAutoimmune pancreatitis (AIP) is the pancreatic manifestation of a systemic fibro- inflammatory disease, characterized by infiltration with lymphoplasmacytic cells and extensive fibrosis, which leads to morphological changes (swelling, mass forming) and organ dysfunction. Often, but
Janelle C. Waite
Full Text Available The proinflammatory activity of T helper 17 (Th17 cells can be beneficial to the host during infection. However, uncontrolled or inappropriate Th17 activation has been linked to several autoimmune and autoinflammatory pathologies. Indeed, preclinical and clinical data show that Th17 cells are associated with several autoimmune diseases such as arthritis, multiple sclerosis, psoriasis, and lupus. Furthermore, targeting the interleukin-17 (IL-17 pathway has attenuated disease severity in preclinical models of autoimmune diseases. Interestingly, a recent report brings to light a potential role for Th17 cells in the autoinflammatory disorder adult-onset Still's disease (AOSD. Whether Th17 cells are the cause or are directly involved in AOSD remains to be shown. In this paper, we discuss the biology of Th17 cells, their role in autoimmune disease development, and in AOSD in particular, as well as the growing interest of the pharmaceutical industry in their use as therapeutic targets.
inflammatory response; rather, autoimmune response would keep affecting decreased heart function in. RHD patients who ... untreated children. Nearly 30 - 45 % of the affected children could ..... Technology Department of Anhui Province (PR.
Saini, Vandana; Gupta, Mamta; Mishra, S K
Auto-immune hepatitis first presenting in the early postpartum period is rare. Immunosuppressive effects of pregnancy result in delayed manifestation of auto-immune hepatitis, and in established cases, the spontaneous improvements are there. Auto-immune hepatitis should be considered in the differential diagnosis of liver dysfunction first presenting in the early postpartum period. A case of postpartum hepatitis of auto-immune aetiology is being presented here. It is disease of unknown aetiology, characterised by inflammation of liver (as evidenced by raised serum transaminases, presence of interface hepatitis on histological examination), hypergammaglobulinaemia (> 1.5 times normal), presence of auto-antibodies [(antinuclear antibodies (ANA)], smooth muscle antibody (SMA) and antibody to liver-kidney microsome type 1 (LKM1) in the absence of viral markers ie, hepatitis B (HBsAg) and C (AntiHCV) and excellent response to corticosteroid therapy.
Nepom, Gerald T; Gebe, John A
The CD4+ T cell response is critical for cellular autoimmunity in human T1D, but incomplete understanding of issues of specific cell frequency, avidity, function, and correlation with disease status presents...
Allelein, S; Feldkamp, J; Schott, M
Autoimmune diseases of the thyroid gland are considered to be the most frequent cause of thyroid gland disorders. Autoimmune thyroid diseases consist of two subgroups: autoimmune thyroiditis (AIT) and Graves' disease. The AIT is the most common human autoimmune disease. Infiltration of the thyroid gland with cytotoxic T‑cells can lead to an initial thyrotoxicosis und during the course to hypothyroidism due to destruction of the thyroid gland. Substitution with Levothyroxine is indicated for manifest hypothyroidism and subclinical hypothyroidism with increased thyroid antibodies with the intention of normalizing the serum thyroid stimulating hormone (TSH). Graves' disease is characterized by the appearance of stimulating TSH receptor antibodies leading to hyperthyroidism. Endocrine ophthalmopathy may also occur. Ablative therapy with radioiodine therapy or thyroidectomy is administered to patients with Graves' disease without remission after at least 1 year of antithyroid drug therapy.
Hessa Al Buainain
Full Text Available Anetoderma is a rare elastolytic disorder characterized by circumscribed areas of flaccid skin due to the loss of elastic tissue in the dermis. Primary anetoderma is frequently observed in patients with autoimmune diseases or abnormalities especially with antiphospholipid antibodies with or without antiphospholipid syndrome. In this case report we discuss a patient with primary anetoderma with positive antithyroid peroxidase antibodies, which is consistent with autoimmune thyroiditis.
Larsen, Finn Stolze
Autoimmune hepatitis (AIH) is a progressive inflammatory diseases of unknown origin that is characterised by a necro-inflammatory and fibrotic process and may result in liver failure or uncompensated liver cirrhosis. Normally AIH is responsive to immunosuppressive therapy, and treatment aims...... and tacrolimus) might salvage patients from transplantation. Mycophenolate mofetil may also improve liver tests and reduce the requirement for corticosteroids. Besides, sirolimus is effective for treatment of de novo autoimmune hepatitis that sometimes develops after liver transplantation. Initial experience...
Ni Choileain, Niamh
Approximately 20% of the population is affected by autoimmune or inflammatory diseases mediated by an abnormal immune response. A characteristic feature of autoimmune disease is the selective targeting of a single cell type, organ or tissue by certain populations of autoreactive T-cells. Examples of such diseases include rheumatoid arthritis, insulin-dependent diabetes mellitus, and systemic lupus erythematosus (SLE), all of which are characterized by chronic inflammation, tissue destruction and target organ malfunction. Although strong evidence links most autoimmune diseases to specific genes, considerable controversy prevails regarding the role of regulatory T-cell populations in the disease process. These cells are now also believed to play a key role in mediating transplantation tolerance and inhibiting the induction of tumor immunity. Though the concept of therapeutic immune regulation aimed at treating autoimmune pathology has been validated in many animal models, the development of strategies for the treatment of human autoimmune disorders remains in its infancy. The main obstacles to this include the conflicting findings of different model systems, as well as the contrasting functions of regulatory T-cells and cytokines involved in the development of such disorders. This review examines the role of regulatory T-cells in the pathogenesis of autoimmunity and describes the therapeutic potential of these cells for the prevention of immune-mediated pathologies in the future. Although much remains to be learned about such pathologies, a clearer understanding of the mechanisms by which regulatory T-cells function will undoubtedly lead to exciting new possibilities for immunotherapeutics.
Full Text Available The idea that infectious agents can induce autoimmune diseases in genetically susceptible subjects has been a matter of discussion for years. Moreover, increased incidence of autoimmune diseases and introduction of prophylactic vaccinations from early childhood suggest that these two trends are linked. In the medical literature and even non-professional media, case reports or events temporally related to vaccination are reported. It raises the issue of vaccination safety. In everyday practice medical professionals, physicians, rheumatologists and other specialists will be asked their opinion of vaccination safety. The decision should be made according to evidence-based medicine and the current state of knowledge. The purpose of this paper is to discuss a potential mechanism which links infections, vaccinations and autoimmunity. We present an overview of published case reports, especially of systemic connective tissue diseases temporally related to vaccination and results from case-nested studies. As yet, no conclusive evidence supports a causal relationship between vaccination and autoimmune diseases. It has to be determined whether the performed studies are sufficiently Epsteinasensitive to detect the link. The debate is ongoing, and new data may be required to explain the pathogenesis of autoimmunity. We would like to underscore the need for prophylactic vaccination in patients with autoimmune rheumatic diseases and to break down the myth that the vaccines are contraindicated in this target group.
Full Text Available Increasing evidences have pointed out the relevance of Natural Killer (NK cells in organ specific and systemic autoimmune diseases. NK cells bear a plethora of activating and inhibiting receptors that can play a role in regulating reactivity with autologous cells. The activating receptors recognize natural ligands upregulated on virus-infected or stressed or neoplastic cells. Of note, several autoimmune diseases are thought to be linked to viral infections as one of the first event in inducing autoimmunity. Also, it is conceivable that autoimmunity can be triggered when a dysregulation of innate immunity occurs, activating T and B lymphocytes to react with self-components. This would imply that NK cells can play a regulatory role during adaptive immunity; indeed, innate lymphoid cells (ILC, comprising the classical CD56+ NK cells, have a role in maintaining or alterating tissue homeostasis secreting protective and/or proinflammatory cytokines. In addition, NK cells display activating receptors involved in natural cytotoxicity and the activating isoforms of receptors for HLA class I that can interact with healthy host cells and induce damage without any evidence of viral infection or neoplastic-induced alteration. In this context, the interrelationship among ILC, extracellular matrix components and mesenchymal stromal cells can be considered a key point for the control of homeostasis. Herein, we summarize evidences for a role of NK cells in autoimmune diseases and will give a point of view of the interplay between NK cells and self-cells in triggering autoimmunity.
Witkowska-Sędek, Ewelina; Borowiec, Ada; Kucharska, Anna; Chacewicz, Karolina; Rumińska, Małgorzata; Demkow, Urszula; Pyrżak, Beata
Turner syndrome is associated with increased incidence of autoimmune diseases, especially those of the thyroid gland. The aim of this study was to assess the prevalence of thyroid autoimmunity among pediatric patients with Turner syndrome. The study was retrospective and included 41 girls with Turner syndrome aged 6-18 years. Free thyroxine (FT4), thyroid stimulating hormone (TSH), anti-thyroid peroxidase (TPO-Ab) antibodies, anti-thyroglobulin (TG-Ab) antibodies, and karyotype were investigated. The correlation between karyotype and incidence of thyroid autoimmunity was also examined. Eleven patients (26.8%) were positive for TPO-Ab and/or TG-Ab. Three girls from that subgroup were euthyroid, 5 had subclinical hypothyroidism, and 3 were diagnosed with overt hypothyroidism. Out of these 11 patients affected by thyroid autoimmunity, 6 girls had mosaic karyotype with X-isochromosome (n = 4) or with deletions (n = 2), and 5 had the 45,X karyotype. The study findings confirmed a high incidence of thyroid autoimmunity in girls with Turner syndrome, but we failed to observe an association between the incidence of thyroid autoimmunity and karyotype. We conclude that it is important to monitor thyroid function in patients with Turner syndrome because they are prone to develop hypothyroidism.
Ordookhani, Arash; Burman, Kenneth D
There are contradictory results on the effect of hypothyroidism on the changes in hemostasis. Inadequate population-based studies limited their clinical implications, mainly on the risk of venous thromboembolism (VTE). This paper reviews the studies on laboratory and population-based findings regarding hemostatic changes and risk of VTE in hypothyroidism and autoimmune thyroid disorders. A comprehensive literature search was conducted employing MEDLINE database. The following words were used for the search: Hypothyroidism; thyroiditis, autoimmune; blood coagulation factors; blood coagulation tests; hemostasis, blood coagulation disorders; thyroid hormones; myxedema; venous thromboembolism; fibrinolysis, receptors thyroid hormone. The papers that were related to hypothyroidism and autoimmune thyroid disorder and hemostasis are used in this review. Overt hypothyroidism is more associated with a hypocoagulable state. Decreased platelet count, aggregation and agglutination, von Willebrand factor antigen and activity, several coagulation factors such as factor VIII, IX, XI, VII, and plasminogen activator-1 are detected in overt hypothyrodism. Increased fibrinogen has been detected in subclinical hypothyroidism and autoimmune thyroid disease rendering a tendency towards a hypercoagulability state. Increased factor VII and its activity, and plasminogen activator inhibitor-1 are among several findings contributing to a prothrombotic state in subclinical hypothyroidism. Overt hypothyroidism is associated with a hypocoagulable state and subclinical hypothyroidism and autoimmune thyroid disorders may induce a prothrombotic state. However, there are contradictory findings for the abovementioned thyroid disorders. Prospective studies on the risk of VTE in various levels of hypofunctioning of the thyroid and autoimmune thyroid disorders are warranted.
Loddo, Italia; Romano, Claudio; Cutrupi, Maria Concetta; Sciveres, Marco; Riva, Silvia; Salpietro, Annamaria; Ferraù, Valeria; Gallizzi, Romina; Briuglia, Silvana
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. Copyright © 2015 Elsevier Masson SAS. All rights reserved.
Krátký, Jan; Jiskra, Jan
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.
Marcus Mottershead; James Neuberger
Liver transplantation remains an effective treatment for those with end-stage disease and with intractable liver-related symptoms.The shortage of organs for transplantation has resulted in the need for rationing.A variety of approaches to selection and allocation have been developed and vary from country to country.The shortage of donors has meant that new approaches have to be adopted to make maximal use of the available organs;these include splitting grafts,use of extended criteria livers,livers from nonheart-beating donors and from living donors.Post transplantation, most patients will need life-long immunosuppression,although a small proportion can have immunosuppression successfully withdrawn.Newer immunosuppressive drugs and different strategies may allow a more targeted approach with a reduction in sideeffects and so improve the patient and graft survival.For autoimmune diseases, transplantation is associated with significant improvement in the quality and length of life.Disease may recur after transplantation and may affect patient and graft survival.
Antibodies against various neural surface antigens induce cognitive impairments. Anti-VGKC (voltage gated potassium channel) complex antibodies are well known as one of the causative autoantibodies. An anti-VGKC antibody was identified as the autoantibody in acquired neuromyotonia (Isaacs' syndrome), which causes muscle cramps and difficulty in opening the palm of the hands. However, this antibody also tests positive in autoimmune limbic encephalitis, which has a subacute progress and causes poor memory or epilepsy attacks. Typical cases have a distinctive adult-onset, frequent, brief dystonic seizure semiology that predominantly affects the arms and ipsilateral face. It has now been termed faciobrachial dystonic seizures. In recent years, the true target antigens of the anti-VGKC antibody of this VGKC limbic encephalitis have been recognized as leucine rich glioma inactivated protein (LGI)-1 and others. These antibodies to amnesia-related LGI-1 in limbic encephalitis neutralize the LGI-1-ADAM22 (an anchor protein) interaction and reduce synaptic AMPA receptors. There have been reports of limbic encephalitis associated with anti-VGKC complex antibodies mimicking Creutzfeldt-Jakob disease (CJD). Less than 2% of the patients with sporadic CJD (sCJD) develop serum anti-VGKC complex antibodies and, when positive, only at low titres. Low titres of these antibodies occur only rarely in suspected patients with sCJD, and when present, should be interpreted with caution.
Watt, Torquil; Bjørner, Jakob; Grønvold, Mogens
PURPOSE: To evaluate the relationship between thyroid variables and health-related quality of life (QoL) in patients with autoimmune hypothyroidism, using the thyroid-specific QoL questionnaire ThyPRO. METHODS: In a cross-sectional study, responses to the ThyPRO from 199 outpatients with autoimmune...
Flavia Di Bari
Full Text Available The year following parturition is a critical time for the de novo appearance or exacerbation of autoimmune diseases, including autoimmune thyroid disease. The vast majority of postpartum thyroid disease consists of postpartum thyroiditis (PPT and the minority by Graves’ disease and non-autoimmune thyroiditis. PPT has a worldwide prevalence ranging from 1 to 22% and averaging 5% based on a review published in 2012. Several factors confer risk for the development of PPT. Typically, the clinical course of PPT is characterized by three phases: thyrotoxic, hypothyroid, and euthyroid phase. Approximately half of PPT women will have permanent hypothyroidism. The best humoral marker for predictivity, already during the first trimester of gestation, is considered positivity for thyroperoxidase autoantibodies (TPOAb, though only one-third to half of such TPOAb-positive pregnant women will develop PPT. Nutraceuticals (such as selenium or omega-3-fatty acid supplements seem to have a role in prevention of PPT. In a recent study on pregnant women with stable dietary habits, we found that the fish consumers had lower rates of positivity (and lower serum levels of both TPOAb and thyroglobulin Ab compared to meat eaters. Finally, we remind the reader of other diseases that can be observed in the postpartum period, either autoimmune or non-autoimmune, thyroid or non-thyroid.
Muratori, Paolo; Granito, Alessandro; Quarneti, Chiara; Ferri, Silvia; Menichella, Rita; Cassani, Fabio; Pappas, Georgios; Bianchi, Francesco B; Lenzi, Marco; Muratori, Luigi
Autoimmune hepatitis affects mainly women. It is subdivided into type 1 and type 2 according to the autoantibody profile and without immunosuppression usually evolves to cirrhosis and end-stage liver failure. We evaluated clinical, biochemical, immunological and genetic features and treatment response of 163 consecutive Italian patients with autoimmune hepatitis. At diagnosis, type 1 autoimmune hepatitis showed more inflamed liver histology and more pronounced cholestasis, whereas type 2 was more common in children. Male and female patients shared similar clinical, biochemical and immunological features. Of 89 patients with 5-year follow-up or longer, 23 patients irrespective of presenting clinical, biochemical and immunological features achieved complete remission (normal transaminases and gammaglobulin levels) which was maintained with minimal steroid dosage; attempt at treatment withdrawal led to disease exacerbation. Complete responders had more often HLA DRB1*0401 (p = 0.011) and their risk of disease progression was lower (p < 0.0001). Type 1 and type 2 autoimmune hepatitis is one and the same disease. Autoimmune hepatitis has similar features in male and female patients. HLA DRB1*0401 positive patients are more likely to achieve complete remission. Continuous low-dose steroids are necessary to maintain remission, significantly reducing the risk of disease progression.
Carabotti, Marilia; Lahner, Edith; Esposito, Gianluca; Sacchi, Maria Carlotta; Severi, Carola; Annibale, Bruno
Abstract Autoimmune gastritis is often suspected for its hematologic findings, and rarely the diagnosis is made for the presence of gastrointestinal symptoms. Aims of this cross-sectional study were to assess in a large cohort of patients affected by autoimmune gastritis the occurrence and the pattern of gastrointestinal symptoms and to evaluate whether symptomatic patients are characterized by specific clinical features. Gastrointestinal symptoms of 379 consecutive autoimmune gastritis patients were systematically assessed and classified following Rome III Criteria. Association between symptoms and anemia pattern, positivity to gastric autoantibodies, Helicobacter pylori infection, and concomitant autoimmune disease were evaluated. In total, 70.2% of patients were female, median age 55 years (range 17–83). Pernicious anemia (53.6%), iron deficiency anemia (34.8%), gastric autoantibodies (68.8%), and autoimmune disorders (41.7%) were present. However, 56.7% of patients complained of gastrointestinal symptoms, 69.8% of them had exclusively upper symptoms, 15.8% only lower and 14.4% concomitant upper and lower symptoms. Dyspepsia, subtype postprandial distress syndrome was the most represented, being present in 60.2% of symptomatic patients. Univariate and multivariate analyses showed that age gastritis is associated in almost 60% of cases with gastrointestinal symptoms, in particular dyspepsia. Dyspepsia is strictly related to younger age, no smoking, and absence of anemia. PMID:28072728
Coati, Irene; Fassan, Matteo; Farinati, Fabio; Graham, David Y; Genta, Robert M; Rugge, Massimo
Western countries are seeing a constant decline in the incidence of Helicobacter pylori-associated gastritis, coupled with a rising epidemiological and clinical impact of autoimmune gastritis. This latter gastropathy is due to autoimmune aggression targeting parietal cells through a complex interaction of auto-antibodies against the parietal cell proton pump and intrinsic factor, and sensitized T cells. Given the specific target of this aggression, autoimmune gastritis is typically restricted to the gastric corpus-fundus mucosa. In advanced cases, the oxyntic epithelia are replaced by atrophic (and metaplastic) mucosa, creating the phenotypic background in which both gastric neuroendocrine tumors and (intestinal-type) adenocarcinomas may develop. Despite improvements in our understanding of the phenotypic changes or cascades occurring in this autoimmune setting, no reliable biomarkers are available for identifying patients at higher risk of developing a gastric neoplasm. The standardization of autoimmune gastritis histology reports and classifications in diagnostic practice is a prerequisite for implementing definitive secondary prevention strategies based on multidisciplinary diagnostic approaches integrating endoscopy, serology, histology and molecular profiling. PMID:26576102
Full Text Available Objective: To report first-hand narrative experience of autoimmune encephalitis and to briefly review currently available evidence of autoimmune encephalitis in cancer patients treated with immune checkpoint inhibitors. Setting: A case study is presented on the management of a patient who developed autoimmune encephalitis during nivolumab monotherapy occurring after 28 weeks on anti-PD-1 monotherapy (nivolumab 3 mg/kg every 2 weeks for non-small cell lung cancer. Results: No substantial improvement was observed by antiepileptic treatment. After administration of 80 mg methylprednisolone, neurologic symptoms disappeared within 24 h and the patient fully recovered. Conclusions: Immune checkpoint inhibitor treatment can lead to autoimmune encephalitis. Clinical trial data indicate a frequency of autoimmune encephalitis of ≥0.1 to <1% with a higher probability during combined or sequential anti-CTLA-4/anti-PD-1 therapy than during anti-PD-1 or anti-PD-L1 monotherapy. Further collection of evidence and translational research is warranted.
Nacu, Aliona; Andersen, Jintana Bunpan; Lisnic, Vitalie; Owe, Jone Furlund; Gilhus, Nils Erik
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
Juarez A S Quaresma
Full Text Available Human T-lymphotropic virus type-1 (HTLV-1 infection is associated with adult T-cell leukemia/lymphoma (ATL. Tropical spastic paraparesis/HTLV-1-associated myelopathy (PET/HAM is involved in the development of autoimmune diseases including Rheumatoid Arthritis (RA, Systemic Lupus Erythematosus (SLE, and Sjögren’s Syndrome (SS. The development of HTLV-1-driven autoimmunity is hypothesized to rely on molecular mimicry, because virus-like particles can trigger an inflammatory response. However, HTLV-1 modifies the behavior of CD4+ T cells on infection and alters their cytokine production. A previous study showed that in patients infected with HTLV-1, the activity of regulatory CD4+ T cells and their consequent expression of inflammatory and anti-inflammatory cytokines are altered. In this review, we discuss the mechanisms underlying changes in cytokine release leading to the loss of tolerance and development of autoimmunity.
Full Text Available Autoimmune cholangitis (AIC was first described in 1987 as immunocholangitis in three women who presented with signs and symptoms of primary biliary cholangitis (PBC, but who were antimitochondrial (AMA negative and antinuclear antibodies (ANA positive, and responded to immunosuppressive therapy with azathioprine and prednisolone (1. AIC is a rare chronic cholestatic inflammatory disease characterized by the presence of high ANA or smooth muscle antibodies (SMA but AMA seronegativity. Histologically, AIC exhibits bile duct injury (2. In terms of therapeutics, in addition to response to ursodeoxycholic acid, a prompt response to corticosteroids has also been reported in earlier stages, distinguishing it from PBC. Herein the authors describe two cases with mixed signs of PBC and autoimmune hepatitis (AIH. The diagnostic differentiation between these diseases (AIC, PBC and AIH is essential because of the different therapeutic strategies. Our cases highlight the importance of clinician awareness of the autoimmune spectrum of liver diseases.
Chavez-Tapia, Norberto C; Martinez-Salgado, Julio; Granados, Julio; Uribe, Misael; Tellez-Avila, Felix I
AIM: To describe the outcome and prognosis in a cohort of patients with acute liver failure due to autoimmune hepatitis without liver transplantation. METHODS: A retrospective trial was conducted in 11 patients with acute liver failure due to autoimmune hepatitis who attended the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubiran. Demographic, biochemical and severity indexes, and treatment and outcome were assessed. RESULTS: Among the 11 patients, with a median age of 31 years, 72% had inflammatory response syndrome, and six patients received corticosteroids. The mortality rate within four weeks was 56%, and the one-year survival was 27%. In the survivors, severity indexes were lower and 83% received corticosteroids. CONCLUSION: We observed a relatively high survival rate in patients with acute liver failure due to autoimmune hepatitis. This survival rate could be influenced by severity of the disease and/or use of corticosteroids. PMID:17465474
Marder, Wendy; Littlejohn, Emily A
The autoimmune connective tissue diseases predominantly affect women and often occur during the reproductive years. Thus, specialized issues in pregnancy planning and management are commonly encountered in this patient population. This chapter provides a current overview of pregnancy as a risk factor for onset of autoimmune disease, considerations related to the course of pregnancy in several autoimmune connective tissue diseases, and disease management and medication issues before and during pregnancy and the postpartum period. A major theme that has emerged across these inflammatory diseases is that active maternal disease during pregnancy is associated with adverse pregnancy outcomes, and that maternal and fetal health can be optimized when conception is planned during times of inactive disease and through maintaining treatment regimens compatible with pregnancy. PMID:27421217
Full Text Available Cholangiocarcinoma (CCA is a very aggressive and lethal tumor, which arises from the epithelial cells of bile ducts. CCA comprises about 3% of all gastrointestinal malignancies and its incidence is on the rise in the recent years. Anatomically, it is classified into intrahepatic, perihilar, or extrahepatic (distal CCA. There are a number of risk factors associated with CCA including primary sclerosing cholangitis, fibropolycystic liver disease, parasitic infection, viral hepatitis, chronic liver disease, and genetic disorders like Lynch syndrome. Autoimmune hepatitis is also recently reported to have an association with development of CCA. We report an interesting case of perihilar CCA in the setting of autoimmune hepatitis along with a literature review. This case highlights the importance of early treatment and close clinical follow-up of patients with autoimmune hepatitis for development of CCA.
Our understanding of the pathogenic mechanisms and possible treatments of autoimmune diseases has significantly increased over the past decade. Nonetheless, numerous major issues remain open and such issues span from epidemiology to clinimetrics and from the role of infectious agents to the search for accurate biomarkers in paradigmatic conditions such as systemic lupus erythematosus, rheumatoid arthritis, and spondyloarthropathies. In the case of cardiovascular comorbidities of autoimmune diseases or, more generally, the pathogenesis of atherosclerosis, fascinating evidence points to a central role of autoimmunity and metabolic dysfunctions and a possible role of therapies targeting inflammation to ameliorate both conditions. Basic science and translational medicine contribute to identify common mechanisms that underlie different autoimmune diseases, as in the case of tumor necrosis factor alpha, and more recently vitamin D, autoantibodies, T and B regulatory cells, and microRNA. Finally, new therapies are expected to significantly change our approach to autoimmune diseases, as represented by the recent FDA approval of the first oral JAK inhibitor. The present article moves from the major topics that were discussed at the 2013 Asian Congress of Autoimmunity in Hong Kong to illustrate the most recent data from leading journals in autoimmunity and immunology. Copyright © 2014 Elsevier B.V. All rights reserved.
Rugge, M; Fassan, M; Pizzi, M; Zorzetto, V; Maddalo, G; Realdon, S; De Bernard, M; Betterle, C; Cappellesso, R; Pennelli, G; de Boni, M; Farinati, F
Among Western populations, the declining incidence of Helicobacter pylori infection coincides with a growing clinical impact of autoimmune gastritis. To describe the histological phenotype of autoimmune gastritis, also to test the prognostic impact of OLGA staging in the autoimmune setting. A single-institutional series (spanning the years 2003-2011) of 562 consecutive patients (M:F ratio: 1:3.7; mean age = 57.6 ± 14.4 years) with serologically confirmed autoimmune gastritis underwent histology review and OLGA staging. Helicobacter pylori infection was ascertained histologically in 44/562 cases (7.8%). Forty six biopsy sets (8.2%) featured OLGA stages III-IV; they included all four cases of incidental epithelial neoplasia (three intraepithelial and one invasive; three of these four cases had concomitant H. pylori infection). There were 230 (40.9%) and 139 (24.7%) cases, respectively, of linear and micro-nodular enterochromaffin-like cell hyperplasia; 19 (3.4%) type I carcinoids were detected. The series included 116 patients who underwent repeated endoscopy/biopsy sampling (mean time elapsing between the two procedures = 54 months; range 24-108). Paired histology showed a significant (P = 0.009) trend towards a stage progression [the stage increased in 25/116 cases (22%); it remained unchanged in 87/116 cases (75%)]. In autoimmune gastritis, the cancer risk is restricted to high-risk gastritis stages (III-IV), and is associated mainly with concomitant H. pylori infection. OLGA staging consistently depicts the time-dependent organic progression of the autoimmune disease and provides key information for secondary gastric cancer prevention strategies. © 2012 Blackwell Publishing Ltd.
Thieblemont, Nathalie; Wright, Helen L; Edwards, Steven W; Witko-Sarsat, Véronique
Human neutrophils have great capacity to cause tissue damage in inflammatory diseases via their inappropriate activation to release reactive oxygen species (ROS), proteases and other tissue-damaging molecules. Furthermore, activated neutrophils can release a wide variety of cytokines and chemokines that can regulate almost every element of the immune system. In addition to these important immuno-regulatory processes, activated neutrophils can also release, expose or generate neoepitopes that have the potential to break immune tolerance and result in the generation of autoantibodies, that characterise a number of human auto-immune diseases. For example, in vasculitis, anti-neutrophil cytoplasmic antibodies (ANCA) that are directed against proteinase 3 or myeloperoxidase are neutrophil-derived autoantigens and activated neutrophils are the main effector cells of vascular damage. In other auto-immune diseases, these neutrophil-derived neoepitopes may arise from a number of processes that include release of granule enzymes and ROS, changes in the properties of components of their plasma membrane as a result of activation or apoptosis, and via the release of Neutrophil Extracellular Traps (NETs). NETs are extracellular structures that contain chromatin that is decorated with granule enzymes (including citrullinated proteins) that can act as neo-epitopes to generate auto-immunity. This review therefore describes the processes that can result in neutrophil-mediated auto-immunity, and the role of neutrophils in the molecular pathologies of auto-immune diseases such as vasculitis, rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). We discuss the potential role of NETs in these processes and some of the debate in the literature regarding the role of this phenomenon in microbial killing, cell death and auto-immunity. Copyright © 2016 Elsevier Ltd. All rights reserved.
Böröcz, Katalin; Hayden, Zsófia; Mészáros, Viktória; Csizmadia, Zsuzsanna; Farkas, Kornélia; Kellermayer, Zoltán; Balogh, Péter; Nagy, Ferenc; Berki, Tímea
The role of autoimmune responses against central nervous system (CNS) antigens in encephalitis presenting with non-classified neurologic or psychiatric symptoms has been appreciated in the past decade. Paraneoplastic limbic encephalitis has a poor prognosis and is most commonly associated with lung, ovarium, and testicular neoplasms, leading to immune reactions against intracellular antigens (anti-Hu/ANNA1, anti-Ri/ANNA2, anti-CV2/CRMP5 and anti-Ma2/Ta). In contrast, the recently described autoimmune encephalitis subtypes present with a broad spectrum of symptoms, respond to autoimmune therapies well and usually associate with autoantibodies against neuronal cell surface receptors (NMDAR, GABA B R, AMPAR) or synaptic proteins (LGI1, CASPR2). Our aim is to bring to awareness the increasing number of autoimmune encephalitis patients requiring neurologic, psychiatric and intensive care and to emphasize the significance of detecting various autoantibodies in diagnosing patients. In the past 6 years, our laboratory received 836 autoimmune encephalitis diagnostic test requests from a total of 717 patients. Serum and cerebrospinal fluid (CSF) samples were analysed with indirect immunofluorescence using a BIOCHIP consisting of cell lines transfected with 6 different receptor proteins. IgG autoantibodies against receptor proteins were present in 7.5% of patients. The frequency of positive samples was the following: NMDAR > LGI1 > GABA B R > CASPR2. Detecting autoantibodies facilitates the diagnosis of autoimmune encephalitis in an early stage. Patients diagnosed early can be effectively treated with plasmapheresis and immunosuppressive drugs. The efficiency of therapies can be monitored by autoantibody detection. Therefore, the diagnostic immune laboratory plays an important role in proper diagnosis and in the prevention of rapidly progressing symptoms. Orv Hetil. 2018; 159(3): 107-112.
Mieli-Vergani, Giorgina; Vergani, Diego; Baumann, Ulrich; Czubkowski, Piotr; Debray, Dominique; Dezsofi, Antal; Fischler, Björn; Gupte, Girish; Hierro, Loreto; Indolfi, Giuseppe; Jahnel, Jörg; Smets, Françoise; Verkade, Henkjan J; Hadžić, Nedim
Paediatric autoimmune liver disease is characterised by inflammatory liver histology, circulating autoantibodies and increased levels of IgG, in the absence of a known etiology. Three conditions have a likely autoimmune pathogenesis: autoimmune hepatitis (AIH), autoimmune sclerosing cholangitis
Magyari, Melinda; Koch-Henriksen, Nils; Pfleger, Claudia C
BACKGROUND: The female preponderance in incidence of multiple sclerosis (MS) calls for investigations into sex differences in comorbidity with other autoimmune diseases (ADs). OBJECTIVES: To determine whether male and female patients with MS have a higher frequency of autoimmune comorbidity than...... controls, and to describe the type and frequency of ADs that are associated with MS. METHODS: Our database was established by linkage of the Danish MS Registry to The Danish National Patient Register and consisted of 1403 patients of both sexes with clinical onset of MS between 2000 and 2004, and 25...
Conclusions: Among Japanese vitiligo patients, there is a subgroup with strong evidence of genetically determined susceptibility to not only vitiligo, but also to autoimmune thyroid disease and other autoimmune disorders.
Donia, Marco; Pedersen, Magnus; Svane, Inge Marie
Patients with preexisting active autoimmune disorders were excluded from clinical trials of immune checkpoint inhibitors. However, patients with autoimmune disorders are diagnosed with cancer at least as frequently as the global population, and clinicians treating patients outside clinical trials...
... Facebook Twitter Home Health Conditions APECED Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy Printable PDF Open All Close All ... view the expand/collapse boxes. Description Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy ( APECED ) is an inherited condition that ...
Waage, J. E.; Kreiner-Møller, E.; Standl, M.
Parallel increases in allergy and autoimmune disease prevalence in recent time suggest shared, but yet unknown, etiologies. Here, we investigated shared genetic loci and molecular pathways to identify possible shared disease mechanisms between allergy and autoimmune diseases.......Parallel increases in allergy and autoimmune disease prevalence in recent time suggest shared, but yet unknown, etiologies. Here, we investigated shared genetic loci and molecular pathways to identify possible shared disease mechanisms between allergy and autoimmune diseases....
Segal, Yahel; Dahan, Shani; Sharif, Kassem; Bragazzi, Nicola Luigi; Watad, Abdulla; Amital, Howard
Autoimmune Syndrome Induced by Adjuvant (ASIA) is a definition aimed to describe the common etiological process at the root of five clinical entities sharing similar symptomatology: macrophagic myofasciitis syndrome (MMF), Gulf War Syndrome (GWS), sick building syndrome (SBS), siliconosis, and post vaccination autoimmune phenomena. ASIA illustrates the role of environmental immune stimulating agents, or adjuvants, in the instigation of complex autoimmune reactions among individuals bearing a genetic preponderance for autoimmunity. The value of ASIA lies first in the acknowledgment it provides for patients suffering from these as yet ill-defined medical conditions. Equally important is the spotlight it sheds for further research of these poorly understood conditions sharing a common pathogenesis. In this article we elaborate on the significance of ASIA, review the current evidence in support of the syndrome, and address recent reservations raised regarding its validity. Copyright © 2018 Elsevier B.V. All rights reserved.
van den Berg, AP
Background: Autoimmune hepatitis (AIH) is a chronic necro-inflammatory disease of the liver. Early recognition is important in order to prevent the development of cirrosis. This review discusses recent developments in the fields of diagnosis, pathophysiology and management of AIH. Methods: Relevant
Garra, V.; Danese, N.; Rebella, M.
The diagnosis of systemic autoimmune diseases is carried out by combining clinical, paraclinical, imaging and anatomopathological data. However, in many cases is necessary to access other guiding parameters. The capillaroscopy is a technique that consists in the observation of capillary microcirculation in the proximal nail fold hands. The methods used are the videocapillaroscopy (microscopy, stereoscopic)
Leeuw, Karina de
Systemic autoimmune diseases such as systemic lupus erythematosus (SLE) and Wegener’s granulomatosis (WG) are associated with a significantly increased prevalence of cardiovascular disease (CVD) compared to age- and sex-matched controls. Many risk factors are involved in the pathogenesis of
Volta, Umberto; Rodrigo, Luis; Granito, Alessandro; Petrolini, Nunzio; Muratori, Paolo; Muratori, Luigi; Linares, Antonio; Veronesi, Lorenza; Fuentes, Dolores; Zauli, Daniela; Bianchi, Francesco B
In this study, serological screening for celiac disease (CD) was performed in patients with autoimmune cholestasis to define the prevalence of such an association and to evaluate the impact of gluten withdrawal on liver disease associated with gluten sensitive enteropathy. Immunoglobulin A endomysial, human and guinea pig tissue transglutaminase antibodies, and immunoglobulin A and G gliadin antibodies were sought in 255 patients with primary biliary cirrhosis, autoimmune cholangitis, and primary sclerosing cholangitis. Immunoglobulin A endomysial and human tissue transglutaminase antibodies were positive in nine patients (seven primary biliary cirrhosis, one autoimmune cholangitis, and one primary sclerosing cholangitis), whose duodenal biopsy results showed villous atrophy consistent with CD. Two of these patients had a malabsorption syndrome, and one had iron-deficiency anemia. Clinical and biochemical signs of cholestasis did not improve after gluten withdrawal in the three patients with severe liver disease. A longer follow-up of the six celiac patients with mild liver damage is needed to clarify whether gluten restriction can contribute to slow down the progression of liver disease. The high prevalence of CD (3.5%) in autoimmune cholestasis suggests that serological screening for CD should be routinely performed in such patients by immunoglobulin A endomysial or human tissue transglutaminase antibodies.
Poulsen, L O; Tage-Jensen, U; Vyberg, M
A retrospective study concerning ten patients with autoimmune hepatitis (AiH), diagnosed during a 2 1/2-year period is presented. The age of the patients ranged from 25 to 82 years and nine of the patients were women. Their symptoms included jaundice, pruritus, fever, anorexia and fatigue during...
22, IL-23, TNF-α and TGF-β) were determined. We used the immunoenzymatic technology to assess the titer of cytokines. We found that there was no significant variation of TNF-α level in normal controls and autoimmune diseases ...
Prummel, Mark F.; Strieder, Thea; Wiersinga, Wilmar M.
Genetic factors play an important role in the pathogenesis of autoimmune thyroid disease (AITD) and it has been calculated that 80% of the susceptibility to develop Graves' disease is attributable to genes. The concordance rate for AITD among monozygotic twins is, however, well below I and
Hoekstra, PJ; Kallenberg, CGM; Korf, J; Minderaa, RB
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
Bovin, Lone Frier; Brynskov, Jørn; Hegedüs, Laszlo
A central issue in autoimmune disease is whether the underlying inflammation is a repeated stereotypical process or whether disease specific gene expression is involved. To shed light on this, we analysed whether genes previously found to be differentially regulated in rheumatoid arthritis (RA...
Vitfell-Pedersen, Joanna; Jørgensen, Marianne Hørby; Müller, Klaus
Autoimmune hepatitis (AIH) in childhood is a progressive chronic inflammatory liver disease. The aim of this study was to compare the clinical and biochemical characteristics of 33 paediatric patients diagnosed as having AIH with earlier described cohorts, and to examine the effect of early...
who presented with an acute auto-immune haemolytic anaemia. In addition to a persistently positive Coombs test, with specific red cell auto-antibodies, the acidified serum test and the sucrose haemolysis test were repeatedly positive. CASE REPORT. A 24-year-old Indian woman was admitted to hospital in. July 1969.
Krarup, Therese; Hagen, Claus
A 66-year-old man with a headache in the left temporal region which had persisted for eight months is presented. The patient developed polydipsia and polyuria and also suffered from tinnitus, impaired hearing and episodes of double vision. The patient was diagnosed with autoimmune hypophysitis (AH...
Ferraz, Carolina; Paschke, Ralf
Hyperthyroidism is a clinical state that results from high thyroid hormone levels which has multiple etiologies, manifestations, and potential therapies. Excluding the autoimmune Graves disease, autonomic adenomas account for the most import cause of non-autoimmune hyperthyroidism. Activating germline mutations of the TSH receptor are rare etiologies for hyperthyroidism. They can be inherited in an autosomal dominant manner (familial or hereditary, FNAH), or may occur sporadically as a de novo condition, also called: persistent sporadic congenital non-autoimmune hyperthyroidism (PSNAH). These three conditions: autonomic adenoma, FNAH and PSNAH constitute the inheritable and sporadic non-autoimmune hyperthyroidism. Particularities in epidemiology, etiology, molecular and clinical aspects of these three entities will be discussed in this review in order to guide to an accurate diagnosis allowing among others genetic counseling and presymptomatic diagnosis for the affected families. The optimal treatment based on the right diagnosis will avoid consequences of a persistent or relapsing hyperthyroidism. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.
Hoekstra, P; Limburg, P; Kallenberg, C; Minderaa, R; Battistin, L
Tourette's syndrome is a childhood-onset neuropsychiatric disorder characterized by the presence of both multiple motor and vocal tics. While its pathogenesis at a molecular and cellular level remains unknown, recent research findings point to the possible involvement of autoimmunity in at least a
Grayson, Peter C.; Sloan, J. Mark; Niles, John L.; Monach, Paul A.; Merkel, Peter A.
Objectives Reports of an association between antineutrophil cytoplasmic antibodies (ANCA) and autoimmune neutropenia have rarely included cases of proven vasculitis. A case of ANCA-associated vasculitis (AAV) with recurrent neutropenia is described and relevant literature on the association between ANCA, neutropenia, and vasculitis is reviewed. Methods Longitudinal clinical assessments and laboratory findings are described in a patient with AAV and recurrent episodes of profound neutropenia from December 2008 – October 2010. A PubMed database search of the medical literature was performed for papers published from 1960 through October 2010 to identify all reported cases of ANCA and neutropenia. Results A 49 year-old man developed recurrent neutropenia, periodic fevers, arthritis, biopsy-proven cutaneous vasculitis, sensorineural hearing loss, epididymitis, and positive tests for ANCA with specificity for antibodies to both proteinase 3 and myeloperoxidase. Antineutrophil membrane antibodies were detected during an acute neutropenic phase and were not detectable in a post-recovery sample, whereas ANCA titers did not seem to correlate with neutropenia. An association between ANCA and neutropenia has been reported in 74 cases from 24 studies in the context of drug/toxin exposure, underlying autoimmune disease, or chronic neutropenia without underlying autoimmune disease. In these cases, the presence of atypical ANCA patterns and other antibodies were common; however, vasculitis was uncommon and when it occurred was usually limited to the skin and in cases of underlying toxin exposure. Conclusions ANCA is associated with autoimmune neutropenia, but systemic vasculitis rarely occurs in association with ANCA and neutropenia. The interaction between neutrophils and ANCA may provide insight into understanding both autoimmune neutropenia and AAV. PMID:21507463
Zerwas, Stephanie; Larsen, Janne Tidselbak; Petersen, Liselotte; Thornton, Laura M; Quaranta, Michela; Koch, Susanne Vinkel; Pisetsky, David; Mortensen, Preben Bo; Bulik, Cynthia M
Identifying factors associated with risk for eating disorders is important for clarifying etiology and for enhancing early detection of eating disorders in primary care. We hypothesized that autoimmune and autoinflammatory diseases would be associated with eating disorders in children and adolescents and that family history of these illnesses would be associated with eating disorders in probands. In this large, nationwide, population-based cohort study of all children and adolescents born in Denmark between 1989 and 2006 and managed until 2012, Danish medical registers captured all inpatient and outpatient diagnoses of eating disorders and autoimmune and autoinflammatory diseases. The study population included 930 977 individuals (48.7% girls). Cox proportional hazards regression models and logistic regression were applied to evaluate associations. We found significantly higher hazards of eating disorders for children and adolescents with autoimmune or autoinflammatory diseases: 36% higher hazard for anorexia nervosa, 73% for bulimia nervosa, and 72% for an eating disorder not otherwise specified. The association was particularly strong in boys. Parental autoimmune or autoinflammatory disease history was associated with significantly increased odds for anorexia nervosa (odds ratio [OR] = 1.13, confidence interval [CI] = 1.01-1.25), bulimia nervosa (OR = 1.29; CI = 1.08-1.55) and for an eating disorder not otherwise specified (OR = 1.27; CI = 1.13-1.44). Autoimmune and autoinflammatory diseases are associated with increased risk for eating disorders. Ultimately, understanding the role of immune system disturbance for the etiology and pathogenesis of eating disorders could point toward novel treatment targets. Copyright © 2017 by the American Academy of Pediatrics.
Full Text Available Wolfgang Hueber1,2,3, William H Robinson1,21VA Palo Alto Health Care System, Palo Alto, CA, USA; 2Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, CA, USA; 3Novartis Institutes of Biomedical Research, Novartis, Basle, SwitzerlandAbstract: Tremendous progress has been made over the past decade in the development and refinement of genomic and proteomic technologies for the identification of novel drug targets and molecular signatures associated with clinically important disease states, disease subsets, or differential responses to therapies. The rapid progress in high-throughput technologies has been preceded and paralleled by the elucidation of cytokine networks, followed by the stepwise clinical development of pathway-specific biological therapies that revolutionized the treatment of autoimmune diseases. Together, these advances provide opportunities for a long-anticipated personalized medicine approach to the treatment of autoimmune disease. The ever-increasing numbers of novel, innovative therapies will need to be harnessed wisely to achieve optimal long-term outcomes in as many patients as possible while complying with the demands of health authorities and health care providers for evidence-based, economically sound prescription of these expensive drugs. Genomic and proteomic profiling of patients with autoimmune diseases holds great promise in two major clinical areas: (1 rapid identification of new targets for the development of innovative therapies and (2 identification of patients who will experience optimal benefit and minimal risk from a specific (targeted therapy. In this review, we attempt to capture important recent developments in the application of genomic and proteomic technologies to translational research by discussing informative examples covering a diversity of autoimmune diseases.Keywords: proteomics, genomics, autoimmune diseases, antigen microarrays, 2-Dih, rheumatoid arthritis
Utiyama, Shirley R R; Zenatti, Katiane B; Nóbrega, Heloisa A J; Soares, Juliana Z C; Skare, Thelma L; Matsubara, Caroline; Muzzilo, Dominique A; Nisihara, Renato M
Autoimmune liver diseases (ALDs) are known to be associated with systemic autoimmune rheumatic diseases (SARDs) and their autoantibodies. We aimed to study the prevalence of SARDs and related autoantibodies, as well as their prognostic implications in a group of patients with ALDs. This was a cross-sectional study. Sixty patients with ALDs (38.3% with autoimmune hepatitis; 11.7% with primary biliary cirrhosis; 25% with primary sclerosing cholangitis and 25% with overlap syndrome) were studied for the presence of SARDs and their autoantibodies. There was autoimmune rheumatic disease in 20% of the studied sample. Systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) were the commonest (11.6% and 5%, respectively). Antinuclear antibodies (ANAs) were present in 35% of the patients, followed by anti-Ro (20.0%); anti-nucleosome (18.3%); rheumatoid factor (10%) anti-CCP (8.3%); anti-RNP (8.3%); anti-ds-DNA (6.6%); anti-La (3.3%); anti-Sm (3.3%), anti-ribosomal P (3.3%). Anti-Ro (p = 0.0004), anti-La (p = 0.03), anti-RNP (p = 0.04) and anti-Sm (p = 0.03) were commonly found in patients with SARD, but not anti-DNA, anti-nucleosome and anti-ribosomal P. No differences were found in liver function tests regarding to the presence of autoantibodies. There was a high prevalence of SARD and their autoantibodies in ALD patients. Anti-Ro, anti-La, anti-RNP and anti-Sm positivity points to an association with systemic autoimmune rheumatic diseases. The presence of autoantibodies was not related to liver function tests.
Full Text Available Psoriasis (PsO is a chronic relapsing/remitting autoimmune skin disease, associated with an increased risk of other autoimmune disorders. Psoriatic arthritis (PsA is a chronic inflammatory arthritis occurring approximately in 30% of PsO patients. Sporadic cases of association between PsO and autoimmune thyroid disorders (AITDs have been reported. However, two different recent studies did not find any association between them. In patients with PsO and PsA, an association with AITD has been shown by most of the studies in adults, but not in the juvenile form. In PsA women and men, thyroid autoimmunity [positive antithyroid peroxidase (AbTPO antibodies, hypoechoic thyroid pattern] and subclinical hypothyroidism were more prevalent than in the general population. An association has been shown also in patients with PsO, arthritis, and inflammatory bowel disease, who have more frequently AITD. A Th1 immune predominance has been shown in early PsO, and PsA, with high serum CXCL10 (Th1 prototype chemokine, overall in the presence of autoimmune thyroiditis. This Th1 immune predominance might be the immunopathogenetic base of the association of these disorders. A raised incidence of new cases of hypothyroidism, thyroid dysfunction, positive AbTPO, and appearance of a hypoechoic thyroid pattern in PsA patients, especially in women, has been shown recently, suggesting to evaluate AbTPO levels, thyroid function, and thyroid ultrasound, especially in PsA women. Thyroid function follow-up and suitable treatments should be performed regularly in PsA female patients at high risk (thyroid-stimulating hormone within the normal range but at the higher limit, positive AbTPO, hypoechoic, and small thyroid.
Liberal, Rodrigo; Mieli-Vergani, Giorgina; Vergani, Diego
The accurate diagnosis and classification of autoimmune hepatitis (AIH) rely upon the detection of characteristic autoantibodies. Positivity for anti-nuclear (ANA) and/or anti-smooth muscle (SMA) autoantibodies defines AIH type 1 (AIH-1), whereas anti-liver kidney microsomal type 1 (anti-LKM1) and/or anti-liver cytosol type 1 (anti-LC1) define AIH type 2 (AIH-2). ANA and SMA, and less commonly anti-LKM1, have also been detected in de-novo autoimmune hepatitis developing after liver transplantation, a condition that may affect patients transplanted for non-autoimmune liver disease. The diagnostic autoantibodies associated with AIH-1 are also detected in the paediatric AIH/sclerosing cholangitis overlap syndrome, referred to as autoimmune sclerosing cholangitis (ASC). ASC, like adult primary sclerosing cholangitis, is often associated with atypical perinuclear anti-neutrophil cytoplasmic autoantibodies (p-ANCA), although p-ANCA are also detected in other autoimmune liver diseases. These associations highlight the necessity for simple and prompt diagnostic autoantibody testing, and the requirement for the accurate interpretation of the results of the tests in the clinical context. Fine-mapping of antigenic autoantibody targets has facilitated the development of rapid molecular assays that have the potential to revolutionise the field if properly standardised and when used in combination with classical immunofluorescence. Despite their diagnostic significance, the pathogenic role of the various autoantibodies and the mechanisms by which they can potentially inflict damage onto the liver cell remain a topic for further research. Copyright © 2013 Elsevier Ltd. All rights reserved.
Full Text Available Autoantibodies (AAbs against glycolytic enzymes: aldolase, α-enolase, glyceraldehyde-3-phosphate dehydrogenase, and pyruvate kinase are prevalent in sera of patients with blinding retinal diseases, such as paraneoplastic [cancer-associated retinopathy (CAR] and non-paraneoplastic autoimmune retinopathies, as well as in many other autoimmune diseases. CAR is a degenerative disease of the retina characterized by sudden vision loss in patients with cancer and serum anti-retinal AAbs. In this review, we discuss the widespread serum presence of anti-glycolytic enzyme AAbs and their significance in autoimmune diseases. There are multiple mechanisms responsible for antibody generation, including the innate anti-microbial response, anti-tumor response, or autoimmune response against released self-antigens from damaged, inflamed tissue. AAbs against enolase, GADPH, and aldolase exist in a single patient in elevated titers, suggesting their participation in pathogenicity. The lack of restriction of AAbs to one disease may be related to an increased expression of glycolytic enzymes in various metabolically active tissues that triggers an autoimmune response and generation of AAbs with the same specificity in several chronic and autoimmune conditions. In CAR, the importance of serum anti-glycolytic enzyme AAbs had been previously dismissed, but the retina may be without pathological consequence until a failure of the blood–retinal barrier function, which would then allow pathogenic AAbs access to their retinal targets, ultimately leading to damaging effects.
Nielsen, Philip Rising; Kragstrup, Tue Wenzel; Deleuran, Bent Winding
Viruses, bacteria and other infectious pathogens are the major postulated environmental triggers of autoimmunity. In the present nation-wide study we describe the association between infections and 29 autoimmune diseases. We used the Danish Civil Registration System to identify 4.5 million persons...... to the etiology of autoimmune diseases together with genetic factors....... born between 1945 and 2000. Information on infections and autoimmune diseases was obtained from the Danish Hospital Register. The cohort was followed from 1977 to 2012. Incidence rate ratios for developing an autoimmune disease were estimated using poisson regression. We found an association between...
Smyk, Daniel S; Koutsoumpas, Andreas L; Mytilinaiou, Maria G; Rigopoulou, Eirini I; Sakkas, Lazaros I; Bogdanos, Dimitrios P
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
Luc Van Kaer
Full Text Available Tolerance against self-antigens is regulated by a variety of cell types with immunoregulatory properties, such as CD1d-restricted invariant natural killer T (iNKT cells. In many experimental models of autoimmunity, iNKT cells promote self-tolerance and protect against autoimmunity. These findings are supported by studies with patients suffering from autoimmune diseases. Based on these studies, the therapeutic potential of iNKT cells in autoimmunity has been explored. Many of these studies have been performed with the potent iNKT cell agonist KRN7000 or its structural variants. These findings have generated promising results in several autoimmune diseases, although mechanisms by which iNKT cells modulate autoimmunity remain incompletely understood. Here, we will review these preclinical studies and discuss the prospects for translating their findings to patients suffering from autoimmune diseases.
Krysiak, Robert; Okopień, Bogusław
Autoimmune polyglandular syndromes are conditions characterized by the combination of two or more organ-specific disorders. The underestimation oftheir real frequency probable results from physicians' inadequate knowledge of these clinical entities and sometimes their atypical clinical presentation. Because they comprise a wide spectrum of autoimmune disorders, autoimmune polyglandular syndromes are divided into four types, among which type-3 is the most common one. In this article, we report the case of a young female, initially diagnosed with diabetes mellitus who several years later developed full-blown autoimmune polyglandular syndrome type 3 consisting of autoimmune thyroid disorder and latent autoimmune diabetes in adults.The discussed case suggests that in selected patients diabetes insipidus may coexist with autoimmune endocrinopathies and nonendocrine autoimmunopathies, as well as that in some patients idiopathic diabetes insipidus may be secondary to lymphocytic infiltration and destruction of the hypothalamic supraoptic and paraventricular nuclei and/or the supraoptic-hypophyseal tract
De Bellis, A; Sinisi, A A; Pane, E; Dello Iacovo, A; Bellastella, G; Di Scala, G; Falorni, A; Giavoli, C; Gasco, V; Giordano, R; Ambrosio, M R; Colao, A; Bizzarro, A; Bellastella, A
Antipituitary antibodies (APA) but not antihypothalamus antibodies (AHA) are usually searched for in autoimmune hypopituitarism. Our objective was to search for AHA and characterize their hypothalamic target in patients with autoimmune hypopituitarism to clarify, on the basis of the cells stained by these antibodies, the occurrence of autoimmune subclinical/clinical central diabetes insipidus (CDI) and/or possible joint hypothalamic contribution to their hypopituitarism. We conducted a cross-sectional cohort study. Ninety-five APA-positive patients with autoimmune hypopituitarism, 60 without (group 1) and 35 with (group 2) lymphocytic hypophysitis, were studied in comparison with 20 patients with postsurgical hypopituitarism and 50 normal subjects. AHA by immunofluorescence and posterior pituitary function were evaluated; then AHA-positive sera were retested by double immunofluorescence to identify the hypothalamic cells targeted by AHA. AHA were detected at high titer in 12 patients in group 1 and in eight patients in group 2. They immunostained arginine vasopressin (AVP)-secreting cells in nine of 12 in group 1 and in four of eight in group 2. All AVP cell antibody-positive patients presented with subclinical/clinical CDI; in contrast, four patients with GH/ACTH deficiency but with APA staining only GH-secreting cells showed AHA targeting CRH- secreting cells. The occurrence of CDI in patients with lymphocytic hypophysitis seems due to an autoimmune hypothalamic involvement rather than an expansion of the pituitary inflammatory process. To search for AVP antibody in these patients may help to identify those of them prone to develop an autoimmune CDI. The detection of AHA targeting CRH-secreting cells in some patients with GH/ACTH deficiency but with APA targeting only GH-secreting cells indicates that an autoimmune aggression to hypothalamus is jointly responsible for their hypopituitarism.
Mortensen, K H; Cleemann, L; Hjerrild, B E
and karyotype. In conclusion, TS girls and women face a high prevalence of autoimmunity and associated disease with a preponderance towards hypothyroidism and CD. Thus, health care providers dealing with this patient group should be observant and test liberally for these conditions even before clinical symptoms......Individuals with Turner syndrome (TS) are prone to develop autoimmune conditions such as coeliac disease (CD), thyroiditis and type 1 diabetes (T1DM). The objective of the present study was to examine TS of various karyotypes for autoantibodies and corresponding diseases. This was investigated...... hypothyroid. Overall, 18% (19) presented with CD autoantibodies, of whom 26% (five) had CD. Anti-TPO and CD autoantibodies co-existed in 9% (10). Immunoglobulin A deficiency was found in 3% (three) of patients, who all had CD autoantibodies without disease. Among four patients with anti-GAD-65 none had T1DM...
Lepez, Trees; Vandewoestyne, Mado; Deforce, Dieter
Autoimmune thyroid diseases (AITD) show a female predominance, with an increased incidence in the years following parturition. Fetal microchimerism has been suggested to play a role in the pathogenesis of AITD. However, only the presence of fetal microchimeric cells in blood and in the thyroid gland of these patients has been proven, but not an actual active role in AITD. Is fetal microchimerism harmful for the thyroid gland by initiating a Graft versus Host reaction (GvHR) or being the target of a Host versus Graft reaction (HvGR)? Is fetal microchimerism beneficial for the thyroid gland by being a part of tissue repair or are fetal cells just innocent bystanders in the process of autoimmunity? This review explores every hypothesis concerning the role of fetal microchimerism in AITD. PMID:23723083
Full Text Available The neuroelectrophysiological manifestations of four clinical typical neurological autoimmune diseases including multiple sclerosis (MS, Guillain-Barré syndrome (GBS, myasthenia gravis (MG, and polymyositis and dermatomyositis were reviewed in this paper. The diagnostic value of evoked potentials for multiple sclerosis, nerve conduction studies (NCS for Guillain-Barré syndrome, repetitive nerve stimulation (RNS and single-fiber electromyography (SFEMG for myasthenia gravis, and needle electromyography for polymyositis and dermatomyositis were respectively discussed. This review will help to have comprehensive understanding on electrophysiological examinations and their clinical significance in the diagnosis of neurological autoimmune diseases. doi: 10.3969/j.issn.1672-6731.2014.09.004
Parizhskij, Z.M.; Artyunina, G.P.; Trofimova, T.N.
A case was considered in detail of a patient with pulmonary edema of immunnocomplex nature in aerogenic intoxication by nickel tetracarbonyl. It was shown that acute aerogenic intoxication nickel carbonyl by led to unfolded toxic autoimmune syndrome. In this case autoimmune immunecomplex pulmonary lesion (AIPL) menifested by progressing pulmonary edema with expressed parenchymatous respiratory insufficiency played a leading role. Lesion of endothelium of pulmonary capillaries by immune complexes has the most significant in pathogenesis of pulmonary edema. The fact that edema appears due to AIPL, is confirmed by high efficiency of glucocorticoid therapy. Use of glucorticoids serves as a diagnostic test which provides an effective roentgenologic diagnosis of AIPL and differential diagnosis of any other pathological processes in the lungs
Three years ago, the Journal of Autoimmunity and Autoimmunity Reviews launched a series of special issues devoted to the contributions of outstanding scholars in autoimmunology. The special issues are devoted not only to recognize achievements, but also to include a series of dedicated papers that reflect the scholar's work, but also are cutting-edge research and reviews in immunology. This special issue is devoted to Haralampos M. Moutsopoulos of the National University of Athens. His contributions to patient care, teaching, and original research are legion. The papers that are included reflect not only a wide range of scholarship in autoimmunology, but importantly are written by his colleagues and friends, and by former students. They encompass original scholarship in Sjögren's syndrome, but also in a number of effector pathways in both adult and pediatric autoimmunology. Copyright © 2010 Elsevier Ltd. All rights reserved.
Furqan, Saira; Haque, Naeem-ul; Islam, Najmul
Background Graves’ disease and Hashimoto’s thyroiditis are the two autoimmune spectrum of thyroid disease. Cases of conversion from hyperthyroidism to hypothyroidism have been reported but conversion from hypothyroidism to hyperthyroidism is very rare. Although such cases have been reported rarely in the past we are now seeing such conversions from hypothyroidism to hyperthyroidism more frequently in clinical practice. Case presentation We are reporting three cases of middle aged Asian female...
Ordookhani, Arash; Burman, Kenneth D.
Context There are contradictory results on the effect of hypothyroidism on the changes in hemostasis. Inadequate population-based studies limited their clinical implications, mainly on the risk of venous thromboembolism (VTE). This paper reviews the studies on laboratory and population-based findings regarding hemostatic changes and risk of VTE in hypothyroidism and autoimmune thyroid disorders. Evidence Acquisition A comprehensive literature search was conducted employing MEDLINE database. T...
Ana M. C. Faria
Full Text Available Oral tolerance is classically defined as the suppression of immune responses to antigens (Ag that have been administered previously by the oral route. Multiple mechanisms of tolerance are induced by oral Ag. Low doses favor active suppression, whereas higher doses favor clonal anergy/deletion. Oral Ag induces Th2 (IL-4/IL-10 and Th3 (TGF-β regulatory T cells (Tregs plus CD4+CD25+ regulatory cells and LAP+T cells. Induction of oral tolerance is enhanced by IL-4, IL-10, anti-IL-12, TGF-β, cholera toxin B subunit (CTB, Flt-3 ligand, anti-CD40 ligand and continuous feeding of Ag. In addition to oral tolerance, nasal tolerance has also been shown to be effective in suppressing inflammatory conditions with the advantage of a lower dose requirement. Oral and nasal tolerance suppress several animal models of autoimmune diseases including experimental allergic encephalomyelitis (EAE, uveitis, thyroiditis, myasthenia, arthritis and diabetes in the nonobese diabetic (NOD mouse, plus non-autoimmune diseases such as asthma, atherosclerosis, colitis and stroke. Oral tolerance has been tested in human autoimmune diseases including MS, arthritis, uveitis and diabetes and in allergy, contact sensitivity to DNCB, nickel allergy. Positive results have been observed in phase II trials and new trials for arthritis, MS and diabetes are underway. Mucosal tolerance is an attractive approach for treatment of autoimmune and inflammatory diseases because of lack of toxicity, ease of administration over time and Ag-specific mechanism of action. The successful application of oral tolerance for the treatment of human diseases will depend on dose, developing immune markers to assess immunologic effects, route (nasal versus oral, formulation, mucosal adjuvants, combination therapy and early therapy.
Smith, Gideon P; Argobi, Yahya
Pruritus in autoimmune connective tissue diseases is a common symptom that can be severe and affect the quality of life of patients. It can be related to disease activity and severity or occur independent of the disease. Appropriate therapy to control the itch depends on the etiology, and it is therefore essential to first work-up these patients for the underlying trigger. Copyright © 2018 Elsevier Inc. All rights reserved.
Pamfil, Cristina; Candrea, Elisabeta; Berki, Emese; Popov, Horațiu I; Radu, Pompilia I; Rednic, Simona
Autoimmune liver diseases may be associated with extrahepatic autoimmune pathology. We report the case of a 52-year old woman who initially presented to the gastroenterology department for extreme fatigue, pale stools, dark urine and pruritus. Laboratory tests showed significant cholestasis and elevation of aminotransferase levels. Immunological tests revealed positive antinuclear (ANA=1:320) and antimitochondrial antibodies (AMA=1:40) with negative anti-smooth muscle and liver kidney microsomal type 1 antibodies. The biopsy was compatible with overlap syndrome type 1. The patient was commenced on immunosuppressive therapy according to standard of care (azathioprine 50mg, ursodeoxycholic acid and prednisone 0.5mg/kg), with moderate biochemical improvement. She subsequently developed proximal symmetrical weakness and cutaneous involvement and was diagnosed with biopsy-proven dermatomyositis. The immunosuppressive regimen was intensified to 150 mg azathioprine. At the three-month follow-up, her symptoms subsided and aminotransferases and muscle enzymes normalized. Upon further investigation the patient was diagnosed with autoimmune thyroiditis and antiphospholipid syndrome. To our knowledge, this is the first case of primary biliary cirrhosis - autoimmune hepatitis overlap syndrome associated with dermatomyositis, autoimmune thyroiditis and antiphospholipid syndrome.
Rojas, Manuel; Rodriguez, Yhojan; Pacheco, Yovana; Zapata, Elizabeth; Monsalve, Diana M; Mantilla, Rubén D; Rodríguez-Jimenez, Monica; Ramírez-Santana, Carolina; Molano-González, Nicolás; Anaya, Juan-Manuel
To evaluate the relationship between resilience and clinical outcomes in patients with autoimmune rheumatic diseases. Focus groups, individual interviews, and chart reviews were done to collect data on 188 women with autoimmune rheumatic diseases, namely rheumatoid arthritis (n=51), systemic lupus erythematosus (n=70), systemic sclerosis (n=35), and Sjögren's syndrome (n=32). Demographic, clinical, and laboratory variables were assessed including disease activity by patient reported outcomes. Resilience was evaluated by using the Brief Resilience Scale. Bivariate, multiple linear regression, and classification and regression trees were used to analyse data. Resilience was influenced by age, duration of disease, and socioeconomic status. Lower resilience scores were observed in younger patients (50years) had higher resilience scores regardless of socioeconomic status. There was no influence of disease activity on resilience. A particular behaviour was observed in systemic sclerosis in which patients with high socioeconomic status and regular physical activity had higher resilience scores. Resilience in patients with autoimmune rheumatic diseases is a continuum process influenced by age and socioeconomic status. The ways in which these variables along with exercise influence resilience deserve further investigation. Copyright © 2017 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.
Full Text Available Ocular inflammation is one of the leading causes of blindness and loss of vision. Human uveitis is a complex and heterogeneous group of diseases characterized by inflammation of intraocular tissues. The eye may be the only organ involved, or uveitis may be part of a systemic disease. A significant number of cases are of unknown etiology and are labeled idiopathic. Animal models have been developed to the study of the physiopathogenesis of autoimmune uveitis due to the difﬁculty in obtaining human eye inflamed tissues for experiments. Most of those models are induced by injection of speciﬁc photoreceptors proteins (e.g., S-antigen, interphotoreceptor retinoid-binding protein, rhodopsin, recoverin, phosducin. Non-retinal antigens, including melanin-associated proteins and myelin basic protein, are also good inducers of uveitis in animals. Understanding the basic mechanisms and pathogenesis of autoimmune ocular diseases are essential for the development of new treatment approaches and therapeutic agents. The present review describes the main experimental models of autoimmune ocular inflammatory diseases.
Grønbæk, Lisbet; Vilstrup, Hendrik; Deleuran, Bent
IRR, 1.56; 95% CI, 1.26-1.92), celiac disease (aIRR, 5.12; 95% CI, 2.58-10.16), pernicious anemia (aIRR, 2.35; 95% CI, 1.50-3.68), and psoriasis (aIRR, 4.06; 95% CI, 3.32-4.97). There was no increase in the incidence rate for rheumatoid arthritis (aIRR, 0.89; 95% CI, 0.69-1.15); the incidence rate......BACKGROUND & AIMS: Alcoholic cirrhosis is associated with hyperactivation and dysregulation of the immune system. In addition to its ability to increase risk for infections, it also may increase the risk for autoimmune diseases. We studied the incidence of autoimmune diseases among patients...... (controls) of the same sex and age. The incidence rates of various autoimmune diseases were compared between patients with cirrhosis and controls and adjusted for the number of hospitalizations in the previous year (a marker for the frequency of clinical examination). RESULTS: Of the 24,679 patients...
Tozzoli, Renato; D'Aurizio, Federica; Villalta, Danilo; Bizzaro, Nicola
Over the past two decades, we have witnessed an extraordinary change in autoimmune diagnostics, characterized by the progressive evolution of analytical technologies, the availability of new tests, and the explosive growth of molecular biology and proteomics. Aside from these huge improvements, organizational changes have also occurred which brought about a more modern vision of the autoimmune laboratory. The introduction of automation (for harmonization of testing, reduction of human error, reduction of handling steps, increase of productivity, decrease of turnaround time, improvement of safety), consolidation (combining different analytical technologies or strategies on one instrument or on one group of connected instruments) and integration (linking analytical instruments or group of instruments with pre- and post-analytical devices) opened a new era in immunodiagnostics. In this article, we review the most important changes that have occurred in autoimmune diagnostics and present some models related to the introduction of automation in the autoimmunology laboratory, such as automated indirect immunofluorescence and changes in the two-step strategy for detection of autoantibodies; automated monoplex immunoassays and reduction of turnaround time; and automated multiplex immunoassays for autoantibody profiling.
Marmont Alberto M.
Full Text Available Intense immunosuppresion followed by alogenic or autogenic hematopoietic stem cell transplantation is a relatively recent procedure which was used for the first time in severe, refractory cases of systemic lupus erythematosus. Currently three agressive procedures are used in the treatment of autoimmune diseases: high dose chemotherapy without stem cell rescue, intense immunosuppression with subsequent infusion of the alogenic hematopoietic stem cell transplantation combined with or without the selection of CD34+ cells, and the autogenic hematopoietic stem cell transplantation. Proof of the graft-versus-leukemia effect observed define SCT as a form of immunotherapy, with additional evidence of an similar Graft-vs-Autoimmunity effect which is suggestive of a cure for autoimmune diseases in this type of therapy. The use of alogenic SCT improved due to its safety compared to autogenic transplantations. In this report, data of multiply sclerosis and systemic lupus erythematosus are reported, with the conclusion that Immunoablation followed by SCT is clearly indicated in such cases.
Moore, Joseph A; Gliga, Louise; Nagalla, Srikanth
Graves' disease is often associated with other autoimmune disorders, including rare associations with autoimmune hemolytic anemia (AIHA). We describe a unique presentation of thyroid storm and warm AIHA diagnosed concurrently in a young female with hyperthyroidism. The patient presented with nausea, vomiting, diarrhea and altered mental status. Laboratory studies revealed hemoglobin 3.9g/dL, platelets 171×10 9 L -1 , haptoglobin storm and warm AIHA. She was started on glucocorticoids to treat both warm AIHA and thyroid storm, as well as antithyroid medications, propranolol and folic acid. Due to profound anemia and hemodynamic instability, the patient was transfused two units of uncrossmatched packed red blood cells slowly and tolerated this well. She was discharged on methimazole as well as a prolonged prednisone taper, and achieved complete resolution of the thyrotoxicosis and anemia at one month. Hyperthyroidism can affect all three blood cell lineages of the hematopoietic system. Anemia can be seen in 10-20% of patients with thyrotoxicosis. Several autoimmune processes can lead to anemia in Graves' disease, including pernicious anemia, celiac disease, and warm AIHA. This case illustrates a rarely described presentation of a patient with Graves' disease presenting with concurrent thyroid storm and warm AIHA. Copyright © 2017 Elsevier Ltd. All rights reserved.
Sudulagunta, Sreenivasa Rao
Full Text Available Neuromyelitis optica (NMO or Devic’s syndrome is a rare relapsing demyelinating disease of the central nervous system (CNS that mainly affects the spinal cord and optic nerves and shares many clinical and radiological features with multiple sclerosis. The association of NMO with other autoimmune diseases was reported, but very few reports described association with autoimmune thyroid disease. Early differentiation between NMO and multiple sclerosis is very important as the natural course and treatment regimens differ significantly. We report a case of a 50-year-old woman who was admitted initially with vomiting, hiccups and paraesthesias but was not diagnosed with NMO and presented with a severe progression of the disease. The patient was also diagnosed to have autoimmune thyroiditis with lymphocytic infiltration of the thyroid which progressed from hyperthyroidism to hypothyroidism. NMO diagnosis was established with seropositivity for NMO-IgG and MRI showing longitudinally extensive spinal cord lesions (3 or more spinal segments. In spite of treatment, the response was poor due to lack of early diagnosis and aggressive immunosuppressant therapy.
Full Text Available Bidirectional interactions between the immune and the nervous systems are of considerable interest both for deciphering their functioning and for designing novel therapeutic strategies. The past decade has brought a burst of insights into the molecular mechanisms involved in neuro-immune communications mediated by dopamine. Studies of dendritic cells (DCs revealed that they express the whole machinery to synthesize and store dopamine, which may act in an autocrine manner to stimulate dopamine receptors (DARs. Depending on specific DARs stimulated on DCs and T cells, dopamine may differentially favor CD4+ T cell differentiation into Th1 or Th17 inflammatory cells. Regulatory T cells can also release high amounts of dopamine that acts in an autocrine DAR-mediated manner to inhibit their suppressive activity. These dopaminergic regulations could represent a driving force during autoimmunity. Indeed, dopamine levels are altered in the brain of mouse models of multiple sclerosis (MS and lupus, and in inflamed tissues of patients with inflammatory bowel diseases or rheumatoid arthritis. The distorted expression of DARs in peripheral lymphocytes of lupus and MS patients also supports the importance of dopaminergic regulations in autoimmunity. Moreover, dopamine analogs had beneficial therapeutic effects in animal models, and in patients with lupus or rheumatoid arthritis. We propose models that may underlie key roles of dopamine and its receptors in autoimmune diseases.
Full Text Available The prevalence of celiac disease autoimmunity or tissue transglutaminase autoantibodies (TGA amongst patients with type 1 diabetes (T1D and autoimmune thyroid disease (AITD in the Chinese population remains unknown. This study examined the rate of celiac disease autoimmunity amongst patients with T1D and AITD in the Chinese population. The study included 178 patients with type 1 diabetes and 119 with AITD where 36 had both T1D and AITD, classified as autoimmune polyglandular syndrome type 3 variant (APS3v. The study also included 145 patients with type 2 diabetes (T2D, 97 patients with non-autoimmune thyroid disease (NAITD, and 102 healthy controls. Serum islet autoantibodies, thyroid autoantibodies and TGA were measured by radioimmunoassay. TGA positivity was found in 22% of patients with either type 1 diabetes or AITD, much higher than that in patients with T2D (3.4%; p< 0.0001 or NAITD (3.1%; P < 0.0001 or healthy controls (1%; p<0.0001. The patients with APS3v having both T1D and AITD were 36% positive for TGA, significantly higher than patients with T1D alone (p = 0.040 or with AITD alone (p = 0.017. T1D and AITD were found to have a 20% and 30% frequency of overlap respectively at diagnosis. In conclusion, TGA positivity was high in the Chinese population having existing T1D and/or AITD, and even higher when both diseases were present. Routine TGA screening in patients with T1D or AITD will be important to early identify celiac disease autoimmunity for better clinical care of patients.
Farez, Mauricio F; Balbuena Aguirre, María E; Varela, Francisco; Köhler, Alejandro A; Correale, Jorge
Background. Comorbid autoimmune diseases in MS patients have been studied extensively with controversial results. Moreover, no such data exists for Latin-American MS patients. Methods. We conducted a case-control study aimed to establish the prevalence of autoimmune disorders in a cohort of Argentinean MS patients. Results. There were no significant differences in autoimmune disease prevalence in MS patients with respect to controls. The presence of one or more autoimmune disorders did not increase risk of MS (OR 0.85, 95% CI 0.6-1.3). Discussion. Our results indicate absence of increased comorbid autoimmune disease prevalence in MS patients, as well as of increased risk of MS in patients suffering from other autoimmune disorders.
Shen, Jia-ming; Lu, Jin-chun; Yao, Bing
Chronic prostatitis is a highly prevalent disease of unclear etiology. Researches show that autoimmune reaction is one cause of the problem. An effective animal model may help a lot to understand the pathogenesis and find proper diagnostic and therapeutic strategies of the disease. Currently used autoimmune prostatitis-related animal models include those of age-dependent spontaneous prostatitis, autoimmune regulator-dependent spontaneous prostatitis, self antigen-induced prostatitis, and steroid-induced prostatitis. Whether an animal model of autoimmune prostatitis is successfully established can be evaluated mainly from the five aspects: histology, morphology, specific antigens, inflammatory factors, and pain intensity.
Schmidt, Reinhold E; Grimbacher, Bodo; Witte, Torsten
Autoimmunity and immunodeficiency were previously considered to be mutually exclusive conditions; however, increased understanding of the complex immune regulatory and signalling mechanisms involved, coupled with the application of genetic analysis, is revealing the complex relationships between primary immunodeficiency syndromes and autoimmune diseases. Single-gene defects can cause rare diseases that predominantly present with autoimmune symptoms. Such genetic defects also predispose individuals to recurrent infections (a hallmark of immunodeficiency) and can cause primary immunodeficiencies, which can also lead to immune dysregulation and autoimmunity. Moreover, risk factors for polygenic rheumatic diseases often exist in the same genes as the mutations that give rise to primary immunodeficiency syndromes. In this Review, various primary immunodeficiency syndromes are presented, along with their pathogenetic mechanisms and relationship to autoimmune diseases, in an effort to increase awareness of immunodeficiencies that occur concurrently with autoimmune diseases and to highlight the need to initiate appropriate genetic tests. The growing knowledge of various genetically determined pathologic mechanisms in patients with immunodeficiencies who have autoimmune symptoms opens up new avenues for personalized molecular therapies that could potentially treat immunodeficiency and autoimmunity at the same time, and that could be further explored in the context of autoimmune rheumatic diseases.
Alexander M. Goldman
Full Text Available It is characterized by chemical and sometimes clinical hyperthyroidism, without evidence of thyroid autoimmunity that resolves spontaneously by 16 weeks gestation without significant obstetrical complications.
Bashar S. Amr
Full Text Available 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.
Avalos-Díaz, Esperanza; Pérez-Pérez, Elena; Rodríguez-Rodríguez, Mayra; Pacheco-Tovar, María-Guadalupe; Herrera-Esparza, Rafael
Vitiligo is a chronic disease characterized by the dysfunction or destruction of melanocytes with secondary depigmentation. The aim of the present study was to determine the prevalence of vitiligo associated with autoimmune rheumatic diseases. The clinical records from a 10-year database of patients with rheumatic diseases and associated vitiligo was analysed, with one group of patients having autoimmune rheumatic disease and another non-autoimmune rheumatic disease. Available serum samples were used to assess the anti-melanocyte antibodies. A total of 5,251 individual clinical files were archived in the last 10 years, and these patients underwent multiple rheumatology consultations, with 0.3% of the group presenting with vitiligo. The prevalence of vitiligo in the autoimmune rheumatic disease group was 0.672%, which was mainly associated with lupus and arthritis. However, patients with more than one autoimmune disease had an increased relative risk to develop vitiligo, and anti-melanocyte antibodies were positive in 92% of these patients. By contrast, the prevalence was 0.082% in the group that lacked autoimmune rheumatic disease and had negative autoantibodies. In conclusion, the association between vitiligo and autoimmune rheumatic diseases was relatively low. However, the relative risk increased when there were other autoimmune comorbidities, such as thyroiditis or celiac disease. Therefore, the presence of multiple autoimmune syndromes should be suspected.
Full Text Available The field of epigenetics requires that traditional divisions between scientific disciplines give way to cross-fertilization of concepts and ideas from different areas of investigation. Such is the case with research in autoimmunity. Recent discoveries of stimuli that induce autoimmunity reveal that epigenetic marks of autoantigens are recognized by autoreactive B and T cell receptors. Thus, insights into the initiation of autoimmunity, its prevention and therapy will arise from understanding the biochemistry, cell biology and microbiology of autoantigen epigenetics. Here, we highlight potential benefits from the inhibition of a histone modifying enzyme and the administration of a phosphorylated, spliceosome-derived peptide, in the treatment of autoimmunity.
Hansen, Martin P; Matheis, Nina; Kahaly, George J
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
Shimosegawa, Tooru; Kanno, Atsushi
Since the rediscovery and definition of autoimmune pancreatitis (AIP) by Yoshida et al. in 1995, the disease has been attracting attention because of its unique clinical features and practical issues. This disease shows very impressive imaging findings, serological changes, and characteristic histopathology. It occurs most commonly in elderly males with painless jaundice or mild abdominal pain; resemblance in imaging findings between AIP and pancreatobiliary cancers poses an important practical issue of differentiation. With increasing recognition of AIP and accumulation of cases, another important feature of this disease has been revealed, i.e., association of extrapancreatic organ involvements. Initially misunderstood because it can be accompanied by other autoimmune disorders, such as Sjögren's syndrome or primary sclerosing cholangitis (PSC), AIP is now known to be associated with unique types of sialadenitis and cholangitis distinct from Sjögren's syndrome or PSC. Now the concept of "IgG4-related sclerosing disease" has become widely accepted and the list of organs involved continues to increase. With worldwide recognition, an emerging issue is the clinical definition of other possible types of autoimmune-related pancreatitis called "idiopathic duct-centric chronic pancreatitis (IDCP)" and "AIP with granulocyte epithelial lesion (GEL)" and their relation to AIP with lymphoplasmacytic sclerosing pancreatitis (LPSP). The time has arrived to establish clinical diagnostic criteria of AIP based on international consensus and to discuss regional and racial differences in the clinicopathological features of AIP. Consensus guidelines are also required for the ideal use of steroids in the treatment of AIP to suppress recurrence efficiently with minimal side effects. There are many issues to be settled in AIP; international collaboration of experts in the pancreas field is necessary to clarify the entire picture of this unique and important disease.
Shimosegawa, Tooru; Kanno, Atsushi
Since the rediscovery and definition of autoimmune pancreatitis (AIP) by Yoshida et al. in 1995, the disease has been attracting attention because of its unique clinical features and practical issues. This disease shows very impressive imaging findings, serological changes, and characteristic histopathology. It occurs most commonly in elderly males with painless jaundice or mild abdominal pain; resemblance in imaging findings between AIP and pancreatobiliary cancers poses an important practical issue of differentiation. With increasing recognition of AIP and accumulation of cases, another important feature of this disease has been revealed, id est (i.e.), association of extrapancreatic organ involvements. Initially misunderstood because it can be accompanied by other autoimmune disorders, such as Sjogren's syndrome or primary sclerosing cholangitis (PSC), AIP is now known to be associated with unique types of sialadenitis and cholangitis distinct from Sjogren's syndrome or PSC. Now the concept of 'IgG4-related sclerosing disease' has become widely accepted and the list of organs involved continues to increase. With worldwide recognition, an emerging issue is the clinical definition of other possible types of autoimmune-related pancreatitis called 'idiopathic duct-centric chronic pancreatitis (IDCP)' and AIP with granulocyte epithelial lesion (GEL)' and their relation to AIP with lymphoplasmacytic sclerosing pancreatitis (LPSP). The time has arrived to establish clinical diagnostic criteria of AIP based on international consensus and to discuss regional and racial differences in the clinicopathological features of AIP. Consensus guidelines are also required for the ideal use of steroids in the treatment of AIP to suppress recurrence efficiently with minimal side effects. There are many issues to be settled in AIP; international collaboration of experts in the pancreas field is necessary to clarify the entire picture of this unique and important disease. (author)
Rinaldi, Maurizio; Perricone, Roberto; Blank, Miri; Perricone, Carlo; Shoenfeld, Yehuda
Saccharomyces cerevisiae is best known as the baker's and brewer's yeast, but its residual traces are also frequent excipients in some vaccines. Although anti-S. cerevisiae autoantibodies (ASCAs) are considered specific for Crohn's disease, a growing number of studies have detected high levels of ASCAs in patients affected with autoimmune diseases as compared with healthy controls, including antiphospholipid syndrome, systemic lupus erythematosus, type 1 diabetes mellitus, and rheumatoid arthritis. Commensal microorganisms such as Saccharomyces are required for nutrition, proper development of Peyer's aggregated lymphoid tissue, and tissue healing. However, even the commensal nonclassically pathogenic microbiota can trigger autoimmunity when fine regulation of immune tolerance does not work properly. For our purposes, the protein database of the National Center for Biotechnology Information (NCBI) was consulted, comparing Saccharomyces mannan to several molecules with a pathogenetic role in autoimmune diseases. Thanks to the NCBI bioinformation technology tool, several overlaps in molecular structures (50-100 %) were identified when yeast mannan, and the most common autoantigens were compared. The autoantigen U2 snRNP B″ was found to conserve a superfamily protein domain that shares 83 % of the S. cerevisiae mannan sequence. Furthermore, ASCAs may be present years before the diagnosis of some associated autoimmune diseases as they were retrospectively found in the preserved blood samples of soldiers who became affected by Crohn's disease years later. Our results strongly suggest that ASCAs' role in clinical practice should be better addressed in order to evaluate their predictive or prognostic relevance.
Spencer, Chantal Y; Millman, Jennifer; Veiga, Keila; Vicencio, Alfin G
Asthma encompasses numerous phenotypes that may require alternate approaches to diagnosis and therapy, particularly for patients whose symptoms remain poorly controlled despite escalating treatment. We describe 3 patients with apparent asthma who demonstrated unusual findings on cryobiopsy by flexible bronchoscopy and responded to therapy directed against autoimmune disease. Copyright © 2018 by the American Academy of Pediatrics.
Lohse, Ansgar W; Weiler-Norman, Christina; Burdelski, Martin
The Kings College group was the first to describe a clinical syndrome similar to autoimmune hepatitis in children and young adults transplanted for non-immune mediated liver diseases. They coined the term "de novo autoimmune hepatitis". Several other liver transplant centres confirmed this observation. Even though the condition is uncommon, patients with de novo AIH are now seen in most of the major transplant centres. The disease is usually characterized by features of acute hepatitis in otherwise stable transplant recipients. The most characteristic laboratory hallmark is a marked hypergammaglobulinaemia. Autoantibodies are common, mostly ANA. We described also a case of LKM1-positivity in a patients transplanted for Wilson's disease, however this patients did not develop clinical or histological features of AIH. Development of SLA/LP-autoantibodies is also not described. Therefore, serologically de novo AIH appears to correspond to type 1 AIH. Like classical AIH patients respond promptly to treatment with increased doses of prednisolone and azathioprine, while the calcineurin inhibitors cyclosporine or tacrolimus areof very limited value - which is not surprising, as almost all patients develop de novo AIH while receiving these drugs. Despite the good response to treatment, most patients remain a clinical challenge as complete stable remissions are uncommon and flares, relapses and chronic disease activity can often occur. Pathogenetically this syndrome is intriguing. It is not clear, if the immune response is directed against allo-antigens, neo-antigens in the liver, or self-antigens, possibly shared by donor and host cells. It is very likely that the inflammatory milieu due to alloreactive cells in the transplanted organ contribute to the disease process. Either leading to aberrant antigen presentation, or providing co-stimulatory signals leading to the breaking of self-tolerance. The development of this disease in the presence of treatment with calcineurin
The study involved 46 persons. In the majority of patients the exposure dose was 0.155±0.01 Gy. Clinical, ultrasound, immunological, statistical and non-parametric methods were used. Considerable immunological polymorphism of autoimmune thyroiditis in the liquidators has been established; 1) with disturbances in the cellular immunity and low antithyroid antibody index, 2) without disturbances in the cellular immunity with positive indices of antithyroid antibodies, 3) with disturbances in cellular immunity and high indices of TH and MA antibodies
Merrill J. Rowley
Full Text Available The serological presence of autoantibodies is diagnostic of autoimmunity, and these autoantibodies may be present for many years before the presentation of autoimmune disease (AID. Although a pathogenic role has been demonstrated for various autoantibodies reactive with cell surface and extracellular autoantigens, studies using monoclonal antibodies (mAb show not all antibodies in the polyclonal response are pathogenic. Differences depend on Fab-mediated diversity in epitope specificity, Fc-mediated effects based on immunoglobulin (Ig class and subclass, activation of complement, and the milieu in which the reaction occurs. These autoantibodies often occur in organ-specific AID and this review illustrates their pathogenic and highly specific effects. The role of autoantibodies associated with intracellular antigens is less clear. In vitro they may inhibit or adversely affect well-defined intracellular biochemical pathways, yet, in vivo they are separated from their autoantigens by multiple cellular barriers. Recent evidence that Ig can traverse cell membranes, interact with intracellular proteins, and induce apoptosis has provided new evidence for a pathogenic role for such autoantibodies. An understanding of how autoantibodies behave in the polyclonal response and their role in pathogenesis of AID may help identify populations of culprit B-cells and selection of treatments that suppress or eliminate them.
Full Text Available Melca M O Barros, Dante M Langhi Jr, José O Bordin Department of Clinical and Experimental Oncology, Universidade Federal de São Paulo, São Paulo, Brazil Abstract: Autoimmune hemolytic anemia (AIHA is defined as the increased destruction of red blood cells (RBCs in the presence of anti-RBC autoantibodies and/or complement. Classification of AIHA is based on the optimal auto-RBC antibody reactivity temperatures and includes warm, cold-reactive, mixed AIHA, and drug-induced AIHA subtypes. AIHA is a rare disease, and recommendations for transfusion are based mainly on results from retrospective data and relatively small cohort studies, including heterogeneous patient samples or single case reports. In this article, we will review the challenges and solutions to safely transfuse AIHA patients. We will reflect on the indication for transfusion in AIHA and the difficulty in the accomplishment of immunohematological procedures for the selection of the safest and most compatible RBC units. Keywords: hemolytic anemia, RBC autoantibodies, autoimmunity, hemolysis, direct antiglobulin test
Autoimmune pancreatitis (AIP) has been recognized as a distinct type of pancreatitis that is possibly caused by autoimmune mechanisms. AIP is characterized by high serum IgG4 and IgG4-positive plasma cell infiltration in affected pancreatic tissue. Acute phase AIP responds favorably to corticosteroid therapy and results in the amelioration of clinical findings. However, the long-term prognosis and outcome of AIP remain unclear. We have proposed a working hypothesis that AIP can develop into ordinary chronic pancreatitis resembling alcoholic pancreatitis over a long-term course based on several clinical findings, most notably frequent pancreatic stone formation. In this review article, we describe a series of study results to confirm our hypothesis and clarify that: 1) pancreatic calcification in AIP is closely associated with disease recurrence; 2) advanced stage AIP might have earlier been included in ordinary chronic pancreatitis; 3) approximately 40% of AIP patients experience pancreatic stone formation over a long-term course, for which a primary risk factor is narrowing of both Wirsung’s and Santorini’s ducts; and 4) nearly 20% of AIP patients progress to confirmed chronic pancreatitis according to the revised Japanese Clinical Diagnostic Criteria, with independent risk factors being pancreatic head swelling and non-narrowing of the pancreatic body duct. PMID:24884922
Shivaprasad H. Venkatesha
Full Text Available 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.
Full Text Available Autoimmune pancreatitis (AIP is a type of chronic pancreatitis characterized by an autoimmune inflammatory process. Treatment protocols for AIP are still evolving. According to the articles about AIP treatment in recent years, the indications for steroid therapy include specific clinical manifestations (jaundice, abdominal pain, etc., markedly abnormal imaging findings, and extrapancreatic organ involvement. The initial dose of steroid (prednisone is usually 0.6 mg·kg-1·d-1 or 30-40 mg/d; after 3 weeks to 1 month of treatment with the initial dose, the dose is decreased by 5-10 mg every 1-2 weeks until it drops to 2.5-5 mg/d; this dose is maintained for 6 months to 3 years. No consensus has been reached on the adverse effect of steroid on diabetes mellitus complicating AIP. Immunosuppressive agents should be used for the patients with disease relapses or with important extrapancreatic organs involved. Rituximab might become one of the therapies for refractory AIP. Although some patients achieved remission after surgical treatment, surgery is still not recommended as a routine treatment protocol due to the complications after surgery.
Furqan, Saira; Haque, Naeem-ul; Islam, Najmul
Graves' disease and Hashimoto's thyroiditis are the two autoimmune spectrum of thyroid disease. Cases of conversion from hyperthyroidism to hypothyroidism have been reported but conversion from hypothyroidism to hyperthyroidism is very rare. Although such cases have been reported rarely in the past we are now seeing such conversions from hypothyroidism to hyperthyroidism more frequently in clinical practice. We are reporting three cases of middle aged Asian females who presented with classical symptoms of hypothyroidism and the investigations showed elevated thyroid stimulating hormone with positive thyroid antibodies. Diagnosis of autoimmune hypothyroidism was made and thyroxine replacement therapy was initiated. Patients became asymptomatic with normalization of thyroid stimulating hormone level. After few years they developed symptoms of hyperthyroidism with suppressed thyroid stimulating hormone level. Over replacement of thyroxine was considered and the dose of thyroxine was decreased, but they remain symptomatic. After gradual decrease in the dose of thyroxine it was stopped finally. Even after few months of stopping thyroxine, the symptoms of hyperthyroidism did not improve and the biochemical and imaging modalities confirmed that the patients have developed hyperthyroidism. Anti-thyroid treatment was then started and the patients became symptom free. High index of suspicion should be there for possible conversion of hypothyroidism to hyperthyroidism if a patient with primary hypothyroidism develops persistent symptoms of hyperthyroidism. Otherwise it can be missed easily considering it as an over replacement with thyroid hormone.
Iodice, V.; Lauri, C.; Capriotti, G.; Lagana', B.; Germano, V.; D’Amelio, R.; Picchianti Diamanti, A.
B cells arise from stem cells precursor and develop through a tightly regulated and selective process that lead to the generation of different B cell populations such as transitional, mature, memory and plasma cells. These B cell subsets can be identified using flow cytometry by the expression of specific surface antigens. The growing knowledge of the pivotal role played by B cells in the development and progression of autoimmune diseases combined with the advances in monoclonal antibody technology, led in the last years to the generation of different biological agents targeting B cells. In this context, nuclear medicine can offer the possibility to use a panel of biologic radiopharmaceuticals for molecular imaging of inflammatory diseases. Radiopharmaceuticals bind to their targets with high affinity and specificity and have an excellent imaging diagnostic potential for the evaluation of disease activity, selection and monitoring of immune therapies. Several molecules have been radiolabelled for the imaging of T lymphocytes whereas, by now, the anti CD20 rituximab is the only biological therapy targeting B cells that demonstrated to be efficiently radiolabelled and used to detect inflammation in autoimmune patients
Autoimmune encephalitis consists of limbic symptoms and signs associated with antibodies against neuronal cell-surface antigens or intracellular antigens. Some cases are known to be associated with anti-channel or anti-receptor-related molecule antibodies. Whether these cases are paraneoplastic depends on the kinds of antigens that the antibodies are produced against. Other cases due to well-characterized onco-neural antibodies are almost always paraneoplastic and are generally resistant to anti-tumor therapy and/or immunotherapy. An exception is anti-Ma2 antibody-positive encephalitis associated with a testicular tumor. Antibodies for intracellular antigens are considered not to be pathogenic. Rather, the T-cell response is thought to be responsible. These antibodies are useful markers for the diagnosis of paraneoplastic disorders and in the search for underlying cancer, as neurological symptoms often precede tumor diagnosis. There is a relationship among onco-neural antibodies, clinical features, tumor types, and response to immunotherapy. Here we describe the characteristics of autoimmune encephalitis cases with antibodies against different intracellular antigens, such as Hu, Ma2, CRMP5, or amphiphysin.
Sen, Aritro; Kushnir, Vitaly A; Barad, David H; Gleicher, Norbert
An increasing body of evidence suggests that immune-mediated processes affect female reproductive success at multiple levels. Crosstalk between endocrine and immune systems regulates a large number of biological processes that affect target tissues, and this crosstalk involves gene expression, cytokine and/or lymphokine release and hormone action. In addition, endocrine-immune interactions have a major role in the implantation process of the fetal (paternally derived) semi-allograft, which requires a reprogramming process of the maternal immune system from rejection to temporary tolerance for the length of gestation. Usually, the female immune system is supportive of all of these processes and, therefore, facilitates reproductive success. Abnormalities of the female immune system, including autoimmunity, potentially interfere at multiple levels. The relevance of the immune system to female infertility is increasingly recognized by investigators, but clinically is often not adequately considered and is, therefore, underestimated. This Review summarizes the effect of individual autoimmune endocrine diseases on female fertility, and points towards selected developments expected in the near future.
Maruyama, Masahiro; Watanabe, Takayuki; Kanai, Keita; Oguchi, Takaya; Asano, Jumpei; Ito, Tetsuya; Ozaki, Yayoi; Muraki, Takashi; Hamano, Hideaki; Arakura, Norikazu; Kawa, Shigeyuki
Autoimmune pancreatitis (AIP) has been recognized as a distinct type of pancreatitis that is possibly caused by autoimmune mechanisms. AIP is characterized by high serum IgG4 and IgG4-positive plasma cell infiltration in affected pancreatic tissue. Acute phase AIP responds favorably to corticosteroid therapy and results in the amelioration of clinical findings. However, the long-term prognosis and outcome of AIP remain unclear. We have proposed a working hypothesis that AIP can develop into ordinary chronic pancreatitis resembling alcoholic pancreatitis over a long-term course based on several clinical findings, most notably frequent pancreatic stone formation. In this review article, we describe a series of study results to confirm our hypothesis and clarify that: 1) pancreatic calcification in AIP is closely associated with disease recurrence; 2) advanced stage AIP might have earlier been included in ordinary chronic pancreatitis; 3) approximately 40% of AIP patients experience pancreatic stone formation over a long-term course, for which a primary risk factor is narrowing of both Wirsung's and Santorini's ducts; and 4) nearly 20% of AIP patients progress to confirmed chronic pancreatitis according to the revised Japanese Clinical Diagnostic Criteria, with independent risk factors being pancreatic head swelling and non-narrowing of the pancreatic body duct.
Full Text Available Abstract Background In autoimmune haemolytic anaemia (AIHA, autoreactive antibodies directed against red blood cells are up-regulated, leading to erythrocyte death. Mycoplasma suis infections in pigs induce AIHA of both the warm and cold types. The aim of this study was to identify the target autoantigens of warm autoreactive IgG antibodies. Sera from experimentally M. suis-infected pigs were screened for autoreactivity. Results Actin-reactive antibodies were found in the sera of 95% of all animals tested. The reactivity was species-specific, i.e. reactivity with porcine actin was significantly higher than with rabbit actin. Sera of animals previously immunised with the M. suis adhesion protein MSG1 showed reactivity with actin prior to infection with M. suis indicating that molecular mimicry is involved in the specific autoreactive mechanism. A potentially cross-reactive epitope was detected. Conclusions This is the first report of autoreactive anti-actin antibodies involved in the pathogenesis of autoimmune haemolytic anaemia.
Zhernakova, Alexandra; Withoff, Sebo; Wijmenga, Cisca
Many endocrine diseases, including type 1 diabetes mellitus, Graves disease, Addison disease and Hashimoto disease, originate as an autoimmune reaction that affects disease-specific target organs. These autoimmune diseases are characterized by the development of specific autoantibodies and by the
Bøe Wolff, A S; Oftedal, B; Johansson, S
Autoimmune Addison's disease (AAD) is often associated with other components in autoimmune polyendocrine syndromes (APS). Whereas APS I is caused by mutations in the AIRE gene, the susceptibility genes for AAD and APS II are unclear. In the present study, we investigated whether polymorphisms...
Barturen, Guillermo; Beretta, Lorenzo; Cervera, Ricard; van Vollenhoven, Ronald; Alarcón-Riquelme, Marta E.
Autoimmune rheumatic diseases pose many problems that have, in general, already been solved in the field of cancer. The heterogeneity of each disease, the clinical similarities and differences between different autoimmune rheumatic diseases and the large number of patients that remain without a
Autoimmune progesterone dermatitis (APD) is a rare autoimmune response to raised endogenous progesterone levels that occur during the luteal phase of the menstrual cycle. Cutaneous, mucosal lesions and other systemic manifestations develop cyclically during the luteal phase of the menstrual cycle when ...
de Jager, AEJ; van der Hoeven, JH
Objective - To investigate the effect of Rhesus anti-D immunoglobulin (anti-D) in patients with an autoimmune demyelinating neuropathy. Material and methods - Three patients with an autoimmune mediated neuropathy received 1000 IU anti-D weekly for 2 months. Results - Two patients worsened gradually
Full Text Available Autoimmune processes can be found in physiological circumstances. However, they are quenched with properly functioning regulatory mechanisms and do not evolve into full-blown autoimmune diseases. Once developed, autoimmune diseases are characterized by signature clinical features, accompanied by sustained cellular and/or humoral immunological abnormalities. Genetic, environmental, and hormonal defects, as well as a quantitative and qualitative impairment of immunoregulatory functions, have been shown in parallel to the relative dominance of proinflammatory Th17 cells in many of these diseases. In this review we focus on the derailed balance between regulatory and Th17 cells in the pathogenesis of autoimmune diseases. Additionally, we depict a cytokine imbalance, which gives rise to a biased T-cell homeostasis. The assessment of Th17/Treg-cell ratio and the simultaneous quantitation of cytokines, may give a useful diagnostic tool in autoimmune diseases. We also depict the multifaceted role of dendritic cells, serving as antigen presenting cells, contributing to the development of the pathognomonic cytokine signature and promote cellular and humoral autoimmune responses. Finally we describe the function and role of extracellular vesicles in particular autoimmune diseases. Targeting these key players of disease progression in patients with autoimmune diseases by immunomodulating therapy may be beneficial in future therapeutic strategies.
Blegvad, Christoffer; Egeberg, Alexander; Tind Nielsen, Tilde E.
arthritis (adjusted OR 6.61; 2.75–15.87) and vitiligo (adjusted OR 4.76; 1.71–13.20) showed strong associations with psoriasis. In addition to increased risk of selected autoimmune diseases, the presence of psoriasis was associated with increased risk of multiple concurrent autoimmune diseases compared...
Saidova, F Kh; Shakhsuvarov, O M; Guseynov, R G; Akhmedova, L M; Aslanova, Zh B
A state of autoimmunity was studied in 25 patients, suffering diffuse toxic goiter (DTG), and in 20--in nodular euthyroid goiter (NEG) before and after the operation. The level of circulating immune complexes, quantity of cytotoxic lymphocytes, the subpopulation index, the apoptosis marker were determined. There was established, that in NEG autoimmune disorders have occurred rarer and were less severe, than in DTG.
Borgwardt, L.; Pedersen, P.; Peitersen, B.
Autoimmune polyglandular syndrome (APS) is an entity, defined by autoimmunity towards two or more endocrine organs. APS is classified in 3 subgroups (type-1, type-2a, type-2b), according to the organs involved. A case is presented of a 13-year old girl referred to the Department of Paediatrics...
Bratland, Eirik; Husebye, Eystein S
Autoimmune adrenocortical failure, or Addison's disease, is a prototypical organ-specific autoimmune disorder. In common with related autoimmune endocrinopathies, Addison's disease is only manageable to a certain extent with replacement therapy being the only treatment option. Unfortunately, the available therapy does not restore the physiological hormone levels and biorhythm. The key to progress in treating and preventing autoimmune Addison's disease lies in improving our understanding of the predisposing factors, the mechanisms responsible for the progression of the disease, and the interactions between adrenal antigens and effector cells and molecules of the immune system. The aim of the present review is to summarize the current knowledge on the role of T cells and cellular immunity in the pathogenesis of autoimmune Addison's disease. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.
Lauren M.F. Merlo
Full Text Available Indoleamine 2,3-dioxygenase 2 (IDO2, a homolog of the better-studied tryptophan-catabolizing enzyme IDO1, is an immunomodulatory molecule with potential effects on various diseases including cancer and autoimmunity. Here, we review what is known about the direct connections between IDO2 and immune function, particularly in relationship to autoimmune inflammatory disorders such as rheumatoid arthritis and lupus. Accumulating evidence indicates that IDO2 acts as a pro-inflammatory mediator of autoimmunity, with a functional phenotype distinct from IDO1. IDO2 is expressed in antigen-presenting cells, including B cells and dendritic cells, but affects inflammatory responses in the autoimmune context specifically by acting in B cells to modulate T cell help in multiple model systems. Given that expression of IDO2 can lead to exacerbation of inflammatory responses, IDO2 should be considered a potential therapeutic target for autoimmune disorders.
Booy, J D; Takata, J; Tomlinson, G; Urbach, D R
Achalasia is a rare disease of the esophagus that has an unknown etiology. Genetic, infectious, and autoimmune mechanisms have each been proposed. Autoimmune diseases often occur in association with one another, either within a single individual or in a family. There have been separate case reports of patients with both achalasia and one or more autoimmune diseases, but no study has yet determined the prevalence of autoimmune diseases in the achalasia population. This paper aims to compare the prevalence of autoimmune disease in patients with esophageal achalasia to the general population. We retrospectively reviewed the charts of 193 achalasia patients who received treatment at Toronto's University Health Network between January 2000 and May 2010 to identify other autoimmune diseases and a number of control conditions. We determined the general population prevalence of autoimmune diseases from published epidemiological studies. The achalasia sample was, on average, 10-15 years older and had slightly more men than the control populations. Compared to the general population, patients with achalasia were 5.4 times more likely to have type I diabetes mellitus (95% confidence interval [CI] 1.5-19), 8.5 times as likely to have hypothyroidism (95% CI 5.0-14), 37 times as likely to have Sjögren's syndrome (95% CI 1.9-205), 43 times as likely to have systemic lupus erythematosus (95% CI 12-154), and 259 times as likely to have uveitis (95% CI 13-1438). Overall, patients with achalasia were 3.6 times more likely to suffer from any autoimmune condition (95% CI 2.5-5.3). Our findings are consistent with the impression that achalasia's etiology has an autoimmune component. Further research is needed to more conclusively define achalasia as an autoimmune disease. © 2011 Copyright the Authors. Journal compilation © 2011, Wiley Periodicals, Inc. and the International Society for Diseases of the Esophagus.
Kuijpers, T. W.; de Haas, M.; de Groot, C. J.; von dem Borne, A. E.; Weening, R. S.
An 8-year-old boy had been suffering from chronic autoimmune neutropenia for more than 5 years. The neutropenia proved to be resistant to high-dose steroids and intravenous (either low-or high-dose) immunoglobulin (Ig) therapy. The chronic autoimmune thrombocytopenia and recurrent phases of
Betterle, Corrado; Garelli, Silvia; Coco, Graziella; Burra, Patrizia
Type 3 autoimmune polyendocrine syndrome (APS-3) is defined by the presence of an autoimmune thyroid disease and another autoimmune illness, excluding Addison's disease; this is a frequent combination. We report the case of a 55 years old female patient with APS-3, with seven clinical or latent autoimmune manifestations. At 49 years of age she was admitted at the General Hospital for leukopenia, weight loss, tremors, anxiety and diarrhea. The personal history revealed ulcerative colitis and, during the last year, episodes of fever with migrant arthralgia and cutaneous lesions. The patient was evaluated for thyroid function and imaging, mielobiopsy, glycaemic control, gastrointestinal and rheumatologic disorders with specific biochemical tests, imaging and endoscopic procedures. We concluded that the patient was affected by APS-3, characterized by the association of Graves' disease, autoimmune leukopenia, latent autoimmune diabetes of the adult (LADA), autoimmune gastritis, ulcerative colitis, Sjögren's and anti-phospholipid syndromes. The patient started low doses of corticosteroid drugs for leukopenia, underwent (131)I therapy for hyperthyroidism and later started substitutive thyroid therapy with l-thyroxine, insulin therapy for LADA, mesalazine for ulcerative colitis and artificial tears for Sjögren's syndrome. In this article we report a complex case of APS-3, characterized by the association of seven different autoimmune diseases, which required a complex therapeutic strategy.
Morton, J.I.; Siegel, B.V.
The results of the present experiments support the concept of an etiology of autoimmune disease predicated upon innate properties of the hemopoietic stem cell and its differentiated lymphocytic progeny, independent of the host internal environment. It was concluded earlier that the NZB mouse strain possessed an enlarged compartment of cyclically active stem cells, providing an etiological basis for the development of autoimmune disease. Conceivably, a rapidly cycling stem cell population could randomly generate excessive numbers of lymphocytic progeny. Autoantibody formation would represent, then, a manifestation of the consequent hyperresponsiveness to immunological stimuli, both foreign and autologous. Alternatively, there may exist a parallel defect in the homeostatic regulation of both stem cell and immunocyte populations, attributable to either a defect in a shared regulator mechanism or to an unusually high threshold of these cells in response to negative feedback signals
Pedchenko, Vadim; Richard Kitching, A; Hudson, Billy G
Goodpasture's (GP) disease is an autoimmune disorder characterized by the deposition of pathogenic autoantibodies in basement membranes of kidney and lung eliciting rapidly progressive glomerulonephritis and pulmonary hemorrhage. The principal autoantigen is the α345 network of collagen IV, which expression is restricted to target tissues. Recent discoveries include a key role of chloride and bromide for network assembly, a novel posttranslational modification of the antigen, a sulfilimine bond that crosslinks the antigen, and the mechanistic role of HLA in genetic susceptibility and resistance to GP disease. These advances provide further insights into molecular mechanisms of initiation and progression of GP disease and serve as a basis for developing of novel diagnostic tools and therapies for treatment of Goodpasture's disease. Copyright © 2017. Published by Elsevier B.V.
Full Text Available Inter-individual variability has been a major hurdle to optimize disease management. Precision medicine holds promise for improving health and healthcare via tailor-made therapeutic strategies. Herein, we outline the paradigm of “pharmacometabolomics-aided pharmacogenomics” in autoimmune diseases. We envisage merging pharmacometabolomic and pharmacogenomic data (to address the interplay of genomic and environmental influences with information technologies to facilitate data analysis as well as sense- and decision-making on the basis of synergy between artificial and human intelligence. Humans can detect patterns, which computer algorithms may fail to do so, whereas data-intensive and cognitively complex settings and processes limit human ability. We propose that better-informed, rapid and cost-effective omics studies need the implementation of holistic and multidisciplinary approaches.
Stern, Michael E.; Schaumburg, Chris S.; Pflugfelder, Stephen C.
Dry eye is a common ocular surface inflammatory disease that significantly affects quality of life. Dysfunction of the lacrimal function unit (LFU) alters tear composition and breaks ocular surface homeostasis, facilitating chronic inflammation and tissue damage. Accordingly, the most effective treatments to date are geared towards reducing inflammation and restoring normal tear film. The pathogenic role of CD4+ T cells is well known, and the field is rapidly realizing the complexity of other innate and adaptive immune factors involved in the development and progression of disease. The data support the hypothesis that dry eye is a localized autoimmune disease originating from an imbalance in the protective immunoregulatory and proinflammatory pathways of the ocular surface. PMID:23360156
Full Text Available Myositides comprise a large group of disorders involving limb muscle weakness. In differential diagnosis we have to consider idiopathic myositides, myositides associated with other diseases, and those induced by external factors, e.g. drug-induced. Statins are commonly used drugs, but many patients experience a broad spectrum of adverse effects including symptoms from skeletal muscle. Physicians should pay special attention to patients reporting muscle weakness lasting longer than 12 weeks, despite statin withdrawal, as well as other symptoms: dysphagia, disturbed grip function, elevated creatinine kinase (CK levels and abnormal electromyography. The reported case deals with the problem of differential diagnosis of drug-induced muscle injury, polymyositis with a recently reported myopathy – statin-induced autoimmune necrotizing myositis, related to anti-HMGCR antibodies.
Full Text Available Palmoplantar keratoderma is a heterogeneous group of hereditary and acquired disorders characterized by abnormal thickening of palms and soles. Hypothyroidism is an unusual cause of palmoplantar keratoderma, rarely reported in the literature. We report a case of a 43-year-old woman presented with a 3-month history of a diffuse palmoplantar hyperkeratosis unresponsive to topical keratolytics and corticosteroids. Her past medical and family histories were unremarkable. She complained of recent asthenia, mood changes and constipation. Laboratory evaluation revealed an autoimmune thyroiditis with hypothyroidism. Other causes of acquired palmoplantar keratoderma were excluded. After hormonal replacement therapy institution, a gradual improvement of skin condition was observed. The diagnosis of underlying causes for acquired palmoplantar keratoderma can be a difficult task; however its recognition is essential for successful treatment results. Although a very rare association, hypothyroidism must be suspected in patients with acquired palmoplantar keratoderma, particularly when it occurs in association with systemic symptoms.
Cascio, Michael J; Jen, Kuang-Yu
Levamisole was previously used for its immunomodulatory properties to treat rheumatoid arthritis and some cancers. However, because of serious side-effects, it was taken off the market in the United States. Recently, levamisole has reemerged as a popular cocaine adulterant. Some individuals who consume levamisole-adulterated cocaine can develop a life-threatening autoimmune syndrome. In this review, the medical consequences of levamisole exposure and postulated mechanisms by which levamisole induces these adverse effects are discussed. Although agranulocytosis and cutaneous vasculitis are the major findings in patients who develop cocaine/levamisole-associated autoimmune syndrome (CLAAS), more recent experience indicates that other organ systems can be involved as well. Current studies point to neutrophil activation and neutrophil extracellular trap formation with subsequent antineutrophil cytoplasmic antibody-mediated tissue injury as a possible mechanism of CLAAS. In the past decade, the detrimental effects of levamisole have reemerged because of its popularity as a cocaine adulterant. Although infrequent, some individuals develop a systemic autoimmune syndrome characterized by immune-mediated agranulocytosis and antineutrophil cytoplasmic antibody-mediated vasculitis. Mechanistically, neutrophil antigens appear to be a major player in inducing CLAAS. Prompt cessation of levamisole exposure is key to treatment, although relapses are frequent because of the addictive effects of cocaine and the high prevalence of levamisole within the cocaine supply.
Wang Gangduo; Cai Ping; Ansari, G.A.S.; Khan, M. Firoze
Reactive oxygen and nitrogen species (RONS) are implicated in the pathogenesis of several autoimmune diseases. Also, increased lipid peroxidation and protein nitration are reported in systemic autoimmune diseases. Lipid peroxidation-derived aldehydes (LPDAs) such as malondialdehyde (MDA) and 4-hydroxynonenal (HNE) are highly reactive and bind proteins covalently, but their potential to elicit an autoimmune response and contribution to disease pathogenesis remain unclear. Similarly, nitration of protein could also contribute to disease pathogenesis. To assess the status of lipid peroxidation and/or RONS, autoimmune-prone female MRL+/+ mice (5-week old) were treated with trichloroethene (TCE), an environmental contaminant known to induce autoimmune response, for 48 weeks (0.5 mg/ml via drinking water), and formation of antibodies to LPDA-protein adducts was followed in the sera of control and TCE-treated mice. TCE treatment led to greater formation of both anti-MDA- and -HNE-protein adduct antibodies and higher serum iNOS and nitrotyrosine levels. The increase in TCE-induced oxidative stress was associated with increases in anti-nuclear-, anti-ssDNA- and anti-dsDNA-antibodies. These findings suggest that TCE exposure not only leads to oxidative/nitrosative stress, but is also associated with induction/exacerbation of autoimmune response in MRL+/+ mice. Further interventional studies are needed to establish a causal role of RONS in TCE-mediated autoimmunity
Soriano, Alessandra; Nesher, Gideon; Shoenfeld, Yehuda
Vaccinations have been used as an essential tool in the fight against infectious diseases, and succeeded in improving public health. However, adverse effects, including autoimmune conditions may occur following vaccinations (autoimmune/inflammatory syndrome induced by adjuvants--ASIA syndrome). It has been postulated that autoimmunity could be triggered or enhanced by the vaccine immunogen contents, as well as by adjuvants, which are used to increase the immune reaction to the immunogen. Fortunately, vaccination-related ASIA is uncommon. Yet, by defining individuals at risk we may further limit the number of individuals developing post-vaccination ASIA. In this perspective we defined four groups of individuals who might be susceptible to develop vaccination-induced ASIA: patients with prior post-vaccination autoimmune phenomena, patients with a medical history of autoimmunity, patients with a history of allergic reactions, and individuals who are prone to develop autoimmunity (having a family history of autoimmune diseases; asymptomatic carriers of autoantibodies; carrying certain genetic profiles, etc.). Copyright © 2014 Elsevier Ltd. All rights reserved.
Proust-Lemoine, Emmanuelle; Guyot, Sylvie
Auto-immune polyendocrine syndrome type 1 (APS1) also called Auto-immune Polyendocrinopathy Candidiasis Ectodermal Dystrophy (APECED) is a rare monogenic childhood-onset auto-immune disease. This autosomal recessive disorder is caused by mutations in the auto-immune regulator (AIRE) gene, and leads to autoimmunity targeting peripheral tissues. There is a wide variability in clinical phenotypes in patients with APSI, with auto-immune endocrine and non-endocrine disorders, and chronic mucocutaneous candidiasis. These patients suffer from oral diseases such as dental enamel hypoplasia and candidiasis. Both are frequently described, and in recent series, enamel hypoplasia and candidiasis are even the most frequent components of APS1 together with hypoparathyroidism. Both often occur during childhood (before 5 years old for canrdidiasis, and before 15 years old for enamel hypoplasia). Oral candidiasis is recurrent all life long, could become resistant to azole antifungal after years of treatment, and be carcinogenic, leading to severe oral squamous cell carcinoma. Oral components of APS1 should be diagnosed and rigorously treated. Dental enamel hypoplasia and/or recurrent oral candidiasis in association with auto-immune diseases in a young child should prompt APS1 diagnosis. Copyright © 2017 Elsevier Masson SAS. All rights reserved.
Kolypetri, P; Randell, E; Van Vliet, B N; Carayanniotis, G
Recent studies have shown that high salt (HS) intake exacerbates experimental autoimmune encephalomyelitis and have raised the possibility that a HS diet may comprise a risk factor for autoimmune diseases in general. In this report, we have examined whether a HS diet regimen could exacerbate murine autoimmune thyroiditis, including spontaneous autoimmune thyroiditis (SAT) in non-obese diabetic (NOD.H2h4) mice, experimental autoimmune thyroiditis (EAT) in C57BL/6J mice challenged with thyroglobulin (Tg) and EAT in CBA/J mice challenged with the Tg peptide (2549–2560). The physiological impact of HS intake was confirmed by enhanced water consumption and suppressed aldosterone levels in all strains. However, the HS treatment failed to significantly affect the incidence and severity of SAT or EAT or Tg-specific immunoglobulin (Ig)G levels, relative to control mice maintained on a normal salt diet. In three experimental models, these data demonstrate that HS intake does not exacerbate autoimmune thyroiditis, indicating that a HS diet is not a risk factor for all autoimmune diseases. PMID:24528002
Sang Jin Kim
Full Text Available Polyglandular autoimmune syndrome is defined as multiple endocrine gland insufficiencies accompanied by autoimmune diseases of the endocrine and nonendocrine system. After Schmidt introduced a case of nontuberculosis adrenal gland dysfunction with thyroiditis in 1926, Neufeld defined polyglandular autoimmune syndrome by I, II, and III subtypes in 1980 by their presentation of occurrence age, heredity methods, relationship with human leukocyte antigen, and accompanying diseases. We report a case of a 32-year-old female with polyglandular autoimmune syndrome III accompanied by type 1 diabetes mellitus that was treated with insulin (36 units per day for 11 years. She had insulin deficiency and Hashimoto thyroiditis as an autoimmune disorder. In addition, she had several features similar to Albright's hereditary osteodystrophy including short stature, truncal obesity, round face, short neck, low intelligence (full IQ 84, and decreased memory. Although Albright's hereditary osteodystrophy is morphological evidence of pseudohypoparathyroidism or pseudopseudohypoparathyroidism, she had primary hypoparathyroidism on laboratory results. Here, we report a case of polyglandular autoimmune syndrome III with type 1 diabetes mellitus, autoimmune thyroiditis, and primary hypoparathyroidism, accompanied by clinical features similar to Albright's hereditary osteodystrophy.
Adams Waldorf, Kristina M.; Nelson, J. Lee
Pregnancy has both short-term effects and long-term consequences. For women who have an autoimmune disease and subsequently become pregnant, pregnancy can induce amelioration of the mother’s disease, such as in rheumatoid arthritis, while exacerbating or having no effect on other autoimmune diseases like systemic lupus erythematosus. That pregnancy also leaves a long-term legacy has recently become apparent by the discovery that bi-directional cell trafficking results in persistence of fetal cells in the mother and of maternal cells in her offspring for decades after birth. The long-term persistence of a small number of cells (or DNA) from a genetically disparate individual is referred to as microchimerism. While microchimerism is common in healthy individuals and is likely to have health benefits, microchimerism has been implicated in some autoimmune diseases such as systemic sclerosis. In this paper, we will first discuss short-term effects of pregnancy on women with autoimmune disease. Pregnancy-associated changes will be reviewed for selected autoimmune diseases including rheumatoid arthritis, systemic lupus erythematosus and autoimmune thyroid disease. The pregnancy-induced amelioration of rheumatoid arthritis presents a window of opportunity for insights into both immunological mechanisms of fetal-maternal tolerance and pathogenic mechanisms in autoimmunity. A mechanistic hypothesis for the pregnancy-induced amelioration of rheumatoid arthritis will be described. We will then discuss the legacy of maternal-fetal cell transfer from the perspective of autoimmune diseases. Fetal and maternal microchimerism will be reviewed with a focus on systemic sclerosis (scleroderma), autoimmune thyroid disease, neonatal lupus and type I diabetes mellitus. PMID:18716941
Refaat, Rania; Harth, Marc; Proschek, Petra; Lindemayr, Sebastian; Vogl, Thomas J.
We report a case of histopathologically proven autoimmune pancreatitis in an 11-year-old boy. Abdominal US and MRI showed a focal swelling of the pancreatic head, the latter also showing delayed contrast enhancement. There was diffuse irregular pancreatic duct narrowing, compression of the intrapancreatic common bile duct, and mild proximal biliary dilatation on MR cholangiopancreatography. Laboratory results revealed normal serum IgG and subclass 4 with negative autoimmune antibodies, and slightly elevated carbohydrate antigen 19-9. This highlights the differentiation of autoimmune pancreatitis from pancreatic head cancer and, to a lesser extent, other forms of pancreatitis in children. (orig.)
Refaat, Rania [Johann-Wolfgang-Goethe University, Department of Diagnostic and Interventional Radiology, Frankfurt am Main (Germany); Ain Shams University, Department of Diagnostic and Interventional Radiology, Cairo (Egypt); Harth, Marc; Proschek, Petra; Lindemayr, Sebastian; Vogl, Thomas J. [Johann-Wolfgang-Goethe University, Department of Diagnostic and Interventional Radiology, Frankfurt am Main (Germany)
We report a case of histopathologically proven autoimmune pancreatitis in an 11-year-old boy. Abdominal US and MRI showed a focal swelling of the pancreatic head, the latter also showing delayed contrast enhancement. There was diffuse irregular pancreatic duct narrowing, compression of the intrapancreatic common bile duct, and mild proximal biliary dilatation on MR cholangiopancreatography. Laboratory results revealed normal serum IgG and subclass 4 with negative autoimmune antibodies, and slightly elevated carbohydrate antigen 19-9. This highlights the differentiation of autoimmune pancreatitis from pancreatic head cancer and, to a lesser extent, other forms of pancreatitis in children. (orig.)
Mikhina, M S; Molashenko, N V; Troshina, E A; Orlova, E M; Sozaeva, L S; Eystein, S H; Breivik, S
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.
Winther, Kristian H.; Bonnema, Steen; Hegedüs, Laszlo
PURPOSE OF REVIEW: This review provides an appraisal of recent evidence for or against selenium supplementation in patients with autoimmune thyroid diseases, and discusses possible effect mechanisms. RECENT FINDINGS: Epidemiological data suggest an increased prevalence of autoimmune thyroid...... diseases under conditions of low dietary selenium intake. Two systematic reviews have evaluated controlled trials among patients with autoimmune thyroiditis and report that selenium supplementation decreases circulating thyroid autoantibodies. The immunomodulatory effects of selenium might involve reducing...... proinflammatory cytokine release. However, clinically relevant effects of selenium supplementation, including improvement in quality of life, are more elusive. In Graves’ disease, some, but not all, trials indicate that adjuvant selenium supplementation enhances the restoration of biochemical euthyroidism...
Benros, Michael E; Eaton, William W; Mortensen, Preben B
diseases involve multiple organs and general dysfunction of the immune system, which could affect the brain and induce psychiatric symptoms. Most studies have been cross-sectional, observing an increased prevalence of a broad number of autoimmune diseases in people with psychotic disorders. Furthermore......, there is some evidence of associations of psychosis with a family history of autoimmune disorders and vice versa. Additionally, several autoimmune diseases, individually and in aggregate, have been identified as raising the risk for psychotic disorders in longitudinal studies. The associations have been...
Choi, Dae Han; Kim, Hae Kyung; Park, Tae Il; John, Byung Min; Kang, Sung Hwan; Lee, Yoon Serk; Kim, Tae Hyun; Lee, Uh Joo; Lee, Tae Seung; Yoon, Gwi Ok
Overlap of autoimmune hepatitis and systemic lupus erythematosus (SLE) is a comparatively rare condition. Although both autoimmune hepatitis and SLE can share common autoimmune features such as polyarthralgia, hypergammaglobulinemia and positive ANA, it has been considered as two different entities. We report a case of anti-LKM1 positive autoimmune hepatitis who developed SLE two years later. The presence of interface hepatitis with lymphoplasma cell infiltrates and rosette formation points to the autoimmune hepatitis rather than SLE hepatitis. Autoimmune hepatitis is infrequently accompanied by SLE, therefore, it could be recommended to investigate for SLE in patients with autoimmune hepatitis.
De Leeuw, K.; Kallenberg, Cees; Bijl, Marc; Shoenfeld, Y.; Gershwin, M.E.; Shoenfeld, Y; Gershwin, ME
Systemic autoimmune diseases such as systemic lupus erythematosus and Wegener's granulomatosis are associated with a significantly increased prevalence of cardiovascular disease (CVD) compared with age- and sex-matched controls. Many risk factors are involved in the pathogenesis of atherosclerosis,
Arefieva, A S; Smoldovskaya, O V; Tikhonov, A A; Rubina, A Yu
Allergic and autoimmune diseases represent immunopathological reactions of an organism to antigens. Despite that the allergy is a result of exaggerated immune response to foreign antigens (allergens) and autoimmune diseases are characterized by the pathological response to internal antigens (autoantigens), the underlying mechanisms of these diseases are probably common. Thus, both types of diseases represent variations in the hypersensitivity reaction. A large percentage of both the adult and pediatric population is in need of early diagnostics of these pathologies of the immune system. Considering the diversity of antibodies produced in allergic and autoimmune disease and the difficulties accompanying clinical diagnosing, molecular diagnostics of these pathological processes should be carried out in several stages, including screening and confirmatory studies. In this review, we summarize the available data on the molecular diagnostics and therapy of allergic and autoimmune diseases and discuss the basic similarities and differences in the mechanisms of their development.
Wu, Hsin-Jung; Wu, Eric
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.
Cotsapas, Chris; Voight, Benjamin F.; Rossin, Elizabeth
Genome-wide association (GWA) studies have identified numerous, replicable, genetic associations between common single nucleotide polymorphisms (SNPs) and risk of common autoimmune and inflammatory (immune-mediated) diseases, some of which are shared between two diseases. Along with epidemiologic...
Nielsen, Philip Finn Rising; Benros, Michael Eriksen; Dalsgaard, Søren
attention-deficit/hyperactivity disorder (ADHD). METHOD: A cohort was formed of all singletons born in Denmark from 1990 to 2007, resulting in a study population of 983,680 individuals followed from 1995 to 2012. Information on autoimmune diseases was obtained from the Danish National Hospital Register......OBJECTIVE: Recent studies have suggested that autoimmune diseases and immune activation play a part in the pathogenesis of different neurodevelopmental disorders. This study investigated the association between a personal history and a family history of autoimmune disease and the risk of developing....... Individuals with ADHD were identified through the Danish National Hospital Register and the Danish Psychiatric Central Register. RESULTS: In total, 23,645 children were diagnosed with ADHD during the study period. Autoimmune disease in the individual was associated with an increased risk of ADHD...
Tasić, J; Macukanović, L; Pavlović, M; Koraćević, S; Govedarević, N; Kitić, Lj; Tijanić, I; Bakić, M
Basic principles in the therapy of idiopathic autoimmune hemolytic anemia induced by warm antibody were glucocorticoides and splenectomy. Immunosupresive drugs, plasmaferesis and intravenous high doses gamma globulin therapy are also useful. In secundary autoimmune hemolytic anemia induced by warm antibody we treated basic illness. During the period of 1990-1992 we treated 21 patients with primary autoimmune hemolytic anemia and 6 patients with secondary /4 CLL and 2 Non-Hodgkin's lymphoma/. Complete remission we found as a normalisation of reticulocites and hemoglobin level respectively. Complete remission by corticoides we got in 14/21 patients, partial response in 2/21 respectively. Complete response by splenectomy we got in 2/3 splenoctomized patients (idiopathic type). For successful treatment secondary hemolytic anemias we treated primary diseases (CLL and malignant lymphoma) and we got in 4/6 patients complete remission. Our results were standard in both type of autoimmune hemolytic anaemias induced by warm antibody.
Feldt-Rasmussen, Ulla; Rasmussen, Ase Krogh
Coexistence of differentiated thyroid cancer (DTC) and thyroid autoimmune diseases could represent a mere coincidence due to the frequent occurrence of autoimmunity, but there may also be a pathological and causative link between the two conditions. The coincidence of DTC with Hashimoto's disease...... has been variably reported at between 0.5 and 22.5% and of DTC with Graves' disease between 0 and 9.8%. In this review available evidence for thyroid autoimmunity in DTC is summarized and it is concluded that thyroid cancer does coexist with thyroid autoimmunity, implying that patients treated...... TgAb measurements may be used as a surrogate marker for recurrence of thyroid cancer during the long-term monitoring of DTC patients....
Feldt-Rasmussen, Ulla; Rasmussen, Ase Krogh
Coexistence of differentiated thyroid cancer (DTC) and thyroid autoimmune diseases could represent a mere coincidence due to the frequent occurrence of autoimmunity, but there may also be a pathological and causative link between the two conditions. The coincidence of DTC with Hashimoto's disease...... has been variably reported at between 0.5 and 22.5% and of DTC with Graves' disease between 0 and 9.8%. In this review available evidence for thyroid autoimmunity in DTC is summarized and it is concluded that thyroid cancer does coexist with thyroid autoimmunity, implying that patients treated...... TgAb measurements may be used as a surrogate marker for recurrence of thyroid cancer during the long-term monitoring of DTC patients....
Auto-immune haematological complications occurring during treatment for malignant Iymphoproliferative diseases are described in 5 patients. There appeared to be a temporal relationship between the development of these complications and the administration of chemotherapeutic drugs or extensive radiotherapy.
Albert J Czaja
Full Text Available BACKGROUND: Autoimmune hepatitis may have cholestatic features that are outside the classical phenotype and that resemble findings in other immune-mediated liver diseases. These cholestatic phenotypes have been designated ‘overlap syndromes’.
Hollan, Ivana; Meroni, Pier Luigi; Ahearn, Joseph M; Cohen Tervaert, J W; Curran, Sam; Goodyear, Carl S; Hestad, Knut A; Kahaleh, Bashar; Riggio, Marcello; Shields, Kelly; Wasko, Mary C
Various autoimmune rheumatic diseases (ARDs), including rheumatoid arthritis, spondyloarthritis, vasculitis and systemic lupus erythematosus, are associated with premature atherosclerosis. However, premature atherosclerosis has not been uniformly observed in systemic sclerosis. Furthermore, although experimental models of atherosclerosis support the role of antiphospholipid antibodies in atherosclerosis, there is no clear evidence of premature atherosclerosis in antiphospholipid syndrome (APA). Ischemic events in APA are more likely to be caused by pro-thrombotic state than by enhanced atherosclerosis. Cardiovascular disease (CVD) in ARDs is caused by traditional and non-traditional risk factors. Besides other factors, inflammation and immunologic abnormalities, the quantity and quality of lipoproteins, hypertension, insulin resistance/hyperglycemia, obesity and underweight, presence of platelets bearing complement protein C4d, reduced number and function of endothelial progenitor cells, apoptosis of endothelial cells, epigenetic mechanisms, renal disease, periodontal disease, depression, hyperuricemia, hypothyroidism, sleep apnea and vitamin D deficiency may contribute to the premature CVD. Although most research has focused on systemic inflammation, vascular inflammation may play a crucial role in the premature CVD in ARDs. It may be involved in the development and destabilization of both atherosclerotic lesions and of aortic aneurysms (a known complication of ARDs). Inflammation in subintimal vascular and perivascular layers appears to frequently occur in CVD, with a higher frequency in ARD than in non-ARD patients. It is possible that this inflammation is caused by infections and/or autoimmunity, which might have consequences for treatment. Importantly, drugs targeting immunologic factors participating in the subintimal inflammation (e.g., T- and B-cells) might have a protective effect on CVD. Interestingly, vasa vasorum and cardiovascular adipose tissue may
Full Text Available CLL has been defined as presence of more than 5000 small mature appearing monoclonal B lymphocytes with a specific immunophenotype in peripheral blood. It is a well-known fact that CLL is associated with autoimmune cytopenias. CLL cells are CD5+ B lymphocytes, and usually are not the “guilty” cells which produce autoantibodies. T cell defect is another characteristic of CLL and the total number of T cells is increased, and there is inversion of the CD4/CD8 ratio. Autoimmune hemolytic anemia (AIHA is the most common autoimmune complication of CLL and has been reported in 10-25% of CLL patients. However, the stage-adjusted estimated rate of AIHA in CLL is about 5%. Conversely, CLL is three times more common in patients who present with AIHA. Direct agglutinin test (DAT is positive in 7-14% of CLL patients but AIHA may also occur in DAT negative patients. Autoimmune thrombocytopenia (AIT is the second most common complication of CLL and has been reported in 2-3% of patients. DAT is positive in AIT but presence of antiplatelet antibodies is neither diagnostic nor reliable. Autoimmune neutropenia (AIN and pure red cell aplasia (PRCA are very rare complications of CLL and like other autoimmune complications of CLL may occur at any clinical stage. It is believed that most case reports of AIN and PRCA in CLL actually belong to large granular lymphocytic leukemia (LGL. Non-hematologic autoimmune complications of CLL including cold agglutinin disease (CAD, paraneoplastic pemphigus (PNP, acquired angioedema, and anti-myelin associated globulin are rare. Before starting any treatment, clinicians should distinguish between autoimmune cytopenias and massive bone marrow infiltration since autoimmune complications of CLL are not necessarily equal to advanced disease with poor prognosis. According to IWCLL guideline, steroids are the mainstay of treatment of simple autoimmunity. Intravenous immunoglobulin (IVIg, cyclosporine, and rituximab are used in
Amarapurkar, D N; Amarapurkar, A D
To evaluate the prevalence and clinical profile of autoimmune hepatitis (AIH) in patients with chronic liver disease. Four hundred and thirty five consecutive patient with chronic liver disease seen in our department from January 1997 to December 1998 were studied with detailed history and clinical examination. All the patients underwent liver function tests, ultrasonography, isotope liver scanning, viral markers, autoimmune markers ANA, ASMA, LKM1 and AMA (by immunofluorescence technique) and liver histology whenever permissible. Appropriate work up for Wilson's disease was done whenever suspected clinically. Diagnosis of autoimmune hepatitis was made by the composite scoring system by international autoimmune hepatitis group. Twenty out of the 435 patients met the criteria of definite autoimmune hepatitis and seven patient had probable autoimmune hepatitis. Forty out of 408 patients showed markers of autoimmunity positive but did not qualify diagnosis of AIH on composite scores. Demographic profile of 27 patients with autoimmune hepatitis was as follows; male:female ratio 1:8, mean age 39.8 +/- 13 years (Range 4-65 years); mode of presentation as cirrhosis 11/27 (40.7%), chronic hepatitis 12/27 (44.4%) and acute hepatitis 4/27 (14.8%). Elevated serum bilirubin levels were seen in 12 (44.4%) patients while mean serum aminotransferases levels were 249 +/- 343 and 262 +/- 418 respectively. Other disease associations seen were as follows: diabetes in 4 (14.8%), rheumatoid arthritis in 3 (11%), hypothyroidism in 2 (7.4%) and ulcerative colitis in 1 (3.7%). The pattern of autoimmune markers was ANA +ve 23/27 (85%) (+ve titres of ANA > 1:80 in adults and 1:20 in children), ASMA +ve in 16/27 (59.2%) (+ve titres of ASMA > 1:40) and LKM1 in 3 patients. AMA in tires less than 1:80 was found in 3 patients. Liver histology changes seen were lymphoplasmacytic infiltrates (100%), bridging necrosis (93%), liver cell rossetting (80%) and fibrosis with or without cirrhosis (50
Yadlapati, Sujani; Efthimiou, Petros
Specific autoimmune and inflammatory rheumatic diseases have been associated with an increased risk of malignant lymphomas. Conditions such as rheumatoid arthritis (RA), primary Sjögren’s syndrome (pSS), systemic lupus erythematosus (SLE), dermatomyositis, and celiac disease have been consistently linked to malignant lymphomas. Isolated cases of lymphomas associated with spondyloarthropathies and autoinflammatory diseases have also been reported. Direct association between autoimmunity and ly...
Full Text Available Autoimmune pancreatitis (AIP is a special type of chronic pancreatitis that originates from an autoimmune-mediated mechanism. AIP has unique radiological, serological, and histopathological features, often accompanied by peripancreatic lesions. AIP may be easily confused with pancreatic cancer and cholangiocarcinoma. It is necessary to diagnose AIP while integrating a variety of clinical indicators. Steroid therapy should be performed for patients diagnosed with AIP, and surgical treatment can be selected if necessary.
Brunetti, Luigia; Francavilla, Ruggiero; Miniello, Vito L
The etiology of chronic urticaria (CU) in childhood often remains unrecognized. Recently, in adults it has been shown that approximately 40% of patients with CU have autoimmune urticaria (AU); however, no data are available in children.......The etiology of chronic urticaria (CU) in childhood often remains unrecognized. Recently, in adults it has been shown that approximately 40% of patients with CU have autoimmune urticaria (AU); however, no data are available in children....
Ginanjar, Eka; Yulianto, Yulianto
This case study aim to evaluate the response of steroid treatment for autoimmune endocarditis. Valvular heart disease is relatively rising in both congenital and acquired cases, but the autoimmune endocarditis remains rare. In this case, a 34 year old woman with clinical manifestation resembling systemic lupus erythematosus (SLE) is diagnosed with Libman-sacks Endocarditis. After six months of steroid treatment, her clinical manifestations and heart structure improved.
Marjolein A. C. Mattheij
Full Text Available We describe a girl, now 9 years of age, with chronic idiopathic thrombocytopenic purpura, persistent nonmalignant lymphadenopathy, splenomegaly, recurrent infections, and autoimmune hemolytic anemia. Her symptoms partly fit the definitions of both autoimmune lymphoproliferative syndrome (ALPS and common variable immunodeficiency disorders (CVIDs. Genetic analysis showed no abnormalities in the ALPS-genes FAS, FASLG, and CASP10. The CVID-associated TACI gene showed a homozygous polymorphism (Pro251Leu, which is found also in healthy controls.
Benros, Michael E; Nielsen, Philip R; Nordentoft, Merete
Autoimmune diseases have been associated with an increased risk of schizophrenia. It has been suggested that brain-reactive autoantibodies are part of the mechanisms behind this association. Furthermore, an increased permeability of the blood-brain barrier has been observed during periods...... of infection and inflammation. The authors therefore investigated whether autoimmune diseases combined with exposures to severe infections may increase the risk of schizophrenia...
Kerr, Jonathan R
Human parvovirus B19 is a single-stranded DNA virus which preferentially targets the erythroblasts in the bone marrow. B19 infection commonly causes erythema infectiosum, arthralgia, fetal death, transient aplastic crisis in patients with shortened red cell survival, and persistent infection in people who are immunocompromised. Less common clinical manifestations include atypical skin rashes, neurological syndromes, cardiac syndromes, and various cytopenias. B19 infection has also been associated with development of a variety of different autoimmune diseases, including rheumatological, neurological, neuromuscular, cardiovascular, haematological, nephrological and metabolic. Production of a variety of autoantibodies has been demonstrated to occur during B19 infection and these have been shown to be key to the pathogenesis of the particular disease process in a significant number of cases, for example, production of rheumatoid factor in cases of B19-associated rheumatoid arthritis and production of anti-glutamic acid decarboxylase (GAD) in patients with B19-associated type 1 diabetes mellitus. B19 infection has also been associated with the development of multiple autoimmune diseases in 12 individuals. Documented mechanisms in B19-associated autoimmunity include molecular mimicry (IgG antibody to B19 proteins has been shown to cross react with a variety of recognised human autoantigens, including collagen II, keratin, angiotensin II type 1 receptor, myelin basic protein, cardiolipin, and platelet membrane glycoprotein IIb/IIIa), B19-induced apoptosis with presentation of self-antigens to T lymphocytes, and the phospholipase activity of the B19 unique VP1 protein. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
Full Text Available Introduction. Autoimmune polyglandular syndrome type 2 is defined as adrenal insufficiency associated with autoimmune primary hypothyroidism and/or with autoimmune type 1 diabetes mellitus, but very rare with myasthenia gravis. Case report. We presented a case of an autoimmune polyglandular syndrome, type 2 associated with myasthenia gravis. A 49-year-old female with symptoms of muscle weakness and low serum levels of cortisol and aldosterone was already diagnosed with primary adrenal insufficiency. Primary hypothyroidism was identified with low values of free thyroxine 4 (FT4 and raised values of thyroidstumulating hormone (TSH. The immune system as a cause of hypothyroidism was confirmed by the presence of thyroid antibodies to peroxidase and TSH receptors. Myasthenia gravis was diagnosed on the basis of a typical clinical feature, positive diagnostic tests and an increased titre of antibodies against the acetylcholine receptors. It was not possible to confirm the immune nature of adrenal insufficiency by the presence of antibodies to 21- hydroxylase. The normal morphological finding of the adrenal glands was an indirect confirmation of the condition as well as the absence of other diseases that might have led to adrenal insufficiency and low levels of both serum cortisol and aldosterone. Hormone replacement therapy, anticholinergic therapy and corticosteroid therapy for myasthenia gravis improved the patient’s general state of health and muscle weakness. Conclusion. This case report indicates a need to examine each patient with an autoimmune disease carefully as this condition may be associated with another autoimmune diseases.
Barbuti, Margherita; Carvalho, André F; Köhler, Cristiano A; Murru, Andrea; Verdolini, Norma; Guiso, Giovanni; Samalin, Ludovic; Maes, Michael; Stubbs, Brendon; Perugi, Giulio; Vieta, Eduard; Pacchiarotti, Isabella
Accumulating evidence points to the pathophysiological relevance between immune dysfunction and mood disorders. High rates of thyroid dysfunction have been found in patients with bipolar disorder (BD), compared to the general population. A systematic review of the relationship between BD and thyroid autoimmunity was performed. Pubmed, EMBASE and PsycINFO databases were searched up till January 28th, 2017. This review has been conducted according to the PRISMA statements. Observational studies clearly reporting data among BD patients and the frequency of autoimmune thyroid pathologies were included. 11 original studies met inclusion criteria out of 340 titles first returned from the global search. There is evidence of increased prevalence of circulating thyroid autoantibodies in depressed and mixed BD patients, while there is no evidence showing a positive relationship between BD and specific autoimmune thyroid diseases. There is a controversy about the influence of lithium exposure on circulating thyroid autoantibodies, even if most of studies seem not to support this association. A study conducted on bipolar twins suggests that autoimmune thyroiditis is related to the genetic vulnerability to develop BD rather than to the disease process itself. Females are more likely to develop thyroid autoimmunity. The samples, study design and outcomes were heterogeneous. Thyroid autoimmunity has been suggested to be an independent risk factor for bipolar disorder with no clear association with lithium exposure and it might serve as an endophenotype for BD. Copyright © 2017 Elsevier B.V. All rights reserved.
Kalkan, Çağdaş; Soykan, Irfan
Elderly patients with autoimmune gastritis might have different symptoms than those of young patients. The aim of the present study was to compare presented symptoms and laboratory parameters associated with autoimmune gastritis in both old and young age groups. A total of 355 patients with autoimmune gastritis were stratified into two groups: 65 years or older (n = 119, mean age 69.47 ± 5.027 years), and under 65 years (n = 236, mean age 45.79 ± 10.51 years). These two groups were then evaluated and compared by means of clinical symptoms, concurrent autoimmune diseases, serum gastrin, vitamin B 12 and chromogranin A levels, and the presence of enterochromograffin-like cell hyperplasia. Among 119 older patients, 35 had dyspeptic symptoms, and 84 patients were referred for vitamin B 12 and/or iron deficiency. In the younger group (n = 236), there were more patients who had dyspeptic symptoms (36 vs 200, P gastritis that are older and younger than 65 years-of-age. Elderly patients with autoimmune gastritis were investigated more commonly for vitamin B 12 and/or iron deficiency. Polyautoimmunity and multiple autoimmune syndrome were more common, and serum gastrin and chromogranin A levels were significantly higher in older patients. Geriatr Gerontol Int 2017; 17: 1090-1095. © 2016 Japan Geriatrics Society.
Full Text Available Anthraquinones are a class of aromatic compounds with a 9,10-dioxoanthracene core. So far, 79 naturally occurring anthraquinones have been identified which include emodin, physcion, cascarin, catenarin, and rhein. A large body of literature has demonstrated that the naturally occurring anthraquinones possess a broad spectrum of bioactivities, such as cathartic, anticancer, anti-inflammatory, antimicrobial, diuretic, vasorelaxing, and phytoestrogen activities, suggesting their possible clinical application in many diseases. Despite the advances that have been made in understanding the chemistry and biology of the anthraquinones in recent years, research into their mechanisms of action and therapeutic potential in autoimmune disorders is still at an early stage. In this paper, we briefly introduce the etiology of autoimmune diabetes, an autoimmune disorder that affects as many as 10 million worldwide, and the role of chemotaxis in autoimmune diabetes. We then outline the chemical structure and biological properties of the naturally occurring anthraquinones and their derivatives with an emphasis on recent findings about their immune regulation. We discuss the structure and activity relationship, mode of action, and therapeutic potential of the anthraquinones in autoimmune diabetes, including a new strategy for the use of the anthraquinones in autoimmune diabetes.
Weetman, Anthony P
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
Mieli-Vergani, Giorgina; Vergani, Diego
Autoimmune hepatitis (AIH) is characterized by inflammatory liver histology, circulating non-organ-specific autoantibodies, and increased levels of immunoglobulin (Ig) G in the absence of a known etiology. Two types of childhood AIH are recognized according to seropositivity: smooth muscle antibody (SMA) and/or antinuclear antibody (ANA), which is AIH type 1; and antibodies to liver-kidney microsome type 1 (anti-LKM1), which is AIH type 2. There is a female predominance in both. Autoimmune hepatitis type 2 presents more acutely, at a younger age, and commonly with IgA deficiency; however, 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 two 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. The 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. Copyright Thieme Medical Publishers.
Granito, Alessandro; Muratori, Paolo; Ferri, Silvia; Pappas, Georgios; Quarneti, Chiara; Lenzi, Marco; Bianchi, Francesco B; Muratori, Luigi
Autoimmune hepatitis (AIH) is a chronic progressive hepatitis, characterized by interface hepatitis with lymphoplasmacellular infiltrates on liver biopsy, high serum globulin level and circulating autoantibodies. It is classified into two types, according to autoantibody profile: type 1 is characterized by anti-nuclear (ANA) and/or anti-smooth muscle (SMA) antibodies; type 2 by anti-liver kidney microsomal type 1 (anti-LKM-1) antibodies. AIH affects all ages, may be asymptomatic, frequently has an acute onset, and can present as fulminant hepatitis. The diagnosis of AIH is based on a scoring system codified by an international consensus. Corticosteroids alone or in conjunction with azathioprine is the treatment of choice in patients with AIH and results in remission induction in over 80% of patients. Alternative proposed strategies in patients who have failed to achieve remission on standard therapy or patients with drug toxicity include the use of cyclosporine, tacrolimus, budesonide or mycophenolate mofetil. Liver transplantation is the treatment of choice in managing decompensated disease, however AIH can recur or develop de novo after liver transplantation.
Full text: Learning objectives: to learn about the main imaging diagnostic findings of AIP and the International Consensus Diagnostic Criteria (ICDC); to understand the best strategies for distinguishing AIP from pancreatic cancer; to emphasise the central role of radiology in the era of “clinical decision making” Autoimmune Pancreatitis (AIP) was first described in 1961 and represents a rare form of immune mediated chronic pancreatitis which is characterised by a marked infiltration of lymphocytes and plasma cells into pancreatic tissue. Whilst the majority of cases present with diffuse gland involvement, approximately 30% of patient’s demonstrate either segmental or focal involvement of the pancreas. Clinical presentation is very variable with patients describing a range of symptoms. Imaging plays a central role in the diagnosis and management of AIP and knowledge of the radiological appearances, which can vary significantly due to the various degrees of fibrosis and inflammatory infiltrate, is critical. Cardinal features include focal or diffuse pancreatic enlargement with the loss of normal lobular architecture. Post contrast enhancement features of the pancreas may also be useful. In addition, pancreatic duct involvement as demonstrated by single or multiple focal strictures with limited more proximal dilatation is common as well as infiltration of the common bile duct.Whilst multimodality appearances may suggest a diagnosis of AIP correlation with clinical history, serology and histopathology is mandatory in order to accurately diagnose atypical cases
Terry F. Davies
Full Text Available The autoimmune thyroid diseases (AITDs (Graves’ disease and Hashimoto’s thyroiditis are complex genetic diseases which most likely have more than 20 genes contributing to the clinical phenotypes. To date, the genes known to be contributing fall into two categories: immune regulatory genes (including HLA, CTLA4, PTPN22, CD40, CD25, and FCRL3 and thyroid-specific genes (TG and TSHR. However, none of these genes contribute more than a 4-fold increase in risk of developing one of these diseases, and none of the polymorphisms discovered is essential for disease development. Hence, it appears that a variety of different gene interactions can combine to cause the same clinical disease pattern, but the contributing genes may differ from patient to patient and from population to population. Furthermore, this possible mechanism leaves open the powerful influence of the environment and epigenetic modifications of gene expression. For the clinician, this means that genetic profiling of such patients is unlikely to be fruitful in the near future.
Proctor, R.D.; Rofe, C.J.; Bryant, T.J.C.; Hacking, C.N.; Stedman, B.
Autoimmune pancreatitis (AIP) remains one of the rarer forms of pancreatitis but has become increasingly well recognized and widely diagnosed as it is an important differential, particularly due to the dramatic response to appropriate therapy. It is now best considered as part of a multisystem disease and the notion of “IgG4-related systemic sclerosing disease” has become widely recognized as the number of extra-pancreatic associations of AIP grows. More recently AIP has been classified into two subtypes: lymphoplasmacytic sclerosing pancreatitis (LPSP) and idiopathic duct-centric pancreatitis (IDCP) with distinct geographical, age and sex distributions for the two subtypes, in addition to different pathological characteristics. The role of imaging is crucial in AIP and should be considered in conjunction with clinical, serological, and histopathological findings to make the diagnosis. Radiologists are uniquely placed to raise the possibility of AIP and aid the exclusion of significant differentials to allow the initiation of appropriate management and avoidance of unnecessary intervention. Radiological investigation may reveal a number of characteristic imaging findings in AIP but appearances can vary considerably and the focal form of AIP may appear as a pancreatic mass, imitating pancreatic carcinoma. This review will illustrate typical and atypical appearances of AIP on all imaging modes. Emphasis will be placed on the imaging features that are likely to prove useful in discriminating AIP from other causes prior to histopathological confirmation. In addition, examples of relevant differential diagnoses are discussed and illustrated
García-Leiva, Jorge; Ríos-Vaca, Aurelio; Torre-Delgadillo, Aldo
Autoimmune hepatitis (AIH) is an inflammatory disease of unknown cause characterized by periportal hepatitis, increased serum globulins and the presence of certain antibodies. The disorder can be classified in three types. Type 1 AIH is characterized by the presence of antinuclear antibodies (ANA) and smooth muscle autoantibodies (SMA) in up to 70-80% of patients. ANA and SMA can be the only antibodies present in 13 and 33% of cases respectively. Type 2 AIH is defined by the presence of liver and kidney antimicrosomal antibodies (LKM1). Type 2 AIH is the only form of the disease in which the autoantigen has been identified: cytochrome mono-oxygenase (P-450 IID6) CYP2D6. In type 3 AIH the presence of anti-SLA/LP (soluble liver antigen/liver pancreas) targets a cytosolic protein involved in the incorporation of selenocysteine into peptidic chains. The pathophysiology of AIH is complex and involves genetic predisposition, previous exposure to antigens (autoantigens), presence of triggering factors and defects in immunoregulation. In spite of the advances in the understanding of AIH, the role of autoantibodies in the pathophysiology of this disease has not been fully established and their presence does not clearly distinguish any prognostic groups. Further investigations will help in the diagnosis of this disorder, the comprehension of its origins and the establishment of new forms of treatment.
Bogdanos, Dimitrios P; Mieli-Vergani, Giorgina; Vergani, Diego
Autoantibody detection assists in the diagnosis and allows differentiation of autoimmune hepatitis (AIH) type 1 (AIH-1), characterized by antinuclear antibody (ANA) and/or smooth muscle antibody (SMA), and type 2 (AIH-2), distinguished by the presence of antibodies to liver-kidney microsome type 1 (anti-LKM1) and/or antibodies to liver cytosol type 1 (anti-LC1). Detection of atypical perinuclear antineutrophil cytoplasmic antibodies (pANCA) and anti-soluble liver antigen (SLA) antibodies can act as an additional pointer toward the diagnosis of AIH, particularly in the absence of the conventional autoantibodies. Routine autoantibody testing by indirect immunofluorescence has been recently complemented by molecular assays based on purified or recombinant antigens. Although the AIH-1-specific ANA and SMA targets need better definition, those of anti-LKM1 and anti-LC1 in AIH-2 have been clearly identified; the fine specificity of antibody reactivity and its clinical relevance to disease pathogenesis are the focus of ongoing investigation. This article critically discusses the current knowledge of the diagnostic and clinical significance of AIH-related autoantibody reactivities, focusing on key issues that the physician needs to be aware of to be able to request the appropriate testing and to interpret correctly the laboratory results within the clinical context of the patient. Copyright Thieme Medical Publishers.
Hyung Jik Lee
Full Text Available We report a case of severe hypothyroidism with nongoitrous, autoimmune thyroiditis and pituitary hyperplasia in a 13-year-old boy, who presented with sudden palsy on the left side of his face. Prednisolone and antiviral medication was administered. However, the facial palsy did not improve completely. The medications were replaced with thyroxine, and the facial palsy recovered. Endocrinological testing showed severe hypothyroidism as follows: thyroid stimulating hormone (TSH level >100 µIU/mL, T4 of 1.04 µg/dL, T3 of 0.31 ng/mL, and free T4 of 0.07 ng/dL. Level of serum antithyroid peroxidase antibodies was 1,933.39 IU/mL, and that of antithyroglobulin antibodies was 848.16 IU/mL. Level of TSH receptor antibodies was >40 IU/L. Bioassay result for TSH receptor stimulating antibodies was negative. Thyroid sonography revealed no increase in the size or vascularity of the bilateral gland. Thyroid scintigraphy with 99mTc showed decreased uptake, and magnetic resonance imaging demonstrated an enlarged pituitary gland.
Rork, Jillian F.; Rashighi, Mehdi; Harris, John E.
Purpose of review Vitiligo and alopecia areata are common, disfiguring skin diseases. Treatment options are limited and include non-targeted approaches such as corticosteroids, topical calcineurin inhibitors, narrow band UVB phototherapy, and other immune-modifying agents. The purpose of this article is to review shared, novel mechanisms between vitiligo and alopecia areata, as well as discuss how they inform the development of future targeted treatments. Recent findings Vitiligo and alopecia areata are both autoimmune diseases, and striking similarities in pathogenesis have been identified at the level of both the innate and adaptive immune system. Increased reactive oxygen species and high cellular stress level have been suggested as the initiating trigger of the innate immune system in both diseases, and genome-wide association studies have implicated risk alleles that influence both innate and adaptive immunity. Most importantly, mechanistic studies in mouse models of vitiligo and alopecia areata have specifically implicated an IFN-γ-driven immune response, including IFN-γ, IFN-γ-induced chemokines, and cytotoxic CD8+ T cells as the main drivers of disease pathogenesis. These recent discoveries may reveal an effective strategy to develop new treatments, and several proof-of-concept clinical studies support this hypothesis. Summary The identification of IFN-γ-driven immune signaling pathways has enabled discoveries of potential new treatments for vitiligo and alopecia areata, and supports initiation of larger clinical trials. PMID:27191524
Anne E Bygrave
Full Text Available Systemic lupus erythematosus (SLE is a multisystem autoimmune disorder in which complex genetic factors play an important role. Several strains of gene-targeted mice have been reported to develop SLE, implicating the null genes in the causation of disease. However, hybrid strains between 129 and C57BL/6 mice, widely used in the generation of gene-targeted mice, develop spontaneous autoimmunity. Furthermore, the genetic background markedly influences the autoimmune phenotype of SLE in gene-targeted mice. This suggests an important role in the expression of autoimmunity of as-yet-uncharacterised background genes originating from these parental mouse strains. Using genome-wide linkage analysis, we identified several susceptibility loci, derived from 129 and C57BL/6 mice, mapped in the lupus-prone hybrid (129 x C57BL/6 model. By creating a C57BL/6 congenic strain carrying a 129-derived Chromosome 1 segment, we found that this 129 interval was sufficient to mediate the loss of tolerance to nuclear antigens, which had previously been attributed to a disrupted gene. These results demonstrate important epistatic modifiers of autoimmunity in 129 and C57BL/6 mouse strains, widely used in gene targeting. These background gene influences may account for some, or even all, of the autoimmune traits described in some gene-targeted models of SLE.
Bharat Rakeshkumar Sharma
Full Text Available Introduction: The prevalence of autoimmune thyroid disease (AITD is 10–12% in the general population worldwide. Among various disorders co-existing with AITD, the concomitance of celiac disease (CD with AITD results in poor absorption of thyroid medications and results in higher doses of the same. Institution of gluten-free diet (GFD in this cohort helps reduce medication doses. Aim: To screen patients with AITD for the presence of celiac autoimmunity (CA. Materials and Methods: A total of 280 consecutive patients with AITD attending the thyroid Out-patient Department of a tertiary care hospital were screened for the presence of tissue transglutaminase antibodies (immunoglobulin A tissue transglutaminase. Those with a positive titer (but < 10 times the upper limit of normal underwent upper gastrointestinal endoscopy and duodenal mucosal biopsy for the diagnosis of CD, followed by institution of GFD in confirmed cases. Results: Of a total of 280 (182 females and 98 males patients with AITD screened, 24 (8.6% turned out to be positive for CA. Of 24 (8.6%, 15 (8.24% females and 9 (9.18% males were positive for CA. There was no statistically significant difference in the thyroxine doses required for normalization of thyroid function and the weight of the patients in CA positive and CA negative patients. Conclusions: The prevalence of CD in patients with AITD is much greater than in the general population. This forms the basis for screening patients with AITD for presence of CD.
Full Text Available Although the role of interleukin-2 (IL-2 and interferon gamma (gIFN is still poorly understood in hyperthyroid diseases, it is reasonable to assume that these cytokines may be present at higher levels in Graves' disease (GD than in other primarily non-autoimmune thyroid diseases. In order to look for an easy method to distinguish GD from primarily non-autoimmune causes of hyperthyroidism, we compared 13 healthy individuals with 21 treated and untreated hyperthyroid GD patients and with 19 patients with hyperthyroidism due to other etiologies: 7 cases of multinodular goiter, 5 cases of excessive hormone replacement and 7 cases of amiodarone-associated hyperthyroidism. All patients presented low TSH levels and a dubious clinical thyroid state. We found a good correlation between TSH and serum IL-2 levels (r = 0.56; PgIFN (P<0.01 levels were lower in the hyperthyroid group of patients than in control subjects, suggesting a depressed TH1 pattern in the T-cell subset of hyperthyroid patients. GD had normal IL-2 levels, while patients with other forms of thyrotoxicosis presented decreased IL-2 levels (P<0.05. There was no difference between treated and untreated GD patients. We suggest that the direct measurement of serum IL-2 level may help to confirm hyperthyroidism caused by GD.
Full Text Available Exposure to trichloroethene (TCE, a ubiquitous environmental contaminant, has been linked to a variety of autoimmune diseases (ADs including SLE, scleroderma and hepatitis. Mechanisms involved in the pathogenesis of ADs are largely unknown. Earlier studies from our laboratory in MRL+/+ mice suggested the contribution of oxidative/nitrosative stress in TCE-induced autoimmunity, and N-acetylcysteine (NAC supplementation provided protection by attenuating oxidative stress. This study was undertaken to further evaluate the contribution of nitrosative stress in TCE-mediated autoimmunity and to identify proteins susceptible to nitrosative stress. Groups of female MRL +/+ mice were given TCE, NAC or TCE + NAC for 6 weeks (TCE, 10 mmol/kg, i.p., every 4th day; NAC, ∼ 250 mg/kg/day via drinking water. TCE exposure led to significant increases in serum anti-nuclear and anti-histone antibodies together with significant induction of iNOS and increased formation of nitrotyrosine (NT in sera and livers. Proteomic analysis identified 14 additional nitrated proteins in the livers of TCE-treated mice. Furthermore, TCE exposure led to decreased GSH levels and increased activation of NF-κB. Remarkably, NAC supplementation not only ameliorated TCE-induced nitrosative stress as evident from decreased iNOS, NT, nitrated proteins, NF-κB p65 activation and increased GSH levels, but also the markers of autoimmunity, as evident from decreased levels of autoantibodies in the sera. These findings provide support to the role of nitrosative stress in TCE-mediated autoimmune response and identify specific nitrated proteins which could have autoimmune potential. Attenuation of TCE-induced autoimmunity in mice by NAC provides an approach for designing therapeutic strategies.
Thyroid autoimmunity involves loss of tolerance to thyroid proteins in genetically susceptible individuals in association with environmental factors. In central tolerance, intrathymic autoantigen presentation deletes immature T cells with high affinity for autoantigen-derived peptides. Regulatory T cells provide an alternative mechanism to silence autoimmune T cells in the periphery. The TSH receptor (TSHR), thyroid peroxidase (TPO), and thyroglobulin (Tg) have unusual properties (“immunogenicity”) that contribute to breaking tolerance, including size, abundance, membrane association, glycosylation, and polymorphisms. Insight into loss of tolerance to thyroid proteins comes from spontaneous and induced animal models: 1) intrathymic expression controls self-tolerance to the TSHR, not TPO or Tg; 2) regulatory T cells are not involved in TSHR self-tolerance and instead control the balance between Graves' disease and thyroiditis; 3) breaking TSHR tolerance involves contributions from major histocompatibility complex molecules (humans and induced mouse models), TSHR polymorphism(s) (humans), and alternative splicing (mice); 4) loss of tolerance to Tg before TPO indicates that greater Tg immunogenicity vs TPO dominates central tolerance expectations; 5) tolerance is induced by thyroid autoantigen administration before autoimmunity is established; 6) interferon-α therapy for hepatitis C infection enhances thyroid autoimmunity in patients with intact immunity; Graves' disease developing after T-cell depletion reflects reconstitution autoimmunity; and 7) most environmental factors (including excess iodine) “reveal,” but do not induce, thyroid autoimmunity. Micro-organisms likely exert their effects via bystander stimulation. Finally, no single mechanism explains the loss of tolerance to thyroid proteins. The goal of inducing self-tolerance to prevent autoimmune thyroid disease will require accurate prediction of at-risk individuals together with an antigen
García-Carrasco, M; Mendoza-Pinto, C; Macias Díaz, S; Vera-Recabarren, M; Vázquez de Lara, L; Méndez Martínez, S; Soto-Santillán, P; González-Ramírez, R; Ruiz-Arguelles, A
P-glycoprotein (Pgp) is a transmembrane protein of 170 kD encoded by the multidrug resistance 1 (MDR-1) gene, localized on chromosome 7. More than 50 polymorphisms of the MDR-1 gene have been described; a subset of these has been shown to play a pathophysiological role in the development of inflammatory bowel disease, femoral head osteonecrosis induced by steroids, lung cancer and renal epithelial tumors. Polymorphisms that have a protective effect on the development of conditions such as Parkinson disease have also been identified. P-glycoprotein belongs to the adenosine triphosphate binding cassette transporter superfamily and its structure comprises a chain of approximately 1280 aminoacid residues with an N-C terminal structure, arranged as 2 homologous halves, each of which has 6 transmembrane segments, with a total of 12 segments with 2 cytoplasmic nucleotide binding domains. Many cytokines like interleukin 2 and tumor necrosis factor alpha increase Pgp expression and activity. Pgp functions as an efflux pump for a variety of toxins in order to protect particular organs and tissues as the central nervous system. Pgp transports a variety of substrates including glucocorticoids while other drugs such as tacrolimus and cyclosporine A act as modulators of this protein. The most widely used method to measure Pgp activity is flow cytometry using naturally fluorescent substrates such as anthracyclines or rhodamine 123. The study of drug resistance and its association to Pgp began with the study of resistance to chemotherapy in the treatment of cancer and antiretroviral therapy for human immunodeficiency virus; however, the role of Pgp in the treatment of systemic lupus erythematosus, rheumatoid arthritis and psoriatic arthritis has been a focus of study lately and has emerged as an important mechanism by which treatment failure occurs. The present review analyzes the role of Pgp in these autoimmune diseases. Copyright © 2015 Elsevier B.V. All rights reserved.
Khashan, Ali S
Autoimmune diseases (AID) predominantly affect women of reproductive age. While basic molecular studies have implicated persisting fetal cells in the mother in some AID, supportive epidemiological evidence is limited. We investigated the effect of vaginal delivery, caesarean section (CS) and induced abortion on the risk of subsequent maternal AID. Using the Danish Civil Registration System (CRS) we identified women who were born between 1960 and 1992. We performed data linkage between the CRS other Danish national registers to identify women who had a pregnancy and those who developed AID. Women were categorised into 4 groups; nulligravida (control group), women who had 1st child by vaginal delivery, whose 1st delivery was by CS and who had abortions. Log-linear Poisson regression with person-years was used for data analysis adjusting for several potential confounders. There were 1,035,639 women aged >14 years and 25,570 developed AID: 43.4% nulligravida, 44.3% had their first pregnancy delivered vaginally, 7.6% CS and 4.1% abortions. The risk of AID was significantly higher in the 1st year after vaginal delivery (RR = 1.1[1.0, 1.2]) and CS (RR = 1.3[1.1, 1.5]) but significantly lower in the 1st year following abortion (RR = 0.7[0.6, 0.9]). These results suggest an association between pregnancy and the risk of subsequent maternal AID. Increased risks of AID after CS may be explained by amplified fetal cell traffic at delivery, while decreased risks after abortion may be due to the transfer of more primitive fetal stem cells. The increased risk of AID in the first year after delivery may also be related to greater testing during pregnancy.
Jiménez-Rivera, Carolina; Ling, Simon C; Ahmed, Najma; Yap, Jason; Aglipay, Mary; Barrowman, Nick; Graitson, Samantha; Critch, Jeff; Rashid, Mohsin; Ng, Vicky L; Roberts, Eve A; Brill, Herbert; Dowhaniuk, Jenna K; Bruce, Garth; Bax, Kevin; Deneau, Mark; Guttman, Orlee R; Schreiber, Richard A; Martin, Steven; Alvarez, Fernando
Autoimmune hepatitis (AIH) is a progressive inflammatory liver disease of unknown etiology, with limited population-based estimates of pediatric incidence. We reported the incidence of pediatric AIH in Canada and described its clinical characteristics. We conducted a retrospective cohort study of patients aged <18 years diagnosed with AIH between 2000-2009 at all pediatric centers in Canada. A total of 159 children with AIH (60.3% female, 13.2% type 2 AIH) were identified. Annual incidence was 0.23 per 100000 children. Median age at presentation for type 1 was 12 years (interquartile range: 11-14) versus 10 years for type 2 (interquartile range: 4.5-13) (P = .03). Fatigue (58%), jaundice (54%), and abdominal pain (49%) were the most common presenting symptoms. Serum albumin (33 vs 38 g/L; P = .03) and platelet count (187 000 vs 249 000; P <.001) were significantly lower and the international normalized ratio (1.4 vs 1.2; P <.001) was higher in cirrhotic versus noncirrhotic patients. Initial treatment included corticosteroids (80%), azathioprine (32%), and/or cyclosporine (13%). Response to treatment at 1 year was complete in 90%, and partial in 3%. 3% of patients had no response, and 3% responded and later relapsed. Nine patients underwent liver transplantation, and 4 patients died at a mean follow-up of 4 years. AIH is uncommon in children and adolescents in Canada. Type 1 AIH was diagnosed 5.5 times more frequently than type 2 AIH. Most patients respond well to conventional therapy, diminishing the need for liver transplantation. Copyright © 2015 by the American Academy of Pediatrics.
Vogrig, Alberto; Joubert, Bastien; Ducray, Francois; Thomas, Laure; Izquierdo, Cristina; Decaestecker, Kévin; Martinaud, Olivier; Gerardin, Emmanuel; Grand, Sylvie; Honnorat, Jérome
To identify the clinical and radiological features that should raise suspicion for the autoimmune encephalitis (AE)-like presentation of glioblastoma. This is an observational, retrospective case series of patients referred to the French National Reference Center on Paraneoplastic Neurological Diseases for suspected AE (possible, probable or definite, using the 2016 criteria) who later received a final diagnosis of glioblastoma according to 2016 WHO criteria. An extensive literature search was also conducted for similar existing cases. Between 2014 and 2016, 306 patients were referred to our center for suspected AE. Six of these patients (2%) later developed pathologically confirmed glioblastoma. Thirteen patients (9 male) were included for analysis (6 from the present series and 7 from the literature); median age was 63. Initially, a diagnosis of AE was clinically suspected based on: working memory deficits (77%), seizures (62%) (including status epilepticus in 23%), and psychiatric symptoms (46%). Initial brain MRI was not in favor of a typical glioblastoma pattern and showed bilateral (54%) or unilateral selective limbic involvement. Five patients exhibited initial slight contrast enhancement. A clear inflammatory CSF was present in five patients and three from the literature showed autoantibody positivity (NMDAR, VGKC, GluRepsilon2). Median delay between suspicions of AE to GBM diagnosis was 3 months (range 1.5-24) and one patient from the literature was diagnosed post-mortem. An alternative diagnosis of glioblastoma should be considered in patients presenting initially as AE, especially in patients who do not fulfill the criteria for definite AE and in those with a poor clinical evolution despite initial improvement.
R K Chaudhary
Full Text Available Autoimmune hemolytic anemia (AIHA is not an uncommon clinical disorder and requires advanced, efficient immunohematological and transfusion support. Many AIHA patients have underlying disorder and therefore, it is incumbent upon the clinician to investigate these patients in detail, as the underlying condition can be of a serious nature such as lymphoproliferative disorder or connective tissue disorder. Despite advances in transfusion medicine, simple immunohematological test such as direct antiglobulin test (DAT still remains the diagnostic hallmark of AIHA. The sensitive gel technology has enabled the immunohematologist not only to diagnose serologically such patients, but also to characterize red cell bound autoantibodies with regard to their class, subclass and titer in a rapid and simplified way. Detailed characterization of autoantibodies is important, as there is a relationship between in vivo hemolysis and strength of DAT; red cell bound multiple immunoglobulins, immunoglobulin G subclass and titer. Transfusing AIHA patient is a challenge to the immunohematologist as it is encountered with difficulties in ABO grouping and cross matching requiring specialized serological tests such as alloadsorption or autoadsorption. At times, it may be almost impossible to find a fully matched unit to transfuse these patients. However, transfusion should not be withheld in a critically ill patient even in the absence of compatible blood. The "best match" or "least incompatible units" can be transfused to such patients under close supervision without any serious side-effects. All blood banks should have the facilities to perform the necessary investigations required to issue "best match" packed red blood cells in AIHA. Specialized techniques such as elution and adsorption, which at times are helpful in enhancing blood safety in AIHA should be established in all transfusion services.
Lopez-Chiriboga, A. Sebastian; Komorowski, Lars; Kümpfel, Tania; Probst, Christian; Hinson, Shannon R.; Pittock, Sean J.
Objective: To describe retrospectively the clinical associations of immunoglobulin G (IgG) targeting metabotropic glutamate receptor 1 (mGluR1-IgG). Methods: Specimens of 9 patients evaluated on a service basis in the Mayo Clinic Neuroimmunology Laboratory by tissue-based immunofluorescence assay (IFA) yielded a robust, synaptic immunostaining pattern consistent with mGluR1-IgG (serum, 9; CSF, 2 available). Transfected HEK293 cell-based assay (CBA) confirmed mGluR1 specificity in all 11 specimens. A further 2 patients were detected in Germany primarily by CBA. Results: The median symptom onset age for the 11 patients was 58 years (range 33–81 years); 6 were male. All 9 Mayo Clinic patients had subacute onset of cerebellar ataxia, 4 had dysgeusia, 1 had psychiatric symptoms, and 1 had cognitive impairment. All were evaluated for malignancy, but only 1 was affected (cutaneous T-cell lymphoma). One developed ataxia post–herpes zoster infection. Head MRIs were generally atrophic or normal-appearing, and CSF was inflammatory in just 1 of 5 tested, though mGluR1-IgG was detected in both specimens submitted. Five patients improved (attributable to immunotherapy in 4, spontaneously in 1), 3 stabilized (attributable to immunotherapy in 2, cancer therapy in 1), and 1 progressively declined (untreated). The 2 German patients had ataxia, but fulfilled multiple sclerosis diagnostic criteria (1 relapsing-remitting, 1 progressive). However, both had histories of hematologic malignancy (acute lymphocytic leukemia and mantle cell lymphoma), and had mGluR1-IgG detected in serum by CBA (weakly positive on tissue-based IFA). Conclusions: mGluR1 autoimmunity represents a treatable form of cerebellar ataxia. Dysgeusia may be a diagnostic clue. Paraneoplastic, parainfectious, or idiopathic causes may occur. PMID:26888994
Full Text Available Wiskott-Aldrich Syndrome (WAS is a severe X-linked Primary Immunodeficiency (PID that affects 1 to 10 out of 1 million male individuals. WAS is caused by mutations in the WAS Protein (WASP expressing gene that leads to the absent or reduced expression of the protein. WASP is a cytoplasmic protein that regulates the formation of actin filaments in hematopoietic cells. WASP deficiency causes many immune cell defects both in humans and in the WAS murine model, the Was-/- mouse. Both cellular and humoral immune defects in WAS patients contribute to the onset of severe clinical manifestations, in particular microthrombocytopenia, eczema, recurrent infections and a high susceptibility to develop autoimmunity and malignancies. Autoimmune diseases affect from 22% to 72% of WAS patients and the most common manifestation is autoimmune hemolytic anemia, followed by vasculitis, arthritis, neutropenia, inflammatory bowel disease and IgA nephropathy. Many groups have widely explored immune cell functionality in WAS partially explaining how cellular defects may lead to pathology. However, the mechanisms underlying the occurrence of autoimmune manifestations have not been clearly described yet. In the present review, we report the most recent progresses in the study of immune cell function in WAS that have started to unveil the mechanisms contributing to autoimmune complications in WAS patients.
T E Naumova
Full Text Available DNA-abzymes enzymes in autoimmune diseases in clinic and experiment T.E. Naumova, O.M. Durova, A.G. Gabibov, Z.S. Alekberova, S. V. Suchkov DNA-hydrolyzing autoantibodies (AAB or DNA-abzymes can be found in autoimmune diseases in clinic and experiment. Technology of serum express screening for presence of DNA abzymes is described. Comparative study of DNA-hydrolising activity in patients with different forms of systemic and organ-specific autoimmune diseases was performed. Blood of clinically healthy donors was usually free of IgG DNA-abzymes. DNA-abzymes were most often revealed in patients with systemic lupus erythematosus (SLE and rheumatoid arthritis (RA less often in patients with organ-specific forms of autoimmune disturbances. The results of the study confirm the hypothesis of autoimmune origin of IgG DNA abzymes and demonstrate the possibility to use them in clinical practice for monitoring to disease activity in SLE and RA.
Full Text Available Major histocompatibility complex (MHC genes, also known as human leukocyte antigen genes (HLA in humans, are the prevailing contributors of genetic susceptibility to autoimmune diseases such as Type 1 Diabetes (T1D, Multiple Sclerosis (MS, and Rheumatoid arthritis (RA, among others (Todd and Wicker, 2001;MacKay et al., 2002;Hafler et al., 2007. Although the pathways through which MHC molecules afford autoimmune risk or resistance remain to be fully mapped out, it is generally accepted that they do so by shaping the central and peripheral T cell repertoires of the host towards autoimmune proclivity or resistance, respectively. Disease-predisposing MHC alleles would both spare autoreactive thymocytes from central tolerance and bias their development towards a pathogenic phenotype. Protective MHC alleles, on the other hand, would promote central deletion of autoreactive thymocytes and skew their development towards non-pathogenic phenotypes. This interpretation of the data is at odds with two other observations: that in MHC-heterozygous individuals, resistance is dominant over susceptibility; and that it is difficult to understand how deletion of one or a few clonal autoreactive T cell types would suffice to curb autoimmune responses driven by hundreds if not thousands of autoreactive T cell specificities. This review provides an update on current advances in our understanding of the mechanisms underlying MHC class II-associated autoimmune disease susceptibility and/or resistance and attempts to reconcile these seemingly opposing concepts.
Kalkan, Çağdaş; Soykan, Irfan; Soydal, Çiğdem; Özkan, Elgin; Kalkan, Emra
Symptoms of patients with autoimmune gastritis are not specific, and some patients may present symptoms suggestive of delayed gastric emptying. This study aims to investigate whether any delay in gastric emptying of solid food exists in patients with autoimmune gastritis and, if so, to identify the factors that might affect delayed gastric emptying. A total of 165 patients (106 women) diagnosed as having autoimmune gastritis were analyzed by means of a gastric emptying test. All patients underwent a standardized scintigraphic gastric emptying study. Patients with delayed gastric emptying and normal gastric emptying tests were then compared by means of factors that might affect gastric emptying. Also 65 patients with functional dyspepsia who had a gastric emptying study constituted the control group. The median gastric emptying T ½ time was 127.43 min (min-max 50-953) for patients with AIG and 81 min (min-max 21-121.6) for functional dyspepsia patients (p gastritis, gastric emptying is generally delayed. Autoimmune gastritis is an important etiology to explain the finding of delayed gastric emptying on a radionuclide test. This new finding is likely to be relevant to clinicians when evaluating and initiating appropriate medical treatment for patients with autoimmune gastritis manifesting upper gastrointestinal symptoms.
Rae, William; Ward, Daniel; Mattocks, Christopher J; Gao, Yifang; Pengelly, Reuben J; Patel, Sanjay V; Ennis, Sarah; Faust, Saul N; Williams, Anthony P
Primary immunodeficiencies (PIDs) are rare inborn errors of immunity that have a heterogeneous phenotype that can include severe susceptibility to life-threatening infections from multiple pathogens, unique sensitivity to a single pathogen, autoimmune/inflammatory (AI/I) disease, allergies and/or malignancy. We present a diverse cohort of monogenic PID patients with and without AI/I diseases who underwent clinical, genetic and immunological phenotyping. Novel pathogenic variants were identified in IKBKG , CTLA4 , NFKB1 , GATA2 , CD40LG and TAZ as well as previously reported pathogenic variants in STAT3 , PIK3CD , STAT1 , NFKB2 and STXBP2 . AI/I manifestations were frequently encountered in PIDs, including at presentation. Autoimmunity/inflammation was multisystem in those effected, and regulatory T cell (Treg) percentages were significantly decreased compared with those without AI/I manifestations. Prednisolone was used as the first-line immunosuppressive agent in all cases, however steroid monotherapy failed long-term control of autoimmunity/inflammation in the majority of cases and additional immunosuppression was required. Patients with multisystem autoimmunity/inflammation should be investigated for an underlying PID, and in those with PID early assessment of Tregs may help to assess the risk of autoimmunity/inflammation.
Kaur, Gagandeep; Mohindra, Kanika; Singla, Shifali
Autoimmune reactions reflect an imbalance between effector and regulatory immune responses, typically develop through stages of initiation and propagation, and often show phases of resolution (indicated by clinical remissions) and exacerbations (indicated by symptomatic flares). The fundamental underlying mechanism of autoimmunity is defective elimination and/or control of self-reactive lymphocytes. Periodontal diseases are characterized by inflammatory conditions that directly affect teeth-supporting structures, which are the major cause of tooth loss. Several studies have demonstrated the involvement of autoimmune responses in periodontal disease. Evidence of involvement of immunopathology has been reported in periodontal disease. Bacteria in the dental plaque induce antibody formation. Autoreactive T-cells, natural killer cells, ANCA, heat shock proteins, autoantibodies, and genetic factors are reported to have an important role in the autoimmune component of periodontal disease. The present review describes the involvement of autoimmune responses in periodontal diseases and also the mechanisms underlying these responses. Copyright © 2016 Elsevier B.V. All rights reserved.
Yang Zandong; Chen Meng; Carter, Jeffrey D.; Nunemaker, Craig S.; Garmey, James C.; Kimble, Sarah D.; Nadler, Jerry L.
Type 1 diabetes mellitus (T1DM) is an autoimmune disease leading to near complete pancreatic β-cell destruction. New evidence suggests that β-cell regeneration is possible, but ongoing autoimmune damage prevents restoration of β-cell mass. We tested the hypothesis that simultaneously blocking autoimmune cytokine damage and supplying a growth-promoting stimulus for β-cells would provide a novel approach to reverse T1DM. Therefore, in this study we combined lisofylline to suppress autoimmunity and exendin-4 to enhance β-cell proliferation for treating autoimmune-mediated diabetes in the non-obese diabetic (NOD) mouse model. We found that this combined therapy effectively reversed new-onset diabetes within a week of therapy, and even maintained euglycemia up to 145 days after treatment withdrawal. The therapeutic effect of this regimen was associated with improved β-cell metabolism and insulin secretion, while reducing β-cell apoptosis. It is possible that such combined therapy could become a new strategy to defeat T1DM in humans
Janahi, Noor M; Santos, Derek; Blyth, Christine; Bakhiet, Moiz; Ellis, Mairghread
Autoimmunity has been identified in a significant number of neuropathies, such as, proximal neuropathies, and autonomic neuropathies associated with diabetes mellitus. However, possible correlations between diabetic peripheral neuropathy and autoimmunity have not yet been fully investigated. This study was conducted to investigate whether autoimmunity is associated with the pathogenesis of human diabetic peripheral neuropathy. A case-control analysis included three groups: 30 patients with diabetic peripheral neuropathy, 30 diabetic control patients without neuropathy, and 30 healthy controls. Blood analysis was conducted to compare the percentages of positive antinuclear antibodies (ANA) between the three groups. Secondary analysis investigated the correlations between the presence of autoimmune antibodies and sample demographics and neurological manifestations. This research was considered as a pilot study encouraging further investigations to take place in the near future. Antinuclear antibodies were significantly present in the blood serum of patients with diabetic peripheral neuropathy in comparison to the control groups (pneuropathy group were 50 times higher when compared to control groups. Secondary analysis showed a significant correlation between the presence of ANA and the neurological manifestation of neuropathy (Neuropathy symptom score, Neuropathy disability score and Vibration Perception Threshold). The study demonstrated for the first time that human peripheral diabetic neuropathy may have an autoimmune aetiology. The new pathogenic factors may lead to the consideration of new management plans involving new therapeutic approaches and disease markers. Copyright © 2015 Elsevier B.V. All rights reserved.
Strassner, James P; Harris, John E
Vitiligo is an autoimmune disease of the skin that leads to life-altering depigmentation and remains difficult to treat. However, clinical observations and translational studies over 30-40 years have led to the development of an insightful working model of disease pathogenesis: Genetic risk spanning both immune and melanocyte functions is pushed over a threshold by known and suspected environmental factors to initiate autoimmune T cell-mediated killing of melanocytes. While under cellular stress, melanocytes appear to signal innate immunity to activate T cells. Once the autoimmune T cell response is established, the IFN-γ-STAT1-CXCL10 signaling axis becomes the primary inflammatory pathway driving both progression and maintenance of vitiligo. This pathway is a tempting target for both existing and developing pharmaceuticals, but further detailing how melanocytes signal their own demise may also lead to new therapeutic targets. Research in vitiligo may be the future key to understand the pathogenesis of organ-specific autoimmunity, as vitiligo is common, reversible, progresses over the life of the individual, has been relatively well-defined, and is quite easy to study using translational and clinical approaches. What is revealed in these studies can lead to innovative treatments and also help elucidate the principles that underlie similar organ-specific autoimmune diseases, especially in cases where the target organ is less accessible. PMID:27764715
Full Text Available γδ T cells are a minor population of T cells that express the TCR γδ chains, mainly distributed in the mucosal and epithelial tissue and accounting for less than 5% of the total T cells in the peripheral blood. By bridging innate and adaptive immunity, γδ T cells play important roles in the anti-infection, antitumor, and autoimmune responses. Previous research on γδ T cells was primarily concentrated on infectious diseases and tumors, whereas their functions in autoimmune diseases attracted much attention. In this paper, we summarized the various functions of γδ T cells in two prototypical autoimmune connective tissue diseases, that is, SLE and RA, elaborating on their antigen-presenting capacity, secretion of proinflammatory cytokines, immunomodulatory effects, and auxiliary function for B cells, which contribute to overproduction of proinflammatory cytokines and pathogenic autoantibodies, ultimately leading to the onset of these autoimmune diseases. Elucidation of the roles of γδ T cells in autoimmune diseases is not only conducive to in-depth understanding of the pathogenesis of these diseases, but also beneficial in providing theoretical support for the development of γδ T-cell-targeted therapy.
Ravel, G.; Christ, M.; Horand, F.; Descotes, J.
Although the wide clinical experience shows that vaccines are generally safe, concern has been expressed for a causal link between vaccines and autoimmune diseases. Even though the mechanisms of autoimmunity are ill-elucidated, the role of pre-existing risk factors including genetic predisposition and environmental factors is largely accepted. The present study was undertaken to test the hypothesis that vaccines can promote autoimmunity in genetically-prone individuals when simultaneously exposed to a chemical known to induce autoimmune reactions. Female lupus-prone (NZBxNZW) F 1 mice were given 1 μg or 10 μg of a hepatitis B vaccine at 2-week intervals in conjunction with 40 μg of mercuric chloride three times per week for 6 weeks. A marked increase in serum IgG levels and a slight increase in anti-nuclear autoantibody (ANA) levels were seen in the mice given 10 μg of the vaccine plus mercuric chloride. No straightforward conclusion can be drawn from these results because of the extreme experimental conditions of this study. Nevertheless, the results tend to support the hypothesis that vaccination could enhance the risk of autoimmunity in genetically susceptible individuals when exposed to certain environmental chemicals
O V Paramonova
Full Text Available The problem of a pathology of a thyroid gland at rheumatic diseases, in particular at rheumatoid arthritis, remains actual and to this day. The work purpose was studying antitelogenesis to thyroid hormones at patients with mixt autoimmune pathology. In whey of blood of patients with RA and autothyroid pathology are found out antibodies (AB to Т3 and Т4, their concentration correlates with activity of pathological process. It is shown, that level AB to Т3 and Т4 authentically differs from the maintenance of the given antibodies in whey of blood of healthy faces. Level of antibodies to thyroid hormones can be considered as the criterion predicting development of pathology of a thyroid gland at patients with RA.
Mohammad Hosseini, Akbar; Majidi, Jafar; Baradaran, Behzad; Yousefi, Mehdi
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
Shakov, Rada; DePasquale, Joseph R; Elfarra, Hossam; Spira, Robert S
Autoimmune pancreatitis (AuP) is a chronic pancreatic inflammation secondary to an underlying autoimmune mechanism. After early reports of a particular type of pancreatitis associated with hypergammaglobulinemia, others asserted that there is an autoimmune mechanism involved in some patients with chronic pancreatitis. In 1995 AuP was first described as a distinct clinical entity. Since then, there have been many documented cases of AuP in Japan, and now, perhaps due to increased awareness, more cases are being reported in Europe and the United States. Herein we present our experience with 3 cases of AuP and we review the relevant literature. These 3 cases demonstrate the difficulties that exist in making the diagnosis of AuP and the impact that the diagnosis can have on patient management.
Drayer, Sara M; Laufer, Larry R; Farrell, Maureen E
Autoimmune progesterone dermatitis is an uncommon disease presenting with cyclical skin eruptions corresponding with the menstrual cycle luteal phase. Because symptoms are precipitated by rising progesterone levels, treatment relies on hormone suppression. A 22-year-old nulligravid woman presented with symptoms mistaken for Stevens-Johnson syndrome. A cyclic recurrence of her symptoms was noted, and the diagnosis of autoimmune progesterone dermatitis was made by an intradermal progesterone challenge. After 48 months, she remained refractory to medical management and definitive surgical treatment with bilateral oophorectomy was performed. Autoimmune progesterone dermatitis is a challenging diagnosis owing to its rarity and variety of clinical presentations. Treatment centers on suppression of endogenous progesterone and avoidance of exogenous triggers. When these modalities fail, surgical management must be undertaken.
Hellesen, Alexander; Bratland, Eirik; Husebye, Eystein S
Autoimmunity against the adrenal cortex is the leading cause of Addison's disease in industrialized countries, with prevalence estimates ranging from 93-220 per million in Europe. The immune-mediated attack on adrenocortical cells cripples their ability to synthesize vital steroid hormones and necessitates life-long hormone replacement therapy. The autoimmune disease etiology is multifactorial involving variants in immune genes and environmental factors. Recently, we have come to appreciate that the adrenocortical cell itself is an active player in the autoimmune process. Here we summarize the complex interplay between the immune system and the adrenal cortex and highlight unanswered questions and gaps in our current understanding of the disease. Copyright © 2018 Elsevier Masson SAS. All rights reserved.
Miraghazadeh, Bahar; Cook, Matthew C
NF-κB (nuclear factor-kappa B) is a transcription complex crucial for host defense mediated by innate and adaptive immunity, where canonical NF-κB signaling, mediated by nuclear translocation of RelA, c-Rel, and p50, is important for immune cell activation, differentiation, and survival. Non-canonical signaling mediated by nuclear translocation of p52 and RelB contributes to lymphocyte maturation and survival and is also crucial for lymphoid organogenesis. We outline NF-κB signaling and regulation, then summarize important molecular contributions of NF-κB to mechanisms of self-tolerance. We relate these mechanisms to autoimmune phenotypes described in what is now a substantial catalog of immune defects conferred by mutations in NF-κB pathways in mouse models. Finally, we describe Mendelian autoimmune syndromes arising from human NF-κB mutations, and speculate on implications for understanding sporadic autoimmune disease.
Full Text Available Programmed cell death-1 (PD-1 ligand inhibitors have gained popularity in the treatment of advanced non-small-cell lung cancer. The immune system is regulated by stimulatory and inhibitory signaling and aims to achieve the balance between activation and inhibition. Treatment with immune checkpoint inhibitors enhances immune response, but is also known to diminish immune tolerance and increase autoimmune toxicity. Here we present a case of a patient with advanced squamous cell lung cancer who developed type I diabetes and thyroiditis after treatment with PD-1 checkpoint inhibitor nivolumab. The presence of autoimmune diabetes mellitus and thyroiditis were confirmed by markedly elevated titers of the glutamic acid decarboxylase autoantibody and thyroid peroxidase antibody, respectively. This report serves to heighten awareness of potential autoimmune toxicities related to anti-PD-1 therapy, especially as these toxicities are manageable if identified in a timely manner.
Xiong, Tingting; Turner, Jan-Eric
Abnormal activation of the innate immune system is a common feature of autoimmune and chronic inflammatory diseases. Since their identification as a separate family of leukocytes, innate lymphoid cells (ILCs) have emerged as important effector cells of the innate immune system. Alterations in ILC function and subtype distribution have been observed in a variety of immune-mediated diseases in humans and evidence from experimental models suggests a subtype specific role of ILCs in the pathophysiology of autoimmune inflammation. In this review, we discuss recent advances in the understanding of ILC biology in autoimmune and chronic inflammatory disorders, including multiple sclerosis, inflammatory bowel diseases, psoriasis, and rheumatic diseases, with a special focus on the potential of ILCs as therapeutic targets for the development of novel treatment strategies in humans.
Shiomi, Aoi; Usui, Takashi
Granulocyte macrophage-colony stimulating factor (GM-CSF) is a hematopoietic growth factor, which stimulates the proliferation of granulocytes and macrophages from bone marrow precursor cells. In autoimmune and inflammatory diseases, Th17 cells have been considered as strong inducers of tissue inflammation. However, recent evidence indicates that GM-CSF has prominent proinflammatory functions and that this growth factor (not IL-17) is critical for the pathogenicity of CD4+ T cells. Therefore, the mechanism of GM-CSF-producing CD4+ T cell differentiation and the role of GM-CSF in the development of autoimmune and inflammatory diseases are gaining increasing attention. This review summarizes the latest knowledge of GM-CSF and its relationship with autoimmune and inflammatory diseases. The potential therapies targeting GM-CSF as well as their possible side effects have also been addressed in this review. PMID:25838639
Haerskjold, Ann; Linder, Marie; Henriksen, Lonny
of autoimmune disease were diagnosed among palivizumab-exposed children during the period of observation. Among the children exposed to palivizumab, one child in Denmark developed inflammatory bowel disease; in Sweden, children developed juvenile arthritis (one child), diabetes mellitus (two children), celiac......BACKGROUND: Treatment with biologic pharmaceuticals may be associated with an increased risk of immune-mediated disease. Palivizumab is a humanized monoclonal antibody designed to provide passive immunity against respiratory syncytial virus infection. Palivizumab is primarily used in preterm...... children known to be immunologically immature. The long-term effect of palivizumab in terms of autoimmune diseases has not yet been investigated. AIM: Our objective was to investigate whether exposure to palivizumab was associated with the development of autoimmune diseases in children. METHODS...
Comarmond, Cloé; Cacoub, Patrice
Myocarditis is a major cause of heart disease in young patients and a common precursor of heart failure due to dilated cardiomyopathy. Some auto-immune and/or auto-inflammatory diseases may be accompanied by myocarditis, such as sarcoidosis, Behçet's disease, eosinophilic granulomatosis with polyangiitis, myositis, and systemic lupus erythematosus. However, data concerning myocarditis in such auto-immune and/or auto-inflammatory diseases are sparse. New therapeutic strategies should better target the modulation of the immune system, depending on the phase of the disease and the type of underlying auto-immune and/or auto-inflammatory disease. Copyright © 2017 Elsevier B.V. All rights reserved.
Ibrahim, Hatim; Al Jasser, Abdulelah N; Khan, Sonia A; Tlili, Kalthoum G
Autoimmune encephalitis is rare. Several auto- antibodies are described in autoimmune encephalitis. We describe a case of autoimmune limbic encephalitis associated with positive voltage gated potassium channel (VGKC) antibodies and positive leucine-rich glioma inactivated protein 1 antibodies (LGI1). A 33-year-old Saudi housewife, she presented with 2 months history of cognitive deterioration and recurrent left facio-brachial dystonic seizures followed by generalized tonic clonic seizures. At times the seizures are preceded by rising epigastric aura and shortness of breath. The neurological examination was normal apart from upgoing left plantar reflex. She had borderline IQ of 76 with impaired verbal fluency and impaired visual and verbal memory. Magnetic resonance imaging of the brain showed right mesial temporal non-enhancing lesion. Cerebrospinal fluid examination was positive for LGI1 and VGKC. Optimal seizure control was achieved with immunotherapy.
Egiziano, Giordano; Bernatsky, Sasha; Shah, Ami A
In many autoimmune rheumatic diseases, there is an increased risk of cancer compared to the general population. While reasons for this increased risk have not been elucidated, it has been hypothesized that the link between cancer and autoimmunity may be bidirectional. For instance, chronic inflammation and damage from the rheumatic disease or its therapies may trigger malignant transformation; conversely, antitumor immune responses targeting cancers may become cross-reactive resulting in autoimmunity. In rare rheumatic diseases, longitudinal observational studies can play a critical role in studying these complex relationships, thereby enabling investigators to quantify the extent of cancer risk, identify unique clinical phenotypes associated with cancer, investigate the biological link between these conditions, and define optimal strategies for screening and treatment of the underlying cancer. In this review, we discuss recent data on cancer in the rheumatic diseases and suggest a research agenda to address several gaps in our current knowledge base. Copyright © 2016 Elsevier Ltd. All rights reserved.
Jiang, Yao; Fang, Ronnie H; Zhang, Liangfang
Autoimmune diseases are characterized by overactive immunity, where the body's defense system launches an attack against itself. If left unchecked, this can result in the destruction of healthy tissue and significantly affect patient well-being. In the case of type II autoimmune hypersensitivities, autoreactive antibodies attack the host's own cells or extracellular matrix. Current clinical treatment modalities for managing this class of disease are generally nonspecific and face considerable limitations. In this Topical Review, we cover emerging therapeutic strategies, with an emphasis on novel nanomedicine platforms. Specifically, the use of biomimetic cell membrane-coated nanosponges that are capable of specifically binding and neutralizing pathological antibodies will be explored. There is significant untapped potential in the application of nanotechnology for the treatment of autoimmune diseases, and continued development along this line may help to eventually change the clinical landscape.
Hess, Evelyn V.
Many important clues have been provided by the relationship of certain medications to lupus and other autoimmune syndromes. These are temporary conditions that resolve when the medication is removed. There are now over 70 such medications which have been reported related to these autoimmune conditions. Interest continues to grow in the potential for environmental substances to cause these syndromes. Among those under suspicion are hydrazines, tartrazines, hair dyes, trichloroethylene, industrial emissions and hazardous wastes. Other possible associations include silica, mercury, cadmium, gold and L canavanine. Two recognised outbreaks include 'toxic oil syndrome' related to contaminated rape seed oil in Spain in 1981 and exposure to a contaminated environmental substance associated with an autoimmune attack on muscle tissue in 1989. Recently, there have been proposals made for the definition and identification of environmentally associated immune disorders. The World Health Organisation (WHO) has also provided recent publications for other environmentally related problems. All these aspects will be presented and reviewed in detail
Liu, Xuebin; Fang, Lei; Guo, Taylor B; Mei, Hongkang; Zhang, Jingwu Z
In autoimmune disease, a network of diverse cytokines is produced in association with disease susceptibility to constitute the 'cytokine milieu' that drives chronic inflammation. It remains elusive how cytokines interact in such a complex network to sustain inflammation in autoimmune disease. This has presented huge challenges for successful drug discovery because it has been difficult to predict how individual cytokine-targeted therapy would work. Here, we combine the principles of Chinese Taoism philosophy and modern bioinformatics tools to dissect multiple layers of arbitrary cytokine interactions into discernible interfaces and connectivity maps to predict movements in the cytokine network. The key principles presented here have important implications in our understanding of cytokine interactions and development of effective cytokine-targeted therapies for autoimmune disorders. Copyright © 2012 Elsevier Ltd. All rights reserved.
Dube, Shanta R; Fairweather, DeLisa; Pearson, William S; Felitti, Vincent J; Anda, Robert F; Croft, Janet B
To examine whether childhood traumatic stress increased the risk of developing autoimmune diseases as an adult. Retrospective cohort study of 15,357 adult health maintenance organization members enrolled in the Adverse Childhood Experiences (ACEs) Study from 1995 to 1997 in San Diego, California, and eligible for follow-up through 2005. ACEs included childhood physical, emotional, or sexual abuse; witnessing domestic violence; growing up with household substance abuse, mental illness, parental divorce, and/or an incarcerated household member. The total number of ACEs (ACE Score range = 0-8) was used as a measure of cumulative childhood stress. The outcome was hospitalizations for any of 21 selected autoimmune diseases and 4 immunopathology groupings: T- helper 1 (Th1) (e.g., idiopathic myocarditis); T-helper 2 (Th2) (e.g., myasthenia gravis); Th2 rheumatic (e.g., rheumatoid arthritis); and mixed Th1/Th2 (e.g., autoimmune hemolytic anemia). Sixty-four percent reported at least one ACE. The event rate (per 10,000 person-years) for a first hospitalization with any autoimmune disease was 31.4 in women and 34.4 in men. First hospitalizations for any autoimmune disease increased with increasing number of ACEs (p or=2 ACEs were at a 70% increased risk for hospitalizations with Th1, 80% increased risk for Th2, and 100% increased risk for rheumatic diseases (p Childhood traumatic stress increased the likelihood of hospitalization with a diagnosed autoimmune disease decades into adulthood. These findings are consistent with recent biological studies on the impact of early life stress on subsequent inflammatory responses.
Temboury Molina, M Carmen; Rivero Martín, M José; de Juan Ruiz, Jesús; Ares Segura, Susana
Autoimmune thyroid disease is amongst the most frequent endocrine disorders during pregnancy. It is associated with an increase in perinatal morbidity, congenital defects, neurological damage, fetal and neonatal thyroid dysfunction. Maternal thyroid hormones play a key role in child neurodevelopment. We aimed to evaluate the thyroid function and the clinical course of neonates born from mothers with autoimmune thyroid disease during the first months of life in order to define the follow-up. We monitored thyroid function and clinical status during the first months in 81 newborns of mothers with autoimmune thyroid disease; 16 had Graves disease and 65 autoimmune thyroiditis. A percentage of 4.93 newborns had congenital defects, and 8.64% neonates showed an increase in thyrotropin (TSH) (>9.5 μUI/mL 2 times) and required thyroxin within the first month of life. A 85.7% of these showed a negative newborn screening (due to a later increase of TSH). A higher TSH value in the newborn was related to an older age of the mother, higher levels of thyroid peroxidase (TPO) antibody during pregnancy and lower birth weight. A higher free thyroxine (FT4) value in the newborn was related to fewer days of life and mothers with Graves disease. We recommend the evaluation of TSH, T4 and TPO antibodies before 10 weeks in all pregnant women with follow-up if maternal thyroid autoimmunity or disorders is detected. It is also recommended to test children's serum TSH and FT4 at 48 h of life in newborns of mothers with autoimmune thyroid disease and repeat them between the 2nd and 4th week in children with TSH>6 μUI/mL. Careful endocrine follow-up is advised in pregnant women and children if hyperthyroidism is detected. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.
Liu, Juan; Cao, Xuetao
Dendritic cells (DCs) are professional antigen-presenting cells (APC) with significant phenotypic heterogeneity and functional plasticity. DCs play crucial roles in initiating effective adaptive immune responses for elimination of invading pathogens and also in inducing immune tolerance toward harmless components to maintain immune homeostasis. The regulatory capacity of DCs depends on their immature state and distinct subsets, yet not restricted to the immature state and one specialized subset. The tolerogenicity of DC is controlled by a complex network of environmental signals and cellular intrinsic mechanisms. Regulatory DCs play an important role in the maintenance of immunological tolerance via the induction of T cell unresponsiveness or apoptosis, and generation of regulatory T cells. DCs play essential roles in driving autoimmunity via promoting the activation of effector T cells such as T helper 1 and T helper 17 cells, and/or suppressing the generation of regulatory T cells. Besides, a breakdown of DCs-mediated tolerance due to abnormal environmental signals or breakdown of intrinsic regulatory mechanisms is closely linked with the pathogenesis of autoimmune diseases. Novel immunotherapy taking advantage of the tolerogenic potential of regulatory DCs is being developed for treatment of autoimmune diseases. In this review, we will describe the current understanding on the generation of regulatory DC and the role of regulatory DCs in promoting tolerogenic immune responses and suppressing autoimmune responses. The emerging roles of DCs dysfunction in the pathogenesis of autoimmune diseases and the potential application of regulatory DCs in the treatment of autoimmune diseases will also be discussed. Copyright © 2015 Elsevier Ltd. All rights reserved.
Silbergeld, Ellen K.; Silva, Ines A.; Nyland, Jennifer F.
Mercury (Hg) has long been recognized as a neurotoxicant; however, recent work in animal models has implicated Hg as an immunotoxicant. In particular, Hg has been shown to induce autoimmune disease in susceptible animals with effects including overproduction of specific autoantibodies and pathophysiologic signs of lupus-like disease. However, these effects are only observed at high doses of Hg that are above the levels to which humans would be exposed through contaminated fish consumption. While there is presently no evidence to suggest that Hg induces frank autoimmune disease in humans, a recent epidemiological study has demonstrated a link between occupational Hg exposure and lupus. In our studies, we have tested the hypothesis that Hg does not cause autoimmune disease directly, but rather that it may interact with triggering events, such as genetic predisposition, exposure to antigens, or infection, to exacerbate disease. Treatment of mice that are not susceptible to Hg-induced autoimmune disease with very low doses and short term exposures of inorganic Hg (20-200 μg/kg) exacerbates disease and accelerates mortality in the graft versus host disease model of chronic lupus in C57Bl/6 x DBA/2 mice. Furthermore, low dose Hg exposure increases the severity and prevalence of experimental autoimmune myocarditis (induced by immunization with cardiac myosin peptide in adjuvant) in A/J mice. To test our hypothesis further, we examined sera from Amazonian populations exposed to Hg through small-scale gold mining, with and without current or past malaria infection. We found significantly increased prevalence of antinuclear and antinucleolar antibodies and a positive interaction between Hg and malaria. These results suggest a new model for Hg immunotoxicity, as a co-factor in autoimmune disease, increasing the risks and severity of clinical disease in the presence of other triggering events, either genetic or acquired
Fredriksen, Jason R.; Carr, Carrie M.; Koeller, Kelly K.; Verdoorn, Jared T.; Kotsenas, Amy L. [Mayo Clinic, Department of Radiology, Rochester, MN (United States); Gadoth, Avi; Pittock, Sean J. [Mayo Clinic, Department of Neurology, Rochester, MN (United States)
Glutamic acid decarboxylase (GAD65) has been implicated in a number of autoimmune-associated neurologic syndromes, including autoimmune epilepsy. This study categorizes the spectrum of MRI findings in patients with a clinical diagnosis of autoimmune epilepsy and elevated serum GAD65 autoantibodies. An institutional database search identified patients with elevated serum GAD65 antibodies and a clinical diagnosis of autoimmune epilepsy who had undergone brain MRI. Imaging studies were reviewed by three board-certified neuroradiologists and one neuroradiology fellow. Studies were evaluated for cortical/subcortical and hippocampal signal abnormality, cerebellar and cerebral volume loss, mesial temporal sclerosis, and parenchymal/leptomeningeal enhancement. The electronic medical record was reviewed for relevant clinical information and laboratory markers. A study cohort of 19 patients was identified. The majority of patients were female (84%), with a mean age of onset of 27 years. Serum GAD65 titers ranged from 33 to 4415 nmol/L (normal < 0.02 nmol/L). The most common presentation was medically intractable, complex partial seizures with temporal lobe onset. Parenchymal atrophy was the most common imaging finding (47%), with a subset of patients demonstrating cortical/subcortical parenchymal T2 hyperintensity (37%) or abnormal hippocampal signal (26%). No patients demonstrated abnormal parenchymal/leptomeningeal enhancement. The most common MRI finding in GAD65-associated autoimmune epilepsy is disproportionate parenchymal atrophy for age, often associated with abnormal cortical/subcortical T2 hyperintensities. Hippocampal abnormalities are seen in a minority of patients. This constellation of findings in a patient with medically intractable epilepsy should raise the possibility of GAD65 autoimmunity. (orig.)
Full Text Available Melatonin is the main secretory product synthesized and secreted by the pineal gland during the night. Melatonin is a pleitropic molecule with a wide distribution within phylogenetically distant organisms and has a great functional versatility, including the regulation of circadian and seasonal rhythms and antioxidant and anti-inflammatory properties. It also possesses the capacity to modulate immune responses by regulation of the TH1/TH2 balance and cytokine production. Immune system eradicates infecting organisms without serious injury to host tissues, but sometimes these responses are inadequately controlled, giving rise to called hypersensitivity diseases, or inappropriately targeted to host tissues, causing the autoimmune diseases. In clinical medicine, the hypersensitivity diseases include the allergic or atopic diseases and the hallmarks of these diseases are the activation of TH2 cells and the production of IgE antibody. Regarding autoimmunity, at the present time we know that the key events in the development of autoimmunity are a failure or breakdown of the mechanisms normally responsible for maintaining self-tolerance in B lymphocytes, T lymphocytes, or both, the recognition of self-antigens by autoreactive lymphocytes, the activation of these cells to proliferate and differentiate into effector cells, and the tissue injury caused by the effector cells and their products. Melatonin treatment has been investigated in atopic diseases, in several animal models of autoimmune diseases, and has been also evaluated in clinical autoimmune diseases. This review summarizes the role of melatonin in atopic diseases (atopic dermatitis and asthma and in several autoimmune diseases, such as arthritis rheumatoid, multiple sclerosis, systemic lupus erythematosus, type 1 diabetes mellitus, and inflammatory bowel diseases.
Full Text Available Thymic carcinomas are tumors of the anterior mediastinum derived from the epithelial cells of the thymus gland. Malignancies linked to thymoma lead to the loss of self-tolerance leading to autoimmune diseases, including myasthenia gravis, pure red cell aplastic anemia, systemic lupus erythematosus and pemphigus etc. In recent years, three main mechanisms have been proposed to elucidate these interactions, such as immature T cell theory, tumor-gene theory and the combination mechanism of cellular and humoral immunity. In fact, the resection of the thymoma is beneficial to many patients of thymoma related autoimmune diseases. DOI: 10.11855/j.issn.0577-7402.2014.08.16
Ding, Liping; Wang, Xiaohui; Hong, Xiaoping; Lu, Liwei; Liu, Dongzhou
The inteleukin-36 (IL-36) cytokines include IL-36α, IL-36β, IL-36γ and IL-36Ra, which belong to the IL-1 family and exert pro-inflammatory effects on various target cells such as keratinocytes, synoviocytes, dendritic cells and T cells. Emerging evidence has suggested a role of IL-36 in the pathogenesis of many inflammatory diseases. Here, we provide a brief review on the activation of IL-36 family cytokines and their involvement in autoimmunity and inflammatory diseases, which will provide further insights in understanding the functions of IL-36 family cytokines in the pathophysiology of autoimmunity and inflammatory diseases.
Nexø, Bjørn A; Villesen, Palle; Nissen, Kari K
factors. Viruses including human endogenous retroviruses have long been linked to the occurrence of autoimmunity, but never proven to be causative factors. Endogenous viruses are retroviral sequences embedded in the host germline DNA and transmitted vertically through successive generations in a Mendelian...... manner. In this study by means of genetic epidemiology, we have searched for the involvement of endogenous retroviruses in three selected autoimmune diseases: multiple sclerosis, type 1 diabetes mellitus, and rheumatoid arthritis. We found that at least one human endogenous retroviral locus...
Brandão Neto, Rodrigo Antonio; de Carvalho, Jozélio Freire
Autoimmune adrenalitis, or autoimmune Addison disease (AAD), is the most prevalent cause of primary adrenal insufficiency in the developed world. AAD is rare and can easily be misdiagnosed as other conditions. The diagnosis depends on demonstrating inappropriately low cortisol production and the presence of high titers of adrenal cortex autoantibodies (ACAs), along with excluding other causes of adrenal failure using other tests as necessary. The treatment corticosteroid replacement, and the prognosis following the treatment is the same as the normal population. Spontaneous recovery of adrenal function has been described but is rare. Copyright © 2014 Elsevier B.V. All rights reserved.
Full Text Available Background. Endometriosis is a comon, complex gynecological syndrom defined as the growth of endometrial glands and stroma in an extra-uterine location. It affects 5 – 20 % of women of reproductive age.1 Nowadays, prevailing opinion about endometriosis is based on presumption, that endometriosis is a result of changed immune system, according to autoimmune theory.2, 3 Characteristics of autoimmune disease that are also found in endometriosis are female preponderance, multiorgan involvement, family occurence, possible genetic basis, response to hormonal manipulation, tissue damage, polyclonal B lymphocite activation, immunological abnormalities in T lymphocite and B lymphocite function and associated autoimmune disease. Women with endometriosis are more frequently affected by asthma, rheumatoid arthritis, systemic lupus erythematosus, Sjögren syndrom and Hashimoto’s thyroiditis. Autoimmune disease is characterized by the production of autoantibodies against components of apoptotic cells. Anti-endometrial antibodies of IgG and IgM classes could be detected in 60 % of endometriosis patients. They show reactivity in glandular epithelium and stroma. Anti-endothelial antibodies specifically react with vascular endothelium and might be with anti-endometrial antibodies partially responsible for failure of implantation leading to infertility, wich is common in endometriosis patients. Anti-nuclear antibodies are frequent serological findings in patients with autoimmune disease, and could be detected in 29–47 % of women with endometriosis.4 Generation of anti-nuclear antibodies is a risk factor for development of other autoimmune disease in women of reproductive age. Studies have shown conflicting results on the presence of anti-ovarian antibodies in the serum of endometriosis patients and in the peritoneal fluid. Their presence is one of the possible causes of infertility. Conclusions. Ethiopathogenesis of endometriosis still remains uncelar but
Linneberg, Allan; Madsen, Flemming; Skaaby, Tea
After 100 years of experience with allergen-specific immunotherapy (SIT), an issue that is still unresolved is whether SIT can act as a trigger of, or as a risk factor for, autoimmune disease. We searched the literature for evidence on this topic.......After 100 years of experience with allergen-specific immunotherapy (SIT), an issue that is still unresolved is whether SIT can act as a trigger of, or as a risk factor for, autoimmune disease. We searched the literature for evidence on this topic....
Borgwardt, L.; Pedersen, P.; Peitersen, B.
Autoimmune polyglandular syndrome (APS) is an entity, defined by autoimmunity towards two or more endocrine organs. APS is classified in 3 subgroups (type-1, type-2a, type-2b), according to the organs involved. A case is presented of a 13-year old girl referred to the Department of Paediatrics...... with hypothyroidism, subsequently diagnosed adrenocortical insufficiency and impending Addison crisis, typical for APS-type 2a. In the paper we discuss the need for more attention to APS in clinical work Udgivelsesdato: 2008/9/29...
Lisyany, N.I.; Liubich, L.D.
Autoimmune hypothesis as to the development of radiation-induced brain injuries stands high among the concepts of the CNS post-radiation damage pathogenesis. To study the changes occurring in a living organism affected by a small-dose radiation due to incorporated radionuclides as well as to create adequate models are of critical importance in the post-Chernobyl period. The effects of chronic small-dose inner radiation on the development of autoimmune responses were evaluated by determining the level of the CNS proteins and protein-induced antibodies to the CNS components. (author)
Full Text Available An 18-year old girl with segmental vitiligo involving the left side of the trunk and left upper limb with segmental morphea involving the right side of trunk and right upper limb without any deeper involvement is illustrated. There was no history of preceding drug intake, vaccination, trauma, radiation therapy, infection, or hormonal therapy. Family history of stable vitiligo in her brother and a history of type II diabetes mellitus in the father were elicited. Screening for autoimmune diseases and antithyroid antibody was negative. An autoimmune link explaining the co-occurrence has been proposed. Cutaneous mosiacism could explain the presence of both the pathologies in a segmental distribution.
Stoian, Dana; Craciunescu, Mihalea; Timar, Romulus; Schiller, Adalbert; Pater, Liana; Craina, Marius
Thyroid autoimmune disease, a widespread phenomenon in female population, impairs thyroid function during pregnancy. Identifying cases, which will develop hypothyroidism during pregnancy, is crucial in the follow-up process. The study group comprised 108 females, with ages between 20-40 years; with known inactive autoimmune thyroid disease, before pregnancy that became pregnant in the study follow-up period. They were monitored by means of clinical, hormonal and immunological assays. Supplemental therapy with thyroid hormones was used, where needed. Maternal age and level of anti-thyroid antibodies were used to predict thyroid functional impairment.
Ameratunga, Rohan; Gillis, David; Gold, Michael
Autoimmune/autoinflammatory syndrome induced by adjuvants (ASIA) was described in 2011. Over time the condition and its triggers have broadened to include several autoimmune disorders, the macrophagic myofasciitis syndrome, the Gulf war syndrome, the sick building syndrome, siliconosis...
Kavelaars, A; Heijnen, CJ; Tennekes, R; Bruggink, JE; Koolhaas, JM
Neuroendocrine-immune interactions are thought to be important in determining susceptibility to autoimmune disease. Animal studies have revealed that differences in susceptibility to experimental autoimmune encephalomyelitis (EAE) are related to:reactivity in the hypothalamo-pituitary-adrenal axis.
Nesse, Willem; Dijkstra, Pieter U.; Abbas, Frank; Spijkervet, Fred K. L.; Stijger, Astrid; Tromp, Jan A. H.; van Dijk, Johan L.; Vissink, Arjan
Background: Associations between periodontitis and cardiovascular and autoimmune diseases are most often assessed in patients with a particular cardiovascular or autoimmune disease. To prevent selection bias, this study assesses the existence of associations between periodontitis and cardiovascular
Nesse, Willem; Dijkstra, Pieter U.; Abbas, Frank; Spijkervet, Fred K. L.; Stijger, Astrid; Tromp, Jan A. H.; van Dijk, Johan L.; Vissink, Arjan
Background: Associations between periodontitis and cardiovascular and autoimmune diseases are most often assessed in patients with a particular cardiovascular or autoimmune disease. To prevent selection bias, this study assesses the existence of associations between periodontitis and cardiovascular
Full Text Available 17959357 Toll like receptors and autoimmunity: a critical appraisal. Papadimitraki ...ml) Show Toll like receptors and autoimmunity: a critical appraisal. PubmedID 17959357 Title Toll like receptors and auto
Said, Ashraf; Elbahrawy, Ashraf; Alfiomy, Mohamed; Abdellah, Mohamed; Shahat, Khaled; Salah, Mohamed; Mostafa, Sadek; Elwassief, Ahmed; Aboelfotoh, Attef; Abdelhafeez, Hafez; El-Sherif, Assem
A 55-year-old Egyptian woman with chronic hepatitis C undergoing treatment with pegylated interferon (Peg-IFN) alfa-2a plus ribavirin was referred to our hospital on November 2010 with prolonged easy fatigability and an attack of syncope; she had no prior history of autoimmune disorders or allergy. Laboratory investigations documented the presence of Peg-IFN induced autoimmune haemolytic anaemia and autoimmune thyroiditis. Intravenous γ globulin (IVGG) failed to correct the autoimmune process...
Autoimmune polyglandular syndrome type 1 in a 12-year-old Ugandan girl. ... Journal of Endocrinology, Metabolism and Diabetes of South Africa ... Autoimmune polyglandular syndrome type 1 (APS-1), also known as autoimmune polyendocrinopathy-candidiasisectodermal dystrophy syndrome, is a very rare disorder of ...
Visser, Jeroen; Rozing, Jan; Sapone, Anna; Lammers, Karen; Fasano, Alessio; Fromm, M; Schulzke, JD
Autoimmune diseases are characterized by tissue damage and loss of function due to an immune response that is directed against specific organs. This review is focused on celiac disease (CD), an autoimmune enteropathy, and type I diabetes (TID), a hyperglycosaemia caused by a destructive autoimmune
AUTOIMMUNITY AS A POSSIBLE MECHANISM OF PROLACTIN-INDUCED PROSTATITIS. RW Luebke, CB Copeland, and LR Bishop. US EPA, Research Triangle Park, NCStoker et al. reported inflammation of the lateral prostate (LP) lobes in 120 day old Wistar rats after manipulation of prolac...
Hoekstra, PJ; Minderaa, RB
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
Chen, Ji-Qing; Szodoray, Peter; Zeher, Margit
Autoimmune diseases are a family of chronic systemic inflammatory disorders, characterized by the dysregulation of the immune system which finally results in the break of tolerance to self-antigen. Several studies suggest that Toll-like receptors (TLRs) play an essential role in the pathogenesis of autoimmune diseases. TLRs belong to the family of pattern recognition receptors (PRRs) that recognize a wide range of pathogen-associated molecular patterns (PAMPs). TLRs are type I transmembrane proteins and located on various cellular membranes. Two main groups have been classified based on their location; the extracelluar group referred to the ones located on the plasma membrane while the intracellular group all located in endosomal compartments responsible for the recognition of nucleic acids. They are released by the host cells and trigger various intracellular pathways which results in the production of proinflammatory cytokines, chemokines, as well as the expression of co-stimulatory molecules to protect against invading microorganisms. In particular, TLR pathway-associated proteins, such as IRAK, TRAF, and SOCS, are often dysregulated in this group of diseases. TLR-associated gene expression profile analysis together with single nucleotide polymorphism (SNP) assessment could be important to explain the pathomechanism driving autoimmune diseases. In this review, we summarize recent findings on TLR pathway regulation in various autoimmune diseases, including Sjögren's syndrome (SS), systemic lupus erythematosus (SLE), multiple sclerosis (MS), rheumatoid arthritis (RA), systemic sclerosis (SSc), and psoriasis.
Kallenberg, C. G. M.; Stegeman, C. A.; Bootsma, H.; Biji, M.; Limburg, P. C.
Serial assessment of levels of autoantibodies has been proposed as being clinically useful in certain systemic autoimmune diseases. In particular, attention has been given to anti-dsDNA antibodies in systemic lupus erythematosus (SLE) and ANCA in the ANCA-associated vasculitides (AAV). Much
Kremer, Joel M
The Corrona US national registry collects data concerning patient status from both the rheumatologist and patient at routine clinical encounters. Corrona has functioning disease registries in rheumatoid arthritis, psoriatic arthritis, spondyloarthropathies, psoriasis and inflammatory bowel disease. Corrona merges data concerning long-term effectiveness and safety, as well as comparative and cost effectiveness of agents to treat these autoimmune diseases.
Fletcher, J M
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 gammadelta 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, gammadelta, CD8(+) and regulatory T cells as well as the possible development of new therapeutic approaches for MS based on manipulating these T cell subtypes.
Maassen, C.B.M.; Claassen, E.
In this study we present new data showing strain-specific differences on the effect of commercially available probiotic drinks in an EAE rat autoimmune model for multiple sclerosis. In this particular model, we conclude that these drinks do not enhance but rather suppress the disease. We suggest
Cole, Charles R; Yutzey, Katherine E; Brar, Anoop K; Goessling, Lisa S; Van Vickle-Chavez, Sarah J; Cunningham, Madeleine W; Eghtesady, Pirooz
Structural congenital heart disease (CHD) has not previously been linked to autoimmunity. In our study, we developed an autoimmune model of structural CHD that resembles hypoplastic left heart syndrome (HLHS), a life-threatening CHD primarily affecting the left ventricle. Because cardiac myosin (CM) is a dominant autoantigen in autoimmune heart disease, we hypothesized that immunization with CM might lead to transplacental passage of maternal autoantibodies and a prenatal HLHS phenotype in exposed fetuses. Elevated anti-CM autoantibodies in maternal and fetal sera, as well as IgG reactivity in fetal myocardium, were correlated with structural CHD that included diminished left ventricular cavity dimensions in the affected progeny. Further, fetuses that developed a marked HLHS phenotype had elevated serum titers of anti-β-adrenergic receptor Abs, as well as increased protein kinase A activity, suggesting a potential mechanism for the observed pathological changes. Our maternal-fetal model presents a new concept linking autoimmunity against CM and cardiomyocyte proliferation with cardinal features of HLHS. To our knowledge, this report shows the first evidence in support of a novel immune-mediated mechanism for pathogenesis of structural CHD that may have implications in its future diagnosis and treatment.
Papp, Gabor; Boros, Peter; Nakken, Britt; Szodoray, Peter; Zeher, Margit
In physiological circumstances, various tolerogenic mechanisms support the protection of self-structures during immune responses. However, quantitative and/or qualitative changes in regulatory immune cells and mediators can evoke auto-reactive immune responses, and upon susceptible genetic background, along with the presence of other concomitant etiological factors, autoimmune disease may develop. In transplant immunology, tolerogenic mechanisms are also critical, since the balance between of alloantigen-reactive effector cells and the regulatory immune cells will ultimately determine whether a graft is accepted or rejected. Better understanding of the immunological tolerance and the potential modulations of immune regulatory processes are crucial for developing effective therapies in autoimmune diseases as well as in organ transplantation. In this review, we focus on the novel insights regarding the impaired immune regulation and other relevant factors contributing to the development of auto-reactive and graft-reactive immune responses in autoimmune diseases and transplant rejection, respectively. We also address some promising approaches for modification of immune-regulatory processes and tolerogenic mechanisms in autoimmunity and solid organ transplantation, which may be beneficial in future therapeutic strategies. Copyright © 2017 Elsevier B.V. All rights reserved.
Marta Sofia Mendes Oliveira
Full Text Available Autoimmune hepatitis is a chronic liver inflammation resulting from deregulation of immune tolerance mechanisms. Multiple sclerosis is also an inflammatory disease in which the insulating covers of nerve cells in the brain and spinal cord are damaged. Here we present a case of an 18 year old female with multiple sclerosis was treated with glatiramer acetate and with interferon beta 1a at our hospital. Seven months after initiating treatment, liver dysfunction occurred. Clinical and laboratory findings were suggestive of drug-induced hepatitis, which led to discontinuation of treatment with interferon. Facing a new episode of acute hepatitis one year later, she was subjected to a liver biopsy, and the analysis of autoantibodies was positive for smooth muscle antibodies. Given the diagnosis of autoimmune hepatitis she started therapy with prednisolone and azathioprine, with good clinical and analytical response. Besides, the demyelinating lesions of multiple sclerosis became lower. In conclusion, there are only a few cases that describe the association of autoimmune hepatitis with multiple sclerosis, and there is a chance both diseases have the same autoimmune inflammatory origin.
Grode, Louise; Bech, Bodil H; Jensen, Thomas Møller
AIM: The aim of this study was to describe and identify potential trends with respect to prevalence, incidence, age, sex, and autoimmune comorbidity of celiac disease (CD). PATIENTS AND METHODS: A Danish nationwide cohort study of CD using data from The National Patient Register. Patients...
Winther, Kristian H; Bonnema, Steen J; Hegedüs, Laszlo
This review provides an appraisal of recent evidence for or against selenium supplementation in patients with autoimmune thyroid diseases, and discusses possible effect mechanisms. Epidemiological data suggest an increased prevalence of autoimmune thyroid diseases under conditions of low dietary selenium intake. Two systematic reviews have evaluated controlled trials among patients with autoimmune thyroiditis and report that selenium supplementation decreases circulating thyroid autoantibodies. The immunomodulatory effects of selenium might involve reducing proinflammatory cytokine release. However, clinically relevant effects of selenium supplementation, including improvement in quality of life, are more elusive. In Graves' disease, some, but not all, trials indicate that adjuvant selenium supplementation enhances the restoration of biochemical euthyroidism, and might benefit patients with mild Graves' orbitopathy. The use of selenium supplementation as adjuvant therapy to standard thyroid medication may be widespread, but a growing body of evidence yields equivocal results. The available evidence from trials does not support routine selenium supplementation in the standard treatment of patients with autoimmune thyroiditis or Graves' disease. However, correction of moderate to severe selenium deficiency may offer benefits in preventing, as well as treating, these disorders. Molecular mechanisms have been proposed, but further studies are needed.
Swedo, Susan E.; Grant, Paul J.
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…
The association of granuloma annulare (GA) and autoimmune thyroiditis has been documented in the literature in 13 previous cases. However, the pathogenesis of GA remains obscure. Possible pathogenetic factors suggested include: humoral and delayed type hypersensitivity, vascular damage, metabolic disorder, or, ...
Autoimmune hepatitis (AIH) is a rare cause of chronic liver disease (CLD). It presents with ... chronic viral hepatitis and alcoholic liver disease, making it difficult to diagnose in .... effects.2,5,9 We opted for the Budesonide/AZA therapy because ...
Danneskiold-Samsøe, Bente; Bartels, Else Marie; Dreyer, Lene
Many autoimmune diseases like rheumatoid arthritis (RA) show gender differences. RA is triggered by an interaction between genetic, hormonal, environmental and behavioural factors. 75% of cases are women under the age of 60; lover the age 60 the gender ratio is 1:1. Different genotypes predispose...
Inflammasomes are intracellular multiprotein complexes that coordinate anti-pathogenic host defense during inflammatory responses in myeloid cells, especially macrophages. Inflammasome activation leads to activation of caspase-1, resulting in the induction of pyroptosis and the secretion of pro-inflammatory cytokines including interleukin (IL)-1β and IL-18. Although the inflammatory response is an innate host defense mechanism, chronic inflammation is the main cause of rheumatic diseases, such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), ankylosing spondylitis (AS), and Sjögren's syndrome (SS). Since rheumatic diseases are inflammatory/autoimmune disorders, it is reasonable to hypothesize that inflammasomes activated during the inflammatory response play a pivotal role in development and progression of these diseases. Indeed, previous studies have provided important observations that inflammasomes are actively involved in the pathogenesis of inflammatory/autoimmune rheumatic diseases. In this review, we summarize the current knowledge on several types of inflammasomes during macrophage-mediated inflammatory responses and discuss recent research regarding the role of inflammasomes in the pathogenesis of inflammatory/autoimmune rheumatic diseases. This avenue of research could provide new insights for the development of promising therapeutics to treat inflammatory/autoimmune rheumatic diseases.
Nielsen, Signe Modvig; Høi-Hansen, Christina Engel; Uldall, Peter
Autoimmune synaptic encephalitis (ASE) is a recently recognized disease entity. The early and correct diagnosis of ASE is of importance, since the prognosis depends on the early onset of treatment. We present two Danish case reports of ASE: a 15-year-old boy presenting with a severe course of N...
Full Text Available Specific autoimmune and inflammatory rheumatic diseases have been associated with an increased risk of malignant lymphomas. Conditions such as rheumatoid arthritis (RA, primary Sjögren’s syndrome (pSS, systemic lupus erythematosus (SLE, dermatomyositis, and celiac disease have been consistently linked to malignant lymphomas. Isolated cases of lymphomas associated with spondyloarthropathies and autoinflammatory diseases have also been reported. Direct association between autoimmunity and lymphomagenesis has been reinforced by large epidemiological studies. It is still uncertain whether disease specific determinants or phenotypic or treatment related characteristics increase likelihood of lymphomagenesis in these patients. For example, recent literature has indicated a positive correlation between severity of inflammation and risk of lymphomas among RA and Sjögren’s syndrome patients. It is also debated whether specific lymphoma variants are more commonly seen in accordance with certain chronic autoimmune arthritis. Previous studies have revealed a higher incidence of diffuse large B-cell lymphomas in RA and SLE patients, whereas pSS has been linked with increased risk of mucosa-associated lymphoid tissue lymphoma. This review summarizes recent literature evaluating risk of lymphomas in arthritis patients and disease specific risk determinants. We also elaborate on the association of autoimmune arthritis with specific lymphoma variants along with genetic, environmental, and therapeutic risk factors.
We present a middle aged lady positive HIV who developed liver disease one year after initiation of anti-retroviral therapy (ART). Laboratory and histo pathology finding supported a diagnosis of autoimmune hepatitis (AIH). She responded well to immuno-suppressive therapy and is currently doing well on maintenance ...
t'Hart, B. A.; Vervoordeldonk, M.; Heeney, J. L.; Tak, P. P.
Before autoimmune diseases in humans can be treated with gene therapy, the safety and efficacy of the used vectors must be tested in valid experimental models. Monkeys, such as the rhesus macaque or the common marmoset, provide such models. This publication reviews the state of the art in monkey
Wang, E Q; Radjenovic, M; Castrillón, M A; Feng, G H Y; Murrell, D F
Autoimmune blistering diseases (AIBD) are known to negatively impact upon quality of life (QoL); however, there is a paucity of research on the effect of AIBD on work productivity. AIBD can be quite disfiguring in terms of a patient's appearance due to their blistering nature. To determine the impact of AIBD on work productivity and to determine whether patients are stigmatized at work due to their appearance. Sixty-one patients with AIBD completed the Work Productivity and Activity Impairment Questionnaire-Specific Health Problem (WPAIQ-SHP), the Dermatology Life Quality Index (DLQI), the Autoimmune Bullous Disease Quality of Life (ABQOL) and the Treatment of Autoimmune Bullous Disease Quality of Life questionnaires (TABQOL). Non-responders to treatment had more work and activity impairment compared to responders. Worse WPAIQ-SHP scores were correlated with higher ABQOL, TABQOL and DLQI scores. Approximately 14.8% of subjects experienced stigmatization at work due to their appearance. The most common body areas stigmatized were easily visible sites, particularly the hands, arms and feet, with the majority of occurrences related to co-workers; for some patients, this stigmatization occurred on a daily basis. Loss of productivity at work was statistically much higher in those with higher disease severity, ABQOL & TABQOL scores and in non-responders to treatment. Autoimmune blistering diseases negatively impacts upon work productivity and activity. Stigmatization was common in the workplace which leads to increased stress, itself a stimulator of pemphigus. © 2018 European Academy of Dermatology and Venereology.
Gram-Kampmann, Eva-Marie; Lillevang, Søren T; Detlefsen, Sönke
Autoimmune enteropathy (AE) is an immune mediated illness of the intestinal mucosa. The cause is unknown, and the diagnosis is based on typical characteristics displayed. There is no gold standard for treatment. We present two adult cases of AE and demonstrate the challenges in establishing....... Use of WCE as a diagnostic tool was invaluable in establishing the diagnosis of AE....
Blank, M; Krause, I; Magrini, L
Rheumatic fever (RF) and the antiphospholipid syndrome (APS) are autoimmune diseases that share similar cardiac and neurological pathologies. We assessed the presence of shared epitopes between M protein, N-acetyl-beta-D-glucosamine (GlcNAc) and beta2 glycoprotein-I (beta2GPI), the pathogenic...
Maat, P.; de Beukelaar, J.W.; Jansen, C.; Schuur, M.; van Duijn, C.M.; van Coevorden, M.H.; de Graaff, E.; Titulaer, E.; Rozemuller, A.J.M.; Sillevis Smitt, P.
Objective: To determine the clinical features and presence in CSF of antineuronal antibodies in patients with pathologically proven autoimmune encephalitis derived from a cohort of patients with suspected Creutzfeldt-Jakob disease (CJD). Methods: The Dutch Surveillance Centre for Prion Diseases
Ahmed Salem; Diaa Hamouda; Alyssa Parian
Autoimmune pancreatitis (AIP) is a rare form of chronic pancreatitis that has only recently been recognized as a separate type of pancreatitis in the last two decades. The histopathological features of this distinct form of pancreatitis was first described as early as 1961 when the French Henry Sarles.
Sydney K Elizer
Full Text Available T cells are critically dependent on cellular proliferation in order to carry out their effector functions. Autoimmune strains are commonly thought to have uncontrolled T cell proliferation; however, in the murine model of autoimmune diabetes, hypo-proliferation of T cells leading to defective AICD was previously uncovered. We now determine whether lupus prone murine strains are similarly hyporesponsive. Upon extensive characterization of T lymphocyte activation, we have observed a common feature of CD4 T cell activation shared among three autoimmune strains-NOD, MRL, and NZBxNZW F1s. When stimulated with a polyclonal mitogen, CD4 T cells demonstrate arrested cell division and diminished dose responsiveness as compared to the non-autoimmune strain C57BL/6, a phenotype we further traced to a reliance on B cell mediated costimulation, which underscores the success of B cell directed immune therapies in preventing T cell mediated tissue injury. In turn, the diminished proliferative capacity of these CD4 T cells lead to a decreased, but activation appropriate, susceptibility to activation induced cell death. A similar decrement in stimulation response was observed in the CD8 compartment of NOD mice; NOD CD8 T cells were distinguished from lupus prone strains by a diminished dose-responsiveness to anti-CD3 mediated stimulation. This distinction may explain the differential pathogenetic pathways activated in diabetes and lupus prone murine strains.
Harris, G [Kennedy Inst. of Rheumatology, London (UK). Div. of Experimental Pathology; Cramp, W A; Edwards, J C; George, A M; Sabovljev, S A; Hart, L; Hughes, G R.V. [Hammersmith Hospital, London (UK); Denman, A M [Northwich Park Hospital, Harrow (UK); Yatvin, M B [Wisconsin Clinical Cancer Center, Madison (USA)
The proliferation of peripheral blood lymphocytes, cultured with Con A, can be inhibited by ionizing radiation. Lymphocytes from patients with conditions associated with autoimmunity, such as rheumatoid arthritis, systemic lupus erythematosus and polymyositis, are more radiosensitive than those from healthy volunteers or patients with conditions not associated with autoimmunity. Nuclear material isolated from the lymphocytes of patients with autoimmune diseases is, on average, lighter in density than the nuclear material from most healthy controls. This difference in density is not related to increased sensitivity to ionizing radiation but the degree of post-irradiation change in density (lightening) is proportional to the initial density, i.e. more dense nuclear material always shows a greater upward shift after radiation. The recovery of pre-irradiation density of nuclear material, 1 h after radiation exposure, taken as an indication of DNA repair, correlates with the radiosensitivity of lymphocyte proliferation (Con A response); failure to return to pre-irradiation density being associated with increased sensitivity of proliferative response. These results require extension but, taken with previously reported studied of the effects of DNA methylating agents, support the idea that DNA damage and its defective repair could be important in the aetio-pathogenesis of autoimmune disease.
Effraimidis, Grigoris; Wiersinga, Wilmar M.
The last 10 years have seen some progress in understanding the etiology of autoimmune thyroid disease (AITD). The female preponderance can now be explained - at least in part - by fetal microchimerism and X-chromosome inactivation. The number of identified susceptibility genes for AITD is increasing
Opazo, Maria C.; Ortega-Rocha, Elizabeth M.; Coronado-Arrázola, Irenice; Bonifaz, Laura C.; Boudin, Helene; Neunlist, Michel; Bueno, Susan M.; Kalergis, Alexis M.; Riedel, Claudia A.
The human body is colonized by millions of microorganisms named microbiota that interact with our tissues in a cooperative and non-pathogenic manner. These microorganisms are present in the skin, gut, nasal, oral cavities, and genital tract. In fact, it has been described that the microbiota contributes to balancing the immune system to maintain host homeostasis. The gut is a vital organ where microbiota can influence and determine the function of cells of the immune system and contributes to preserve the wellbeing of the individual. Several articles have emphasized the connection between intestinal autoimmune diseases, such as Crohn's disease with dysbiosis or an imbalance in the microbiota composition in the gut. However, little is known about the role of the microbiota in autoimmune pathologies affecting other tissues than the intestine. This article focuses on what is known about the role that gut microbiota can play in the pathogenesis of non-intestinal autoimmune diseases, such as Grave's diseases, multiple sclerosis, type-1 diabetes, systemic lupus erythematosus, psoriasis, schizophrenia, and autism spectrum disorders. Furthermore, we discuss as to how metabolites derived from bacteria could be used as potential therapies for non-intestinal autoimmune diseases. PMID:29593681
Two patients with auto-immune thrombocytopenic purpura are reported who continued to bleed despite high doses of corticosteroids, immunosuppressive therapy and splenec- tomy. The addition of vincristine to their therapeutic regimen produced a response in each case and both patients are now off all therapy without ...
Full Text Available Over the past two decades, heat shock proteins (HSPs have been implicated in inflammatory responses and autoimmunity. HSPs were originally believed to maintain protein quality control in the cytosol. However, they also exist extracellularly and appear to act as inflammatory factors. Recently, a growing body of evidence suggested that the other class of stress proteins such as, endoplasmic reticulum (ER stress proteins, which originally act as protein quality control factors in the secretory pathway and are induced by ER stress in inflammatory lesions, also participate in inflammation and autoimmunity. The immunoglobulin heavy-chain binding protein (Bip/glucose-regulated protein 78 (Grp78, homocysteine-induced ER protein (Herp, calnexin, calreticulin, glucose-regulated protein 94 (Grp94/gp96, oxygen-regulated protein 150 (ORP150 and heat shock protein 47 (Hsp47/Serpin H1, which are expressed not only in the ER but also occasionally at the cell surface play pathophysiological roles in autoimmune and inflammatory diseases as pro- or anti-inflammatory factors. Here we describe the accumulating evidence of the participation of ER stress proteins in autoimmunity and inflammation and discuss the critical differences between the two classes of stress proteins.
Wiersinga, Wilmar M.
Smoking is a risk factor for Graves disease. However, Carle et al. have demonstrated that individuals have a transient increased risk of developing overt autoimmune hypothyroidism in the first 2 years after quitting smoking. The mechanisms involved in these two opposing effects of smoking on the
Li, Cheuk Wun; Menconi, Francesca; Osman, Roman; Mezei, Mihaly; Jacobson, Eric M; Concepcion, Erlinda; David, Chella S; Kastrinsky, David B; Ohlmeyer, Michael; Tomer, Yaron
We previously showed that an HLA-DR variant containing arginine at position 74 of the DRβ1 chain (DRβ1-Arg74) is the specific HLA class II variant conferring risk for autoimmune thyroid diseases (AITD). We also identified 5 thyroglobulin (Tg) peptides that bound to DRβ1-Arg74. We hypothesized that blocking the binding of these peptides to DRβ1-Arg74 could block the continuous T-cell activation in thyroiditis needed to maintain the autoimmune response to the thyroid. The aim of the current study was to identify small molecules that can block T-cell activation by Tg peptides presented within DRβ1-Arg74 pockets. We screened a large and diverse library of compounds and identified one compound, cepharanthine that was able to block peptide binding to DRβ1-Arg74. We then showed that Tg.2098 is the dominant peptide when inducing experimental autoimmune thyroiditis (EAT) in NOD mice expressing human DRβ1-Arg74. Furthermore, cepharanthine blocked T-cell activation by thyroglobulin peptides, in particular Tg.2098 in mice that were induced with EAT. For the first time we identified a small molecule that can block Tg peptide binding and presentation to T-cells in autoimmune thyroiditis. If confirmed cepharanthine could potentially have a role in treating human AITD. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.
Hinson, Shannon R; Lennon, Vanda A; Pittock, Sean J
Neuromyelitis optica (NMO) spectrum disorders (SD) represent an evolving group of central nervous system (CNS)-inflammatory autoimmune demyelinating diseases unified by a pathogenic autoantibody specific for the aquaporin-4 (AQP4) water channel. It was historically misdiagnosed as multiple sclerosis (MS), which lacks a distinguishing biomarker. The discovery of AQP4-IgG moved the focus of CNS demyelinating disease research from emphasis on the oligodendrocyte and myelin to the astrocyte. NMO is recognized today as a relapsing disease, extending beyond the optic nerves and spinal cord to include brain (especially in children) and skeletal muscle. Brain magnetic resonance imaging abnormalities, identifiable in 60% of patients at the second attack, are consistent with MS in 10% of cases. NMOSD-typical lesions (another 10%) occur in AQP4-enriched regions: circumventricular organs (causing intractable nausea and vomiting) and the diencephalon (causing sleep disorders, endocrinopathies, and syndrome of inappropriate antidiuresis). Advances in understanding the immunobiology of AQP4 autoimmunity have necessitated continuing revision of NMOSD clinical diagnostic criteria. Assays that selectively detect pathogenic AQP4-IgG targeting extracellular epitopes of AQP4 are promising prognostically. When referring to AQP4 autoimmunity, we suggest substituting the term "autoimmune aquaporin-4 channelopathy" for the term "NMO spectrum disorders." Randomized clinical trials are currently assessing the efficacy and safety of newer immunotherapies. Increasing therapeutic options based on understanding the molecular pathogenesis is anticipated to improve the outcome for patients with AQP4 channelopathy. © 2016 Elsevier B.V. All rights reserved.
Myasthenia gravis (MG) is an acquired autoimmune disorder causing skeletal muscle fatigue and weakness. This is a report of one woman and her daughter presenting with myasthenia and gravis and Grave\\'s disease. It highlights possible hereditary component of this condition which has not been commonly reported in ...
Riber, Sara Schødt; Ali, Mulham; Bergseth, Sara Hveding
of this study was to develop a large animal model for abdominal aortic aneurysm induction through autoimmunity by performing sheep-to-pig xenotransplantation. Methods Six pigs underwent a xenotransplantation procedure where the infrarenal porcine aorta was replaced by a decellularized sheep aorta...
Maria C. Opazo
Full Text Available The human body is colonized by millions of microorganisms named microbiota that interact with our tissues in a cooperative and non-pathogenic manner. These microorganisms are present in the skin, gut, nasal, oral cavities, and genital tract. In fact, it has been described that the microbiota contributes to balancing the immune system to maintain host homeostasis. The gut is a vital organ where microbiota can influence and determine the function of cells of the immune system and contributes to preserve the wellbeing of the individual. Several articles have emphasized the connection between intestinal autoimmune diseases, such as Crohn's disease with dysbiosis or an imbalance in the microbiota composition in the gut. However, little is known about the role of the microbiota in autoimmune pathologies affecting other tissues than the intestine. This article focuses on what is known about the role that gut microbiota can play in the pathogenesis of non-intestinal autoimmune diseases, such as Grave's diseases, multiple sclerosis, type-1 diabetes, systemic lupus erythematosus, psoriasis, schizophrenia, and autism spectrum disorders. Furthermore, we discuss as to how metabolites derived from bacteria could be used as potential therapies for non-intestinal autoimmune diseases.
Yanovich, O.O.; Titov, L.P
The statistical analysis has shown undulation the incidence of thyroiditis since 1998. The prevalence of diabetes mellitus is characterized by a constant increase of cases. Data testify to the tendency of increasing the prevalence autoimmune diseases in Republic of Belarus. (authors)
Nissen, Mette; Blaabjerg, Morten
with status epilepticus. GABAB encephalitis is associated with small-cell lung cancer or neuroendocrine lung tumour. This is a case report of a patient having status epilepticus due to GABAB encephalitis. In cases which are presumed to be autoimmune it is important that treatment starts immediately instead...
Northrup, Laura; Sullivan, Bradley P; Hartwell, Brittany L; Garza, Aaron; Berkland, Cory
Current therapies to treat autoimmune diseases often result in side effects such as nonspecific immunosuppression. Therapies that can induce antigen-specific immune tolerance provide an opportunity to reverse autoimmunity and mitigate the risks associated with global immunosuppression. In an effort to induce antigen-specific immune tolerance, co-administration of immunomodulators with autoantigens has been investigated in an effort to reprogram autoimmunity. To date, identifying immunomodulators that may skew the antigen-specific immune response has been ad hoc at best. To address this need, we utilized splenocytes obtained from mice with experimental autoimmune encephalomyelitis (EAE) in order to determine if certain immunomodulators may induce markers of immune tolerance following antigen rechallenge. Of the immunomodulatory compounds investigated, only dexamethasone modified the antigen-specific immune response by skewing the cytokine response and decreasing T-cell populations at a concentration corresponding to a relevant in vivo dose. Thus, antigen-educated EAE splenocytes provide an ex vivo screen for investigating compounds capable of skewing the antigen-specific immune response, and this approach could be extrapolated to antigen-educated cells from other diseases or human tissues.
Billings, Monisha; Dye, Bruce A.; Iafolla, Timothy; Grisius, Margaret; Alevizos, Ilias
Introduction Oral candidiasis (OC) is a potential oral complication in Sjögren’s Syndrome (SS). Some studies indicate that the low stimulated salivary flow and not low unstimulated salivary flow is associated with OC in SS, while others report that the underlying autoimmune disorders contributes to OC, based solely on correlation coefficients. Given the conflicting and limited existing evidence, we purposed to ascertain the role of both salivary gland dysfunction (hyposalivation based on unstimulated and stimulated flow rates) and autoimmunity (SS, other autoimmune disorders) in OC among those with SS, other salivary gland dysfunction and non-salivary gland dysfunction controls (NSGD). Methods A nested case-control study was designed within a larger NIH/NIDCR cohort. Descriptive analyses, non-parametric tests, comparative analyses, and multivariate logistic regression analyses were undertaken. Results Data on 1,526 subjects (701 SS, 247 ISS, 355 Sicca, and 223 NSGD) were obtained from the source cohort of 2,046 and analyzed for this current study. The median whole unstimulated salivary flow rate (WUS, ml/15min) was lower in SS (0.8, interquartile range (IQR) 1.8) compared to ISS (5.5, IQR 5.2, pcandidiasis. Conclusion Salivary gland dysfunction (hyposalivation with WUS being a stronger predictor than TSS) and autoimmunity (SS, other autoimmune disorders, medications i.e., DMARDS) are both independent predictors of OC. Diabetes mellitus is an independent predictor of OC among those with salivary gland dysfunction. Our findings suggest that these independent predictors should be considered in the prevention and management of OC in this population. PMID:27998016
Frasca, Daniela; Diaz, Alain; Romero, Maria; Thaller, Seth; Blomberg, Bonnie B
The adipose tissue (AT) contributes to systemic and B cell intrinsic inflammation, reduced B cell responses and secretion of autoimmune antibodies. In this study we show that adipocytes in the human obese subcutaneous AT (SAT) secrete several pro-inflammatory cytokines and chemokines, which contribute to the establishment and maintenance of local and systemic inflammation, and consequent suboptimal immune responses in obese individuals, as we have previously shown. We also show that pro-inflammatory chemokines recruit immune cells expressing the corresponding receptors to the SAT, where they also contribute to local and systemic inflammation, secreting additional pro-inflammatory mediators. Moreover, we show that the SAT generates autoimmune antibodies. During the development of obesity, reduced oxygen and consequent hypoxia and cell death lead to further release of pro-inflammatory cytokines, "self" protein antigens, cell-free DNA and lipids. All these stimulate class switch and the production of autoimmune IgG antibodies which have been described to be pathogenic. In addition to hypoxia, we have measured cell cytotoxicity and DNA damage mechanisms, which may also contribute to the release of "self" antigens in the SAT. All these processes are significantly elevated in the SAT as compared to the blood. We definitively found that fat-specific IgG antibodies are secreted by B cells in the SAT and that B cells express mRNA for the transcription factor T-bet and the membrane marker CD11c, both involved in the production of autoimmune IgG antibodies. Finally, the SAT also expresses RNA for cytokines known to promote Germinal Center formation, isotype class switch, and plasma cell differentiation. Our results show novel mechanisms for the generation of autoimmune antibody responses in the human SAT and allow the identification of new pathways to possibly manipulate in order to reduce systemic inflammation and autoantibody production in obese individuals.
Agarwal, N; Handa, R; Acharya, S K; Wali, J P; Dinda, A K; Aggarwal, P
Hepatitis C virus (HCV) infection is associated with several autoimmune markers. Despite HCV being common in India, no information on this aspect is available. This study was undertaken to ascertain the frequency and clinical significance of autoimmune markers like rheumatoid factor (RF), antinuclear antibodies (ANA), antibodies to double stranded deoxyribonucleic acid (dsDNA), anti neutrophil cytoplasmic antibody (ANCA), anti smooth muscle antibodies (ASMA), anti liver kidney microsomal 1 antibodies (anti LKM1), anti gastric parietal cell antibodies (anti GPCA), anti mitochondrial antibodies (AMA), anti cardiolipin antibodies (ACL) and cryoglobulins in HCV infection and to determine the effect of treatment on these markers. Twenty five patients with chronic hepatitis C and 25 healthy controls were studied. Cryoglobulins were detected by cryoprecipitation, RF by latex agglutination, anti dsDNA and ACL by ELISA while indirect immunofluorescence was used to detect all other autoantibodies. Eighteen patients (72%) demonstrated autoimmune markers. RF, cryoglobulins and anti LKM1 antibodies were the most frequently detected markers (in 32% patients each). ASMA, perinuclear ANCA (pANCA), ANA and anti GPCA were seen in 24, 20, 12 and 4 per cent patients respectively. None of the patients exhibited ACL, AMA or antibodies to dsDNA. No antibodies were detected in healthy controls. Sixty per cent of the patients had rheumatological symptoms. Of the seven patients followed up after treatment with alpha interferon, only two exhibited persistence of RF, while symptoms and other markers disappeared. Rheumatological symptoms and autoimmune markers are common in HCV infection and are usually overlooked. Patients with unexplained joint pains and/or palpable purpura should be screened for HCV. Further studies are needed to delineate fully the link between infection and autoimmunity.
Djilali-Saiah, Idriss; Fakhfakh, Amin; Louafi, Hamida; Caillat-Zucman, Sophie; Debray, Dominique; Alvarez, Fernando
Type 2 autoimmune hepatitis (AIH) is characterized by the presence of anti-liver kidney microsome (anti-LKM-1) and/or anti-liver cytosol type 1 (anti-LC1) autoantibodies. However, the correlation between these autoantibodies and the genetic background has not been studied. Frequencies of HLA class II alleles were compared between the 60 Caucasian children with type 2 AIH and 313 control subjects. The anti-LKM1 antibody reactivity directed against antigenic sites of CYP2D6 was analysed by ELISA. HLA-DQB1 *0201 allele was found to be the primary genetic determinant of susceptibility to type 2 AIH by conferring the highest odd-ratio (OR = 6.4). HLA-DRB1 *03 allele was significantly increased (P LKM1 and anti-LC1 autoantibodies as well as in those with only anti-LC1(+) compared to those with anti-LKM1(+) alone. In contrast, HLA-DRB1 *07 allele was significantly associated (P LKM1(+) alone compared to groups with both anti-LKM and anti-LC1 or with LC1+ alone. Children with the DRB1 *07 allele develop anti-LKM1 autoantibodies having a more restricted specificity (2 epitopes) than to those having HLA-DRB1 *03 allele (5 epitopes). The HLA-DR locus is involved in autoantibody expression, while the DQ locus appears to be a critical determinant for the development of type 2 AIH.
Bonilla Abadía, Fabio; Muñoz Buitrón, Evelyn; Ochoa, Carlos D.; Carrascal, Edwin; Cañas Dávila, Carlos Alberto
The localized scleroderma (LS) known as morphea, presents a variety of clinical manifestations that can include systemic involvement. Current classification schemes divide morphea into categories based solely on cutaneous morphology, without reference to systemic disease or autoimmune phenomena. This classification is likely incomplete. Autoimmune phenomena such as vitiligo and Hashimoto thyroiditis associated with LS have been reported in some cases suggesting an autoimmune basis. To our kno...
Helmberger, T. [Klinikum Bogenhausen, Staedt. Klinikum, Institut fuer Diagnostische und Interventionelle Radiologie, Neuroradiologie und Nuklearmedizin, Muenchen (Germany)
Autoimmune pancreatitis (AIP) is a rare disease, the pathophysiological understanding of which has been greatly improved over the last years. The most common form, type 1 AIP belongs to the IgG4-related diseases and must be distinguished from type 2 AIP, which is a much rarer entity associated with chronic inflammatory bowel disease. Clinically, there is an overlap with pancreatic cancer. Imaging and further criteria, such as serological and histological parameters are utilized for a differentiation between both entities in order to select the appropriate therapy and to avoid the small but ultimately unnecessary number of pancreatectomies. The diagnostics of AIP are complex, whereby the consensus criteria of the International Association of Pancreatology have become accepted as the parameters for discrimination. These encompass five cardinal criteria and one therapeutic criterion. By applying these criteria AIP can be diagnosed with a sensitivity of 84.9 %, a specificity of 100 % and an accuracy of 93.8 %. The diagnosis of AIP is accomplished by applying several parameters of which two relate to imaging. As for the routine diagnostics of the pancreas these are ultrasound, computed tomography (CT) and magnetic resonance imaging (MRI). Important for the differential diagnosis is the exclusion of signs of local and remote tumor spread for which CT and MRI are established. The essential diagnostic parameter of histology necessitates sufficient sample material, which cannot usually be acquired by a fine needle biopsy. CT or MRI are the reference standard methods for identification of the optimal puncture site and imaging-assisted (TruCut) biopsy. In patients presenting with unspecific upper abdominal pain, painless jaundice combined with the suspicion of a pancreatic malignancy in imaging but a mismatch of secondary signs of malignancy, AIP should also be considered as a differential diagnosis. As the diagnosis of AIP only partially relies on imaging radiologists also
Aaltonen, J.; Bjoerses, P.; Peltonen, L. [National Public Health Institute, Helsinki (Finland)] [and others
Autoimmune reactions encoupled to many human diseases are still only partially understood. Unravelling the molecular pathogenesis of inherited diseases with a strong autoimmune component in their clinical expression could help to dissect individual components in the molecular background of abnormal immune response. One such genetic disorder is autosomal recessive autoimmune polyglandular disease type I (PGD I), also known as autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED, MIM 240300). The disease is especially enriched in the genetically isolated population of Finland and we have assigned the APECED locus to human chromosome 21q22.3 in 14 Finnish families by linkage analyses. The best positional lod score of 6.49 was observed with marker D21S49. Based on the history of the Finns, the gene pool of this population clearly demonstrates the consequences of a founder effect and consequent isolation. In the Finnish population, we can take advantage of linkage disequilibrium and allelic association studies to more precisely define the critical DNA region for our disease gene of interest than would be possible by linkage analyses alone. We are now able to define the chromosomal region of interest between two flanking markers locating 1 cM apart. Linkage disequilibrium is observed with three of the markers used in the analyses and this suggests a distance of less than 500 kb to the disease locus, well approachable with molecular cloning techniques. Overlapping YAC and cosmid clones spanning our region of interest will facilitate the cloning of APECED gene in the near future.
Bonilla-Abadía, Fabio; Muñoz-Buitrón, Evelyn; Ochoa, Carlos D; Carrascal, Edwin; Cañas, Carlos A
The localized scleroderma (LS) known as morphea, presents a variety of clinical manifestations that can include systemic involvement. Current classification schemes divide morphea into categories based solely on cutaneous morphology, without reference to systemic disease or autoimmune phenomena. This classification is likely incomplete. Autoimmune phenomena such as vitiligo and Hashimoto thyroiditis associated with LS have been reported in some cases suggesting an autoimmune basis. To our knowledge this is the first case of a morphea forming part of a multiple autoimmune syndrome (MAS) and presenting simultaneously with autoimmune thrombocytopenic purpura and central nervous system vasculitis. We report an uncommon case of a white 53 year old female patient with LS as part of a multiple autoimmune syndrome associated with pneumonitis, autoimmune thrombocytopenic purpura and central nervous system vasculitis presenting a favorable response with thrombopoietin receptor agonists, pulses of methylprednisolone and cyclophosphamide. Is likely that LS have an autoimmune origin and in this case becomes part of MAS, which consist on the presence of three or more well-defined autoimmune diseases in a single patient.
Full Text Available Abstract Background The localized scleroderma (LS known as morphea, presents a variety of clinical manifestations that can include systemic involvement. Current classification schemes divide morphea into categories based solely on cutaneous morphology, without reference to systemic disease or autoimmune phenomena. This classification is likely incomplete. Autoimmune phenomena such as vitiligo and Hashimoto thyroiditis associated with LS have been reported in some cases suggesting an autoimmune basis. To our knowledge this is the first case of a morphea forming part of a multiple autoimmune syndrome (MAS and presenting simultaneously with autoimmune thrombocytopenic purpura and central nervous system vasculitis. Case presentation We report an uncommon case of a white 53 year old female patient with LS as part of a multiple autoimmune syndrome associated with pneumonitis, autoimmune thrombocytopenic purpura and central nervous system vasculitis presenting a favorable response with thrombopoietin receptor agonists, pulses of methylprednisolone and cyclophosphamide. Conclusion Is likely that LS have an autoimmune origin and in this case becomes part of MAS, which consist on the presence of three or more well-defined autoimmune diseases in a single patient.
Cedillo, Maribel; Libman, Ingrid M; Arena, Vincent C; Zhou, Lei; Trucco, Massimo; Ize-Ludlow, Diego; Pietropaolo, Massimo; Becker, Dorothy J
The current increase in childhood type 1 diabetes (T1D) and obesity has led to two conflicting hypotheses and conflicting reports regarding the effects of overweight on initiation and spreading of islet cell autoimmunity vs earlier clinical manifestation of preexisting autoimmune β-cell damage driven by excess weight. The objective of the study was to address the question of whether the degree of β-cell autoimmunity and age are related to overweight at diabetes onset in a large cohort of T1D youth. This was a prospective cross-sectional study of youth with autoimmune T1D consecutively recruited at diabetes onset. The study was conducted at a regional academic pediatric diabetes center. Two hundred sixty-three consecutive children younger than 19 years at onset of T1D participated in the study. Relationships between body mass index and central obesity (waist circumference and waist to height ratio) and antigen spreading (islet cell autoantibody number), age, and cardiovascular (CVD) risk factors examined at onset and/or 3 months after the diagnosis were measured. There were no significant associations between number of autoantibodies with measures of adiposity. Age relationships revealed that a greater proportion of those with central obesity (21%) were in the youngest age group (0-4 y) compared with those without central obesity (6%) (P = .001). PATIENTS with central obesity had increased CVD risk factors and higher onset C-peptide levels (P obesity accelerates progression of autoantibody spreading once autoimmunity, marked by standard islet cell autoantibody assays, is present. Central obesity was present in almost one-third of the subjects and was associated with early CVD risk markers already at onset.
Botta, Silvia; Roveto, Silvana; Rimoldi, Daniel
Autoimmune polyendocrine syndrome (APS) is the association of autoimmune endocrine diseases, with other autoimmune nonendocrine disorders. APS types 1, 2 and 4 include autoimmune adrenalitis; this suggests the presence of autoantibodies. A specific serological marker for these is the anti 21- hydroxilase autoantibody (a21-OH). APS type 2 is the association of autoimmune adrenalitis, to autoimmune thyroid disease and/or diabetes mellitus, all these are induced by autoantibodies. Alopecia, vitiligo, myasthenia and other manifestations can be minor components. We sought to establish the prevalence of seric a21-OH in patients with positive anti-microsomal fraction autoantibodies, autoimmune thyroid disease and/or non-endocrine autoimmune diseases. We also aimed to diagnose incomplete forms of APS and to follow up patients at risk of progression to complete forms of APS. A population of 72 patients and another of 60 controls with negative anti-microsomal fraction autoantibodies were studied. Elevated seric a21-OH were found in two patients. Patient A with 47 U/ml had autoimmune hypothyroidism and myasthenia; and patient B with 8.75 U/ml had autoimmune hypothyrodism and vitiligo; they both lacked adrenal insufficiency. Seric a21-OH had a prevalence of 2.8%. Regarding the adrenal component, patients A and B had an incomplete and latent APS type 2. Considering a21-OH as markers of latent endocrine autoimmune diseases and taking into account the eventual risk of developing clinical manifestations, periodic biochemical and clinical follow-ups are recommended.
Paquette, R L; Meshkinpour, A; Rosen, P J
Autoimmune myelofibrosis is an uncommon disorder in which patients present with anemia and thrombocytopenia in conjunction with limited clinical manifestations of autoimmune disease or an exacerbation of previously established SLE. The presence of leukoerythroblastosis in a patient with SLE may suggest the presence of myelofibrosis. Conversely, the absence of splenomegaly in a patient with presumed idiopathic myelofibrosis may suggest an autoimmune etiology. Patients with autoimmune myelofibrosis universally have a positive ANA test and frequently have either elevated anti-DNA titers or a positive LE cell preparation. Because physical manifestations of autoimmune disease may not be evident at presentation, all patients found to have myelofibrosis should have an ANA test. Peripheral blood cytopenias in autoimmune myelofibrosis frequently respond to glucocorticoids but regression of bone marrow fibrosis may be incomplete. Hematologic response to treatment parallels that of the associated autoimmune disease.
Jorgensen, C S; Levantino, G; Houen, Gunnar
Annexin XI, a calcyclin-associated protein, has been shown to be identical to a 56,000 Da antigen recognized by antibodies found in sera from patients suffering from systemic autoimmune diseases. In this work hexahistidine-tagged recombinant annexin XI (His6- rAnn XI) was used as antigen in ELISA...... experiments for determination of autoantibodies to annexin XI in sera of patients with systemic rheumatic autoimmune diseases. Immunoblotting with HeLa cell extract and with His6-rAnn XI as antigen was used for confirmation of positive ELISA results. We found eleven anti-annexin XI positive sera (3.9%) out...... of 282 sera from patients with systemic rheumatic diseases. The highest number of annexin XI positive sera were found in primary antiphospholipid syndrome (3/17), and in subacute lupus erythematosus (1/6), while lower frequencies of positive sera were found in patients with systemic sclerosis (5...
Heegaard, Niels H. H.; Carlsen, Anting Liu; Skovgaard, Kerstin
killer cells, neutrophil granulocytes, and monocyte-macrophages. Exploratory studies (only validated in a few cases) also show that specific profiles of circulating miRNAs are associated with different systemic autoimmune diseases including systemic lupus erythematosus (SLE), systemic sclerosis......, extracellular miRNA is protected against degradation by complexation with carrier proteins and/or by being enclosed in subcellular membrane vesicles. This, together with their tissue- and disease-specific expression, has fuelled the interest in using circulating microRNA profiles as harbingers of disease, i.......e., as diagnostic analytes and as clues to dysregulated pathways in disease. Many studies show that inflammation and immune dysregulation, e.g., in autoimmune diseases, are associated with distinct miRNA expression changes in targeted tissues and in innate and adaptive immunity cells such as lymphocytes, natural...
Full Text Available Introduction, objective: To present a case report in which the finding of non-coeliac gluten sensitivity was decisive for the treatment of a complex autoimmune disease. Materials and methods: A 43-year-old woman with polyarthritis, psoriatic features, anti-SSA/Ro and anti-cyclic citrullinated peptide antibodies, with refractory course, was evaluated for gluten sensitivity despite negative serology for coeliac disease. Results: The patient carried the HLA DQ2 haplotype and duodenal biopsy showed lymphocytic enteritis. A gluten-free diet resolved the clinical picture and permitted tapering of immunosuppressive therapy. Conclusion: Non-coeliac gluten sensitivity can be associated with autoimmunity despite the absence of the specific autoantibodies of coeliac disease.
Sánchez-Berná, Isabel; Santiago-Díaz, Carlos; Jiménez-Alonso, Juan
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. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.
Wesley H. Brooks
Full Text Available Polyamines are small cations with unique combinations of charge and length that give them many putative interactions in cells. Polyamines are essential since they are involved in replication, transcription, translation, and stabilization of macro-molecular complexes. However, polyamine synthesis competes with cellular methylation for S-adenosylmethionine, the methyl donor. Also, polyamine degradation can generate reactive molecules like acrolein. Therefore, polyamine levels are tightly controlled. This control may be compromised in autoimmune diseases since elevated polyamine levels are seen in autoimmune diseases. Here a hypothesis is presented explaining how polyamines can stabilize autoantigens. In addition, the hypothesis explains how polyamines can inappropriately activate enzymes involved in NETosis, a process in which chromatin is modified and extruded from cells as extracellular traps that bind pathogens during an immune response. This polyamine-induced enzymatic activity can lead to an increase in NETosis resulting in release of autoantigenic material and tissue damage.
Sequeira, Jedon; Boily, Gino; Bazinet, Stephanie; Saliba, Sarah; He Xiaohong; Jardine, Karen; Kennedy, Christopher; Staines, William; Rousseaux, Colin; Mueller, Rudi; McBurney, Michael W.
The sirt1 gene encodes a protein deacetylase with a broad spectrum of reported substrates. Mice carrying null alleles for sirt1 are viable on outbred genetic backgrounds so we have examined them in detail to identify the biological processes that are dependent on SIRT1. Sera from adult sirt1-null mice contain antibodies that react with nuclear antigens and immune complexes become deposited in the livers and kidneys of these animals. Some of the sirt1-null animals develop a disease resembling diabetes insipidus when they approach 2 years of age although the relationship to the autoimmunity remains unclear. We interpret these observations as consistent with a role for SIRT1 in sustaining normal immune function and in this way delaying the onset of autoimmune disease
Schaub, M; Issazadeh-Navikas, Shohreh; Stadlbauer, T H
Blockade of the CD28-B7 or CD40L-CD40 T cell costimulatory signals prevents induction of experimental autoimmune encephalomyelitis (EAE). However, the effect of simultaneous blockade of these signals in EAE is unknown. We show that administration of either MR1 (to block CD40L) or CTLA4Ig (to block...... B7) after immunization or after the first attack protects from EAE. Treatment with a combination of CTLA4Ig and MR1 provides additive protection, and is associated with complete absence of mononuclear cell infiltrates in the central nervous system, and marked suppression of proliferation of primed T...... cells in the periphery. Selective B7-1 blockade did not protect from EAE. These observations have implications for therapy of autoimmune diseases....
Camprubí, Cristina; Monk, David
In the 19th century Gregor Mendel defined the laws of genetic inheritance by crossing different types of peas. From these results arose his principle of equivalence: the gene will have the same behaviour whether it is inherited from the mother or the father. Today, several key exceptions to this principle are known, for example sex-linked traits and genes in the mitochondrial genome, whose inheritance patterns are referred to as 'non mendelian'. A third, important exception in mammals is that of genomic imprinting, where transcripts are expressed in a monoallelic fashion from only the maternal or the paternal chromosome. In this chapter, we discuss how parent-of-origin effects and genomic imprinting may play a role in autoimmunity and speculate how imprinted miRNAs may influence the expression of many target autoimmune associated genes.
Full Text Available Primary biliary cirrhosis (PBC is a chronic progressive autoimmune cholestatic liver disease characterized by highly specific antimitochondrial antibodies (AMAs and the specific immune-mediated injury of small intrahepatic bile ducts. Unique apoptotic feature of biliary epithelial cells (BECs may contribute to apotope presentation to the immune system, causing unique tissue damage in PBC. Perpetuation of inflammation may result in senescence of BECs, contributing to irreversible loss of bile duct. In addition to the classic liver manifestations, focal inflammation and tissue damage are also seen in salivary glands and urinary tract in a significant proportion of PBC patients. These findings provide potent support to the idea that molecular mimicry may be involved in the breakdown of autoimmune tolerance and mucosal immunity may lead to a systematic epithelitis in PBC patients. Thus, PBC is considered a generalized epithelitis in clinical practice.
Full Text Available Epstein-Barr virus (EBV infects B-, T-, and NK cells and has been associated not only with a wide range of lymphoid malignancies but also with autoimmune diseases such as lupus erythematosus, rheumatoid arthritis and, in particular, multiple sclerosis. Hence, effective immunotherapeutic approaches to eradicate EBV infection might overthrow cancer and autoimmunity incidence. However, currently no effective anti-EBV immunotherapy is available. Here we use the concept that protein immunogenicity is allocated in rare peptide sequences and search the Epstein-Barr nuclear antigen 1 (EBNA1 sequence for peptides unique to the viral protein and absent in the human host. We report on a set of unique EBV EBNA1 peptides that might be used in designing peptide-based therapies able to specifically hitting the virus or neutralizing pathogenic autoantibodies.
Brix, Thomas Heiberg; Hansen, Pia Skov; Rudbeck, Annette Beck
CONTEXT: Low birth weight has been proposed as a risk factor for the development of antibodies toward thyroid peroxidase (TPOAb) and thyroglobulin (TgAb) in adult life. However, the association could also be due to genetic or environmental factors affecting both birth weight and the development...... of thyroid autoantibodies. The effect of these confounders can be minimized through investigation of twin pairs. OBJECTIVE AND DESIGN: To examine the impact of low birth weight on the development of thyroid autoimmunity, we studied whether within-twin-cohort and within-twin-pair differences in birth weight......, gestational age, TSH, and smoking) did not change the findings of nonsignificant regression coefficients. CONCLUSION: Low birth weight per se has no evident role in the etiology of thyroid autoimmunity....
Ziegler, Anette-G.; Pflueger, Maren; Winkler, Christiane; Achenbach, Peter; Akolkar, Beena; Krischer, Jeffrey P.; Bonifacio, Ezio
The incidence of type 1 diabetes is rising worldwide, particularly in young children. Since type 1 diabetes is preceded by autoimmunity to islet antigens, there must be a consequent increase in the incidence of islet autoimmunity in young children or a more rapid rate of progression to diabetes once islet autoimmunity initiates. This study was to determine whether the incidence of islet autoimmunity or the rate of progression from autoimmunity to diabetes onset has changed over a 20-year peri...
Full Text Available Constant increase in the incidence of autoimmune thyroiditis (AIT in different regions of Ukraine puts this problem in actual number that determines the need to identify features of the clinical course of AIT, the principles of differentiated treatment depending on the nature of the metabolic changes and taking into account regional differences in thyroid pathology, particularly AIT. The paper presents data on the study of features of clinical course and complex treatment of AIT.
COJOCARU, Inimioara Mihaela; COJOCARU, Manole; SILOSI, Isabela; VRABIE, Camelia Doina
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 ...
Full Text Available 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
Torres-Ruiz, J; Sulli, A; Cutolo, M; Shoenfeld, Y
Biological rhythms are fundamental for homeostasis and have recently been involved in the regulatory processes of various organs and systems. Circadian cycle proteins and hormones have a direct effect on the inflammatory response and have shown pro- or anti-inflammatory effects in animal models of autoimmune diseases. The cells of the immune system have their own circadian rhythm, and the light-dark cycle directly influences the inflammatory response. On the other hand, patients with autoimmune diseases characteristically have sleep disorders and fatigue, and in certain disease, such as rheumatoid arthritis (RA), a frank periodicity in the signs and symptoms is recognized. The joint symptoms predominate in the morning, and apparently, subjects with RA have relative adrenal insufficiency, with a cortisol peak unable to control the late night load of pro-inflammatory cytokines. Transatlantic flights represent a challenge in the adjustment of biological rhythms, since they imply sleep deprivation, time zone changes, and potential difficulties for drug administration. In patients with autoimmune diseases, the use of DMARDs and prednisone at night is probably best suited to lessen morning symptoms. It is also essential to sleep during the trip to improve adaptation to the new time zone and to avoid, as far as possible, works involving flexible or nocturnal shifts. The study of proteins and hormones related to biological rhythms will demonstrate new pathophysiological pathways of autoimmune diseases, which will emphasize the use of general measures for sleep respect and methods for drug administration at key daily times to optimize their anti-inflammatory and immune modulatory effects.
Benros, Michael E; Mortensen, Preben B; Eaton, William W
Immunological hypotheses have become increasingly prominent when studying the etiology of schizophrenia. Autoimmune diseases, and especially the number of infections requiring hospitalization, have been identified as significant risk factors for schizophrenia in a dose-response relationship, whic...... diseases and infections should be considered in the treatment of individuals with schizophrenia symptoms, and further research is needed of the immune system's possible contributing pathogenic factors in the etiology of schizophrenia....
Type 1 diabetes (T1D) is an autoimmune disease characterized by the selective loss of the insulin-producing β-cells residing in the islets of Langerhans in the pancreas. Cytokines are involved in diabetes development in the nonobese diabetic (NOD) mouse model. NOD mice over-expressing the suppressor of cytokine signaling (SOCS-1) specifically in the β-cells are protected from T1D. Previous studies showed that immune cells infiltrated the pancreas of SOCS-1-transgenic (tg)...
Daniel Alvarenga Fernandes
Full Text Available Abstract We present a case of immunoglobulin G4 (IgG4-related disease with pancreatic and extrapancreatic involvement, including the biliary and renal systems. Given the importance of imaging methods for the diagnosis of IgG4-related disease and its differentiation from pancreatic adenocarcinoma, we emphasize important abdominal computed tomography and magnetic resonance imaging findings related to this recently recognized systemic autoimmune disease.
Kawicka, Anna; Regulska-Ilow, Bożena; Regulska-Ilow, Bożena
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
Marta, Guilherme Nader; de Campos, Fernando Peixoto Ferraz
Immune thrombocytopenia (ITP) is an entity characterized by a platelet count of less than 100 × 109/L in the absence of other causes of thrombocytopenia, such as viral infections, rheumatic diseases, or drugs. Grave’s disease is also an autoimmune condition in which thrombocytopenia is often observed. Moreover, in the literature, many reports show a marked interference of the thyroid dysfunction (mainly hyperthyroidism) in the control of thrombocytopenia. Although this issue still remains deb...
Full Text Available The intestinal epithelial lining, together with factors secreted from it, forms a barrier that separates the host from the environment. In pathologic conditions, the permeability of the epithelial lining may be compromised allowing the passage of toxins, antigens, and bacteria in the lumen to enter the blood stream creating a “leaky gut.” In individuals with a genetic predisposition, a leaky gut may allow environmental factors to enter the body and trigger the initiation and development of autoimmune disease. Growing evidence shows that the gut microbiota is important in supporting the epithelial barrier and therefore plays a key role in the regulation of environmental factors that enter the body. Several recent reports have shown that probiotics can reverse the leaky gut by enhancing the production of tight junction proteins; however, additional and longer term studies are still required. Conversely, pathogenic bacteria that can facilitate a leaky gut and induce autoimmune symptoms can be ameliorated with the use of antibiotic treatment. Therefore, it is hypothesized that modulating the gut microbiota can serve as a potential method for regulating intestinal permeability and may help to alter the course of autoimmune diseases in susceptible individuals.
Silvia Martina Ferrari
Full Text Available 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 (CXCL9, 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.
Full Text Available Abstract Background Experimental autoimmune encephalomyelitis is a widely used animal model to understand not only multiple sclerosis but also basic principles of immunity. The disease is scored typically by observing signs of paralysis, which do not always correspond with pathological changes. Methods Experimental autoimmune encephalomyelitis was induced in transgenic mice expressing an injury responsive luciferase reporter in astrocytes (GFAP-luc. Bioluminescence in the brain and spinal cord was measured non-invasively in living mice. Mice were sacrificed at different time points to evaluate clinical and pathological changes. The correlation between bioluminescence and clinical and pathological EAE was statistically analyzed by Pearson correlation analysis. Results Bioluminescence from the brain and spinal cord correlates strongly with severity of clinical disease and a number of pathological changes in the brain in EAE. Bioluminescence at early time points also predicts severity of disease. Conclusion These results highlight the potential use of bioluminescence imaging to monitor neuroinflammation for rapid drug screening and immunological studies in EAE and suggest that similar approaches could be applied to other animal models of autoimmune and inflammatory disorders.
Ayas, Zeynep Özözen; Kotan, Dilcan; Aras, Yeşim Güzey
Autoimmune neurological syndrome is a group of disorders caused by cancer affecting nervous system by different immunological mechanisms. In this study, we aim to study the clinical symptoms, cerebrospinal fluid (CSF) findings, autoantibody tests, computed tomography (CT), magnetic resonance imaging (MRI) signs and treatment outcome of patients with autoimmune syndromes. In this study, 7 patients (4 male, 3 female) diagnosed with autoimmune neurological syndrome were retrospectively examined. Five of patients were diagnosed with limbic encephalitis, two of them were paraneoplastic cerebellar degeneration. Confusion and seizure were the most seen symptoms. Two patients had psychiatric disturbances (28,5%) followed by seizure. Headache was seen in 2 patients (% 28,5), disartria in 1 patient (% 14,2), and gait disorder in 2 patients (28,5%). The duration of symptoms was 46 (3-150) days on average. CSF abnormalities were detected in 2 patients. CT and MRI of the brain was available in all patients. Five patients had involvement of mesiotemporal region, two patients had diffuse cerebellar atrophy. One of patients had anti-GABAR B1 positivity. Tumors were detected in 2 patients while investigation for paraneoplasia screening. Remission is only possible with the detection and treatment of the malignancy. Early diagnosis and treatment are of paramount importance. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Paoli, Donatella; Gilio, Barbara; Piroli, Emanuela; Gallo, Mariagrazia; Lombardo, Francesco; Dondero, Franco; Lenzi, Andrea; Gandini, Loredana
To evaluate the presence of antisperm antibodies in testicular cancer patients 1 month after orchiectomy and before radiotherapy or chemotherapy. Clinical study. Department of andrology and seminology at a university hospital. One hundred ninety patients with testicular cancer. Determination of semen parameters and autoimmune reaction evaluated on the sperm surface and in blood serum. Autoimmune reaction on the sperm surface by the direct immunobead test (IBT), and in blood serum by the indirect IBT and the gelatin agglutination test (GAT), was evaluated 1 month after orchiectomy and before beginning chemotherapy or radiotherapy. Of the 190 patients, 11 (5.8%) were positive for antisperm antibody by GAT. On indirect IBT, 3 of the 11 GAT-positive patients were positive to IgG class only, with values of 22%, 24%, and 40%. Of the 11 GAT-positive patients, 4 showed no antibody bound to the sperm surface, and 3 were positive to IgG class only (28%, 21%, and 38%), with binding exclusively on the tail. Direct IBT could not be performed in the remaining 4 patients. Our data support the hypothesis that testicular cancer might not be a possible cause of antisperm autoimmunization and infertility.
Full Text Available Puumala hantavirus (PUUV infection causes nephropathia epidemica (NE, a relatively mild form of haemorrhagic fever with renal syndrome (HFRS. Hypophyseal haemorrhage and hypopituitarism have been described in case reports on patients with acute NE. Chronic hypopituitarism diagnosed months or years after the acute illness has also been reported, without any signs of a haemorrhagic aetiology. The mechanisms leading to the late-onset hormonal defects remain unknown. Here, we present a case of NE-associated autoimmune polyendocrinopathy and hypopituitarism presumably due to autoimmune hypophysitis. Thyroid peroxidase antibody seroconversion occurred between 6 and 12 months, and ovarian as well as glutamate decarboxylase antibodies were found 18 months after acute NE. Brain MRI revealed an atrophic adenohypophysis with a heterogeneous, low signal intensity compatible with a sequela of hypophysitis. The patient developed central (or mixed central and peripheral hypothyroidism, hypogonadism and diabetes insipidus, all requiring hormonal replacement therapy. This case report suggests that late-onset hormonal defects after PUUV infection may develop by an autoimmune mechanism. This hypothesis needs to be confirmed by prospective studies with sufficient numbers of patients.
Huang, Yan-Mei; Hong, Xue-Zhi; Xu, Jia-Hua; Luo, Jiang-Xi; Mo, Han-You; Zhao, Hai-Lu
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.
Full Text Available Multicentric Castleman's disease (MCD is lymphoproliferative disorder characterized by systemic inflammatory symptoms such as fever and weight loss. Human herpes virus-8 (HHV-8 is thought to be a causable pathogen in all HIV-positive and some HIV-negative MCD patients. Furthermore, the term idiopathic MCD (iMCD was recently proposed to represent a group of HIV-negative and HHV-8-negative patients with unknown etiologies. Although the international diagnostic criteria for iMCD require exclusion of infection-related disorders, autoimmune/autoinflammatory diseases and malignant/lymphoproliferative disorders to make an iMCD diagnosis, the relationships and differences between these disorders and MCD have not yet been clarified. We recently reported the first case of MCD with autoimmune lymphoproliferative syndrome (ALPS. Although ALPS was included in the iMCD exclusion criteria as an autoimmune/autoinflammatory disease according to the international diagnostic criteria, there is a lack of evidence on the association between MCD and ALPS. In this study, we review the recent understanding of MCD and discuss the possible association between MCD with ALPS.
Sasiwimonphan, Kewalee; Gorman, Brian; Kawashima, Akira; Chari, Suresh T.; Takahashi, Naoki
Objective: The purpose of our study was to retrospectively evaluate the ultrasound findings of renal involvement in patients with autoimmune pancreatitis. Methods: 15 patients with autoimmune pancreatitis (15 male, 0 female, mean age 66 years old, range 44–85) who had renal involvement documented on CT or MR and had abdominal ultrasound within 1 month were included. Ultrasound images were retrospectively reviewed for presence or absence of renal involvement. Shape and echogenicity of the renal lesions were recorded. Results: In 8 out of 15 patients, at least one renal lesion was identified on ultrasound with a total of 9 kidneys. In 7 kidneys, lesions appeared as ill-defined, non-mass like areas of decreased echogenicity. Three lesions showed associated irregular lobular thickening of the renal parenchyma with bulging contour and 1 showed focal area of parenchymal loss. In 2 kidneys, the lesions were seen as solitary or multiple hypoechoic mass-like areas. Ill-defined, non-mass like lesions on ultrasound corresponded to well-circumscribed wedge-shaped lesions in all but one case on CT or MR. Mass-like lesions on ultrasound corresponded to well-circumscribed round lesions on CT or MR. Conclusion: Most common ultrasound findings of renal involvement in patients with autoimmune pancreatitis were ill-defined area of decreased echogenicity.
Liberal, Rodrigo; Mieli-Vergani, Giorgina; Vergani, Diego
Autoimmune hepatitis (AIH) is a severe life-threatening hepatopathy of unknown etiology, affecting both pediatric and adult populations, and characterised by inflammatory liver histology, circulating non-organ-specific autoantibodies, and hypergammaglobulinaemia. AIH is a very heterogeneous disease with a variety of clinical presentations, ranging from asymptomatic liver test abnormalities to acute severe hepatitis or even acute liver failure. It responds very well to immunosuppressive treatment with prednisolone with or without azathioprine. Patients who are intolerant or fail to respond to standard therapy are candidates for alternative immunosuppressive regimens, the combination of steroids with mycophenolate mofetil or calcineurin inhibitors being the most frequently reported. The pathogenesis of AIH remains not completely understood, although there is evidence that genetic predisposition, molecular mimicry and defective immunoregulatory mechanisms contribute to the autoimmune liver damage. A literature search was conducted using the key-words 'autoimmune hepatitis', 'immunogenetics', 'regulatory T-cells' and 'immunosuppression'. The aim of this review is to discuss recent breakthroughs in the understanding AIH pathogenesis, diagnosis and treatment. Expert commentary: Progress in the understanding of AIH pathogenesis is likely to contribute to the development of novel therapeutic strategies, such as the adoptive transfer of autologous expanded antigen-specific regulatory T-cells.
Full Text Available Autoimmune diseases (ADs are associated with a number of B-cell neoplasms but the associations are selective in regard to the type of neoplasm and the conferred risks are variable. So far no mechanistic bases for these differential associations have been demonstrated. We speculate that developmental origin of B-cells might propose a mechanistic rationale for their carcinogenic response to autoimmune stimuli and tested the hypothesis on our previous studies on the risks of B-cell neoplasms after any of 33 ADs. We found that predominantly germinal center (GC-derived B-cells showed multiple associations with ADs: diffuse large B cell lymphoma associated with 15 ADs, follicular lymphoma with 7 ADs and Hodgkin lymphoma with 11 ADs. Notably, these neoplasms shared significant associations with 5 ADs (immune thrombocytopenic purpura, polymyositis/dermatomyositis, rheumatoid arthritis, Sjogren syndrome and systemic lupus erythematosis. By contrast, primarily non-GC neoplasms, acute lymphocytic leukemia, chronic lymphocytic leukemia and myeloma associated with 2 ADs only and mantle cell lymphoma with 1 AD. None of the neoplasms shared associated ADs. These data may suggest that autoimmune stimulation critically interferes with the rapid cell division, somatic hypermutation, class switch recombination and immunological selection of maturing B-cell in the GC and delivers damage contributing to transformation.
Pascual Corrales, Eider; Andrada, Patricia; Aubá, María; Ruiz Zambrana, Alvaro; Guillén Grima, Francisco; Salvador, Javier; Escalada, Javier; Galofré, Juan C
Some recent studies have related autoimmune thyroid dysfunction and gestational diabetes (GD). The common factor for both conditions could be the existence of pro-inflammatory homeostasis. The study objective was therefore to assess whether the presence of antithyroid antibodies is related to the occurrence of GD. Fifty-six pregnant women with serum TSH levels ≥ 2.5 mU/mL during the first trimester were retrospectively studied. Antithyroid antibodies were measured, and an O'Sullivan test was performed. GD was diagnosed based on the criteria of the Spanish Group on Diabetes and Pregnancy. Positive antithyroid antibodies were found in 21 (37.50%) women. GD was diagnosed in 15 patients, 6 of whom (10.71%) had positive antibodies, while 9 (16.07%) had negative antibodies. Data were analyzed using exact logistic regression by LogXact-8 Cytel; no statistically significant differences were found between GD patients with positive and negative autoimmunity (OR = 1.15 [95%CI = 0.28-4.51]; P=1.00). The presence of thyroid autoimmunity in women with TSH above the recommended values at the beginning of pregnancy is not associated to development of GD. However, GD prevalence was higher in these patients as compared to the Spanish general population, suggesting the need for closer monitoring in pregnant women with TSH levels ≥ 2.5 mU/mL. Copyright © 2013 SEEN. Published by Elsevier Espana. All rights reserved.
Full Text Available The treatment of the rare enteric nervous system (ENS manifestations of paraneoplastic syndromes, which are most frequently associated with small cell lung cancer (SCLC, is poorly understood and described. Patients with neuroendocrine-derived tumors can develop B-cell reactivity towards the tumor with cross-reactivity for neurons located in the submucosal and myenteric ganglia of the ENS. The ensuing autoimmune neuritis causes aperistalsis and severe gastrointestinal (GI dysfunction. Immune-directed therapy is not the standard of care but may be paramount for patient recovery. Our patient, a 63-year-old man with recent symptoms of esophageal dysmotility and newly diagnosed SCLC was hospitalized with nausea, emesis, and constipation. After an extensive work-up that included laparoscopy and celiotomy with bowel resection, we diagnosed what we refer to as Autoimmune Paraneoplastic Chronic Intestinal Pseudoobstruction (AP-CIPO. Unlike the few clinically similar reports, SCLC and AP-CIPO were diagnosed in our patient within weeks of each other, which presented the dilemma of treating the two processes simultaneously. In this report, we review the relevant literature and describe our patient’s course. We believe standard chemotherapy is not effective treatment for AP-CIPO. Based on evidence discussed herein, we suggest initiating autoimmune-directed therapy before or simultaneous with cancer-directed therapy.
Ponsonby, Anne-Louise; McMichael, Anthony; Mei, Ingrid van der
This review examines the epidemiological evidence that suggests ultraviolet radiation (UVR) may play a protective role in three autoimmune diseases: multiple sclerosis, insulin-dependent diabetes mellitus and rheumatoid arthritis. To date, most of the information has accumulated from population studies that have studied the relationship between geography or climate and autoimmune disease prevalence. An interesting gradient of increasing prevalence with increasing latitude has been observed for at least two of the three diseases. This is most evident for multiple sclerosis, but a similar gradient has been shown for insulin-dependent diabetes mellitus in Europe and North America. Seasonal influences on both disease incidence and clinical course and, more recently, analytical studies at the individual level have provided further support for a possible protective role for UVR in some of these diseases but the data are not conclusive. Organ-specific autoimmune diseases involve Th1 cell-mediated immune processes. Recent work in photoimmunology has shown ultraviolet B (UVB) can specifically attenuate these processes through several mechanisms which we discuss. In particular, the possible contribution of an UVR-induced increase in serum vitamin D (1,25(OH) 2 D 3 ) levels in the beneficial immunomodulation of these diseases is discussed
Das Anup K
Full Text Available vAutoimmune hepatitis is a progressive liver disease. Its pathogenesis is unclear, but needs a ‘trigger’ to initiate the disease in a genetically susceptible person. The susceptibility is partly related to MHCII class genes, and more so with human leukocyte antigen (HLA. Several mechanisms have been proposed which, however, cannot fully explain the immunologic findings in autoimmune hepatitis. The susceptibility to any autoimmune disease is determined by several factors where genetic and immunological alterations, along with, environmental factor are active. MHCII antigens as a marker for AIH, or a predictor of treatment response and prognosis has been investigated. Since MHCII antigens show significant ethnic heterogeneity, mutations in MHCII may merely act as only precursors of the surface markers of immune cells, which can be of significance, because the changes in HLA and MHC are missing in certain populations. One such marker is the CTLA-4 (CD152 gene mutation, reported in the phenotypes representing susceptibility to AIH. Other candidate genes of cytokines, TNF, TGF-beta1 etc, have also been investigated but with unvalidated results. Paediatric AIH show differences in genetic susceptibility. Genetic susceptibility or resistance to AIH may be associated with polypeptides in DRB1 with certain amino-acid sequences. Understanding which genes are implicated in genesis and/or disease progression will obviously help to identify key pathways in AIH and provide better insights into its pathogenesis. But studies to identify responsible genes are complex because of the complex trait of AIH.
Denis Leonardo Fontes Jardim
Full Text Available Dengue virus is the most important mosquito-borne viral disease in the world. Co-circulation of the four types of dengue viruses and expansion of dengue epidemic gave rise to infection enhancement and a big expansion of clinical aspects of the disease. Herein we report a case of a 25-year-old white woman with dengue fever and numerous associated autoimmune features. Our patient had proteinuria, an extensive right pleural effusion, a thin pericardial effusion and ascites. She had a low C3 level and positive antinuclear antibody; cryoglobulins were also positive. The numerous autoimmune features of this patient were a diagnostic challenge, since she was a young woman and could be easily mistaken for a rheumatologic patient in a newly open disease. Dengue infection probably was a triggering event causing an abnormal immune response. Therefore, dengue should be suspected in patients with hematological disorders and autoimmune features in endemic regions or those who have travelled to those regions.
Skamagas, Maria; Geer, Eliza B
To describe the course of autoimmune hyperthyroid disease in a patient with corticotropin (ACTH) deficiency treated with glucocorticoids. We report the clinical presentation, laboratory data, imaging studies, and management of a patient with weight loss, fatigue, apathy, hallucinations, and arthritis. Autoimmune hyperthyroidism (positive thyroperoxidase and thyroglobulin antibodies and borderline positive thyrotropin receptor antibody) was diagnosed in a 71-year-old woman. New psychotic symptoms prompted brain magnetic resonance imaging, which revealed a partially empty sella. Undetectable morning cortisol, undetectable ACTH, and failure to stimulate cortisol with synthetic ACTH (cosyntropin 250 mcg) secured the diagnosis of long-standing secondary adrenal insufficiency. Hydrocortisone replacement improved the patient's symptoms, resolved the thyroid disease, and decreased thyroid antibody titers. In retrospect, the patient recalled severe postpartum hemorrhage requiring blood transfusion at age 38 years. A Sheehan event probably occurred 33 years before the patient presented with corticotropin deficiency. Hyperthyroidism accelerated cortisol metabolism and provoked symptoms of adrenal insufficiency. The hypocortisolemic state may precipitate hyperimmunity and autoimmune thyroid disease. Rapid resolution of hyperthyroidism and decreased thyroid antibody titers with glucocorticoid treatment support this hypothesis.
Rose, Noel R.
Most of our current understanding of the genetic predisposition to autoimmune disease can be traced to experiments performed in the decade from 1971 to 1981. Chella David was a key contributor to this research. Many of these early steps came from studies of experimental autoimmune thyroiditis. This model has been especially valuable because essentially the same disease can occur spontaneously in selected strains of animals or can be induced by deliberate immunization. From a genetic point of view, the disease has been investigated in three different species: mice, rats and chickens. The same antigen, thyroglobulin, initiates the disease in all three species. Among the main discoveries were the relationship of autoimmune disease to the major histocompatibility complex (MHC), the interplay of different subregions within the MHC in promoting or retarding development of disease, the differing roles of MHC class II and MHC I class genes in induction and effector phases, respectively, and the cumulative effect of non-MHC genes, each of which represents a small addition to overall susceptibility. Other experiments revealed that genetic differences in thyroglobulin allotypes influence susceptibility to thyroiditis. Thyroid glands differed in different strains in vulnerability to passive transfer of antibody. The first evidence of modulatory genes on the sex-related X chromosome emerged. All of these genetic findings were concurrently translated to the human disease, Hashimoto’s thyroiditis, where thyroglobulin is also the initiating antigen. PMID:21683550
Rovere-Querini, Patrizia; Manfredi, Angelo A; Sabbadini, Maria Grazia
Alterations during apoptosis lead to the activation of autoreactive T cells and the production of autoantibodies. This article discusses the pathogenic potential of cells dying in vivo, dissecting the role of signals that favor immune responses (adjuvants) and the influence of genetic backgrounds. Diverse factors determine whether apoptosis leads or not to a self-sustaining, clinically apparent autoimmune disease. The in vivo accumulation of uncleared dying cells per se is not sufficient to cause disease. However, dying cells are antigenic and their complementation with immune adjuvants causes lethal diseases in predisposed lupus-prone animals. At least some adjuvant signals directly target the function and the activation state of antigen presenting cells. Several laboratories are aggressively pursuing the molecular identification of endogenous adjuvants. Sodium monourate and the high mobility group B1 protein (HMGB1) are, among those identified so far, well known to rheumatologists. However, even the complementation of apoptotic cells with potent adjuvant signals fail to cause clinical autoimmunity in most strains: autoantibodies generated are transient, do not undergo to epitope/spreading and do not cause disease. Novel tools for drug development will derive from the molecular identification of the constraints that prevent autoimmunity in normal subjects.
Full Text Available As major components of innate immunity, NK cells not only exert cell-mediated cytotoxicity to destroy tumors or infected cells, but also act to regulate the functions of other cells in the immune system by secreting cytokines and chemokines. Thus, NK cells provide surveillance in the early defense against viruses, intracellular bacteria, and cancer cells. However, the effecter function of NK cells must be exquisitely controlled to prevent inadvertent attack against normal “self” cells. In an organ such as the liver, where the distinction between immunotolerance and immune defense against routinely processed pathogens is critical, the plethora of NK cells has a unique role in the maintenance of homeostasis. Once self-tolerance is broken, autoimmune liver disease resulted. NK cells act as a “two-edged weapon” and even play opposite roles with both regulatory and inducer activities in the hepatic environment. That is, NK cells act not only to produce inflammatory cytokines and chemokines, but also to alter the proliferation and activation of associated lymphocytes. However, the precise regulatory mechanisms at work in autoimmune liver diseases remain to be identified. In this review, we focus on recent research with NK cells and their potential role in the development of autoimmune liver disease.
Migita, Kiyoshi; Nakamura, Minoru; Abiru, Seigo; Jiuchi, Yuka; Nagaoka, Shinya; Komori, Atsumasa; Hashimoto, Satoru; Bekki, Shigemune; Yamasaki, Kazumi; Komatsu, Tatsuji; Shimada, Masaaki; Kouno, Hiroshi; Hijioka, Taizo; Kohjima, Motoyuki; Nakamuta, Makoto; Kato, Michio; Yoshizawa, Kaname; Ohta, Hajime; Nakamura, Yoko; Takezaki, Eiichi; Nishimura, Hideo; Sato, Takeaki; Ario, Keisuke; Hirashima, Noboru; Oohara, Yukio; Naganuma, Atsushi; Muro, Toyokichi; Sakai, Hironori; Mita, Eiji; Sugi, Kazuhiro; Yamashita, Haruhiro; Makita, Fujio; Yatsuhashi, Hiroshi; Ishibashi, Hiromi; Yasunami, Michio
Recent studies demonstrated an association of STAT4 polymorphisms with autoimmune diseases including systemic lupus erythematosus and rheumatoid arthritis, indicating multiple autoimmune diseases share common susceptibility genes. We therefore investigated the influence of STAT4 polymorphisms on the susceptibility and phenotype of type-1 autoimmune hepatitis in a Japanese National Hospital Organization (NHO) AIH multicenter cohort study. Genomic DNA from 460 individuals of Japanese origin including 230 patients with type-1 autoimmune hepatitis and 230 healthy controls was analyzed for two single nucleotide polymorphisms in the STAT4 gene (rs7574865, rs7582694). The STAT4 rs7574865T allele conferred risk for type-1 autoimmune hepatitis (OR = 1.61, 95% CI = 1.23-2.11; P = 0.001), and patients without accompanying autoimmune diseases exhibited an association with the rs7574865T allele (OR = 1.50, 95%CI = 1.13-1.99; P = 0.005). Detailed genotype-phenotype analysis of type-1 autoimmune hepatitis patients with (n = 44) or without liver cirrhosis (n = 186) demonstrated that rs7574865 was not associated with the development of liver cirrhosis and phenotype (biochemical data and the presence of auto-antibodies). This is the first study to show a positive association between a STAT4 polymorphism and type-1 autoimmune hepatitis, suggesting that autoimmune hepatitis shares a gene commonly associated with risk for other autoimmune diseases.
Alex Magno Coelho Horimoto
Full Text Available ABSTRACT Introduction: Systemic sclerosis (SSc is a connective tissue disease of unknown etiology, characterized by a triad of vascular injury, autoimmunity and tissue fibrosis. It is known that a positive family history is the greatest risk factor already identified for the development of SSc in a given individual. Preliminary observation of a high prevalence of polyautoimmunity and of familial autoimmunity in SSc patients support the idea that different autoimmune phenotypes may share common susceptibility variants. Objectives: To describe the frequency of familial autoimmunity and polyautoimmunity in 60 SSc patients in the Midwest region of Brazil, as well as to report the main autoimmune diseases observed in this association of comorbidities. Methods: A cross-sectional study with recruitment of 60 consecutive patients selected at the Rheumatology Department, University Hospital, Medicine School, Federal University of Mato Grosso do Sul (FMUFMS, as well as interviews of their relatives during the period from February 2013 to March 2014. Results: A frequency of 43.3% of polyautoimmunity and of 51.7% of familial autoimmunity in SSc patients was found. Patients with the presence of polyautoimmunity and familial autoimmunity presented primarily the diffuse form of SSc, but this indicator did not reach statistical significance. The autoimmune diseases most frequently observed in polyautoimmunity patients were: Hashimoto's thyroiditis (53.8%, Sjögren's syndrome (38.5%, and inflammatory myopathy (11.5%. The main autoimmune diseases observed in SSc patients' relatives were: Hashimoto's thyroiditis (32.3%, rheumatoid arthritis (22.6%, and SLE (22.6%. The presence of more than one autoimmune disease in SSc patients did not correlate with disease severity or activity. Conclusions: From the high prevalence of coexisting autoimmune diseases found in SSc patients, we stress the importance of the concept of shared autoimmunity, in order to promote a
Nakagawa, K; Harrison, L C
Endogenous retroviruses (ERVs) are estimated to comprise up to 1% of human DNA. While the genome of many ERVs is interrupted by termination codons, deletions or frame shift mutations, some ERVs are transcriptionally active and recent studies reveal protein expression or particle formation by human ERVs. ERVs have been implicated as aetiological agents of autoimmune disease, because of their structural and sequence similarities to exogenous retroviruses associated with immune dysregulation and their tissue-specific or differentiation-dependent expression. In fact, retrovirus-like particles distinct from those of known exogenous retroviruses and immune responses to ERV proteins have been observed in autoimmune disease. Quantitatively or structurally aberrant expression of normally cryptic ERVs, induced by environmental or endogenous factors, could initiate autoimmunity through direct or indirect mechanisms. ERVs may lead to immune dysregulation as insertional mutagens or cis-regulatory elements of cellular genes involved in immune function. ERVs may also encode elements like tax in human T-lymphotrophic virus type I (HTLV-I) or tat in human immunodeficiency virus-I (HIV-I) that are capable of transactivating cellular genes. More directly, human ERV gene products themselves may be immunologically active, by analogy with the superantigen activity in the long terminal repeat (LTR) of mouse mammary tumour viruses (MMTV) and the non-specific immunosuppressive activity in mammalian type C retrovirus env protein. Alternatively, increased expression of an ERV protein, or expression of a novel ERV protein not expressed in the thymus during acquisition of immune tolerance, may lead to its perception as a neoantigen. Paraneoplastic syndromes raise the possibility that novel ERV-encoded epitopes expressed by a tumour elicit immunity to cross-reactive epitopes in normal tissues. Recombination events between different but related ERVs, to whose products the host is immunologically
Gonçalves, Cristina; Oliveira, Maria Emília; Palha, Ana M; Ferrão, Anabela; Morais, Anabela; Lopes, Ana Isabel
To characterize clinical, laboratorial, and histological profile of pediatric autoimmune gastritis in the setting of unexplained iron deficiency anemia investigation. A descriptive, observational study including pediatric patients with a diagnosis of autoimmune gastritis (positive parietal cell antibody and gastric corpus atrophy) established in a 6 year period (2006-2011) in the setting of refractory iron deficiency anemia (refractoriness to oral iron therapy for at least 6 mo and requirement for intravenous iron therapy) investigation, after exclusion of other potentially contributing causes of anemia. Helicobacter pylori (H. pylori) infection and anti-secretory therapy were also excluded. Data were retrospectively collected from clinical files, including: demographic data (age, gender, and ethnic background), past medical history, gastrointestinal symptoms, familial history, laboratorial evaluation (Hb, serum ferritin, serum gastrin, pepsinogen I/ pepsinogen II, B12 vitamin, intrinsic factor autoantibodies, thyroid autoantibodies, and anti-transglutaminase antibodies), and endoscopic and histological findings (HE, Periodic Acid-Schiff/Alcian blue, gastrin, chromogranin A and immunochemistry analysis for CD3, CD20 and CD68). Descriptive statistical analysis was performed (mean, median, and standard deviation). We report a case-series concerning 3 girls and 2 boys with a mean age of 13.6 ± 2.8 years (3 Caucasian and 2 African). One girl had type I diabetes. Familial history was positive in 4/5 cases, respectively for autoimmune thyroiditis (2/5), sarcoidosis (1/5) and multiple myeloma (1/5). Laboratorial evaluation on admission included: Hb: 9.5 ± 0.7 g/dL; serum ferritin: 4.0 ± 0.9 ng/mL; serum gastrin: 393 ± 286 pg/mL; low pepsinogen I/ pepsinogen II ratio in 1/5 patients; normal vitamin B12 levels (analyzed in 3 patients). Endoscopy findings included: duodenal nodularity (2/5) and gastric fold softening (2/5), and histological evaluation showed
Billings, M; Dye, B A; Iafolla, T; Grisius, M; Alevizos, I
Oral candidiasis (OC) is a potential oral complication in Sjögren's syndrome (SS). Some studies indicate that the low stimulated salivary flow and not low unstimulated salivary flow is associated with OC in SS, while others report that the underlying autoimmune disorders contribute to OC, based solely on correlation coefficients. Given the conflicting and limited existing evidence, we purposed to ascertain the role of both salivary gland dysfunction (hyposalivation based on unstimulated and stimulated flow rates) and autoimmunity (SS, other autoimmune disorders) in OC among those with SS, other salivary gland dysfunction, and non-salivary gland dysfunction controls (NSGD). A nested case-control study was designed within a larger NIH/NIDCR cohort. Descriptive analyses, nonparametric tests, comparative analyses, and multivariate logistic regression analyses were undertaken. Data on 1526 subjects (701 SS, 247 ISS, 355 Sicca, and 223 NSGD) were obtained from the source cohort of 2046 and analyzed for this study. The median whole unstimulated salivary flow rate (WUS, ml 15 min -1 ) was lower in SS (0.8, interquartile range (IQR) 1.8) compared to ISS (5.5, IQR: 5.2, P salivary flow rate (TSS, ml 15 min -1 ) was lowest in SS (7.0, IQR: 12.4, P diabetes mellitus (4.2, 95%CI: 1.2-15.2, P = 0.02) were independent predictors of OC; females had a lower risk than males (OR = 0.29, 95%CI: 0.13-0.67, P = 0.004). Age, race, anti-SSA/SSB autoantibodies, focus score, other medications, anxiety, fatigue, cigarette smoking, alcohol, and caffeine use were not associated with oral candidiasis. Salivary gland dysfunction (hyposalivation with WUS being a stronger predictor than TSS) and autoimmunity (SS, other autoimmune disorders, medications, i.e., DMARDS) are both independent predictors of OC. Diabetes mellitus is an independent predictor of OC among those with salivary gland dysfunction. Our findings suggest that these independent predictors should be considered in the
Alimohammadi, Mohammad; Dubois, Noémie; Sköldberg, Filip; Hallgren, Asa; Tardivel, Isabelle; Hedstrand, Håkan; Haavik, Jan; Husebye, Eystein S; Gustafsson, Jan; Rorsman, Fredrik; Meloni, Antonella; Janson, Christer; Vialettes, Bernard; Kajosaari, Merja; Egner, William; Sargur, Ravishankar; Pontén, Fredrik; Amoura, Zahir; Grimfeld, Alain; De Luca, Filippo; Betterle, Corrado; Perheentupa, Jaakko; Kämpe, Olle; Carel, Jean-Claude
Patients with autoimmune polyendocrine syndrome type 1 (APS-1) suffer from multiple organ-specific autoimmunity with autoantibodies against target tissue-specific autoantigens. Endocrine and nonendocrine organs such as skin, hair follicles, and liver are targeted by the immune system. Despite sporadic observations of pulmonary symptoms among APS-1 patients, an autoimmune mechanism for pulmonary involvement has not been elucidated. We report here on a subset of APS-1 patients with respiratory symptoms. Eight patients with pulmonary involvement were identified. Severe airway obstruction was found in 4 patients, leading to death in 2. Immunoscreening of a cDNA library using serum samples from a patient with APS-1 and obstructive respiratory symptoms identified a putative potassium channel regulator (KCNRG) as a pulmonary autoantigen. Reactivity to recombinant KCNRG was assessed in 110 APS-1 patients by using immunoprecipitation. Autoantibodies to KCNRG were present in 7 of the 8 patients with respiratory symptoms, but in only 1 of 102 APS-1 patients without respiratory symptoms. Expression of KCNRG messenger RNA and protein was found to be predominantly restricted to the epithelial cells of terminal bronchioles. Autoantibodies to KCNRG, a protein mainly expressed in bronchial epithelium, are strongly associated with pulmonary involvement in APS-1. These findings may facilitate the recognition, diagnosis, characterization, and understanding of the pulmonary manifestations of APS-1.
Iakimchuk, K S; Malinnikova, E Iu; Poleshchuk, V F; Mikhaĭlov, M I
The mechanisms of development of autoimmune diseases may be associated with a complex of genetic, immune, hormonal, and infectious factors. Autoimmune diseases include a wide range of systemic and organ-specific diseases, including autoimmune hepatitis (AIH). It is currently assumed that the pathogenesis of AIH is due to compromised immune regulation in the presence of an exogenous triggering factor. Exogenous factors, such as viruses, may be triggers of AIH. There may be different ways of initiating an autoimmune response by viruses, which includes nonspecific T-lymphocyte activation and molecular mimicry. There is much evidence supporting the initiating role of hepatitis viruses in the development of AIH and other autoimmune diseases. The development of AIH symptoms during hepatitis A and E virus infections has been described elsewhere. The creation of animal models of viral hepatitis is required to confirm the hypothesis that the viruses trigger the development of AIH and other autoimmune manifestations.
The incidence of autoimmune diseases has been steadily rising. Concomitantly, the incidence of most infectious diseases has declined. This observation gave rise to the hygiene hypothesis, which postulates that a reduction in the frequency of infections contributes directly to the increase in the frequency of autoimmune and allergic diseases. This hypothesis is supported by robust epidemiological data, but the underlying mechanisms are unclear. Pathogens are known to be important, as autoimmune disease is prevented in various experimental models by infection with different bacteria, viruses and parasites. Gut commensal bacteria also play an important role: dysbiosis of the gut flora is observed in patients with autoimmune diseases, although the causal relationship with the occurrence of autoimmune diseases has not been established. Both pathogens and commensals act by stimulating immunoregulatory pathways. Here, I discuss the importance of innate immune receptors, in particular Toll-like receptors, in mediating the protective effect of pathogens and commensals on autoimmunity.
Frisch, Morten; Nielsen, Nete Munk; Pedersen, Bo Vestergaard
Autoimmune diseases have been little studied in gay men and lesbians. We followed 4.4 million Danes, including 9,615 same-sex married (SSM) persons, for 47 autoimmune diseases in the National Patient Registry between 1989 and 2008. Poisson regression analyses provided first hospitalization rate ratios (RRs) comparing rates between SSM individuals and persons in other marital status categories. SSM individuals experienced no unusual overall risk of autoimmune diseases. However, the risk of autoimmune thyroid dysfunction was increased, notably Hashimoto's thyroiditis (women(SSM), RR = 2.92; 95% confidence interval (CI) 1.74-4.55) and Graves' disease (men(SSM), RR = 1.88; 95% CI 1.08-3.01). There was also an excess of primary biliary cirrhosis (women(SSM), RR = 4.09; 95% CI 1.01-10.7), and of psoriasis (men(SSM), RR = 2.48; 95% CI 1.77-3.36), rheumatic fever (men(SSM), RR = 7.55; 95% CI 1.87-19.8), myasthenia gravis (men(SSM), RR = 5.51; 95% CI 1.36-14.4), localized scleroderma (men(SSM), RR = 7.16; 95% CI 1.18-22.6) and pemphigoid (men(SSM), RR = 6.56; 95% CI 1.08-20.6), while Dupuytren's contracture was reduced (men(SSM), RR = 0.64; 95% CI 0.39-0.99). The excess of psoriasis was restricted to same-sex married men with HIV/AIDS (men(SSM), RR = 10.5; 95% CI 6.44-15.9), whereas Graves' disease occurred in excess only among same-sex married men without HIV/AIDS (men(SSM), RR = 1.99; 95% CI 1.12-3.22). Lesbians and immunologically competent gay men in same-sex marriage face no unusual overall risk of autoimmune diseases. However, the observed increased risk of thyroid dysfunction in these lesbians and gay men deserves further study.
Full Text Available Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections, refers to a disorder in children who manifest symptoms of obsessive-compulsive disorder and/or tic disorders associated with acute exacerbations. Although autoimmune responses following infections with streptococcus have been hypothesized to be responsible, there is still controversies about the pathophysiology and treatment. In this article, the treatment methods of pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections and the role of otolaryngologist were discussed.
Conclusions. Analysis of carbohydrate metabolism on the manifestation stage and over time development of latent autoimmune diabetes in adults as well as reduction of β-cells insulin-producing function associated with autoimmune insulitis and progressing while the development of this form of disease, substantiate the rational for insulin administration as this form of diabetes has been diagnosed. If patients with latent autoimmune diabetes in adults have metabolic syndrome clusters it is quite reasonable to add metformin to insulin.
Cleri, Dennis J; Moser, Robert L; Villota, Francisco J; Wang, Yue; Husain, Syed A; Nadeem, Shahzinah; Anjari, Tarek; Sajed, Mohammad
Warm, active antibody adult autoimmune hemolytic anemia is the most common form of hemolytic anemia not related to drug therapy. Mortality in adult autoimmune hemolytic anemia is related to the inability to successfully treat patients' underlying disease, or the infectious complications of splenectomy and prolonged steroid therapy. Predisposing factors for invasive aspergillosis are neutropenia and steroid therapy. We present a fatal case of aspergillosis complicating a nonneutropenic case of warm active antibody adult autoimmune hemolytic anemia treated with prolonged steroid therapy.
Luis Miguel Blasco Mata
Full Text Available Diastolic heart failure (DHF remains unexplained in some patients with recurrent admissions after full investigation. A study was directed for screening SLE and systemic autoimmune connective tissue disorders in recurrent unexplained DHF patients admitted at a short-stay and intermediate care unit. It was found that systemic autoimmune conditions explained 11% from all of cases. Therapy also prevented new readmissions. Autoimmunity should be investigated in DHF.
Full Text Available Autoimmune diseases are commonly encountered in dermatology practice. While the association of two autoimmune diseases in the same individual is not unknown, it is relatively rare for the second disease to be suspected based on cutaneous manifestations. We present two such cases wherein cutaneous manifestations were the first clue to the development of lupus erythematosus in a setting of autoimmune thyroiditis. Further, we have reviewed literature on this uncommon occurrence and discuss various aspects of this association.
Granito, A; Muratori, L; Pappas, G; Muratori, P; Ferri, S; Cassani, F; Lenzi, M; Bianchi, F B
The usual onset of type 1 autoimmune hepatitis occurs at puberty or around menopause, whereas disease presentation in the advanced age is less often reported. To assess the clinical, immunological and histological features of Type 1 autoimmune hepatitis in elderly Italian patients. We assessed, at diagnosis, the clinical and immunological features of 76 consecutive Italian patients with type 1 autoimmune hepatitis, focusing particularly on a subgroup of 20 patients presenting at > or = 65 years (females 95%, median age 72 years, range 65-82). In comparison with the younger group, at the time of autoimmune hepatitis diagnosis, elderly Italian patients are more often asymptomatic (25% vs. 7%; P = 0.04), are more frequently positive for antinuclear autoantibodies (95% vs. 52%; P = 0.0004) and HLA-DR4 (45% vs. 18%; P = 0.03); among the extra-hepatic manifestations, autoimmune thyroid disorders are prevalent in the elderly group (25% vs. 5%; P = 0.02). However, no difference was observed in the histological/biochemical expression of the liver disease and response to immunosuppression. In elderly Italian patients, autoimmune hepatitis has typical serological and genetic characteristics, is more frequently asymptomatic, although prognosis and response to therapy is similar to that of younger patients. As a concomitant autoimmune thyroid disorder is common, autoimmune hepatitis should be suspected and investigated in elderly patients with autoimmune thyroid disorder and abnormal liver function tests.
Klinkhammer, Brent; Gruchalla, Michael
Heparin-induced thrombocytopenia (HIT) is a drug-induced, immunoglobulin G medicated autoimmune disorder associated with several negative clinical outcomes including increased morbidity, mortality, and increased medical costs. Previous studies have shown associations between comorbid autoimmune diseases, but there is little known about associations between HIT and autoimmunity. To provide clinical data to suggest an association between HIT and autoimmunity. Retrospective chart review of 59 cases with a diagnosis of HIT and 251 matched controls without a HIT diagnosis, comparing the prevalence of autoimmunity in each group. A single, large upper Midwest health care system. Patients with a diagnosis of HIT were significantly more likely to have a comorbid autoimmune disease than those without a HIT diagnosis (55.9% vs 10.8%, P HIT were significantly more likely to have a diagnosis of antiphospholipid syndrome (15.3% vs 0.0%, P HIT were significantly older than controls ( P HIT and autoimmune disease and suggests a need for more research into the relationship between HIT and autoimmunity. These results could alter the anticoagulation management of venous thromboembolism and acute coronary syndrome in patients with a previously identified autoimmune disease. Copyright© Wisconsin Medical Society.
Nelson, Brad H
Research in the fields of basic immunology and autoimmunity has identified several distinct mechanisms through which immune tolerance is established and maintained in the normal host, and additional...
Vigren, Lina; Tysk, Curt; Ström, Magnus; Kilander, Anders F; Hjortswang, Henrik; Bohr, Johan; Benoni, Cecilia; Larson, Lasse; Sjöberg, Klas
Collagenous colitis (CC) is associated with autoimmune disorders. The aim of the present study was to investigate the relationship between CC and autoimmune disorders in a Swedish multicenter study. Patients with CC answered questionnaires about demographic data and disease activity. The patient's files were scrutinized for information about autoimmune diseases. A total number of 116 CC patients were included; 92 women, 24 men, median age 62 years (IQR 55-73). In total, 30.2% had one or more autoimmune disorder. Most common were celiac disease (CeD; 12.9%) and autoimmune thyroid disease (ATD, 10.3%), but they also had Sjögren's syndrome (3.4%), diabetes mellitus (1.7%) and conditions in skin and joints (6.0%). Patients with associated autoimmune disease had more often nocturnal stools. The majority of the patients with associated CeD or ATD got these diagnoses before the colitis diagnosis. Autoimmune disorders occurred in one-third of these patients, especially CeD. In classic inflammatory bowel disease (IBD), liver disease is described in contrast to CC where no cases occurred. Instead, CeD was prevalent, a condition not reported in classic IBD. Patients with an associated autoimmune disease had more symptoms. Patients with CC and CeD had an earlier onset of their colitis. The majority of the patients with both CC and CeD were smokers. Associated autoimmune disease should be contemplated in the follow-up of these patients.
Soelberg, K.; Nilsson, A. C.; Nielsen, C.
Background: Optic neuritis (ON) is an inflammatory optic neuropathy, where the genetic and autoimmune dependency remains poorly characterized. Objective: To investigate autoimmune and immunogenetic aspects of ON. Method: In a prospective population-based cohort 51 patients with ON were included...... antibodies. Coexisting neural autoantibodies were detected in two patients and in 12 patients other systemic autoantibodies were found. Four (8%) had other autoimmune disorders. A family history of autoimmunity was observed in 12 (24%) and of demyelinating disease in six patients (12%). In MS-ON patients...
Visser, Jeroen; Rozing, Jan; Sapone, Anna; Lammers, Karen; Fasano, Alessio
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
Feldt-Rasmussen, Ulla; Bliddal, Sofie; Rasmussen, Åse Krogh
Physiological changes during gestation are important to be aware of in measurement and interpretation of thyroid function tests in women with autoimmune thyroid diseases. Thyroid autoimmune activity is decreasing in pregnancy. Measurement of serum TSH is the first-line screening variable....... Measurement of antithyroperoxidase and/or TSH receptor antibodies adds to the differential diagnosis of autoimmune and nonautoimmune thyroid diseases....... for thyroid dysfunction also in pregnancy. However, using serum TSH for control of treatment of maternal thyroid autoimmunity infers a risk for compromised foetal development. Peripheral thyroid hormone values are highly different among laboratories, and there is a need for laboratory-specific gestational age...
Sakaguchi, N.; Sakaguchi, S.; Miyai, K.
Ionizing radiation can functionally alter the immune system and break self-tolerance. High dose (42.5 Gy), fractionated (2.5 Gy 17 times) total lymphoid irradiation (TLI) on mice caused various organ-specific autoimmune diseases, such as gastritis, thyroiditis, and orchitis, depending on the radiation dosages, the extent of lymphoid irradiation, and the genetic background of the mouse strains. Radiation-induced tissue damage is not the primary cause of the autoimmune disease because irradiation of the target organs alone failed to elicit the autoimmunity and shielding of the organs from irradiation was unable to prevent it. In contrast, irradiation of both the thymus and the peripheral lymphoid organs/tissues was required for efficient induction of autoimmune disease by TLI. TLI eliminated the majority of mature thymocytes and the peripheral T cells for 1 mo, and inoculation of spleen cell, thymocyte, or bone marrow cell suspensions (prepared from syngeneic nonirradiated mice) within 2 wk after TLI effectively prevented the autoimmune development. Depletion of T cells from the inocula abrogated the preventive activity. CD4 + T cells mediated the autoimmune prevention but CD8 + T cells did not. CD4 + T cells also appeared to mediate the TLI-induced autoimmune disease because CD4 + T cells from disease-bearing TLI mice adoptively transferred the autoimmune disease to syngeneic naive mice. Taken together, these results indicate that high dose, fractionated ionizing radiation on the lymphoid organs/tissues can cause autoimmune disease by affecting the T cell immune system, rather than the target self-Ags, presumably by altering T cell-dependent control of self-reactive T cells. 62 refs., 9 figs., 2 tabs
Stephen F Murphy
Full Text Available Chronic pelvic pain syndrome (CPPS is the most common form of prostatitis, accounting for 90-95% of all diagnoses. It is a complex multi-symptom syndrome with unknown etiology and limited effective treatments. Previous investigations highlight roles for inflammatory mediators in disease progression by correlating levels of cytokines and chemokines with patient reported symptom scores. It is hypothesized that alteration of adaptive immune mechanisms results in autoimmunity and subsequent development of pain. Mouse models of CPPS have been developed to delineate these immune mechanisms driving pain in humans. Using the experimental autoimmune prostatitis (EAP in C57BL/6 mice model of CPPS we examined the role of CD4+T-cell subsets in the development and maintenance of prostate pain, by tactile allodynia behavioral testing and flow cytometry. In tandem with increased CD4+IL17A+ T-cells upon EAP induction, prophylactic treatment with an anti-IL17 antibody one-day prior to EAP induction prevented the onset of pelvic pain. Therapeutic blockade of IL17 did not reverse pain symptoms indicating that IL17 is essential for development but not maintenance of chronic pain in EAP. Furthermore we identified a cytokine, IL7, to be associated with increased symptom severity in CPPS patients and is increased in patient prostatic secretions and the prostates of EAP mice. IL7 is fundamental to development of IL17 producing cells and plays a role in maturation of auto-reactive T-cells, it is also associated with autoimmune disorders including multiple sclerosis and type-1 diabetes. More recently a growing body of research has pointed to IL17's role in development of neuropathic and chronic pain. This report presents novel data on the role of CD4+IL17+ T-cells in development and maintenance of pain in EAP and CPPS.
Palla, Amruth R; Kennedy, Devin; Mosharraf, Hossain; Doll, Donald
Recently, immunotherapeutic drugs, including PD-1 inhibitors (nivolumab, pembrolizumab), PD-L1 inhibitors (atezolizumab, avelumab), and CTLA4 inhibitors (ipiliumumab), have emerged as important additions to the armamentarium against certain malignancies and have been incorporated into therapeutic protocols for first-, second-, or third-line agents for these metastatic cancers. Immune checkpoint inhibitor nivolumab is currently FDA approved for the treatment of patients with metastatic malignant melanoma [Redman et al.: BMC Med 2016;14: 20], metastatic non-small cell lung cancer [Guibert and Mazières: Expert Opin Biol Ther 2015;15: 1789-1797], metastatic renal cell cancer [Farolfi et al.: Expert Opin Drug Metab Toxicol 2016;12: 1089-1096], and relapsed or refractory classic Hodgkin's lymphoma [Villasboas and Ansell: Expert Rev Anticancer Ther 2016;16: 5-12]. Given the current and increasing indications for these drugs, it is essential for all physicians to become well versed with their common adverse effects and to be observant for other less documented clinical conditions that could be unmasked with the use of such medications. A definite association between autoimmune hemolytic anemia and the immune checkpoint inhibitor nivolumab has not been clearly documented, although a few cases have been reported recently [Kong et al.: Melanoma Res 2016;26: 202-204; Schwab et al.: Case Rep Oncol 2016;9: 373-378; Tardy et al.: Hematol Oncol 2016, DOI: 10.1002/hon.2338]. We report a case of fatal autoimmune hemolytic anemia refractory to steroids in a patient treated with nivolumab for metastatic lung cancer, and reflect on the other reported cases of autoimmune hemolytic anemia after the use of nivolumab.
Sharif, Kassem; Watad, Abdulla; Bragazzi, Nicola Luigi; Adawi, Mohammad; Amital, Howard; Shoenfeld, Yehuda
Coffee is one of the world's most consumed beverage. In the last decades, coffee consumption has attracted a huge body of research due to its impact on health. Recent scientific evidences showed that coffee intake could be associated with decreased mortality from cardiovascular and neurological diseases, diabetes type II, as well as from endometrial and liver cancer, among others. In this review, on the basis of available data in the literature, we aimed to investigate the association between coffee intake and its influence on the immune system and the insurgence of the most relevant autoimmune diseases. While some studies reported conflicting results, general trends have been identified. Coffee consumption seems to increase the risk of developing rheumatoid arthritis (RA) and type 1 diabetes mellitus (T1DM). By contrast, coffee consumption may exert a protective role against multiple sclerosis, primary sclerosing cholangitis, and ulcerative colitis. Concerning other autoimmune diseases such as systemic lupus erythematosus, psoriasis, primary biliary cholangitis and Crohn's disease, no significant association was found. In other studies, coffee consumption was shown to influence disease course and management options. Coffee intake led to a decrease in insulin sensitivity in T1DM, in methotrexate efficacy in RA, and in levothyroxine absorption in Hashimoto's disease. Further, coffee consumption was associated with cross reactivity with gliadin antibodies in celiac patients. Data on certain autoimmune diseases like systemic sclerosis, Sjögren's syndrome, and Behçet's disease, among others, are lacking in the existent literature. As such, further research is warranted. Copyright © 2017 Elsevier B.V. All rights reserved.
Jane, Andrew O.; Szili, Endre J.; Reed, Joanne H.; Gordon, Tom P.; Voelcker, Nicolas H.
Advances in porous silicon (pSi) technology have led to the development of new sensitive biosensors. The unique optical properties of pSi renders the material a perfect candidate for optical transducers exploiting photoluminescence or white light interference effects. The ability of biosensors exploiting these transduction mechanisms to quickly and accurately detect biological target molecules affords an alternative to current bioassays such as enzyme-linked immunosorbent assays (ELISAs). Here, we present a pSi biosensor that was developed to detect antibodies against the autoimmune protein La. This protein is associated with autoimmune diseases including rheumatic disorders, systematic lupus erythematosus (SLE) and Sjogren's syndrome (SS). A fast and sensitive detection platform such as the one described here can be applied to the rapid diagnosis of these debilitating autoimmune diseases. The immobilisation of the La protein onto pSi films gave a protein receptor-decorated sensor matrix. A cascade of immunological reactions was then initiated to detect anti-La antibody on the functionalised pSi surface. In the presence of o-phenylenediamine (OPD), horseradish peroxidase (HRP)/H IIO II catalysed the formation of an oxidised radical species that accelerated pSi corrosion. pSi corrosion was detected as a blue-shift in the generated interference pattern, corresponding to a decrease in the effective optical thickness (EOT) of the pSi film. Compared to an ELISA, the pSi biosensor could detect the anti-La antibody at a similar concentration (500 - 125 ng/ml). Furthermore, we found that the experimental process can be significantly shortened resulting in detection of the anti-La antibody in 80 minutes compared to a minimum of 5 hours required for ELISA.
Amruth R. Palla
Full Text Available Recently, immunotherapeutic drugs, including PD-1 inhibitors (nivolumab, pembrolizumab, PD-L1 inhibitors (atezolizumab, avelumab, and CTLA4 inhibitors (ipiliumumab, have emerged as important additions to the armamentarium against certain malignancies and have been incorporated into therapeutic protocols for first-, second-, or third-line agents for these metastatic cancers. Immune checkpoint inhibitor nivolumab is currently FDA approved for the treatment of patients with metastatic malignant melanoma [Redman et al.: BMC Med 2016;14: 20], metastatic non-small cell lung cancer [Guibert and Mazières: Expert Opin Biol Ther 2015;15: 1789–1797], metastatic renal cell cancer [Farolfi et al.: Expert Opin Drug Metab Toxicol 2016;12: 1089–1096], and relapsed or refractory classic Hodgkin’s lymphoma [Villasboas and Ansell: Expert Rev Anticancer Ther 2016;16: 5–12]. Given the current and increasing indications for these drugs, it is essential for all physicians to become well versed with their common adverse effects and to be observant for other less documented clinical conditions that could be unmasked with the use of such medications. A definite association between autoimmune hemolytic anemia and the immune checkpoint inhibitor nivolumab has not been clearly documented, although a few cases have been reported recently [Kong et al.: Melanoma Res 2016;26: 202–204; Schwab et al.: Case Rep Oncol 2016;9: 373–378; Tardy et al.: Hematol Oncol 2016, DOI: 10.1002/hon.2338]. We report a case of fatal autoimmune hemolytic anemia refractory to steroids in a patient treated with nivolumab for metastatic lung cancer, and reflect on the other reported cases of autoimmune hemolytic anemia after the use of nivolumab.
Full Text Available Autoimmune diseases (ADs represent a diverse collection of diseases in terms of their demographic profile and primary clinical manifestations. The commonality between them however, is the damage to tissues and organs that arises from the response to self-antigens. The presence of shared pathophysiological mechanisms within ADs has stimulated searches for common genetic roots to these diseases. Two approaches have been undertaken to sustain the “common genetic origin” theory of ADs. Firstly, a clinical genetic analysis showed that autoimmunity aggregates within families of probands diagnosed with primary Sjögren's (pSS syndrome or type 1 diabetes mellitus (T1D. A literature review supported the establishment of a familiar cluster of ADs depending upon the proband's disease phenotype. Secondly, in a same and well-defined population, a large genetic association study indicated that a number of polymorphic genes (i.e. HLA-DRB1, TNF and PTPN22 influence the susceptibility for acquiring different ADs. Likewise, association and linkage studies in different populations have revealed that several susceptibility loci overlap in ADs, and clinical studies have shown that frequent clustering of several ADs occurs. Thus, the genetic factors for ADs consist of two types: those which are common to many ADs (acting in epistatic pleitropy and those that are specific to a given disorder. Their identification and functional characterization will allow us to predict their effect as well as to indicate potential new therapeutic interventions. Both autoimmunity family history and the co-occurrence of ADs in affected probands should be considered when performing genetic association and linkage studies.
Steri, Maristella; Orrù, Valeria; Idda, M Laura; Pitzalis, Maristella; Pala, Mauro; Zara, Ilenia; Sidore, Carlo; Faà, Valeria; Floris, Matteo; Deiana, Manila; Asunis, Isadora; Porcu, Eleonora; Mulas, Antonella; Piras, Maria G; Lobina, Monia; Lai, Sandra; Marongiu, Mara; Serra, Valentina; Marongiu, Michele; Sole, Gabriella; Busonero, Fabio; Maschio, Andrea; Cusano, Roberto; Cuccuru, Gianmauro; Deidda, Francesca; Poddie, Fausto; Farina, Gabriele; Dei, Mariano; Virdis, Francesca; Olla, Stefania; Satta, Maria A; Pani, Mario; Delitala, Alessandro; Cocco, Eleonora; Frau, Jessica; Coghe, Giancarlo; Lorefice, Lorena; Fenu, Giuseppe; Ferrigno, Paola; Ban, Maria; Barizzone, Nadia; Leone, Maurizio; Guerini, Franca R; Piga, Matteo; Firinu, Davide; Kockum, Ingrid; Lima Bomfim, Izaura; Olsson, Tomas; Alfredsson, Lars; Suarez, Ana; Carreira, Patricia E; Castillo-Palma, Maria J; Marcus, Joseph H; Congia, Mauro; Angius, Andrea; Melis, Maurizio; Gonzalez, Antonio; Alarcón Riquelme, Marta E; da Silva, Berta M; Marchini, Maurizio; Danieli, Maria G; Del Giacco, Stefano; Mathieu, Alessandro; Pani, Antonello; Montgomery, Stephen B; Rosati, Giulio; Hillert, Jan; Sawcer, Stephen; D'Alfonso, Sandra; Todd, John A; Novembre, John; Abecasis, Gonçalo R; Whalen, Michael B; Marrosu, Maria G; Meloni, Alessandra; Sanna, Serena; Gorospe, Myriam; Schlessinger, David; Fiorillo, Edoardo; Zoledziewska, Magdalena; Cucca, Francesco
Genomewide association studies of autoimmune diseases have mapped hundreds of susceptibility regions in the genome. However, only for a few association signals has the causal gene been identified, and for even fewer have the causal variant and underlying mechanism been defined. Coincident associations of DNA variants affecting both the risk of autoimmune disease and quantitative immune variables provide an informative route to explore disease mechanisms and drug-targetable pathways. Using case-control samples from Sardinia, Italy, we performed a genomewide association study in multiple sclerosis followed by TNFSF13B locus-specific association testing in systemic lupus erythematosus (SLE). Extensive phenotyping of quantitative immune variables, sequence-based fine mapping, cross-population and cross-phenotype analyses, and gene-expression studies were used to identify the causal variant and elucidate its mechanism of action. Signatures of positive selection were also investigated. A variant in TNFSF13B, encoding the cytokine and drug target B-cell activating factor (BAFF), was associated with multiple sclerosis as well as SLE. The disease-risk allele was also associated with up-regulated humoral immunity through increased levels of soluble BAFF, B lymphocytes, and immunoglobulins. The causal variant was identified: an insertion-deletion variant, GCTGT→A (in which A is the risk allele), yielded a shorter transcript that escaped microRNA inhibition and increased production of soluble BAFF, which in turn up-regulated humoral immunity. Population genetic signatures indicated that this autoimmunity variant has been evolutionarily advantageous, most likely by augmenting resistance to malaria. A TNFSF13B variant was associated with multiple sclerosis and SLE, and its effects were clarified at the population, cellular, and molecular levels. (Funded by the Italian Foundation for Multiple Sclerosis and others.).
Singh, Abinav Kumar; Mahlios, Josh; Mignot, Emmanuel
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
Bogdanos, Dimitrios-P; Invernizzi, Pietro; Mackay, Ian-R; Vergani, Diego
Liver-related autoantibodies are crucial for the correct diagnosis and classification of autoimmune liver diseases (AiLD), namely autoimmune hepatitis types 1 and 2 (AIH-1 and 2), primary biliary cirrhosis (PBC), and the sclerosing cholangitis variants in adults and children. AIH-1 is specified by anti-nuclear antibody (ANA) and smooth muscle antibody (SMA). AIH-2 is specified by antibody to liver kidney microsomal antigen type-1 (anti-LKM1) and anti-liver cytosol type 1 (anti-LC1). SMA, ANA and anti-LKM antibodies can be present in de-novo AIH following liver transplantation. PBC is specified by antimitochondrial antibodies (AMA) reacting with enzymes of the 2-oxo-acid dehydrogenase complexes (chiefly pyruvate dehydrogenase complex E2 subunit) and disease-specific ANA mainly reacting with nuclear pore gp210 and nuclear body sp100. Sclerosing cholangitis presents as at least two variants, first the classical primary sclerosing cholangitis (PSC) mostly affecting adult men wherein the only (and non-specific) reactivity is an atypical perinuclear antineutrophil cytoplasmic antibody (p-ANCA), also termed perinuclear anti-neutrophil nuclear antibodies (p-ANNA) and second the childhood disease called autoimmune sclerosing cholangitis (ASC) with serological features resembling those of type 1 AIH. Liver diagnostic serology is a fast-expanding area of investigation as new purified and recombinant autoantigens, and automated technologies such as ELISAs and bead assays, become available to complement (or even compete with) traditional immunofluorescence procedures. We survey for the first time global trends in quality assurance impacting as it does on (1) manufacturers/purveyors of kits and reagents, (2) diagnostic service laboratories that fulfill clinicians' requirements, and (3) the end-user, the physician providing patient care, who must properly interpret test results in the overall clinical context.
Murphy, Stephen F; Schaeffer, Anthony J; Done, Joseph; Wong, Larry; Bell-Cohn, Ashlee; Roman, Kenny; Cashy, John; Ohlhausen, Michelle; Thumbikat, Praveen
Chronic pelvic pain syndrome (CPPS) is the most common form of prostatitis, accounting for 90-95% of all diagnoses. It is a complex multi-symptom syndrome with unknown etiology and limited effective treatments. Previous investigations highlight roles for inflammatory mediators in disease progression by correlating levels of cytokines and chemokines with patient reported symptom scores. It is hypothesized that alteration of adaptive immune mechanisms results in autoimmunity and subsequent development of pain. Mouse models of CPPS have been developed to delineate these immune mechanisms driving pain in humans. Using the experimental autoimmune prostatitis (EAP) in C57BL/6 mice model of CPPS we examined the role of CD4+T-cell subsets in the development and maintenance of prostate pain, by tactile allodynia behavioral testing and flow cytometry. In tandem with increased CD4+IL17A+ T-cells upon EAP induction, prophylactic treatment with an anti-IL17 antibody one-day prior to EAP induction prevented the onset of pelvic pain. Therapeutic blockade of IL17 did not reverse pain symptoms indicating that IL17 is essential for development but not maintenance of chronic pain in EAP. Furthermore we identified a cytokine, IL7, to be associated with increased symptom severity in CPPS patients and is increased in patient prostatic secretions and the prostates of EAP mice. IL7 is fundamental to development of IL17 producing cells and plays a role in maturation of auto-reactive T-cells, it is also associated with autoimmune disorders including multiple sclerosis and type-1 diabetes. More recently a growing body of research has pointed to IL17's role in development of neuropathic and chronic pain. This report presents novel data on the role of CD4+IL17+ T-cells in development and maintenance of pain in EAP and CPPS.
Swaranjali V. Jain, B Med Sci (Hons MD
Full Text Available Inherited and autoimmune blistering diseases are rare, chronic, and often severe disorders that have the potential to significantly affect patients’ quality of life. The effective management of these conditions requires consideration of the physical, emotional, and social aspects of the disease. Self-esteem is integral to patients’ ability to cope with their illness, participate in treatment, and function in society. This article discusses quality-of-life studies of patients with blistering diseases with a particular focus on self-esteem issues that patients may face.
Pietrosimone, K. M.; Jin, M.; Poston, B.; Liu, P.
Collagen-induced arthritis (CIA) is a common autoimmune animal model used to study rheumatoid arthritis (RA). The development of CIA involves infiltration of macrophages and neutrophils into the joint, as well as T and B cell responses to type II collagen. In murine CIA, genetically susceptible mice (DBA/1J) are immunized with a type II bovine collagen emulsion in complete Freund’s adjuvant (CFA), and receive a boost of type II bovine collagen in incomplete Freund’s adjuvant (IFA) 21 days aft...
Winther, Kristian Hillert; Watt, Torquil; Bjørner, Jakob Bue
Patients with chronic autoimmune thyroiditis have impaired health-related quality of life. The thyroid gland has a high selenium concentration, and specific selenoprotein enzyme families are crucial to immune function, and catalyze thyroid hormone metabolism and redox processes in thyroid cells......-enriched yeast or matching placebo tablets daily for 12 months. The experimental supplement will be SelenoPrecise(R). The primary outcome is thyroid-related quality of life assessed by the Thyroid Patient-Reported Outcome (ThyPRO) questionnaire. Secondary outcomes include serum thyroid peroxidase antibody...
Nielsen, Signe Modvig; Høi-Hansen, Christina Engel; Uldall, Peter
Autoimmune synaptic encephalitis (ASE) is a recently recognized disease entity. The early and correct diagnosis of ASE is of importance, since the prognosis depends on the early onset of treatment. We present two Danish case reports of ASE: a 15-year-old boy presenting with a severe course of N-m......-methyl-D-aspartate-encephalitis including persistent cognitive deficits, and a 59-year-old woman with coeliac disease presenting with leucine-rich glioma inactivated 1-encephalitis including dyskinesia, epilepsy, psychiatric features and vocal tics....
Wang, Ping; Zheng, Song Guo
The regulatory T (Treg) cells play an important role in the maintenance of homeostasis and the prevention of autoimmune diseases. Although most studies are focusing on the role of Treg cells in T cells and T cells-mediated diseases, these cells also directly affect B cells and other non-T cells. This manuscript updates the role of Treg cells on the B cells and B cell-mediated diseases. In addition, the mechanisms whereby Treg cells suppress B cell responses have been discussed.
Nguyen, Khanh-Quynh; Tsou, Wen-I; Kotenko, Sergei; Birge, Raymond B
Receptor tyrosine kinases, Tyro-3, Axl and Mer, collectively designated as TAM, are involved in the clearance of apoptotic cells. TAM ligands, Gas6 and Protein S, bind to the surfaces of apoptotic cells, and at the same time, interact directly with TAM expressed on phagocytes, impacting the engulfment and clearance of apoptotic cells and debris. The well-tuned and balanced actions of TAM may affect a variety of human pathologies including autoimmunity, retinal degeneration, and cancer. This article emphasizes some of the emerging findings and mechanistic insights into TAM functions that are clinically relevant and possibly therapeutically targeted.
transforming lung epithelial cells with human papilloma virus -16 E6, E7 and ras oncogene . Expression of neu or Her-2, Kd or Kb and B7.1 was measured by...in cancer patients undergoing immunotherapy, the most prevalent autoimmune manifestations in humans is thyroiditis, with 45% of women and 20% of men...electro-vaccinated twice, 2 wks apart, with pE2TM encoding the extracellular and transmembrane domains of human Her-2 and either pGITRL or pGITRL
Full Text Available In the last decades, increasingly robust experimental approaches have formally demonstrated that autoimmunity is a physiological process involved in a large range of functions including cognition. On this basis, the recently enunciated “brain superautoantigens” theory proposes that autoimmunity has been a driving force of cognitive evolution. It is notably suggested that the immune and nervous systems have somehow co-evolved and exerted a mutual selection pressure benefiting to both systems. In this two-way process, the evolutionary-determined emergence of neurons expressing specific immunogenic antigens (brain superautoantigens has exerted a selection pressure on immune genes shaping the T-cell repertoire. Such a selection pressure on immune genes has translated into the emergence of a finely tuned autoimmune T-cell repertoire that promotes cognition. In another hand, the evolutionary-determined emergence of brain-autoreactive T-cells has exerted a selection pressure on neural genes coding for brain superautoantigens. Such a selection pressure has translated into the emergence of a neural repertoire (defined here as the whole of neurons, synapses and non-neuronal cells involved in cognitive functions expressing brain superautoantigens. Overall, the brain superautoantigens theory suggests that cognitive evolution might have been primarily driven by internal cues rather than external environmental conditions. Importantly, while providing a unique molecular connection between neural and T-cell repertoires under physiological conditions, brain superautoantigens may also constitute an Achilles heel responsible for the particular susceptibility of Homo sapiens to “neuroimmune co-pathologies” i.e., disorders affecting both neural and T-cell repertoires. These may notably include paraneoplastic syndromes, multiple sclerosis as well as autism, schizophrenia and neurodegenerative diseases. In the context of this theoretical frame, a specific
Bangsgaard, N; Engkilde, K; Menné, T
An inverse relation between contact allergy and autoimmune diseases is suggested from epidemiological studies. The aim of this study was to investigate susceptibility and reactivity in patients with psoriasis, patients with diabetes and healthy controls in an experimental sensitization study. We......-regulatory mechanisms with immunohistochemistry and gene-expression profiles using microarray technology. The sensitization ratios were 26%, 36% and 65% for the psoriatic, diabetic and healthy groups, respectively. Logistic regression analysis gave an odds ratio (OR) for a patient with psoriasis or diabetes type I...
Sebaratnam, Deshan F; Hanna, Anna Marie; Chee, Shien-ning; Frew, John W; Venugopal, Supriya S; Daniel, Benjamin S; Martin, Linda K; Rhodes, Lesley M; Tan, Jeremy Choon Kai; Wang, Charles Qian; Welsh, Belinda; Nijsten, Tamar; Murrell, Dédée F
Quality-of-life (QOL) evaluation is an increasingly important outcome measure in dermatology, with disease-specific QOL instruments being the most sensitive to changes in disease status. To develop a QOL instrument specific to autoimmune bullous disease (AIBD). A comprehensive item generation process was used to build a 45-item pilot Autoimmune Bullous Disease Quality of Life (ABQOL) questionnaire, distributed to 70 patients with AIBD. Experts in bullous disease refined the pilot ABQOL before factor analysis was performed to yield the final ABQOL questionnaire of 17 questions. We evaluated validity and reliability across a range of indices. Australian dermatology outpatient clinics and private dermatology practices. PATIENTS AND EXPOSURE: Patients with a histological diagnosis of AIBD. The development of an AIBD-specific QOL instrument. Face and content validity were established through the comprehensive patient interview process and expert review. In terms of convergent validity, the ABQOL was found to have a moderate correlation with scores on the Dermatology Life Quality Index (R = 0.63) and the General Health subscale of the 36-Item Short Form Health Survey (R = 0.69; P = .009) and low correlation with the Pemphigus Disease Area Index (R = 0.42) and Autoimmune Bullous Disease Skin Disorder Intensity Score (R = 0.48). In terms of discriminant validity, the ABQOL was found to be more sensitive than the Dermatology Life Quality Index (P = .02). The ABQOL was also found to be a reliable instrument evaluated by internal consistency (Cronbach α coefficient, 0.84) and test-retest reliability (mean percentage variation, 0.92). The ABQOL has been shown to be a valid and reliable instrument that may serve as an end point in clinical trials. Future work should include incorporating patient weighting on questions to further increase content validity and translation of the measure to other languages. anzctr.org.au Identifier: ACTRN12612000750886.
Hoetzenecker, Konrad; Zimmermann, Matthias; Hoetzenecker, Wolfram; Schweiger, Thomas; Kollmann, Dagmar; Mildner, Michael; Hegedus, Balazs; Mitterbauer, Andreas; Hacker, Stefan; Birner, Peter; Gabriel, Christian; Gyöngyösi, Mariann; Blyszczuk, Przemyslaw; Eriksson, Urs; Ankersmit, Hendrik Jan
Supernatants of serum-free cultured mononuclear cells (MNC) contain a mix of immunomodulating factors (secretome), which have been shown to attenuate detrimental inflammatory responses following myocardial ischaemia. Inflammatory dilated cardiomyopathy (iDCM) is a common cause of heart failure in young patients. Experimental autoimmune myocarditis (EAM) is a CD4+ T cell-dependent model, which mirrors important pathogenic aspects of iDCM. The aim of this study was to determine the influence of MNC secretome on myocardial inflammation in the EAM model. BALB/c mice were immunized twice with an alpha myosin heavy chain peptide together with Complete Freund adjuvant. Supernatants from mouse mononuclear cells were collected, dialysed, and injected i.p. at Day 0, Day 7, or Day 14, respectively. Myocarditis severity, T cell responses, and autoantibody formation were assessed at Day 21. The impact of MNC secretome on CD4+ T cell function and viability was evaluated using in vitro proliferation and cell viability assays. A single high-dose application of MNC secretome, injected at Day 14 after the first immunization, effectively attenuated myocardial inflammation. Mechanistically, MNC secretome induced caspase-8-dependent apoptosis in autoreactive CD4+ T cells. MNC secretome abrogated myocardial inflammation in a CD4+ T cell-dependent animal model of autoimmune myocarditis. This anti-inflammatory effect of MNC secretome suggests a novel and simple potential treatment concept for inflammatory heart diseases. © The Author 2013. Published by Oxford University Press on behalf of the European Society of Cardiology.
Pestronk, A.; Drachman, D.B.; Teoh, R.; Adams, R.N.
A therapeutic strategy was designed to eliminate the humoral immune response to acetylcholine receptor (AChR) in ongoing experimental autoimmune myasthenia gravis (EAMG). Rats with EAMG were treated with a protocol consisting of three components: (1) A single high dose of cyclophosphamide (200 mg/kg) was used to produce a rapid and sustained fall in the anti-AChR antibody levels by preferential destruction of antibody-producing B-lymphocytes. ''Memory'' lymphocytes were not eliminated by cyclophosphamide. (2) Irradiation (600 rads) was used to eliminate the ''memory'' cells. It eliminated the anamnestic response to a challenge with the antigen AChR. (3) Bone marrow transplantation was used to repopulate the hematopoietic system after the otherwise lethal dose of cyclophosphamide. We used bone marrow from syngeneic rats with active EAMG to simulate an autologous transplant. Rats with EAMG treated with this combined protocol showed a prompt and sustained fall in the anti-AChR antibody levels and had no anamnestic response to a challenge with AChR. Thus, an affected animal's own marrow could be stored and used later for repopulation after cyclophosphamide-irradiation treatment. This treatment eliminates the animal's ongoing immune responses and reconstitutes the immune system in its original state. The success of this approach suggests that, if their safety could be established, similar ''curative'' strategies might be developed for the treatment of patients with severe antibody-mediated autoimmune disorders, such as myasthenia gravis
Ramos-Leví, Ana Maria; Marazuela, Mónica
Hashimoto's thyroiditis (HT) and Graves' disease (GD) are two very common organ-specific autoimmune diseases which are characterized by circulating antibodies and lymphocyte infiltration. Although humoral and cellular mechanisms have been classically considered separately in the pathogenesis of autoimmune thyroid diseases (AITD), recent research suggests a close reciprocal relationship between these two immune pathways. Several B- and T-cell activation pathways through antigen-presenting cells (APCs) and cytokine production lead to specific differentiation of T helper (Th) and T regulatory (Treg) cells. This review will focus on the cellular mechanisms involved in the pathogenesis of AITD. Specifically, it will provide reasons for discarding the traditional simplistic dichotomous view of the T helper type 1 and 2 pathways (Th1/Th2) and will focus on the role of the recently characterized T cells, Treg and Th17 lymphocytes, as well as B lymphocytes and APCs, especially dendritic cells (DCs). Copyright © 2016 SEEN. Publicado por Elsevier España, S.L.U. All rights reserved.
Anette Holck Draborg
Full Text Available Systemic autoimmune diseases (SADs are a group of connective tissue diseases with diverse, yet overlapping, symptoms and autoantibody development. The etiology behind SADs is not fully elucidated, but a number of genetic and environmental factors are known to influence the incidence of SADs. Recent findings link dysregulation of Epstein-Barr virus (EBV with SAD development. EBV causes a persistent infection with a tight latency programme in memory B-cells, which enables evasion of the immune defence. A number of immune escape mechanisms and immune-modulating proteins have been described for EBV. These immune modulating functions make EBV a good candidate for initiation of autoimmune diseases and exacerbation of disease progression. This review focuses on systemic lupus erythematosus (SLE, rheumatoid arthritis (RA, and Sjögren’s syndrome (SS and sum up the existing data linking EBV with these diseases including elevated titres of EBV antibodies, reduced T-cell defence against EBV, and elevated EBV viral load. Together, these data suggest that uncontrolled EBV infection can develop diverse autoreactivities in genetic susceptible individuals with different manifestations depending on the genetic background and the site of reactivation.
Draborg, Anette Holck; Duus, Karen; Houen, Gunnar
Systemic autoimmune diseases (SADs) are a group of connective tissue diseases with diverse, yet overlapping, symptoms and autoantibody development. The etiology behind SADs is not fully elucidated, but a number of genetic and environmental factors are known to influence the incidence of SADs. Recent findings link dysregulation of Epstein-Barr virus (EBV) with SAD development. EBV causes a persistent infection with a tight latency programme in memory B-cells, which enables evasion of the immune defence. A number of immune escape mechanisms and immune-modulating proteins have been described for EBV. These immune modulating functions make EBV a good candidate for initiation of autoimmune diseases and exacerbation of disease progression. This review focuses on systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and Sjögren's syndrome (SS) and sum up the existing data linking EBV with these diseases including elevated titres of EBV antibodies, reduced T-cell defence against EBV, and elevated EBV viral load. Together, these data suggest that uncontrolled EBV infection can develop diverse autoreactivities in genetic susceptible individuals with different manifestations depending on the genetic background and the site of reactivation.
Shen, Bingzheng; Cao, Zhijian; Li, Wenxin; Sabatier, Jean-Marc; Wu, Yingliang
The effective treatment of autoimmune diseases remains a challenge. Voltage-gated potassium Kv1.3 channels, which are expressed in lymphocytes, are a new therapeutic target for treating autoimmune disease. Consequently, Kv1.3 channel-inhibiting venom-derived peptides are a prospective resource for new drug discovery and clinical application. Area covered: Preclinical and clinical studies have produced a wealth of information on Kv1.3 channel-inhibiting venom-derived peptides, especially from venomous scorpions and sea anemones. This review highlights the advances in screening and design of these peptides with diverse structures and potencies. It focuses on representative strategies for improving peptide selectivity and discusses the preclinical research on those venom-derived peptides as well as their clinical developmental status. Expert opinion: Encouraging results indicate that peptides isolated from the venom of venomous animals are a large resource for discovering immunomodulators that act on Kv1.3 channels. Since the structural diversity of venom-derived peptides determines the variety of their pharmacological activities, the design and optimization of venom-peptides for improved Kv1.3 channel-specificity has been advanced through some representative strategies, such as peptide chemical modification, amino acid residue truncation and binding interface modulation. These advances should further accelerate research, development and the future clinical application of venom-derived peptides selectively targeting Kv1.3 channels.
Wolff, A S B; Mitchell, A L; Cordell, H J; Short, A; Skinningsrud, B; Ollier, W; Badenhoop, K; Meyer, G; Falorni, A; Kampe, O; Undlien, D; Pearce, S H S; Husebye, E S
In common with several other autoimmune diseases, autoimmune Addison's disease (AAD) is thought to be caused by a combination of deleterious susceptibility polymorphisms in several genes, together with undefined environmental factors and stochastic events. To date, the strongest genomic association with AAD has been with alleles at the HLA locus, DR3-DQ2 and DR4. The contribution of other genetic variants has been inconsistent. We have studied the association of 16 single-nucleotide polymorphisms (SNPs) within the CD28-CTLA-4-ICOS genomic locus, in a cohort comprising 691 AAD patients of Norwegian and UK origin with matched controls. We have also performed a meta-analysis including 1002 patients from European countries. The G-allele of SNP rs231775 in CTLA-4 is associated with AAD in Norwegian patients (odds ratio (OR)=1.35 (confidence interval (CI) 1.10-1.66), P=0.004), but not in UK patients. The same allele is associated with AAD in the total European population (OR=1.37 (CI 1.13-1.66), P=0.002). A three-marker haplotype, comprising PROMOTER_1661, rs231726 and rs1896286 was found to be associated with AAD in the Norwegian cohort only (OR 2.43 (CI 1.68-3.51), P=0.00013). This study points to the CTLA-4 gene as a susceptibility locus for the development of AAD, and refines its mapping within the wider genomic locus.
Full Text Available Chronic and recurrent uveitis account for approximately 10% of legal blindness in the western world. Autoimmune uveitis is driven by activated CD4(+ T cells that differentiate into effector T helper cells (Th1, Th2, and Th17 which release proinflammatory cytokines that damage the retina. In this study we investigated the effect of the methionine aminopeptidase 2 (MetAP2 inhibitor, Lodamin, on T cell activation and differentiation. MetAp2 is an enzyme which regulates cellular protein synthesis and is highly expressed in T cells. Lodamin was found to suppress T cell receptor (TCR mediated T cell proliferation and reduced the production of Th1 and Th17 cells. Further, Lodamin suppressed overall inflammation in the mouse model of experimental autoimmune uveitis (EAU by a six fold. This effect was attributed in part to a reduction in retinal proinflammatory cytokines, down regulation of MetAP2 expression in purified lymph node CD4(+ T cells, and a general normalization of the systemic immune reaction.
Bazinet, Lauren; D’Amato, Robert J.
Chronic and recurrent uveitis account for approximately 10% of legal blindness in the western world. Autoimmune uveitis is driven by activated CD4+ T cells that differentiate into effector T helper cells (Th1, Th2, and Th17) which release proinflammatory cytokines that damage the retina. In this study we investigated the effect of the methionine aminopeptidase 2 (MetAP2) inhibitor, Lodamin, on T cell activation and differentiation. MetAp2 is an enzyme which regulates cellular protein synthesis and is highly expressed in T cells. Lodamin was found to suppress T cell receptor (TCR) mediated T cell proliferation and reduced the production of Th1 and Th17 cells. Further, Lodamin suppressed overall inflammation in the mouse model of experimental autoimmune uveitis (EAU) by a six fold. This effect was attributed in part to a reduction in retinal proinflammatory cytokines, down regulation of MetAP2 expression in purified lymph node CD4+ T cells, and a general normalization of the systemic immune reaction. PMID:23785488
Full Text Available Adipose tissue produces a wide range of proteins that may influence the immune system. In this study, we assessed the serum levels of leptin, adiponectin, and ghrelin, in association with the measurements of body composition, in 15 female patients with various autoimmune diseases (systemic lupus erythematosus, primary Sjögren's syndrome, sarcoidosis, mixed connective tissue disease, vasculitis, CREST syndrome, and polymyositis and in 15 healthy female controls. There were no statistically significant differences between the patients and controls with regard to serum leptin, serum ghrelin, global fat mass, adiposity, and fat mass in the android or gynoid regions, whereas serum adiponectin levels were higher in patients than controls (16.3±1.6 μg/mL versus 9.7±0.6 μg/mL; =.01. As adiponectin is known to exhibit potent anti-inflammatory properties, a high adiponectinemia in patients with systemic autoimmune disease may mitigate the inflammatory response. However, the precise consequences of these elevated serum adiponectin levels on the metabolic syndrome development and atherosclerotic cardiovascular risk in this patient population still needs to be determined.
Xie, Heng; Zhou, Fubo; Liu, Ling; Zhu, Guannan; Li, Qiang; Li, Chunying; Gao, Tianwen
Vitiligo is a common depigmentation disorder characterized by a loss of functional melanocytes and melanin from epidermis, in which the autoantigens and subsequent autoimmunity caused by oxidative stress play significant roles according to hypotheses. Various factors lead to reactive oxygen species (ROS) overproduction in the melanocytes of vitiligo: the exogenous and endogenous stimuli that cause ROS production, low levels of enzymatic and non-enzymatic antioxidants, disturbed antioxidant pathways and polymorphisms of ROS-associated genes. These factors synergistically contribute to the accumulation of ROS in melanocytes, finally leading to melanocyte damage and the production of autoantigens through the following ways: apoptosis, accumulation of misfolded peptides and cytokines induced by endoplasmic reticulum stress as well as the sustained unfolded protein response, and an 'eat me' signal for phagocytic cells triggered by calreticulin. Subsequently, autoantigens presentation and dendritic cells maturation occurred mediated by the release of antigen-containing exosomes, adenosine triphosphate and melanosomal autophagy. With the involvement of inducible heat shock protein 70, cellular immunity targeting autoantigens takes the essential place in the destruction of melanocytes, which eventually results in vitiligo. Several treatments, such as narrow band ultraviolet, quercetin and α-melanophore-stimulating hormone, are reported to be able to lower ROS thereby achieving repigmentation in vitiligo. In therapies targeting autoimmunity, restore of regulatory T cells is absorbing attention, in which narrow band ultraviolet also plays a role. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
Harpsøe, Maria C; Basit, Saima; Andersson, Mikael
.57) and type 1 diabetes mellitus (HR 2.67; 95% CI, 1.71 to 4.17). Risk of dermatitis herpetiformis increased by 14% (95% CI, 1% to 30%) per BMI unit. Conversely, risk of celiac disease and Raynaud's phenomenon decreased by 7% (95% CI, 1% to 13%) and 12% (95% CI, 4% to 19%) per BMI unit, respectively. Further......BACKGROUND: A possible aetiological link between obesity and certain autoimmune diseases (ADs) has been suggested. We investigated the associations between body mass index (BMI, kg/m2) and 43 ADs. METHODS: 75,008 women participating in the Danish National Birth Cohort were followed during a median......-up, 2430 women (3.2%) developed a total of 2607 new-onset ADs. Risk of any autoimmune disease was increased in obese women (HR, 1.27; 95% CI, 1.11 to 1.46) compared with normal weight women (18.5-≤25 kg/m2). Obese women (BMI≥30 kg/m2) were at increased risk of sarcoidosis (HR 3.59; 95% CI, 2.31 to 5...
Pitkaenen, J.; Rebane, A.; Rowell, J.; Murumaegi, A.; Stroebel, P.; Moell, K.; Saare, M.; Heikkilae, J.; Doucas, V.; Marx, A.; Peterson, P.
Autoimmune regulator (AIRE) is a transcriptional regulator that is believed to control the expression of tissue-specific genes in the thymus. Mutated AIRE is responsible for onset of the hereditary autoimmune disease APECED. AIRE is able to form nuclear bodies (NBs) and interacts with the ubiquitous transcriptional coactivator CBP. In this paper, we show that CBP and AIRE synergistically activate transcription on different promoter reporters whereas AIRE gene mutation R257X, found in APECED patients, interferes with this coactivation effect. Furthermore, the overexpression of AIRE and CBP collaboratively enhance endogenous IFNβ mRNA expression. The immunohistochemical studies suggest that CBP, depending on the balance of nuclear proteins, is a component of AIRE NBs. We also show that AIRE NBs are devoid of active chromatin and, therefore, not sites of transcription. In addition, we demonstrate by 3D analyses that AIRE and CBP, when colocalizing, are located spatially differently within AIRE NBs. In conclusion, our data suggest that AIRE activates transcription of the target genes, i.e., autoantigens in collaboration with CBP and that this activation occurs outside of AIRE NBs
Ye, Fei; Li, Qiutang; Ke, Yan; Lu, Qingjun; Han, Lixia; Kaplan, Henry J; Shao, Hui; Lu, Qingxian
TAM receptors are expressed mainly by dendritic cells and macrophages in the immune system, and mice lacking TAM receptors develop systemic autoimmune diseases because of inefficient negative control of the cytokine signaling in those cells. This study aims to test the susceptibility of the TAM triple knockout (tko) mice to the retina-specific autoantigen to develop experimental autoimmune uveoretinitis (EAU). TAM tko mice that were or were not immunized with interphotoreceptor retinoid-binding protein (IRBP) peptides were evaluated for retinal infiltration of the macrophages and CD3(+) T cells by immunohistochemistry, spontaneous activation of CD4(+) T cells, and memory T cells by flow cytometry and proliferation of IRBP-specific CD4(+) T cells by [(3)H]thymidine incorporation assay. Ocular inflammation induced by IRBP peptide immunization and specific T cell transfer were observed clinically by funduscopy and confirmed by histology. Tko mice were found to have less naive, but more activated, memory T cells, among which were exhibited high sensitivity to ocular IRBP autoantigens. Immunization with a low dose of IRBP and adoptive transfer of small numbers of IRBP-specific T cells from immunized tko mice caused the infiltration of lymphocytes, including CD3(+) T cells, into the tko retina. Mice without TAM receptor spontaneously develop IRBP-specific CD4(+) T cells and are more susceptible to retinal autoantigen immunization. This TAM knockout mouse line provides an animal model with which to study the role of antigen-presenting cells in the development of T cell-mediated uveitis.
Jin Kyeong Choi
Full Text Available Multiple sclerosis (MS is an inflammatory demyelinating disease in which cytokines produced by immune cells that infiltrate the brain and spinal cord play a central role. We show here that the IL-12p35, the alpha subunit of IL-12 or IL-35 cytokine, might be an effective biologic for suppressing neuroinflammatory responses and ameliorating the pathology of experimental autoimmune encephalomyelitis (EAE, the mouse model of human MS. We further show that IL-12p35 conferred protection from neuropathy by inhibiting the expansion of pathogenic Th17 and Th1 cells and inhibiting trafficking of inflammatory cells into the brain and spinal cord. In addition, in vitro exposure of encephalitogenic cells to IL-12p35 suppressed their capacity to induce EAE by adoptive transfer. Importantly, the IL-12p35-mediated expansion of Treg and Breg cells and its amelioration of EAE correlated with inhibition of cytokine-induced activation of STAT1/STAT3 pathways. Moreover, IL-12p35 inhibited lymphocyte proliferation by suppressing the expressions of cell-cycle regulatory proteins. Taken together, these results suggest that IL-12p35 can be exploited as a novel biologic for treating central nervous system autoimmune diseases and offers the promise of ex vivo production of large amounts of Tregs and Bregs for immunotherapy.
Czaja, Albert J
The intestinal microbiome is a reservoir of microbial antigens and activated immune cells. The aims of this review were to describe the role of the intestinal microbiome in generating innate and adaptive immune responses, indicate how these responses contribute to the development of systemic immune-mediated diseases, and encourage investigations that improve the understanding and management of autoimmune hepatitis. Alterations in the composition of the intestinal microflora (dysbiosis) can disrupt intestinal and systemic immune tolerances for commensal bacteria. Toll-like receptors within the intestine can recognize microbe-associated molecular patterns and shape subsets of T helper lymphocytes that may cross-react with host antigens (molecular mimicry). Activated gut-derived lymphocytes can migrate to lymph nodes, and gut-derived microbial antigens can translocate to extra-intestinal sites. Inflammasomes can form within hepatocytes and hepatic stellate cells, and they can drive the pro-inflammatory, immune-mediated, and fibrotic responses. Diet, designer probiotics, vitamin supplements, re-colonization methods, antibiotics, drugs that decrease intestinal permeability, and molecular interventions that block signaling pathways may emerge as adjunctive regimens that complement conventional immunosuppressive management. In conclusion, investigations of the intestinal microbiome are warranted in autoimmune hepatitis and promise to clarify pathogenic mechanisms and suggest alternative management strategies.
Cray, Carolyn; Watson, Toshiba; Zaias, Julia; Altman, Norman H
Fenbendazole is an anthelmintic drug widely used to treat and prevent pinworm infection in laboratory rodents. Data regarding possible side effects of fenbendazole on the immune system are conflicting, potentially due to the design of treatment protocols. The purpose of the current study was to determine the effects of 2 fenbendazole therapeutic regimens (continuous for 5 wk and alternating weeks [that is, 1 wk on, 1 wk off] for 9 wk) on the development of autoimmune disease in (NZB × NZW)F1 mice. No significant differences in survival curves or weight were observed between the treatment groups and cohort mice receiving nonmedicated feed. At the termination of the experiment, there were no differences in tissue pathology. Hematocrit decreased and BUN increased over time in all groups, but no significant differences were present between groups. After the cessation of treatment, mice fed the medicated diet continuously for 5 wk showed an increase in antiDNA antibody. Although this difference was significant, it did not affect survival curves or disease-related tissue or blood changes. These data indicate that common protocols of fenbendazole treatment do not alter the progression of autoimmune disease in (NZB × NZW)F1 mice.
D. Mesquita Jr
Full Text Available The traditional concept that effector T helper (Th responses are mediated by Th1/Th2 cell subtypes has been broadened by the recent demonstration of two new effector T helper cells, the IL-17 producing cells (Th17 and the follicular helper T cells (Tfh. These new subsets have many features in common, such as the ability to produce IL-21 and to express the IL-23 receptor (IL23R, the inducible co-stimulatory molecule ICOS, and the transcription factor c-Maf, all of them essential for expansion and establishment of the final pool of both subsets. Tfh cells differ from Th17 by their ability to home to B cell areas in secondary lymphoid tissue through interactions mediated by the chemokine receptor CXCR5 and its ligand CXCL13. These CXCR5+ CD4+ T cells are considered an effector T cell type specialized in B cell help, with a transcriptional profile distinct from Th1 and Th2 cells. The role of Tfh cells and its primary product, IL-21, on B-cell activation and differentiation is essential for humoral immunity against infectious agents. However, when deregulated, Tfh cells could represent an important mechanism contributing to exacerbated humoral response and autoantibody production in autoimmune diseases. This review highlights the importance of Tfh cells by focusing on their biology and differentiation processes in the context of normal immune response to infectious microorganisms and their role in the pathogenesis of autoimmune diseases.
Full Text Available Multiple sclerosis (MS is an autoimmune disease characterized by chronic inflammation in the central nervous system (CNS, which results in permanent neuronal damage and substantial disability in patients. Autoreactive T cells are important drivers of the disease, however, the efficacy of B cell depleting therapies uncovered an essential role for B cells in disease pathogenesis. They can contribute to inflammatory processes via presentation of autoantigen, secretion of pro-inflammatory cytokines and production of pathogenic antibodies. Recently, B cell aggregates reminiscent of tertiary lymphoid organs (TLOs were discovered in the meninges of MS patients, leading to the hypothesis that differentiation and maturation of autopathogenic B and T cells may partly occur inside the CNS. Since these structures were associated with a more severe disease course, it is extremely important to gain insight into the mechanism of induction, their precise function and clinical significance. Mechanistic studies in patiens are limited. However, a few studies in the MS animal model experimental autoimmune encephalomyelitis (EAE recapitulate TLO formation in the CNS and provide new insight into CNS TLO features, formation and function. This review summarizes what we know so far about CNS TLOs in MS and what we have learned about them from EAE models. It also highlights the areas that are in need of further experimental work, as we are just beginning to understand and evaluate the phenomenon of CNS TLOs.
Muneer G. Hasham
Full Text Available Systemic autoimmune diseases such as systemic lupus erythematosus (SLE and rheumatoid arthritis (RA show significant heart involvement and cardiovascular morbidity, which can be due to systemically increased levels of inflammation or direct autoreactivity targeting cardiac tissue. Despite high clinical relevance, cardiac damage secondary to systemic autoimmunity lacks inducible rodent models. Here, we characterise immune-mediated cardiac tissue damage in a new model of SLE induced by topical application of the Toll-like receptor 7/8 (TLR7/8 agonist Resiquimod. We observe a cardiac phenotype reminiscent of autoimmune-mediated dilated cardiomyopathy, and identify auto-antibodies as major contributors to cardiac tissue damage. Resiquimod-induced heart disease is a highly relevant mouse model for mechanistic and therapeutic studies aiming to protect the heart during autoimmunity.
Jønsson, Viggo; Bock, Johannes E; Hilden, Jørgen
cell autoantibodies and idiopathic thrombocytopenic purpura were equally common in women and men, whereas autoimmune thyroiditis, Sjögren's syndrome, rheumatoid arthritis and systemic lupus erythematosus were seen in higher rates in women than in men. The spectrum of autoimmunity suggests...
Gwizdek, Katarzyna; Michalski, Marek; Wojnicz, Romuald
The Epstein-Barr virus (EBV), also known as human herpesvirus 4, is a member of the Herpesviridae virus family. EBV infection can cause infectious mononucleosis (IM) in the lytic phase of EBV’s life cycle. Past EBV infection is associated with lymphomas, and may also result in certain allergic and autoimmune diseases. Although potential mechanisms of autoimmune diseases have not been clearly elucidated, both genetic and environmental factors, such as infectious agents, are considered to be responsible for their development. In addition, EBV modifies the host immune response. The worldwide prevalence of autoimmune diseases shows how common this pathogen is. Normally, the virus stays in the body and remains dormant throughout life. However, this is not always the case, and a serious EBV-related illness may develop later in life. This explains the chronic course of autoimmune diseases that is often accompanied by exacerbations of symptoms. Based on the present studies, EBV infection can cause autoimmune diseases, such as systemic lupus erythematosus (SLE), multiple sclerosis (MS), rheumatoid arthritis (RA), Sjögren’s syndrome, and autoimmune hepatitis. The EBV has also been reported in patients with autoimmune thyroid disorders. Although EBV is not the only agent responsible for the development of autoimmune thyroid diseases, it can be considered a contributory factor. PMID:27833448